RxPG News : Infertility

Probiotics can increase effectiveness of some antibiotic therapies

Thu, 09 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Antimicrobial treatments for bacterial vaginosis (BV) are effective, but taking lactobacillus tablets alongside metronidazole antibiotic therapy increases effectiveness over taking this antibiotic alone, according to a Cochrane Systematic Review. The researchers also concluded that intravaginal lactobacillus was as effective as oral metronidazole, although they did note unexplained drop-outs from the trials.

BV is a very common vaginal infection. Traditionally, antibiotics in tablet or gel form have been given to treat the disease, but some have unpleasant side effects. BV is usually a mild disease and can pass unnoticed but is associated with an increased risk of HIV transmission.

Treating BV could help reduce susceptibility of women to HIV. Therefore it is important, particularly in the developing world, to establish the most effective and appropriate forms of treatment, says lead researcher Oyinlola Oduyebo, of the Department of Medical Microbiology and Parasitology at the University of Lagos in Lagos Nigeria.

The researchers reviewed 24 trials involving 4,422 people. The antibiotics clindamycin and metronidazole both cured BV in over 90% of cases within two to three weeks, although there was a high rate of relapse. Side effects of metronidazole included nausea and a metallic taste in the mouth. However, it is the cheaper option and therefore likely to remain the most widely used in developing countries. Lactobacillus probiotic taken alongside metronidazole and taken intravaginally both showed significant effectiveness. Hydrogen peroxide and triple sulphonamide cream were not effective.

There are a range of good treatments for BV, but the high relapse rates require more attention and indicate that we need more research into other agents that can increase their effectiveness, said Oduyebo. We also need to understand why so many people dropped out of the Lactobacillus trials as this suggests there are unreported adverse effects.

Will IVF work for a particular patient? The answer may be found in her blood

Wed, 01 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Amsterdam, The Netherlands: For the first time, researchers have been able to identify genetic predictors of the potential success or failure of IVF treatment in blood. Dr. Cathy Allen, from the Rotunda Hospital, Dublin, Ireland, told the 25th annual conference of the European Society of Human Reproduction and Embryology today (Wednesday 1 July) that her research would help understand why IVF works for some patients but not for others.

Previous work in this area has looked at gene profiles in such tissues as the uterine lining, but Dr. Allen and her team chose to examine the gene expression patterns in RNA extracted from peripheral (circulating) blood, an easily accessible biological sample. Blood samples were taken at eight different stages during the period around conception and the early stages of the IVF cycle. Five of these samples came from women who achieved clinical pregnancies, three from those who had implantation failure, and three from subfertile women who conceived spontaneously. Analysis showed that 128 genes showed a more than two-fold difference in expression in early clinical pregnancy compared with a non-pregnant state.

The molecular pathways that were most over-represented in this expression were concerned with angiogenesis (the growth of new blood vessels), endothelin signalling (blood vessel constriction), inflammation, oxidative stress (damage to cell structures), vascular endothelial growth factor (signalling processes in blood vessel growth), and pyruvate metabolism (the supply of energy to cells). All these processes are important in the achievement and maintenance of pregnancy, said Dr. Allen.

We found that the gene expression profiles in blood of patients at the time of pituitary down-regulation showed interesting patterns of gene clustering. Over 200 genes were differentially expressed in patients who went on to achieve an IVF pregnancy compared with those who did not, she said.

The researchers found that the peripheral blood gene expression 'signature' (also known as the transcriptome) before IVF was predictive of IVF outcome. This finding demonstrates the power of high-dimensional technology in biomarker discovery, and highlights the potential for developing clinically useful tools, they say.

One of the most difficult decisions for patients who have had unsuccessful IVF treatments is whether they should undergo further attempts at IVF, or if there are ways to optimise chances of success. The researchers hope that the results generated by this work will lead to the development of a test to aid in IVF decision-making. They say that their work will help to identity biomarkers that can identify events occurring at implantation, the maintenance of pregnancy and successful or unsuccessful pregnancy outcome.

IVF technology has advanced tremendously over the past three decades, yet success after IVF remains an unpredictable outcome, said Dr. Allen. Our work will help understand whether the implantation of embryos is influenced by the constantly changing expression of human genes.

Previous studies in the field of gene-expression have focused on single genes as opposed to genome-wide screening of all the human genes with high density DNA microarrays, as used by Dr. Allen and her team. The advent of tools like microarrays that can simultaneously probe for up to 29,000 genes has radically changed scientific approaches to this type of research. It's like looking at how a team of players perform together rather than focusing on the individual players, said Dr. Allen.

We intend to look further at the most significant genes we have identified as being important in this field in order to be able to understand their exact biological role in reproductive function. We hope that our work will lead to the development of a clinically useful tool to help doctors counsel their patients in the difficult decision-making involved in IVF, she said.

Chromosomal problems affect nearly all human embryos

Wed, 01 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Amsterdam, The Netherlands: For the first time, scientists have shown that chromosomal abnormalities are present in more than 90% of IVF embryos, even those produced by young, fertile couples. Ms Evelyne Vanneste, a PhD student in the Centre for Human Genetics and the University Fertility Center, Leuven University, Belgium, told the 25th annual conference of the European Society of Human Reproduction and Embryology today (Wednesday July 1), that the surprising finding meant that current techniques used in preimplantation genetic screening (PGS), where embryos are screened genetically in order to select the best embryo for transfer, do nothing to improve pregnancy and live birth rates. Indeed, it can lead to potentially viable embryos being discarded, she said.

Ms Vanneste and her team studied each cell from 23 three or four day-old IVF embryos from young (less than 35 years old), fertile couples who had asked for preimplantation genetic diagnosis (PGD). PGD is carried out where one or both parents have a known genetic abnormality, in this case an X-linked disorder or the microdeletions (loss of a tiny piece of a chromosome) that can cause such disorders as the cancer predisposition syndrome neurofibromatosis type 1. The embryos are screened to avoid the implantation of one carrying that abnormality. Such embryos are the most representative of normal human embryogenesis, the process that begins once an egg has been fertilised.

Using new technologies that can detect chromosomal aberrations in the whole genome (all human chromosomes) of a single cell, the team was able to screen embryonic cells at a much higher resolution than previously, and hence identify more chromosomal abnormalities than has been possible using the current technique, fluorescent in situ hybridisation (FISH), which can only analyse ten of the approximately 32,000 genetic regions at the same time.

Until now, the majority of studies analysing the genetic composition of human embryos used low resolution techniques on embryos derived from couples with fertility problems who are at risk for embryonic aneuploidy, an aberrant number of chromosomes, such as three copies of chromosome 21 that results in Down's syndrome. Therefore, little was known about the frequency and type of chromosomal imbalances in embryos from normal, fertile women, said Ms Vanneste. Our new technique has enabled us to show that chromosomal abnormalities are far more common and complex than previously anticipated, even in embryos from young, normal fertile couples. This leads us to believe that such abnormalities must be present in all human IVF-ICSI embryos.

Although in vitro culture conditions are known to have a limited influence on the rate of chromosomal imbalances in IVF/ICSI embryos, it is probable that the chromosome instability observed in vitro also occurs in spontaneous pregnancies since, at most, 30% of human conceptions result in a live birth and more than 50% of spontaneous abortions carry chromosomal aberrations. The high rate of chromosomal abnormalities is almost certainly responsible for the low fecundity of humans compared with other mammals, she added.

The scientists say that their work has important implications for preimplantation genetic screening (PGS) in fertility treatment. PGS is routinely used in many fertility centres for couples who encounter problems with conception, particularly for advanced maternal age, repeated failure of implantation, repeated miscarriages, or severe male fertility problems. In PGS, a single cell is removed from the early embryo for genetic testing, since it is hypothesised that the selection of chromosomally normal embryos for uterine transfer would increase the live birth rate and decrease the spontaneous abortion rate per embryo transferred.

Although PGS is promoted as a way of increasing the chances of a successful pregnancy, said Ms Vanneste, there has never been any significant evidence that it does, in fact, increase live birth rates after IVF. Our findings have shown that almost every cell of a human embryo carries a different genetic composition; consequently, the one cell that is analysed genetically is not representative of the rest of the embryo. If the tested cell is genetically abnormal, the embryo will not be transferred. But the rest of the embryo might be normal and develop into a healthy person. Therefore, the use of PGS means that potentially viable embryos will be discarded. The prevalent chromosomal instability in all early human IVF embryos explains the failure of PGS to improve the live birth rate per embryo transferred.

I think that we have made a crucial breakthrough that will change the way we do preimplantation genetic diagnosis and PGS and help to advance our ability to improve human fertility, said Ms Vanneste.

Daily sex helps to reduce sperm DNA damage and improve fertility

Tue, 30 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Amsterdam, The Netherlands: Daily sex (or ejaculating daily) for seven days improves men's sperm quality by reducing the amount of DNA damage, according to an Australian study presented today (Tuesday) to the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam.

Until now there has been no evidence-based consensus amongst fertility specialists as to whether or not men should refrain from sex for a few days before attempting to conceive with their partner, either spontaneously or via assisted reproduction.

Dr David Greening, an obstetrician and gynaecologist with sub specialist training in reproductive endocrinology and infertility at Sydney IVF, Wollongong, Australia, said: All that we knew was that intercourse on the day of ovulation offered the highest chance of pregnancy, but we did not know what was the best advice for the period leading up to ovulation or egg retrieval for IVF.

I thought that frequent ejaculation might be a physiological mechanism to improve sperm DNA damage, while maintaining semen levels within the normal, fertile range.

To investigate this hypothesis, Dr Greening studied 118 men who had higher than normal sperm DNA damage as indicated by a DNA Fragmentation Index (DFI). Men who had a more than 15% of their sperm (DFI >15%) damaged were eligible for the trial. At Sydney IVF, sperm DNA damage is defined as less than 15% DFI for excellent quality sperm, 15-24% DFI for good, 25-29% DFI for fair and more than 29% DFI for poor quality; but other laboratories can have slightly different ranges.

The men were instructed to ejaculate daily for seven days, and no other treatment or lifestyle changes were suggested. Before they started, levels of DNA damage ranged between 15% and 98% DFI, with an average 34% DFI when measured after three days' abstinence. When the men's sperm was re-assessed on the seventh day, Dr Greening found that 96 men (81%) had an average 12% decrease in their sperm DNA damage, while 22 men (19%) and an average increase in damage of nearly 10%. The average for the whole group dropped to 26% DFI.

Dr Greening said: Although the mean average was 26% which is in the 'fair' range for sperm quality, this included 18% of men whose sperm DNA damage increased as well as those whose DNA damage decreased. Amongst the men whose damage decreased, their average dropped by 12% to just under 23% DFI, which puts them in the 'good' range. Also, more men moved into the 'good' range and out of the 'poor' or 'fair' range. These changes were substantial and statistically highly significant.

In addition, we found that although frequent ejaculation decreased semen volume and sperm concentrations, it did not compromise sperm motility and, in fact, this rose slightly but significantly.

Further research is required to see whether the improvement in these men's sperm quality translates into better pregnancy rates, but other, previous studies have shown the relationship between sperm DNA damage and pregnancy rates.

The optimal number of days of ejaculation might be more or less than seven days, but a week appears manageable and favourable. It seems safe to conclude that couples with relatively normal semen parameters should have sex daily for up to a week before the ovulation date. In the context of assisted reproduction, this simple treatment may assist in improving sperm quality and ultimately achieving a pregnancy. In addition, these results may mean that men play a greater role in infertility than previously suspected, and that ejaculatory frequency is important for improving sperm quality, especially as men age and during assisted reproduction cycles.

New, less invasive genetic test greatly improves pregnancy rates in older women with poor prognosis

Mon, 29 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Amsterdam, The Netherlands: A new test examining chromosomes in human eggs a few hours after fertilisation can identify those that are capable of forming a healthy baby, a researcher told the 25th annual conference of the European Society of Human Reproduction and Embryology today (Monday 29 June). Dr. Elpida Fragouli, from the Department of Obstetrics and Gynaecology, University of Oxford, UK, and Reprogenetics UK, said that her team's work had already enabled seven ongoing pregnancies in a group of older women with a history of multiple failed IVF attempts.

Out of 35 patients who had embryo transfers after the test, we achieved a pregnancy rate of 20%, which is exceptional considering the extremely poor prognosis of the women involved. she said. This represents a doubling of the usual pregnancy rate for women who fall into this category, which is otherwise, at best, under 10% and, at worst, zero. To date, we have two live births from this group, and all the other women who became pregnant have maintained their pregnancies. The study is continuing, and we believe that we will achieve more pregnancies with the help of this technology in the future.

The scientists used the Comparative Genomic Hybridisation (CGH) technique to count the chromosomes in each egg. Unlike conventional screening strategies, using the fluorescent in situ hybridisation (FISH) method, which allows less than half of the chromosomes of an embryonic cell to be examined, CGH enables the evaluation of the entire chromosome complement. CGH was used to examine the fertilised eggs by looking at polar bodies, tiny cells that are a by-product of egg development. The chromosomes of polar bodies provide an indication of whether the corresponding egg is normal or abnormal; if the polar bodies have the wrong number of chromosomes, so does the egg.

Looking at polar bodies is a less invasive way of obtaining information about the chromosome content of an egg and its resulting embryo than other alternatives, such as day-three biopsy, which take place during conventional screening strategies involving the use of the FISH technique. The removal of the polar bodies does not adversely affect the subsequent development of the embryo. Additionally, the results obtained after CGH analysis of polar bodies are not affected by the presence of chromosomal mosaicism (the presence of two populations of cells with different genotypes) and therefore may be more accurate than conventional methods based upon screening of cells removed from embryos.

The scientists examined 400 fertilised eggs generated by women with a very poor reproductive history and with an average age of 42 who were undergoing IVF because of being unable to conceive or to maintain a pregnancy. They found that more than half of all the eggs produced by these women had chromosomal abnormalities, and therefore the resulting embryos were also chromosomally abnormal. Some of the women had a tendency to produce eggs that were extremely abnormal and carried multiple chromosome errors. This could explain the poor reproductive history of these women, the scientists say.

But where we could find fertilised eggs free of chromosomal abnormalities, the resulting embryos were also normal and their transfer to the mother led to pregnancies, said Dr. Fragouli. Results suggest that the use of this technique will improve IVF success rates for poor prognosis patients. It is also likely to achieve a reduction in congenital abnormalities such as Down's syndrome, as well as a reduction in the frequency of spontaneous miscarriage.

The incidence of chromosomal abnormalities in human eggs is closely related to maternal age, and can affect more than 60% of all eggs in women over 40 years of age. Being able to select the right egg can not only lead to more successful IVF, but also enhance the use of single embryo transfer, especially in countries where embryo testing is forbidden and only eggs can be tested. Being able to examine the first polar body means that this test can be used in countries where embryo testing is forbidden by law, said Dr. Fragouli.

We are close to applying technical innovations which will make this test even better, faster, and cheaper. We are also going to be using the test in cases where fertility preservation is required, due to cancer, for example, she said.

Ovarian transplantation: First baby is born after a new technique

Mon, 29 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Amsterdam, The Netherlands: A new technique for transplanting the ovaries of women who have lost their fertility as a result of cancer treatment was outlined to the 25th annual conference of the European Society of Human Reproduction and Embryology today (Monday 29 June). Dr. Pascal Piver, manager of the IVF Centre at Limoges University Hospital, Limoges, France, described a new, two-step method of ovarian transplant that has produced excellent results in women whose ovaries have been frozen because of cancer treatment. He said that his team's technique worked to restore ovarian function quickly and already one patient from his clinic had had a baby and another had become pregnant.

On June 22, a baby girl was born to a mother who had been menopausal for two years as a result of treatment for sickle cell anaemia. After transplanting her own ovarian tissue she started ovulating in four months and became pregnant naturally six months after transplantation. Both mother and baby are doing well, he said.

Dr. Piver and colleagues set out to tackle one of the biggest problems of ovarian transplantation: the low response to stimulation caused by insufficient vascularisation of the transplanted tissue.

In order for a woman to become pregnant, the ovaries need to be responsive to the action of hormones that cause them to release eggs each month, he explained. If the blood supply to the ovaries is insufficient, this will not happen, even though the transplant may look as though it has been successful.

To overcome this problem they carried out a two-stage procedure, first grafting small pieces of the frozen ovarian tissue in the ovarian and peritoneal areas three days before the real transplant. The first graft encourages the growth of blood vessels and paves the way for the ovary to become fully functioning in a shorter time scale than would be possible if all the tissue were to be transplanted at the same time.

The researchers have so far utilised this technique with two patients who had been treated for cancer and had their ovaries frozen. In addition to the first patient, treated for sickle cell anaemia, the second patient had been treated for periarteritis nodosa, an inflammation of medium-sized arteries, which become swollen and damaged from attack by rogue immune cells.

She suffered menopause for eight and a half years before transplantation, said Dr. Piver. But after transplanting half of the frozen ovary, she recovered spontaneous ovulation in four months. Her right fallopian tube had been destroyed by the ovarian retrieval, and the function of the ovary and hence the chances of pregnancy are limited in time. Hence we decided to collect the highest number of eggs we could, and carry out an IVF procedure on this patient.

Six months after the operation, we transferred two blastocysts. A total of 22 oocytes were retrieved and produced 16 embryos, which in turn produced seven blastocysts. Unfortunately the first time round this patient developed an ectopic pregnancy, but she is now pregnant again.

The technique was developed by Dr. Piver and his team, he told the conference. This is the first time that a pregnancy has been obtained after a ten year gap between ovarian cryopreservation and grafting. We believe that it represents a considerable advance on the methods of ovarian transplantation used until now, not least because we are able to obtain large numbers of oocytes. We hope that it will enable more young patients who have been cured of cancer to regain their reproductive health and become pregnant with their own children, he said.

Ovarian transplantation: New technique gives greatly improved results in this delicate operation

Mon, 29 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Amsterdam, The Netherlands: Ultra-fast freezing of ovarian tissue from women who have lost their fertility as a result of cancer treatment can lead to it being used in transplants with the same success rate as fresh tissue, a researcher told the 25th annual conference of the European Society of Human Reproduction and Embryology today (Monday 29 June). Dr. Sherman Silber, Director of the St. Louis Infertility Centre, St. Louis, Missouri, USA, said that freezing tissue by the vitrification method, which avoids ice formation, meant that oocyte (egg) viability was almost identical with that seen in fresh oocytes.

Dr. Silber and colleagues used standard viability testing with fluorescent microscopy to determine the loss or preservation of oocytes in fresh and frozen ovarian tissue of 15 young women undergoing cancer treatment. They also followed up nine homozygotic twin patients after fresh ovary transplantation for the duration of ovarian function and pregnancy outcome, and tested spare tissue that had also been frozen from their ovaries at the time of transplant. Tissue was preserved either by rapid cooling vitrification or by classical slow freezing methods.

We found that 91.9% of the fresh oocytes were viable compared with 88.9% of those vitrified. However, slow freezing resulted in a 56% loss of viability, said Dr. Silber.

Transplantation of the tissue resulted in a duration of ovarian function of more than four years in five of the seven cases followed up for that long, and all patients regained a normal ovarian cycle within four to five months after the transplant. There was no difference in terms of pregnancy or ovulatory menstrual cycling between fresh and frozen grafts. The scientists used the cortical grafting technique, where very thin slices of tissue are transplanted. This technique is much easier to perform than the delicate microvascular technique, which they described last year in an effort to prevent egg loss and to lengthen the duration of ovarian graft function.

With the microvascular technique, the tiny blood vessels supplying the ovary are directly linked, and ischemia time, during which blood supply is restricted, is minimised. However, this is a very difficult operation not available in most reproductive centres. With the cortical grafting technique, ischemia time for revascularisation was always thought to be a limiting factor, not to mention the deleterious effect of freezing. However, very thin cortical slices not only allow the tissue to be frozen by vitrification, but also accelerate the speed of revascularisation of the ovarian graft.

We believed that microvascular transplant would give us a longer duration of ovarian function, said Dr. Silber, but our current research has proved us wrong. This is not only good news for surgeons, but also for patients who will be able to undergo a simpler procedure with equally successful results.

Out of the eight women who received cortical transplants, six have had one or more spontaneous pregnancies, resulting in the birth of seven healthy babies.

We are in the middle of a massive global infertility epidemic, caused by the new structure of our society where women choose not to have children until they are older, said Dr. Silber. As a result, many of them become infertile because of the ageing of their eggs and ovaries.

This procedure is a solution to that social dilemma, allowing women to have children when they are older by preserving their ovaries when they are younger and transplanting them back at a later date. It can also be used to preserve the fertility of young women with cancer who are likely to be cured of their cancer, but who will become sterile as a result of the cancer treatment without such intervention, he said.

ESHRE launches international study of polar body screening

Sun, 28 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Amsterdam, The Netherlands: The efficacy of preimplantation genetic screening (PGS) has been one of the most hotly disputed subjects in assisted reproduction over the past few years. None of the trials carried out so far has shown conclusively whether it works or not. Now the European Society of Human Reproduction and Embryology (ESHRE) Task Force on PGS has decided to try to find out if a novel method of doing PGS using polar body biopsy and chromosome array analysis offers a possible solution.

Professor Joep Geraedts, ESHRE chairman, told the 25th annual conference of the society today (Sunday June 28) that the Task Force would carry out a pilot study of PGS in one of each pair of 23 chromosomes in polar bodies, tiny cells that are a by-product of egg development, in collaboration with BlueGnome, a DNA technology company based in Cambridge, UK. Once a pilot study has shown that the technique is feasible, the researchers intend to carry out an international randomised trial.

The first phase will begin in September 2009 in two centres: the University of Bonn, Germany (Dr. Markus Montag and Professor Hans van der Ven), and SISMER, Bologna, Italy (Dr. Luca Gianaroli and Dr. Cristina Magli). Because this is a new technology, said Dr. Gianaroli, we need to carry out a pilot study in order to be sure that the analysis can be completed within a time period that allows for fresh transfer, as well as to ensure the reliable identification of the chromosomal status of an oocyte in at least 90% of polar body biopsy attempts.

The two centres chosen for the pilot study have considerable experience in the field of polar body biopsy because legislation in their countries restricts the possibility of undertaking embryo biopsy at a later stage of development. The data from the study will be independently analysed by Dr. Sjoerd Repping, from the Academic Medical Centre in Amsterdam, who carried out a randomised trial of PGS on three-day old embryos published in 2007. The researchers hope to present the data at ESHRE 2010 in Rome and to start the RCT with the involvement of at least six centres in different European countries later the same year.

Oocytes to be used in the pilot phase will be obtained from volunteer patients who have given consent for their use in this study. There will be no age restrictions on those donating their eggs.

By biopsying polar bodies at an early stage of egg development, the researchers believe that not only are they using a less invasive method of chromosome analysis, but also a more accurate one. A biopsied blastomere, or very early embryo, is not a true representation of the other cells in that same embryo, said Professor Geraedts. This mosaicism confuses the analyses and we don't know what it means for that embryo in the later stages of its development.

24sure, the novel molecular technique to be used in both phases of the trial was developed by BlueGnome and is based on DNA amplification and microarray technology, which enables scientists to look at all the chromosomes at the same time. This is, in theory, far more powerful than the method of fluorescent in situ hybridisation or FISH, which has been used thus far.

It is because we think this subject is so important, said Professor Geraedts, that we have decided to launch our first-ever clinical study. We hope that we will be able to answer the outstanding questions about PGS once and for all. If we can show that polar body screening works, it will be a major step forward in improving IVF treatment for many women who have persistent difficulty in getting pregnant and maintaining a pregnancy.

Study in pregnant women suggests probiotics may help ward off obesity

Thu, 07 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Amsterdam, the Netherlands: One year after giving birth, women were less likely to have the most dangerous kind of obesity if they had been given probiotics from the first trimester of pregnancy, found new research that suggests manipulating the balance of bacteria in the gut may help fight obesity.

Probiotics are bacteria that help maintain a healthy bacterial balance in the digestive tract by reducing the growth of harmful bacteria. They are part of the normal digestive system and play a role in controlling inflammation. Researchers have for many years been studying the potential of using probiotic supplementation to address a number of intestinal diseases. More recently, obesity researchers have started to investigate whether the balance of bacteria in the gut might play a role in making people fat and whether adjusting that balance could help.

The results of our study, the first to demonstrate the impact of probiotics-supplemented dietary counselling on adiposity, were encouraging, said Kirsi Laitinen, a nutritionist and senior lecturer at the University of Turku in Finland who presented her findings on Thursday at the European Congress on Obesity. The women who got the probiotics fared best. One year after childbirth, they had the lowest levels of central obesity as well as the lowest body fat percentage.

Central obesity, where overall obesity is combined with a particularly fat belly, is considered especially unhealthy, Laitinen said. We found it in 25% of the women who had received the probiotics along with dietary counselling, compared with 43% in the women who received diet advice alone.

In the study, 256 women were randomly divided into three groups during the first trimester of pregnancy. Two of the groups received dietary counselling consistent with what's recommended during pregnancy for healthy weight gain and optimal foetal development. They were also given food such as spreads and salad dressings with monounsaturated and polyunsaturated fatty acids, as well as fibre-enriched pasta and breakfast cereal to take home. One of those groups also received daily capsules of probiotics containing Lactobacillus and Bifidobacterium, which are the most commonly used probiotics. The other group received dummy capsules. A third group received dummy capsules and no dietary counselling. The capsules were continued until the women stopped exclusive breastfeeding, up to 6 months.

The researchers weighed the women at the start of the study. At the end of the study they weighed them again and measured their waist circumference and skin fold thickness. The results were adjusted for weight at the start of the study.

Central obesity - defined as a body mass index (BMI) of 30 or more or a waist circumference over 80 centimetres - was found in 25% of the women who had been given the probiotics as well as diet advice. That compared with 43% of the women who got dietary counselling alone and 40% of the women who got neither diet advice nor probiotics. The average body fat percentage in the probiotics group was 28%, compared with 29% in the diet advice only group and 30% in the third group.

Laitinen said further research is needed to confirm the potential role of probiotics in fighting obesity. One of the limitations of the study was that it did not control for the mothers' weight before pregnancy, which may influence how fat they later become.

She said she and her colleagues will continue to follow the women and their babies to see whether giving probiotics during pregnancy has any influence on health outcomes in the children.

The advantage of studying pregnant women to investigate the potential link between probiotics and obesity is that it allows us to see the effects not only in the women, but also in their children, she said. Particularly during pregnancy, the impacts of obesity can be immense, with the effects seen both in the mother and the child. Bacteria are passed from mother to child through the birth canal, as well as through breast milk and research indicates that early nutrition may influence the risk of obesity later in life. There is growing evidence that this approach might open a new angle on the fight against obesity, either through prevention or treatment.

Latinen's study was funded by the Social Insurance Institution of Finland, the Academy of Finland and the Sigrid Juselius Foundation, a Finnish medical research charity.

Obesity gene associated with susceptibility to polycystic ovary syndrome

Mon, 16 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Researchers have shown that a gene implicated in the development of obesity is also associated with susceptibility to polycystic ovary syndrome (PCOS). The FTO gene has recently been shown to influence a person's predisposition to obesity, and is now the first gene to be associated convincingly with susceptibility to PCOS(1). Carried out by Dr Tom Barber and colleagues from the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and Imperial College London, this research is the first evidence to show a genetic link between obesity and PCOS. The results are being presented at the annual Society for Endocrinology BES meeting in Harrogate.

PCOS is a common condition affecting up to 1 in 10 women of child-bearing age. PCOS affects the ovaries and is characterised by irregular periods, excessive hair growth and is a common cause of infertility. PCOS is strongly associated with obesity, and it is thought that the prevalence of PCOS will increase with rising levels of obesity. The FTO gene is known to influence weight. There are two versions of this gene, one of which is associated with increased weight gain and susceptibility to development of obesity(2).

Dr Tom Barber and colleagues are interested in working out the genetic causes of PCOS and its metabolic consequences. Given the association between PCOS and obesity, they investigated whether variants of the FTO gene also influence susceptibility to PCOS. To this end, they analysed the type of FTO gene carried by 463 PCOS patients and 1336 female population controls. They found that the type of FTO gene a person carried significantly influenced their susceptibility to PCOS. In fact, the version of the gene which is associated with increased weight gain is also associated with PCOS. The data suggest that FTO variants influence PCOS-susceptibility via an effect on fat mass. This is the first gene to be associated convincingly with susceptibility to PCOS and provides genetic evidence to corroborate the well established link between PCOS and obesity.

Researcher Dr Tom Barber said:

Polycystic ovary syndrome is an incredibly common condition affecting 1 in 10 women of reproductive age and is a leading cause of infertility. It is a genetic condition and one that is strongly associated with obesity; it is therefore of huge relevance for women given today's obesity epidemic. Our research shows that a variant of the FTO gene that has previously been shown to be associated with obesity also influences susceptibility to polycystic ovary syndrome. These data provide the first genetic evidence to corroborate the well documented association between these two conditions. Our future work will focus on elucidating the underlying mechanisms of polycystic ovary syndrome and its metabolic consequences with the hope of understanding how this common condition develops. This in turn will instruct future therapeutic developments for women who suffer from polycystic ovary syndrome.

Hormone offers promise as fertility treatment

Mon, 16 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) New research suggests the hormone kisspeptin shows promise as a potential new treatment for infertility. The research is being presented at the annual Society for Endocrinology BES meeting in Harrogate. Scientists led by Dr Waljit Dhillo from Imperial College London, have shown that giving kisspeptin to women with infertility can activate the release of sex hormones which control the menstrual cycle. This research could lead to a new fertility therapy for women with low sex hormone levels.

Kisspeptin is a product of the KISS-1 gene and is a key regulator of reproductive function. Animals and humans lacking kisspeptin function do not go through puberty and remain sexually immature. In a previous study, Dr Waljit Dhillo and colleagues showed that kisspeptin treatment leads to the production of sex hormones in fertile women; they have now extended their research to look at the effects of kisspeptin in women whose periods have stopped due to a hormone imbalance.

In this study, funded by the Medical Research Council, The Wellcome Trust and National Institute for Health Research, a group of ten women who were not menstruating and infertile, were injected with either kisspeptin (n=5) or saline (control, n=5). Blood samples were then taken to measure their levels of luteinising hormone (LH) and follicle stimulating hormone (FSH), two sex hormones essential for ovulation and fertility. Kisspeptin led to a 48-fold increase in LH and 16-fold increase in FSH, when compared to the control treatment.

This is the first study to show that kisspeptin can stimulate sex hormones in women with infertility and presents kisspeptin as a potential new therapy for human infertility.

Researcher Dr Waljit Dhillo from the Department of Investigative Medicine at Imperial College London said:

Infertility is a devastating condition that affects millions of couples worldwide. This research shows that kisspeptin offers huge promise as a treatment for infertility. From our previous results, we know that kisspeptin can stimulate release of reproductive hormones in healthy women. We have now extended this research to show that kisspeptin treatment has the same effect in women with infertility. In fact, our current data show that kisspeptin causes a greater increase in luteinising hormone production in non-menstruating women, than that in fertile women in the previous study. This is a very exciting result and suggests that kisspeptin treatment could restore reproductive function in women with low sex hormone levels. Our future research will focus on determining the best protocol for repeated kisspeptin administration with the hope of developing a new therapy for infertility.

New techniques designed to identify healthy embryos

Wed, 12 Nov 2008 04:43:59 PST

( from http://www.rxpgnews.com ) At the 64th Annual Meeting of the American Society for Reproductive Medicine in San Francisco, researchers today shared new techniques designed to identify healthy embryos while sparing them excessive stress.

As women age, their eggs are more vulnerable to mistakes that can occur in the copying, dividing, and organization of their chromosomes. Although some clinics advise women of advanced maternal age having assisted reproductive technology treatment to have pre-implantation genetic screening (PGS) of their embryos to ensure that only embryos without chromosomal errors are transferred, the ASRM Practice Committee has concluded that the evidence does not support the use of PGS to increase pregnancy rates in women of advanced age. Aneuploidy exists in eggs and embryos of young women as well as older women, and it has been established that embryos containing both normal and aneuploid cells can correct themselves and result in normal live births.

Elpida Fragouli, PhD and her colleagues found that a comprehensive genetic analysis of eggs, done by analyzing the chromosomes they discard in polar bodies, can detect almost twice as many maternally-derived abnormalities as routine PGS done on blastomeres. This approach reduces the risk of injury to embryos. Fifty women, averaging 40-plus years of age, had 293 fertilized eggs chromosomally analyzed via the first and second polar bodies. These zygotes were then frozen for future transfer pending the outcome of their testing. Chromosome errors were found in 43% of first polar bodies and in 40% of second. The technique revealed that these errors could affect any chromosome in the human egg.

Another technique, developed by Dagan Wells, PhD and his team, uses analysis of trophectoderm cells – cells from the outer part of a blastocyct destined to develop into the placenta – to maximize the amount of chromosomal information obtained on an embryo, while minimizing the risk it is exposed to. By using trophectoderm cells, the researchers were able to take several cells from each embryo reducing the risk of misdiagnosis. Cells from 106 blastocysts belonging to 17 patients, averaging 37 years old with histories of failed IVF attempts and miscarriages were examined and full chromosome screens were obtained for 91% of the blastocysts. Although 44% of the embryos were chromosomally abnormal, all of the embryos survived biopsy. Seventy percent of the cycles that went to embryo transfer resulted in clinical pregnancy.

Mandy Katz-Jaffe, PhD and her group are working on a way to use measurements of the gene expression of cumulous cells- protective cells that surround the egg – to gauge the egg’s chromosomal competence. In their experiment, cumulous cells were collected from the eggs of patients undergoing IVF. Chromosomes from the eggs’ first and second polar bodies were analyzed to obtain a comprehensive aneuploidy screen of each egg. Six eggs in the study were found to be normal and six were identified as aneuploid. Then RNA from cumulous cells belonging to each of the 12 eggs was isolated and analyzed to see which genes were active in the cumulous cells. Two new gene sets associated with aneuploid eggs were identified.

UT Health Science Center at Houston to have key role in largest US children's study

Fri, 03 Oct 2008 03:59:37 PST

( from http://www.rxpgnews.com ) The University of Texas Health Science Center at Houston will play a key role in local recruitment for the largest child health study in the United States.

The National Children's Study will follow 100,000 children across the United States from before birth through age 21 to identify genetic and environmental factors that contribute to health disorders and conditions of childhood and adulthood. Across Harris County, 2,000 women will be recruited during pregnancy. In all, there are 105 study locations across the nation.

This is a landmark study. It will be the largest study of women and children that will take place in our lifetime. It should provide valuable information that can help us better understand such conditions as autism, childhood obesity and prematurity, said Sean Blackwell, M.D., principal investigator for The University of Texas Medical School at Houston and associate professor in obstetrics, gynecology and reproductive sciences.

This is a groundbreaking study to assess the influence of gene-environment interactions on the origins of the most important health problems that affect both children and adults. In this respect, this work has the potential to be one of the most informative and useful clinical studies ever conducted, said Giuseppe Colasurdo, M.D., dean of the UT Medical School at Houston. Blackwell, director of Pregnancy and Birth Assessment for the UT portion of the study, and Chris Greeley, M.D., director of the pediatric component, will lead the effort in assessing women and children in Harris County, Colasurdo said.

Both the UT Medical School at Houston and The University of Texas School of Public Health, which are part of the UT Health Science Center, will participate in the study.

By studying children through their different phases of growth and development, researchers will be better able to understand the role genetic and environmental factors have on health and disease. According to a statement by the National Children's Study, Findings from the study will be made available as the research progresses, making potential benefits known to the public as soon as possible. Ultimately, the National Children's Study will be one of the richest research efforts geared towards studying children's health and development and will form the basis of child health guidance, interventions and policy for generations to come.

Researchers at the UT School of Public Health will be able to assess children and pregnant women in Harris Country for exposure to diverse environmental agents in the area, which is home to a number of large petrochemical and port facilities. This information will provide us with a better understanding of how these environmental conditions interact with other factors to influence health outcomes, said Guy S. Parcel, Ph.D., John P. McGovern Professor in Health Promotion and dean of the School of Public Health.

Ken Sexton, Sc.D., professor and director of the Division of Environmental and Occupational Health Sciences, and Beatrice Selwyn, Sc.D., associate professor of epidemiology, will lead the School of Public Health effort to study the impact of the environment on Harris County children.

The UT Health Science Center at Houston will receive $3.5 million from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to fund its efforts.

Due to the strengths of our clinical research programs in obstetrics and neonatology, with the leadership of Drs. Susan Ramin and Kathleen Kennedy and our strong partnerships with the Memorial Hermann Healthcare System and Harris County Hospital District, we are able to be key players in the National Children's Study for Harris County, said Blackwell. This is a unique opportunity for collaborations among investigators from different disciplines. We are very fortunate to have such an infrastructure as the Center for Clinical and Translational Sciences, which I hope will facilitate these efforts.

To conduct the research, the UT Medical School at Houston and the UT School of Public Health will be working with Baylor College of Medicine, which is the lead institution for Harris County, and The University of Texas M.D. Anderson Cancer Center.

Being awarded the NCS grant is a wonderful opportunity for the Houston community. It is absolutely terrific to have joint collaboration among the various medical institutions, said Susan Ramin, M.D., Emma Sue Hightower Professor and chair of obstetrics, gynecology and reproductive sciences at the medical school.

Acupuncture may hold promise for women with hormone disorder

Wed, 03 Sep 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Charlottesville, Va., Sept. 3, 2008 -- Getting pregnant with her first child was difficult, but when Rebecca Killmeyer of Charlottesville, Va. experienced a miscarriage during her second pregnancy, she wasn't sure if she would ever have another baby. When she decided to enter a study testing the impact of acupuncture on women with polycystic ovary syndrome (PCOS) at the University of Virginia Health System, she came out with a miracle.

To our great surprise we were blessed with a third pregnancy during the PCOS study, said Killmeyer. I'm absolutely certain the acupuncture treatments helped me ovulate regularly, which allowed me to become pregnant.

Lisa Pastore, assistant professor of obstetrics and gynecology at UVA Health System and principle researcher of the study, was hoping for results like this. Her goal has been to help women with PCOS have regular menstrual cycles. PCOS causes a hormonal imbalance, interfering with ovulation and ultimately, fertility. With several women in the study reporting pregnancies, Pastore believes that acupuncture could be an important alternative, non-drug therapy for women with this disorder.

Over the last year we have seen women who never had a regular menstrual cycle start having regular periods. We can also boast several pregnancies since the study began, said Pastore. Now we would like to recruit more people to the study in order to complete the study. It is important for research to have enough participants to ensure that the results are scientifically credible and not due to chance.

Scared and skeptical was how Killmeyer described her initial feelings towards the experimental treatment, but soon her worries gave way to relaxation.

When I saw those tiny little needles coming at me I thought to myself, 'I didn't sign up for this!' but I tried it and after a few minutes I was asleep on the table, Killmeyer said. The sessions were completely refreshing after awhile.

Killmeyer learned of her PCOS in 2005. Over the past five years she did not have regular, monthly periods. One month after she started acupuncture treatments she got a period and for the next three months, they continued.

I had finished all my acupuncture treatments and was in the end stages of the study when I became pregnant, Killmeyer said. We had already scheduled our follow-up appt with our fertility doctors when we found out we were pregnant.

Five percent of reproductive age women are affected by PCOS. Symptoms of PCOS can include small cysts on their ovaries, infrequent or irregular vaginal bleeding, male-pattern hair growth, and acne. Insulin resistance and pre-diabetes also can develop.

While there are many traditional drugs and therapies that manage this syndrome, this research is assessing whether acupuncture can be successful in regulating hormones and curing the symptoms of PCOS.

W.M. Keck Foundation grant funds reproductive science research

Mon, 28 Jul 2008 03:59:37 PST

( from http://www.rxpgnews.com ) EVANSTON, Ill. --- Northwestern University has received a three-year, $1.6 million grant from the W.M. Keck Foundation to support reproductive science research focused on understanding the chemical and biological signaling events surrounding fertilization and early embryonic development.

The egg and sperm unite at the time of fertilization and create a new cell called the zygote. This single cell then divides many times, ultimately forming a new individual. How do the egg and sperm mature, and what is the underlying mechanism that controls cellular division and differentiation?

An interdisciplinary team of researchers at Northwestern believes that inorganic molecules -- zinc, calcium, iron and others -- may lie at the heart of this matter. The team's goal is to determine what critical roles these molecules, particularly zinc, play in signal processing. Based on preliminary studies, the team hypothesizes that fluxes in zinc ions mediate the first definitive signal in embryonic development.

Cells communicate by sending signals through networks of small molecules, but little is known about these networks in fertilization and early embryonic development. A better understanding of the role of inorganic molecules in signaling could help with fertility issues as well as shed light on the role of metal metabolism dysfunction in many diseases, including diabetes, cancer and Alzheimer's disease.

The project is being led by Thomas O'Halloran, Charles E. and Emma H. Morrison Professor in Chemistry in the Weinberg College of Arts and Sciences, and Teresa K. Woodruff, Thomas J. Watkins Memorial Professor of Obstetrics and Gynecology at the Feinberg School of Medicine. O'Halloran is an expert in how cells use essential metal nutrients such as zinc, copper and iron at the molecular level, and Woodruff's specialty is in ovarian biology and reproductive science.

This research is focused on an unexplored area of egg and sperm biology, namely, the relationship of physiologically relevant metals to the events surrounding fertilization, said Woodruff. The involvement of inorganic molecules in this process has not been examined, and the development of imaging technologies that are predicted to bring a new level of sensitivity and detection capability to this critical time in biology is exciting.

The team will use the Keck Foundation grant to purchase a custom-built scanning transmission electron microscope with multiple detectors for quantitative images of the inorganic elements in the mouse germ cells. No existing microscope can do this. Furthermore, the movement and flux of these ions will be tracked in live cells using confocal microscopy. New fluorescent nanosensors will be developed specifically for these studies.

The work lies at the interface of reproductive science, chemistry, biophysics and imaging technology. Also on the research team are Vinayak P. Dravid, professor of materials science and engineering at Northwestern and director of the University's NUANCE Center (Atomic and Nanoscale Characterization Experimental Center), and Jonathan Silverstein, M.D., associate professor of surgery and radiology at the University of Chicago Medical Center and associate director of the university's Computation Institute.

Dravid's expertise lies in advanced microscopy and analytical techniques; he will coordinate construction of the electron microscope and develop methods to use the equipment. Silverstein specializes in the application of computers and other technology to the analysis of vast biomedical databases; he will develop software to interpret the data collected using the microscope and will create 3-D images of the eggs showing amounts and distribution of the inorganic molecules.

The origin of the idea, that zinc in particular may play an important role in these signaling pathways, came from the research of graduate student Alison Kim, who is working with O'Halloran and Woodruff. She discovered that zinc was not uniformly distributed in eggs as they matured, which was unexpected.

That got us all thinking, said O'Halloran. Could zinc be a signal in the fertilization process? The evidence was strong enough for us to pursue. We first want to test whether there is a zinc signal pathway and then build a model of how zinc acts in the egg. This is very exciting because zinc's primary role in the body is typically thought to involve catalysis, not signaling.

Should embryos with a hereditary disorder be transferred if no unaffected embryos are available?

Mon, 07 Jul 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Barcelona, Spain: The numbers of cycles of preimplantation genetic diagnosis or screening are rising steadily in Europe with over 2,700 reported in 2004 (the most recent year for which data are available). Fertility centres are able to screen for a growing number of genetically related conditions, but what should doctors do if no embryos without the targeted condition are available for transfer and the parents request that affected embryos should be transferred instead?

Ethicist Dr Wybo Dondorp told the 24th annual meeting of the European Society of Human Reproduction and Embryology in Barcelona today (Monday): Parental requests for transferring affected embryos should not be dismissed beforehand as a sign of irresponsible capriciousness. As the couple's primary wish may be for a child, they may reason that if a non-affected, healthy child is not what they can get, they will also be happy with, and good parents for, a child with a condition they at first intended to avoid. Respect for autonomy at least requires taking such requests seriously, even if, in view of all other considerations, doctors decide not agree to the requests.

Dr Dondorp, who is a senior research fellow at the faculty of Health, Medicine and Life Sciences, department of Health, Ethics and Society at Maastricht University (The Netherlands), said that before couples have preimplantation genetic diagnosis (PGD), fertility clinics should discuss the decision-making process and the particular clinic's policy in their pre-test counselling sessions with prospective parents, so that everyone was clear about what the options were in cases where no unaffected embryos could be obtained.

He said the most important consideration was the welfare of the child, particularly taking into account doctors' professional responsibility to do no harm. A high risk of serious harm is a contraindication for transferring affected embryos. The present consensus is that where the classical indications for PGD are concerned, doctors should, as a general rule, not transfer affected embryos where no non-affected ones are available. In pre-test counselling it should be explained that if no non-affected embryos are available, the only options are trying a new cycle or being advised to reconsider one's reproductive plans such as refraining from reproduction, using donor eggs or sperm, or adoption.

The welfare of the child is closely connected to the classical indication for PGD: a serious disease caused by a single gene mutation for which there are no, or limited, treatments, and, in most cases, presenting early in life. An example is an embryo that is homozygous for cystic fibrosis, where the child will definitely have the disease. In such cases it is inconceivable that doctors would agree to transfer these embryos as it would be at odds with their professional responsibilities.

However, as the use of PGD is being extended increasingly to conditions outside the classical range of indications, transferring affected embryos need not always involve a high risk of serious harm. This is obvious where treatable diseases are concerned, such as MCAD deficiency (where people with a faulty medium-chain acyl-CoA dehydrogenase gene are unable to metabolise fat, but can lead a healthy life by observing a strict diet).

Things are less clear where PGD for hereditary cancer syndromes is concerned. Debate about this is urgent, as centres are already confronted with parental requests to transfer embryos found to have the targeted mutation (e.g. BRCA1 or BRCA2 genes for hereditary breast cancer) in cases where no non-affected ones turned out to be available. How should they respond? That there seems to be more room here to at least discuss the issue has everything to do with the nature of the conditions in question: serious but later onset, incomplete genetic penetrance (not all individuals with the mutation will also have the disease) and availability of some therapeutic options, said Dr Dondorp.

In the case of PGD for hereditary cancer, room for manoeuvre will depend on a case-sensitive evaluation of aspects relevant to the 'high risk of serious harm' criterion, also in view of the family history. If this approach is acceptable and if further debate leads centres to decide that they would not categorically rule this out, pre-test information about centre policy should be adapted accordingly. It must be made clear that there may be, with conditions, room for shared decision-making about transferring affected embryos. But that does not amount to leaving it to the parents, as doctors cannot avoid their professional responsibility for the welfare of the future child.

He concluded: However, professionals may still find it difficult to respond to such requests that lead not only to the deliberate conception of a child in need of special care, but also to the very outcome they set out to prevent when offering PGD to a couple. Is it acceptable to use PGD just for trying to have a better result than one is eventually prepared to accept? This fits in with a wider debate about the morally charged nature of PGD and the proportionality of its uses: is it acceptable to use PGD for avoiding treatable disease, such as MCAD, in the first place?

Together with Professor Guido de Wert, also from Maastricht University, Dr Dondorp is writing a paper to be published in Europe's leading reproductive medicine journal, Human Reproduction, on these issues. This is the first time ethicists have considered the questions that arise as a result of extending the use of PGD to hereditary symptoms such as cancer and MCAD.

New photo 'op' for ovaries may solve some mysteries of infertility

Thu, 19 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) CHICAGO -- What causes a woman's eggs to deteriorate in quality with age, and can that be reversed?

How does the ovary choose an egg -- out of a stash of roughly one million -- to release for ovulation? And can the ovary be influenced to pick a good quality egg rather than one with chromosomal damage?

These questions are much on the mind of fertility researcher Teresa Woodruff. Woodruff, director of the Center for Reproductive Research at Northwestern University's Feinberg School of Medicine, hopes to find the answers and, with them, new treatments for fertility disease and age-related infertility. Her research, funded by a new $6.5 million National Institutes of Health grant, has a novel approach.

Instead of measuring hormones and looking at genes -- the more traditional approaches to infertility research -- Woodruff and colleagues are studying the architecture and behavior of the ovaries.

We're going to approach fertility disease from a new perspective, said Woodruff, the Thomas J. Watkins Professor of Obstetrics and Gynecology at the Feinberg School. If we continue to look at the diseases of women's fertility traditionally, we're not going to solve the problems.

The inner daily workings of the ovary largely remain a mystery waiting to be solved.

We don't understand how each follicle is selected to begin the process of ovulation, Woodruff said. What caused this one to be selected when it's May and you're 19 years old while there might be one sitting right next to it quiescently for another 20 years before it is moved to the position where it can ovulate? Something controls or parcels those follicles over time so that you have enough from puberty until menopause.

There aren't many tools to help researchers examine the way ovaries function. Enter Frank Miller, M.D., who is developing a new imaging device to do exactly that.

Ovaries are small and deep and they are more challenging to look at, said Miller, a professor of radiology at the Feinberg School and medical director of magnetic resonance imaging at Northwestern Memorial Hospital.

So he, along with colleagues in radiology, are designing a non-invasive magnetic resonance elastography device inspired by a larger one currently used for imaging livers.

Miller's new device will resemble a tiny drum, the size based on its future photo op with its subject - ovaries the size of walnuts. The device will generate sound waves (like the sub-woofer system of a car, Miller says) to measure the rigidity of the ovaries.

Ovary rigidity is important to measure because it is one of the symptoms of polycystic ovary syndrome, a metabolic disease that is the leading cause of hormone-related infertility. In the syndrome, a woman's follicles do not function or ovulate normally.

We hope that we will soon be able to understand more about age-related infertility and polycystic ovary syndrome, Woodruff said. We're tackling problems that have been difficult to solve.

Experts highlight gaps in knowledge on caring for survivors of teenage and young adult cancers

Tue, 10 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) London, UK: Over 95% of patients with testicular cancer are cured nowadays, but this success has produced a new problem for cancer survivors, the medical profession and national governments, a cancer expert will tell Teenage Cancer Trust's Fifth International Conference on Teenage and Young Adult Cancer Medicine, which is meeting in London on Monday and Tuesday (June 9 and 10).

Dr Craig Nichols, director of program development and director of the germ cell tumor and lymphoma program at the Providence Cancer Center (Oregon, USA) will tell the conference: Patients with testicular cancer, and, indeed, several other of the more treatable cancers, have great expectations of a cure, but this also imparts an additional responsibility of ensuring that the medical and social consequences of the disease and the cure have a minimum impact.

We are returning an extra 50-60 years of life to teenagers and young adults who have been treated successfully for cancer. This shifts the emphasis from 'can we cure this disease?' to 'can we retain this near perfect cure rate as well as reducing the short and long term side effects of treatment, minimising the fertility consequences of therapy, reducing the long term risk of a second cancer and metabolic syndrome, and developing pre-emptive strategies for managing psychosocial consequences of cancer and cancer treatment at a young age?'.

The medical profession and national governments need to develop strategies for meeting this challenge. They need to recognise that care cannot just stop when the patient is cured of the cancer, and that there is a huge cost still to be faced in terms of long-term care and support and in terms of collateral damage. Maximising the chances for good health for the next 50 years of life has very calculable social benefits, and people are beginning to realise this now. This is a fundamental shift.

Nearly three-quarters of children with cancer survive into adulthood, but a north American study has shown that, 30 years after diagnosis, 42% are affected by severe disease or a life-threatening condition, or have died. In the UK, there are approximately 30,000 survivors of cancer diagnosed before the age of 15, and given that cancer is more common between the ages of 15-24 than in childhood and assuming cure rates are similar to those for children, there are probably over 30,000 survivors of cancer diagnosed when they were aged between 15-24.

Dr Nichols will explain that cancer patients face a double whammy: There are two aspects: the burden of the disease and the burden of treatment. Each makes a long-term contribution to the patient's quality of life.

Problems for cancer survivors include: the increased risk of a second cancer arising either from the first cancer or from its treatment, infertility caused by chemotherapy and radiotherapy, hypertension, kidney problems, the metabolic syndrome (a collection of disorders such as obesity, high cholesterol levels, high blood pressure and insulin resistance) and hormonal disorders. Survivors of testicular cancer may have life-long problems with low sperm counts, low testosterone levels and poor semen quality. Patients who have survived cancer as children, teenagers or young adults often have psychosocial problems as well.

We are beginning to learn more about the psychosocial consequences such as body image, employment and sexual health, says Dr Nichols. There's a higher incidence of lower performance in life generally among cancer survivors. They have undergone a big life disruption at a formative time in their lives. There needs to be recognition of this so that we can try to identify problems and risks early on and be pre-emptive in our use of psychosocial interventions and use of medications.

Traditionally, paediatricians have tended to drive initiatives on caring for cancer survivors because they recognised the problem some time ago. In the USA, the challenge is being met by the establishment of Adolescent and Young Adult Clinics and Specialised Survivorship Clinics under the auspices of the National Cancer Institute. In the UK, the government's recently published Cancer Reform Strategy announced the setting up of a new National Cancer Survivorship Initiative to consider a range of approaches to caring for cancer survivors.

Simon Davies, chief executive of Teenage Cancer Trust, says: We know that this is a major issue that affects a lot of our patients and is increasingly going up the national agenda. I have just been invited to join the National Health Improvement Agency's working group on improving services to survivors of childhood cancers. I am also a member of the National Cancer Research Institute's Teenage and Young Adult Clinical Studies Development Group. One of their three strands of work is survivorship led by Professor Mike Hawkins.

Speaking before the conference started, Prof Mike Hawkins, director of the Centre for Childhood Cancer Survivor Studies at the University of Birmingham (UK) agrees that survivorship following cancer in childhood, teenage or young adult years is becoming an increasingly important area in the UK and it has been highlighted by the cancer czar, Professor Mike Richards. Prof Hawkins and his colleagues plan to follow-up approximately 25,000 survivors of cancer diagnosed between the ages of 15-24 between 1970-2000 in order to discover the specific problems this age group face.

He identifies three key areas where there need to be improvements:

'Cancer was one of the best things to happen to me... but I worry about the future'

Tue, 10 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) London, UK: For Dan Savage, surviving testicular cancer has been a spur to him making the most of his life and taking more adventurous decisions, and he says, that in retrospect, it was probably one of the best things that has happened to him. But as he approaches the end of his fifth year in remission from the disease, when he will be signed off as cured by the medical profession, he worries that from now on he will have no regular medical checks that might pick up early signs of the cancer returning. It will be down to him to contact the cancer clinic if he is worried about any new symptoms.

Dan, aged 25, is now an award-winning artist. He has set up his own studio in York (UK) and specialises in creating glass artwork for architectural spaces. He is also an ambassador for Teenage Cancer Trust and will be speaking at the charity's Fifth International Conference on Teenage and Young Adult Cancer Medicine on Tuesday.

Dan was 20 and studying art at Lancaster University when he discovered a lump the size of half a pea in his right testicle. After having surgery at Lancaster he was transferred to St James's hospital in Leeds for chemotherapy.

The chemotherapy was largely precautionary. The outward appearance of the tumour suggested it had been caught early, but when they dissected it, they found it was quite developed, just on the brink of spreading and they didn't want to take that risk. Also they found that I had the most aggressive form of testicular cancer, teratoma, says Dan.

Dan feels he got off fairly lightly, although the chemotherapy made him very sick and he lost his hair. Looking back now, he says: Having cancer, for me, was one of the best things to happen. It gave me a real drive to succeed and make the most of my life. I know, from speaking to other cancer survivors, that many of them agree. I have gained more confidence. Starting up my own business isn't necessarily what I would have done prior to having cancer. Cancer didn't stop his studies: he went back to university, completed his degree and went on to do a Masters degree in Glass. He has also married his long-term girlfriend.

Dan has not suffered any particular problems following his treatment, although he finds he is more susceptible to common colds and other illnesses that are going around.

I'm much more aware now of my own body and if anything is slightly out of kilter, I'm probably a lot more paranoid about it, he says. On a day-to-day basis I'm fairly relaxed, but if I have an ache or pain I start to worry.

One thing I am getting a bit worried about is that I'm coming up to five years in remission, and will be signed off by the doctors in June. Thereafter it's up to me. People say I'm cured but I don't see it like that. Something could crop up. It worries me that I won't have any more medical checks. I know that if I find anything that's odd I can go straight back to the clinic rather than the GP, which is good because the GP route was a bit of a nightmare. So that is reassuring. But I get reassurance from having regular checks, from having a blood test and even if I don't hear anything after the blood test has been taken, I still know someone has seen it and it's OK. I would prefer to keep the checks going for longer.

Before his chemotherapy the doctors talked to him about fertility and he had sperm samples frozen. The samples were good quality, but, as he was young, fit and healthy (apart from the cancer), he knows he has a good chance of his fertility returning to normal levels, although he hasn't re-visited the fertility clinic to check yet.

Dan says he has become very health conscious in terms of fitness levels and diet. I drink a lot of green tea!

Just like penguins and other primates, people trade sex for resources

Thu, 10 Apr 2008 03:59:37 PST

( from http://www.rxpgnews.com ) ANN ARBOR, Mich.---Female penguins mate with males who bring them pebbles to build egg nests. Hummingbirds mate to gain access to the most productive flowers guarded by larger males.

New research shows that even affluent college students who don't need resources will still attempt to trade sexual currency for provisions, said Daniel Kruger, research scientist at the University of Michigan School of Public Health.

The exchange of resources for sex---referred to by scientists as nuptial gifts---has occurred throughout history in many species, including humans, Kruger said. The male of the species offers protection and resources to the female and offspring in exchange for reproductive rights. For example, an arranged marriage can be considered a contract to trade resources.

However, the recent findings suggest that such behaviors are hard wired, and persist no matter how much wealth, resources or security that people obtain.

It's remarkable to find these patterns in the students in the study, Kruger said. We have seen many examples where people do this out of necessity, but we still see these tendencies in people who are already well provided for.

In addition, there are predictable, sexual differences in the types of exchanges attempted. Men are more likely to attempt to exchange investment for sex, females were more likely to attempt to exchange sex for investment, Kruger said.

For the study, researchers interviewed 475 U-M undergraduate students to discover if they attempted exchanges in reproductively relevant currencies outside of dating or formally committed relationships, and if they were aware of attempts others tried with them. While the study population was limited to students, these types of exchanges happen all over the world in different cultures and species, he said.

The majority of students were well aware of their own attempts to trade reproductive currency, Kruger said. However, if they were in committed relationships, they did not view the partnership as trading in reproductive currencies, he said.

Overall, the strategy of attempting to exchange investment for sex is only successful about 25 percent of the time, the paper found. Some of the attempted trades included: tickets to the U-M versus Ohio State game; studying assistance; laundry washed; a Louis Vuitton bag; and voice lessons among other things.

Students in the study were 18-26 years old. For exchange attempts made, 27 percent of men and 14 percent of women reported attempts to trade investment for sex, 5 percent of men and 9 percent of women reported attempts to trade sex for investment. Of exchange attempts initiated by others, 14 percent of men and 20 percent of women reported that someone else attempted to trade investment for sex with them, and 8 percent of men and 5 percent of women reported that someone else attempted to trade sex for their investment.

A sample of older individuals, especially one that is more representative of the general population, would likely report higher frequencies of experiences, Kruger said. The assumption is an older population would have more unmet needs and would be more sexually active.

In fact, Kruger said the findings were remarkable in that any exchanges were reported at all, considering the subjects' youth and affluence---in other words, they don't want for much yet they still attempt these exchanges.

The confirmation of hypothetical predictions regarding these exchanges once again demonstrates the power of an evolutionary framework for understanding human psychology and behavior, Kruger said.

A new method to avoid multiple IVF pregnancies

Sun, 16 Mar 2008 16:03:28 PST

( from http://www.rxpgnews.com ) New York, March 16 - In a new study, scientists have identified genetic markers that allow the selection of eggs with the best chance of successful pregnancy after in vitro fertilisation -.

The study, by researchers at the Universite Laval in Canada, holds the potential of both improving the success rate of single embryo transfer as well as cutting the instances of multiple pregnancies, Sciencedaily reported.

Findings of the study, for which an international patent has been filed, have been published on the website of the journal Human Reproduction.

Eggs recovered in the course of the IVF process are surrounded by follicular cells, which are removed before the actual fertilisation procedure begins.

'While in the ovaries, these cells and the eggs are in very close interaction,' explained Marc-Andre Sirard, who led the study.

'A first experiment we conducted on bovine follicular cells led us to believe that these cells might possess specific markers that would be able to give us information about the quality of an egg.'

With the help of 40 women recruited in a fertility clinic, researchers compared follicular cells surrounding eggs that ultimately led to successful pregnancies - in other words 'good' eggs -- to cells surrounding ovules that did not result in pregnancy.

This comparison led to the identification of five genes expressed more abundantly in follicular cells surrounding good eggs.

Currently, the way to assess which embryos are to be transferred into a woman's uterus is based on visible criteria such as appearance and division rate.

'At least 30 percent of embryos that look normal through visual examination nonetheless show chromosome abnormalities,' explained Sirard, illustrating the limits of this type of assessment.

The method developed by Sirard's team makes it possible to objectively select ovules that have the best chance of success without altering the integrity of the embryos.

This new genomic tool could also solve an ethical problem confronting both fertility clinic doctors and the people who consult them: In order to increase the chances of pregnancy, many embryos are implanted simultaneously into the woman in the hope that at least one will survive.

This procedure along with improved IVF techniques has led to an increase in multiple pregnancies.

Even if doctors now tend to transfer fewer embryos, multiple pregnancies still occur in 30 percent of couples who resort to IVF in North America and 23 percent in European couples.

'By selecting the embryo with the best potential, it would be possible to limit the number of embryos transferred, and thus the number of multiple pregnancies, while maintaining good success rates,' said Sirard.

Fertility in developing countries: words into action

Wed, 12 Mar 2008 03:59:37 PST

( from http://www.rxpgnews.com ) For almost 30 years - since the world's first test-tube baby was born in July 1978 - the benefits of modern infertility treatments have been largely confined to couples in developed countries. There, we have seen more than 3 million babies born as a result of IVF and, in some countries, as many as 4 per cent of all babies born conceived by modern fertility techniques.

The plight of couples in developing countries, especially women, has been acknowledged, but rarely advanced from words into action. Now, a task force of ESHRE (the European Society of Human Reproduction and Embryology), the world's leading professional organisation in reproductive medicine, has devised a programme of fertility treatment for developing countries which aims to integrate fertility clinics within broader family health services. Two pilot IVF services have already opened in Africa.

According to Professor Oluwole Akande from University College Hospital in Ibadan, Nigeria, infertility in developing countries raises complex problems beyond those known to developed nations. In poor resource areas, he says, the need for infertility treatment in general, and IVF in particular, is great. The inability to have children can create enormous problems, particularly for the woman. She might be disinherited, ostracised, accused of witchcraft, abused by local healers, separated from her spouse, or abandoned to a second-class life in a polygamous marriage.

There are many reasons why infertility treatment has not been widely introduced in developing countries. The main explanations are poverty and limited health resources, but there is also the paradox that most of the countries where needs are greatest are also the countries where population growth is running out of control.

Says Dr Willem Ombelet, from the Genk Institute for Fertility Technology in Genk, Belgium, and co-ordinator of the ESHRE task force: It is for these reasons that the ESHRE task force plans are to integrate infertility treatment within existing family planning and mother-care services. The most important goal is to provide treatment which is safe, affordable and culturally acceptable.

The ESHRE programme proposes three levels of treatment, but its cornerstone is the provision of affordable IVF. Currently, one cycle of IVF treatment in Europe or the USA costs between US$ 5000 and 10,000. A system of low-cost IVF now being pilot-studied in Khartoum and Cape Town aims to provide one cycle of IVF for less than $200.

One of the instigators of the low-cost IVF scheme, Dr. Luca Gianaroli from the SISMER Reproductive Medicine Unit, in Bologna, Italy, says: It's a different approach to IVF. We will not be able to treat every type of infertility, but many women with tubal damage as a result of infection can be helped. While the scheme has limited laboratory facilities for incubation, embryo selection and embryo freezing, Gianaroli says triplets and high-order pregnancies will be avoided.

The cornerstones in the treatment of infertility in low-resource settings, says Ombelet, are the simplification of techniques, minimizing of complications, training for healthcare workers, and the incorporation of fertility treatments into existing healthcare programmes.

Teenage fathers are more likely to have babies affected by birth problems

Fri, 08 Feb 2008 16:59:37 PST

( from http://www.rxpgnews.com ) Teenage fathers are at increased risk of having babies born with birth problems ranging from pre-term delivery or low birth weight, through to death in or near to the time of delivery, according to new research published on (Thursday 7 February).

In contrast, the study also found that older fathers, aged 40 and over, were not at increased risk of having babies affected by these problems. The results were independent of the age of the mother or other maternal factors that might be expected to have an impact on birth outcomes.

Congenital heart defects increasing among IVF twins

Sun, 03 Feb 2008 13:29:37 PST

( from http://www.rxpgnews.com ) The prevalence of congenital heart disease (CHD) among in vitro fertilization (IVF) pregnancies was similar to that of the general population, but there is an increasing risk of CHD among twins resulting from IVF, according to research by Yale School of Medicine researchers.

Working with the Fetal Cardiovascular Center at Yale University and Yale-New Haven Hospital, a central referral center for the State of Connecticut, Bahtiyar and his colleagues examined almost 2,000 patients using fetal echocardiography. The study lasted from January 1, 2006 through July 31, 2007. Among those patients, 250 women were specifically seen due to pregnancy resulting from in vitro fertilization. They did not have other medical problems that would require echocardiograms. The team conducted 357 fetal echocardiograms for 347 fetuses on these 250 women. Approximately 30 percent had twin pregnancies.

“We found that twin pregnancies conceived through IVF have a higher prevalence of CHD than singletons,” said Bahtiyar, who saw a three-fold increase. “IVF twins are usually fraternal, but past studies of identical twins also showed up to a 13-fold increase in congenital heart defects.”

Bahtiyar said that previous reports of increased CHD risk in pregnancies conceived via IVF may be due, in part, to a higher frequency of multiple pregnancies resulting from this form of conception. “The increased twinning seems to be the cause of the abnormality and not IVF per se.”

Bahtiyar and his team plan to increase the number of study subjects to replicate these preliminary results.

“The next step is to explore why this is happening,” he said. “Knowing about the risk of these defects will help increase the likelihood of survival after birth.”

Wild chimpanzees appear not to regularly experience menopause

Thu, 13 Dec 2007 04:59:37 PST

( from http://www.rxpgnews.com ) CAMBRIDGE, Mass. -- A pioneering study of wild chimpanzees has found that these close human relatives do not routinely experience menopause, rebutting previous studies of captive individuals which had postulated that female chimpanzees reach reproductive senescence at 35 to 40 years of age.

Together with recent data from wild gorillas and orangutans, the finding -- described this week in the journal Current Biology -- suggests that human females are rare or even unique among primates in experiencing a lengthy post-reproductive lifespan.

We find no evidence that menopause is common among wild chimpanzee populations, says lead author Melissa Emery Thompson, a postdoctoral researcher in anthropology at Harvard University. While some female chimpanzees do technically outlive their fertility, it's not at all uncommon for individuals in their 40s and 50s -- quite elderly for wild chimpanzees -- to remain reproductively active.

While wild chimpanzees and humans both experience fertility declines starting in the fourth decade of life, most other human organ systems can remain healthy and functional for many years longer, far outstripping the longevity of the reproductive system and giving many women several decades of post-reproductive life.

By contrast, in chimpanzees reproductive declines occur in tandem with overall mortality. A chimpanzee's life expectancy at birth is only 15 years, and just 7 percent of individuals live to age 40. But females who do reach such advanced ages tend to remain fertile to the end, Emery Thompson and her colleagues found, with 47 percent giving birth once after age 40, including 12 percent observed to give birth twice after age 40.

Fertility in chimpanzees declines at a similar pace to the decline in survival probability, whereas human reproduction nearly ceases at a time when mortality is still very low, the researchers write in Current Biology. This suggests that reproductive senescence in chimpanzees, unlike in humans, is consistent with the somatic aging process.

In other words, human evolution has resulted in an extended life span without complementary extended reproduction.

Why hasn't reproduction kept pace with the general increase in human longevity It may be because there hasn't been anything for natural selection to act on, though there is heritable variation in age of menopause, Emery Thompson says. However, it may be that the advantage older females gain by assisting their grandchildren outstrips any advantage they might get by reproducing themselves.

The oldest known wild chimpanzee, who died earlier this year at approximately age 63, gave birth to her last offspring just eight years ago, at about 55. Female chimpanzees only give birth every 6 to 8 years, on average, and they generally begin reproducing at age 13 to 15. This makes the chimpanzee reproductive profile much longer and flatter than that of humans, whose procreation is concentrated from age 25 to 35.

Emery Thompson and her colleagues gathered data from six wild chimpanzee populations in Tanzania, Uganda, Guinea, and Gambia. They compared these chimpanzees' fertility patterns to those seen among two well-studied human foraging populations, in Botswana and Paraguay.

Cow infections could provide clue to preventing infertility in women

Thu, 25 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers at the Royal Veterinary College, London, have made a significant breakthrough in their understanding of how infection of the uterus damages fertility in cows. Their findings, which show that common uterine infections can damage the ovaries, may provide insights into how to treat infections such as Chlamydia in humans.

Funded by the Wellcome Trust and the Biotechnology and Biological Sciences Research Council, researchers led by Professor Martin Sheldon studied the effect that uterine disease has on the reproductive system in cows. Their findings, published today in the journal Reproduction, suggest that the cow's innate immune system may affect key stages in the reproductive cycle, including suppressing the release of the female sex hormone oestrogen and causing failure to ovulate.

Approximately a million dairy cows get uterine disease each year in the UK, affecting not only milk production but also the cow's ability to reproduce. Cows already have an unusually low chance of conceiving � a 30% chance compared to over 60% in sheep � so if their fertility falls further and they are unable to conceive, they become uneconomical to keep and may be culled.

In cows, uterine disease is usually caused by bacteria entering the uterus after the cow has given birth. The same route of infection can also occur in women; however, humans may also be affected by sexually transmitted infections such as Chlamydia. Although the infections are usually successfully treated with antibiotics, the infertility often persists.

Using the bacterium E. coli, Professor Sheldon and colleagues examined the effect that bacteria have on the granulosa cells that line each egg-containing follicle in the ovary. These granulosa cells nurture the egg until the follicle bursts to release the egg, and they make oestradiol (a form of the sex hormone oestrogen), which encourages the female to copulate. The researchers found that even after treatment of uterine disease, the follicle still contains toxin left over from the breakdown of the pathogen.

The researchers also found that granulosa cells, which protect the egg inside the follicle, play a part in the immune response to infection by recognising that the toxin has entered the follicle and inhibiting production of oestradiol.

We believe that granulosa cells may play a role in 'quality control' relating to ovulation, says Professor Sheldon. Infection can potentially damage the genetic make-up of an egg, and these 'errors' would be passed down from generation to generation. By suppressing the release of oestrogen � in effect, reducing sexual behaviour � the granulosa are preventing those defects being passed on.

Professor Sheldon believes that these findings open up a new, previously overlooked, avenue for treating uterine disease in cows.

The emphasis on treating uterine disease has so far always been on clearing infection in the uterus, he says. We need to remember that the infection also affects the ovaries and may cause lasting damage. We may need to treat the disease with anti-inflammatory drugs or develop new anti-toxins.

The findings mirror those from research previously carried out in mice, suggesting that granulosa may be a part of the innate immune system in other mammals, possibly including humans.

It appears that bacteria have a lasting effect on fertility in cattle and possibly humans, says Professor Sheldon. Our research suggests a mechanism for how this may occur and offers hope for developing new treatments to prevent this from happening.

Immune cells promote blood vessel formation in mouse endometriosis

Thu, 18 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A discovery in mice of immune cells that promote the formation of new blood vessels could lead to new treatments for endometriosis, a painful condition associated with infertility that affects up to 15 percent of women of reproductive age.

The formation of new blood vessels, or angiogenesis, is known to encourage the growth of tumors and endometriosis lesions. A team led by Ofer Fainaru, MD, PhD, a research associate in the Vascular Biology Program at Children's Hospital Boston and Harvard Medical School, found that dendritic cells�highly specialized immune cells�help trigger angiogenesis in a mouse model of endometriosis. Their findings were published online last month in the FASEB journal. Judah Folkman, MD, director of Children�s Vacular Biology Program, who helped found the field of angiogenesis, was the paper�s senior author.

Endometriosis occurs when endometrium, a tissue normally found in the inner lining of the uterus, grows elsewhere in the body�most commonly in the abdominal cavity. The misplaced endometrial tissue begins as small lesions, or masses, but once blood vessels are recruited, the lesions grow larger and respond to female hormones, resulting in inflammation, cyclic pelvic pain, and infertility.

In the mouse model, the researchers observed that dendritic cells infiltrate endometriosis lesions, and near the sites where they invade, new blood vessels form. Injecting mice with excess dendritic cells caused their lesions to gain more blood vessels and to grow larger.

The researchers also found that dendritic cells have a strikingly similar effect on intra-abdominal tumors.

When the researchers grew dendritic cells together with endothelial cells�the cells that line blood vessel walls�the endothelial cells migrated towards the dendritic cells. The team hypothesizes that dendritic cells, after embedding in a new lesion or tumor, act like foremen on a building team: they call in, direct and support endothelial cells that build the new blood vessels.

We believe that targeting dendritic cells may prove to be a promising strategy for treating conditions dependent on angiogenesis, such as endometriosis and cancer, says Fainaru. But first, the team must demonstrate that dendritic cells are essential�that without these cells in mice, new blood vessels do not form.

Our next step would be to look for specific dendritic cell inhibitors that could have the potential to block angiogenesis in these conditions, says Fainaru.

The team hopes to develop cell-specific therapy for angiogenesis-dependent diseases that will be more effective and less toxic than current treatments. Currently, the most effective treatment for endometriosis is surgically removing the lesions, but this does not prevent them from growing back�as large and symptomatic as before. If dendritic cells are indeed ringmasters and not sideliners in new blood vessel growth, locally knocking them out just after an initial surgery, or altering them in some way, could render the lesions tiny and harmless.

Similarly, potential dendritic-cell inhibitors, when added to other agents that stop new blood vessels from forming, could enhance doctors� ability to choke off growing tumors, Fainaru adds.

In-vitro fertilization improved with 3-D/4-D-guided embryo transfer and new placement target

Tue, 16 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Beverly Hills, Calif. and Washington DC (ASRM Annual Meeting) - October 15, 2007 - The pregnancy rate for patients undergoing in-vitro fertilization (IVF) is improved when doctors use advanced 3D/4D imaging to guide the placement of embryos to the point where the endometrium is most receptive to implantation, according to a study presented at the 63rd Annual Meeting of the American Society for Reproductive Medicine (ASRM).

Placing embryos in the optimal location within the uterus is a key factor determining the success of in-vitro fertilization. The study's lead author, Robert Gergely, M.D., has identified a new embryo placement target as the point where the fallopian tubes would intersect if they were extended beyond their natural length.

This imaginary intersection, which has been dubbed the Maximal Implantation Potential (MIP) Point, is where embryos typically implant and develop in natural pregnancies. Precision in embryo placement has become especially critical in recent years given the trend to limit the number of embryos transferred during in-vitro fertilization to just a single embryo in order to reduce the likelihood of multiple births.

The study, titled Maximal Implantation Potential (MIP) Point - Suggested Target for Optimal Embryo Placement Within the Uterine Cavity During Embryo Transfer (ASRM: P-665), was led by Dr. Gergely, who serves as medical director of the 3D Sonography Center of Beverly Hills (Beverly Hills, Calif.), and was formerly acting director of obstetrics at Cedars Sinai Medical Center in Los Angeles.

The six-year retrospective, observational study evaluated 5,073 patients with a mean age of 38.3 years who received in-vitro fertilization using 3D/4D-guided embryo transfer at the Southern California Reproductive Center (Beverly Hills, Calif.). In each case, embryo placement was targeted to the new Maximal Implantation Potential (MIP) Point.

The patients achieved an overall pregnancy rate of 40.34 percent, which is 10.04 percent higher than the rate achieved at the Center prior to Dr. Gergely's introduction of the 3D/4D-guided MIP Point technique in 2001. Earlier study results based on 1,222 patients were published in the August 2005 issue of the journal Fertility and Sterility (Vol. 84, No. 2).

The study included in-vitro fertilization patients from UCLA Medical Center, Cedars Sinai Medical Center and independent fertility specialists in the Los Angeles area. A total of 21 physicians employed Dr. Gergely's technique. Once introduced, the MIP Point was accepted over time as the optimal target for embryo placement by all of the physicians, and the 3D/4D-guided embryo transfer technique was adopted as the standard operating procedure for all embryo transfers.

The old technique for placing embryos using 2D ultrasound alone was essentially a guessing game, said Dr. Gergely. While 3D imaging allows doctors to visualize the entire uterine cavity and identify the MIP Point, it's only with the addition of 4D imaging that we can target and guide embryos to the optimal, most natural location for each patient.

The MIP Point varies from patient to patient depending on the shape of the uterus. Using 3D/4D imaging to target the MIP Point enables doctors to more effectively individualize embryo transfer and improve the pregnancy rate.

With the new technique, Dr. Gergely uses 3D ultrasound to locate the patient's MIP Point. He then uses 4D ultrasound to help the specialist performing the embryo transfer guide the catheter tip in real time to the target location. Once the tip of the catheter is over the MIP Point, the embryo is released. When this occurs, a distinct flash on the 4D image indicates the moment the embryo is placed, as well as its precise location.

Using 3D/4D-guided embryo transfer to target the MIP Point places embryos where nature intended, and where they have the best chance to implant and develop, added Dr. Gergely.

Dr. Gergely cautions that even with the new technique, there remains significant room to improve the IVF pregnancy rate, which can be affected by several factors including the quality of embryos and receptivity of the endmetrium.

In birds, expecting to mate leads to higher fertilization rates

Thu, 04 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) From an evolutionary perspective, the primary task of an organism is to pass along its genes to future generations. Such genetic transmission is usually assumed to be instinctive. However, a new study shows that species also learn to adapt to their surroundings in order to increase their �reproductive fitness�� the likelihood that they will successfully reproduce.

One form of learning that increases reproductive fitness is Pavlovian conditioning, the ability to associate a neutral stimulus with a stimulus of significance. The classic example comes from Ivan Pavlov and his dogs that eventually salivated at just the sound of a bell, because the bell had been preciously paired with a slab of meat. However, when it comes to reproduction, does learning contribute to more offspring

Researchers from the University of Texas at Austin decided to test this in the laboratory. Nicolle Matthews and colleagues set out to examine whether learning can contribute to reproductive fitness in a particularly challenging situation � when two males compete to fertilize the egg of a single female.

Matthews hypothesized that if two males mate with the same female compete to fertilize her eggs, paternity will favor the male that received a signal or conditioned stimulus before the mating session.

Using quail, Matthews put the males into two chambers for thirty minutes; they repeated this for five days. One chamber was green and was located on the floor near a noisy room and the other chamber was white, had a tilted floor, and was located in an isolated room on a table. Whenever the quails were in one of the two chambers, they were allowed access to a female. Thus, the quail learned to anticipate a chance to copulate whenever they were placed in this chamber but not when they were in the other.

On the test day, each female was allowed to copulate with two males. One of the males was in the chamber where he expected to receive access to a female and the other male was in a chamber where he did not expect a female. Using genetic markers, the researchers then collected the eggs of the female quail and tested the paternity.

The results, which appear in the September issue of Psychological Science, a journal of the Association for Psychological Science, are clear: The males who were placed in the context that led them to anticipate access to a female just before copulation fertilized seventy-two percent of the eggs laid by the female quail. In other words, the quail who knew they were going to have the opportunity to mate produced more offspring. This is a significant finding because typically when two males mate in quick succession with the same female, no differences in paternity are found, which Matthews confirmed in a follow-up experiment.

The researchers point out that the conditioning most likely had an effect on the rate of sperm release without changing sperm quality or concentration. �Learning and individual experience can bias genetic transmission and the evolutionary changes that result from sexual competition,� write the authors.

Fetal cell 'transplant' could be a hidden link between childbirth and reduced risk of breast cancer

Tue, 02 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) PHILADELPHIA � Some benefits of motherhood are intangible, but one has been validated through biostatistical research: women who bear children have a reduced risk of developing breast cancer. In Seattle, Washington, researchers at the University of Washington and Fred Hutchinson Cancer Research Center believe they have identified a source of this protective effect: fetal cells �transplanted� to the mother before birth.

Their findings are presented in the October 1 issue of Cancer Research, a journal of the American Association for Cancer Research.

The ability of cells from a growing fetus to take up long-term residence within its mother is a phenomenon called fetal microchimerism. According to the researchers, while fetal microchimerism has been implicated as a mechanism of autoimmune disease, it may also benefit mothers by putting the immune system on alert for malignant cells to destroy.

To test the idea, the researchers recruited 82 women, 35 of whom had been diagnosed with breast cancer. Approximately two-thirds of the women studied have had children, and more than half of the participants had given birth to at least one son. The researchers took blood samples from each participant and searched them for male DNA, as they reasoned it is a relatively definitive matter to detect the male Y chromosome amid the mother�s native � and obviously female � cells within a blood sample.

Among the women with breast cancer, only five had male DNA in their bloodstream. Three of the five previously gave birth to sons, one had had an abortion and the other had never been knowingly pregnant. In total, about 14 percent of all women in the breast cancer group had male DNA in their bloodstream compared to 43 percent of women in the non-breast cancer group.

Our research found that these persisting fetal cells may be giving a woman an edge against developing breast cancer,� said lead author Vijayakrishna K. Gadi, M.D., Ph.D., assistant professor at the University of Washington and research associate at the Fred Hutchinson Cancer Research Center. �This experiment of nature is all the more fascinating because for years doctors treated a number of different cancers by transplanting cells from one person to another.

According to Dr. Gadi, these findings could provide a starting point for future research on the role of fetal microchimerism in the prevention of cancer. In addition, there are other reasons for male DNA to be in a woman�s peripheral blood, such as miscarriage and abortion � or possibly even blood transfusion or a male twin that was reabsorbed into the womb at an early stage of the pregnancy.

IVF technique enables pregnancy without multiple births, Stanford researchers find

Mon, 01 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) STANFORD, Calif. - An in vitro fertilization technique that can avoid multiple births appears to be effective for women older than 35, according to researchers at the Stanford University School of Medicine.

More than half the women in a retrospective study became pregnant after undergoing the procedure, called a single blastocyst transfer, which transferred just one embryo into the womb.

Nearly 60 percent of IVF procedures in the United States are performed on women older than 35, and the study's senior author, Amin Milki, MD, believes the findings are good news for those women who wish to become pregnant with just one child.

Although these results represent a selected group of patients, we believe that they should serve as encouragement to patients and providers who are considering single blastocyst transfer in the older IVF population, Milki and his co-authors noted in the study, which was recently published online in the journal Fertility and Sterility.

During the transfer procedure, an embryo is bathed in a culture of nutrients for five days until it reaches a developmental landmark known as the blastocyst stage. At that point, doctors are able to determine which embryos are most likely to thrive long term; they then transfer the best-quality ones into a woman's uterus.

The American Society for Reproductive Medicine currently recommends that doctors transfer two or more embryos into women older than 35, in an effort to maximize a patient's chance of becoming pregnant. This practice can lead to twins or higher-order multiples - as well as subsequent health risks - but Milki said this doesn't stop most patients from undergoing the procedure.

Many patients would prefer not to have two babies at once, said Milki, professor of obstetrics and gynecology and director of Stanford's IVF program. But because the success rate is higher when multiple embryos are transferred, women are willing to take the gamble.

In recent years, many reproductive specialists - especially those in Europe - have embraced single embryo transfer as a way to prevent multiple gestations. And data now exist showing the procedure's effectiveness among women of younger reproductive age.

Scant data exist on single blastocyst transfer in women over 35, so Milki and his colleagues decided to review the outcomes of older patients who underwent the procedure at Stanford. Milki said the procedure had been offered to those women with good-quality embryos, and the patients who elected to have only one embryo transferred did so as a way to avoid twin pregnancy. He noted that half the patients already had one child and wanted just one more, while others hoped to avoid the health complications associated with carrying multiples.

After reviewing the data from 45 patients ranging in age from 35 to 43 (with a mean age of 37.3), Milki and his colleagues found that 28 patients (62.2 percent) conceived, and 23 (51.1 percent) had pregnancies that went beyond the first trimester. Milki called this an excellent pregnancy rate - especially considering that the national success rate of IVF procedures for women in this age group is around 25 percent. But he pointed out that the women in this study all had good-quality embryos and had a relatively good chance of becoming pregnant.

This offers reassurance that a woman can still expect a good pregnancy rate without gambling with twins, said Milki. He added that the findings demonstrate a clear role for the procedure in older IVF patients, and he said Stanford's IVF program plans to continue offering the procedure as an option for patients.

Milki did caution that the findings are not applicable to every woman over the age of 35. For women with lower-quality embryos, transferring two or three embryos might be the better way to pursue a pregnancy.

Of mice and men: new male contraceptives successful in rodents and humans

Fri, 28 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Pills, sponges, IUDs, diaphragms-- women have many options for planning their fertility, none of them quite perfect. But what if men want to help out? They have only two options -- vasectomy, which is usually permanent, and condoms, which are crucial for dating but get old in long-term relationships. Will men ever have a way to reliably make sure that nobody is every calling them Daddy before they are ready?

For decades, pundits have predicted new contraceptives for men within the next 5 to 10 years. But judging from work presented today at the second Future of Male Contraception conference, we may finally be getting closer. Some highlights from the second day of the conference:

- Researchers from the University of Washington tried a hormone regimen based on two products already available on the market. They used testosterone gel, which is marketed for men with low testosterone, plus a progestin shot used as a female contraceptive under the name DepoProvera. The men got a shot once every 3 months and rubbed on a gel every day, and it worked well at knocking out sperm in 90% of them. However, men's opinions of the method varied widely: 6 dropped out, and of the remaining 38, half of them were satisfied or very satisfied, a third were dissatisfied or very dissatisfied, and the rest were undecided or had mixed feelings.

- Shepherd Medical Company announced the results of their very first U.S. study in men of the Intra Vas Device (a vasectomy alternative): after 6 months, 92% of the men had no sperm or almost no sperm. The Intra Vas Device blocks sperm in the vas deferens, the tube sperm swim through (the same tube that is cut in vasectomy). The set of plugs can be removed if a man changes his mind, so it is much easier to get sperm flowing again than after vasectomy. Animal studies have shown that fertility returns if the IVD is removed after short-term use, but that doesn't guarantee successful pregnancy after long-term use. The next step will be to find funding for long-term studies of effectiveness and fertility return.

- Columbia University researchers took advantage of the importance of vitamin A to design a new contraceptive approach. Men who are extremely low in vitamin A lose their fertility-- but they also become extremely sick, so avoiding vitamin A doesn't work as a contraceptive. Instead, Professor Debra Wolgemuth discovered a drug that had been abandoned by a pharmaceutical company precisely because it interfered with vitamin A receptors in the testes. Her team tested it in mice, and it worked with no health effects. The receptors are everywhere, but the testis is exquisitely sensitive to the drug. So we can use a dose that is so low it has no effect on the rest of the body.

So the drug doesn't harm mice-- but will it be fine in men Dr. Wolgemuth thinks the chances are good. There's extensive toxicology data in rats and rabbits -- and at much higher doses-- because industry is developing it for other uses. So we're optimistic that there would be no adverse side effects in humans as well.

So how long must we wait? Advocates say it all depends on men speaking up. We've seen today that the pipeline is full-- everything from new targets to actual human trials, explains Kirsten Thompson, director of the International Male Contraception Coalition. And the demand is there-- hundreds of men have voiced their opinion on our website MaleContraceptives.org and in surveys. So it's just a question of whether policymakers act on that demand. Elaine Lissner, director of the Male Contraception Information Project, concurs. We could have something like the IVD on the market in 4-5 years, if we make an all-out effort with funding and focus. But if we continue with just a study here and a study there, it could be an eternity.

Primate sperm competition: speed matters

Mon, 24 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers at UC San Diego and UC Irvine have found evidence that supports the theory that reproductive competition during the evolution of primate species has occurred at the level of sperm cell motility. In a paper published online by the Journal of the Royal Society Interface, a team led by Michael Berns, an adjunct professor of bioengineering at UCSD and a professor of biomedical engineering at the Beckman Laser Institute at UC Irvine, and UCSD Ph.D. candidate Jaclyn Nascimento reported that sperm cells from the more promiscuous chimpanzee and rhesus macaque species swim much faster and with much greater force than those of humans and gorillas, species where individual females mate primarily with only one male during a reproductive cycle.

Female chimps and macaques typically mate with several males in a social group, so that a male with faster and stronger swimming sperm cells would in theory be more likely to successfully fertilize an egg.

�Rapidly swimming sperm cells would be evolutionarily favored when the mating pattern is polygamous and that is consistent with our measurements of chimp and rhesus macaque sperm,� said Nascimento.

The research team found significantly lower swimming forces and slower swimming speeds with human sperm, and the slowest of all belonged to gorillas. �Dominant silverbacks are known to effectively discourage other males from mating with the females in their harems, so faster sperm wouldn�t seem to be an advantage to them,� Nascimento said.

However the researchers were surprised that the speed and force of human sperm fell in between the gorillas and the chimps. �Maybe humans haven�t always been as monogamous as we had thought,� Berns said.

Beginning more than 35 years ago, scientists began using laser beams to trap individual atoms, microscopic particles, DNA molecules, and various cells. Berns has been a pioneer in the design of �laser tweezers,� which rely on the momentum inherent in laser light: when the path of laser light bends as it passes through a small transparent object such as a cell, some of the light�s momentum is transferred to the cell, effectively holding, or trapping it. The brighter the laser, the more firmly the cell is held.

After attending a talk at the Center for Reproduction of Endangered Species (CRES) at the San Diego Zoo about the theory that faster sperm could have an advantage in the reproductive success of polygamous primates, Berns modified his laser tweezers so that after a cell was trapped, the light intensity could be reduced in a precise manner. Such a timed decay in laser brightness allows a trapped sperm cell to escape at the point at which its swimming force exceeds the trapping force. The adjustable laser tweezers and sperm-tracking software allowed the team led by Berns and Nascimento to precisely and accurately measure swimming force and speed of hundreds of individual sperm cells from males of the four primate species.

�While biologists have been interested in this sperm competition question for years, it required the collaboration of biologists, physicists and engineers to design the right equipment to test the theory,� said Berns.

Multiple corticosteroid injections in pregnant women may increase cerebral palsy

Fri, 21 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CHAPEL HILL -- When pregnant women are at high risk for preterm birth, giving them a single injection of corticosteroids has been shown to reduce the baby�s chances of having serious lung problems after birth.

But some women receive multiple injections of corticosteroids, and a new study shows that repeat courses of corticosteroids are linked to an increased rate of cerebral palsy among children of these mothers.

�Our study shows that you get almost all of the benefit from a single round of therapy and that multiple rounds raise the risk of cerebral palsy, which is a severely disabling condition,� said John M. Thorp, M.D., a study co-author and McAllister distinguished professor of obstetrics and gynecology at the University of North Carolina at Chapel Hill School of Medicine.

�That�s why we concluded that exposure to repeat courses should be limited,� Thorp said.

The study results are published in the Sept. 20, 2007, issue of the New England Journal of Medicine. The lead author is Ronald J. Wapner, M.D., of Drexel University in Philadelphia. The study was conducted for the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development, which provided grant funding. Research took place at 14 sites across the United States, including UNC-Chapel Hill.

The researchers followed women between 23 weeks and 32 weeks pregnant who remained pregnant after an initial dose of corticosteroids. They were randomly assigned to receive weekly courses of the corticosteriod betamethasone or placebo injections.

Children born to women enrolled in the study were given physical and neurological examinations at ages 2 to 3 years old. A total of 556 children were examined. Of these, 486 (87.4 percent) had physical exams and 465 (83.6 percent) were evaluated for brain function using a measurement tool called the Bayley Scales of Infant Development.

The researchers found that there were no meaningful differences in weight, head circumference or Bayley scores between children whose mothers received a single dose of corticosteroids. However, six children in the group whose mothers received multiple injections had cerebral palsy, compared to only one child in the placebo group.

�Although not statistically significant, the rate of cerebral palsy in infants exposed to multiple courses is of concern and suggests that exposure to repeat courses of antenatal corticosteroids should be limited,� the researchers concluded.

The Sept. 20 issue also includes a separate study that examined the same question and an editorial that discusses both studies. The editorial was written by Alan D. Stiles, M.D., Brewer distinguished professor and chairman of pediatrics in the UNC School of Medicine.

The other study reached similar results, with one key difference: the researchers found smaller head sizes among the infants exposed to repeat courses of corticosteroids. But the study authors reached a different conclusion from Thorp and his co-authors, in favor of using repeat courses.

In the editorial, Stiles noted that both studies found that repeat courses produced better results than single courses in terms of reducing lung problems in the infants. However, both studies also found lower birth weights in the infants exposed to repeat courses.

�More information is needed before it is clear which strategy is optimal,� Stiles wrote. �Further study is warranted of school-age neurodevelopmental performance, including the possible increased risk of cerebral palsy among these children, as well as among offspring of women in other trials of weekly corticosteroid therapy, with attention to the doses used.�

Species still have more viable offspring if they can choose their best mate

Tue, 18 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Athens, Ga. -- When it comes to picking a mate, Crosby, Stills, Nash and Young had an answer: �If you can�t be with the one you love, love the one you�re with.� As it turns out, that may be a cardinal rule in the animal kingdom, too.

New research that crosses several species boundaries shows that when animals must choose less-than-preferred (to them) mates, females and males apparently have ways to compensate that increase the chance their offspring will survive. The study, just published in the Proceedings of the National Academy of Sciences, adds weight to the Compensation Hypothesis, a proposal that has given insight into how individuals can pass on their genes even under less than ideal circumstances.

�It�s always better for offspring if parents can mate with preferred partners, but it�s becoming clear that when parents can�t have that preferred partner, they have ways of making up for it,� said Patricia Adair Gowaty, a Distinguished Research Professor of Ecology and Genetics at the University of Georgia and lead author of the study. �When female �choosers� were in enforced pairs with males they did not prefer, they laid more eggs. Similarly, when males are paired with females they do not prefer, they ejaculate more sperm. This compensation seems to be a way of making the best of a bad job.�

Co-authors of the paper were Wyatt Anderson, Alumni Foundation Distinguished Professor of Genetics, and Yong-Kyu Kim, an assistant research scientist in Anderson�s lab, both at UGA; Cynthia K. Bluhm of the Delta Waterfowl and Wetlands Research Station in Canada; Lee C. Drickamer of Northern Arizona University; and Allen J. Moore of Centre for Ecology and Conservation at the University of Exeter in the United Kingdom.

One of the new study�s strongest arguments for the Compensation Hypothesis is that it includes experimental results in Tanzanian cockroaches, fruit flies, pipefish, wild mallards and feral house mice. When each species faced experimental constraints on free expression of their mate preferences, individuals found ways around the predicament that could improve the chances that offspring could survive and perhaps even flourish.

�Just how an individual finds its best mate isn�t really known,� said Gowaty, �though there�s some evidence that he or she may be somehow sensing the advantage of the potential mate�s immune system in relation to the chooser�s own.� She points out that many factors are probably at work, including behavioral cues and what potential resources a mate may bring.

While the strategies for dealing with nonpreferred mates can help offspring, advantages for the mating pairs themselves are less clear. In experimental situations, for example, females mated to non-preferred males didn�t live as long as females mated to their preferred choice.

One interesting aspect of the study is its implication that all individuals in a species have a flexible response to such problems as constraints on expression of their mating preferences. If that�s true, it hints that compensation may evolve�which could add an unexpected wrinkle to the story of natural selection.

�How compensation evolves is crucial,� Anderson said.

The issues at stake are, in fact, even broader.

�The study also has implications for conservation because it suggests that the best way to keep species alive may be, if possible, to let individuals choose their own mates,� said Gowaty.

The Compensation Hypothesis is Gowaty�s work and was first published only four years ago, though she has been working on it for more than a decade.

Just how�and if�the hypothesis works in humans remains unknown, since studying the subject remains practically (and ethically) improbable. Still, the idea remains a deep part of popular culture.

When Mick Jagger sings �You can�t always get what you want,� most of us nod. And then we start to plot a way around the problem.

Women prescribed drugs linked to birth defects not often advised to use birth control

Mon, 17 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) PITTSBURGH, Sept. 17 � Although prescription medications that may increase the risk of birth defects are commonly used by women in their childbearing years, only about half receive contraceptive counseling from their health care providers, according to a large-scale study from the University of Pittsburgh School of Medicine reported in the Sept. 18 issue of the Annals of Internal Medicine.

�We found that over the course of a year, one in six women of reproductive age filled a prescription for a medication labeled by the Food and Drug Administration as increasing the risk of fetal abnormalities,� said Eleanor Bimla Schwarz, M.D., assistant professor in the departments of medicine and obstetrics, gynecology and reproductive medicine at the University of Pittsburgh School of Medicine and first study author. �Unfortunately, many women filling prescriptions that can increase risk of birth defects remain at risk of pregnancy.�

Half of pregnancies in the United States are unintended, according to national estimates. While regular use of contraception can prevent unplanned pregnancies, women filling prescriptions that can increase the risk of birth defects are no more likely to use contraception than other women, the study authors note.

For this investigation, Dr. Schwarz and colleagues studied patient data related to all prescriptions filled by 488,175 reproductive-aged women enrolled with a large managed health care plan during 2001. Prescriptions involved drugs considered safe for use in pregnancy and those labeled as posing a fetal risk.

The researchers examined use of contraception and results of pregnancy tests. When they compared medications labeled as increasing the risk of birth defects to safer medications, the researchers found little difference in rates of contraceptive counseling, use of contraception or subsequent pregnancy test results.

�Many women � and perhaps their physicians � may be unaware of the risks associated with the use of some medications, the chance that women may become pregnant, or both,� said Dr. Schwarz, who also is an assistant investigator at the Pitt-affiliated Magee-Womens Research Institute. �The scary thing is that we know women in other primary care health care settings are even less likely to get information about birth control.�

While about half of the women in this study had received contraceptive counseling, other studies have shown that nationwide, only about 20 percent of women are advised to use birth control when they receive potentially dangerous medications.

�While efforts are needed to ensure that women get information about birth control and the risk of medication-induced birth defects, it also is important to realize that different birth control methods are not equally effective,� she said. �Women who were using the most effective methods of contraception, such as the intrauterine device or IUD, were least likely to have a positive pregnancy test after filling a prescription for a potentially dangerous medication.�

The researchers found that internists and family practitioners prescribed the largest proportion (48 percent) of riskier medications to women of childbearing age. Psychiatrists prescribed 15 percent of these drugs; dermatologists, 12 percent; obstetrician/gynecologists, 6 percent; and pediatricians, 3 percent, according to the study.

�Women should not avoid using prescription medications, but clinicians need to remember that sometimes birth control is needed until a woman is ready to have a healthy pregnancy and a healthy baby,� Dr. Schwarz added.

New cell death pathway involved in sperm development

Mon, 17 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Heavy and bulky sperm would not be good swimmers. To trim down, sperm rely on cell death proteins called caspases, which facilitate the removal of unwanted cellular material and radically remodel these cells into their sleek, light shape. New research from scientists at the Howard Hughes Medical Institute and Rockefeller University has now uncovered a new pathway that regulates these killer proteins, yielding new knowledge about caspase function as well as insights into the causes of human infertility. The findings are reported in the

Cell death caspases, when activated, were thought to condemn a cell to certain death. But a few years ago Hermann Steller, head of the Laboratory of Cancer and Apoptosis Biology, and his colleagues discovered that caspases also function without entirely killing cells; instead, they are used to shape cells by dismantling unwanted bulk. �This process is very similar to apoptosis, or cell suicide,� explains Steller, who is Strang Professor at Rockefeller and an investigator at HHMI, �but in this case cells live.� And in Drosophila, when this cell death-like program goes awry, males become sterile.

Though quite a bit has been learned about how caspases are activated, very little is known about how unwanted caspase activity is restricted so that healthy, productive cells aren�t mistakenly target for death. So Steller and his colleagues wanted to figure out how caspases, which are expressed in all cells, are activated at the right time and at the right place; and in this case, how they do not kill off a cell entirely.

The researchers screened more than 1,000 sterile male fruitflies, looking for cellular differences between sterile flies and fertile ones. They then mapped these differences back to the genes to identify mutations along the Drosophila genome that made these fruitflies sterile. This process eventually pointed them to three distinct genes that encode different protein components of a complex called Cullin-3 ubiquitin ligase.

Cullins are members of the E3 ubiquitin ligase family, which label other proteins with ubiquitin, a molecule that marks them for degradation. It turns out that Cullin-3, in conjunction with two other proteins, activates caspases by degrading a caspase inhibitor. This, in turn, initiates a cell death-like program at the right time and at the right place � in the developing testes of Drosophila � and gets rid of unwanted cytoplasm and organelles. Before this study, only IAPs, another class of E3 ubiquitin ligases, had been identified as caspase regulators. Now, Steller and his group have found a new major player that regulates these killer proteins.

One of the proteins that form the Cullin-based complex in Drosophila has also been linked to male infertility in mice and humans. In mice, a mutation in the gene that encodes a protein called Klh110 causes male sterility. In humans, male infertility has been linked to this gene as well, although it is still not known whether this is due to the inability of Cullins to activate caspases and promote sperm differentiation.

The Steller lab initially focused on the role of Cullins during sperm development, but there is already data indicating that they also function to regulate caspases in somatic cells. It appears that cells use several different mechanisms simultaneously to protect themselves against unwanted caspase activity and death. This information provides new opportunities to develop drugs that can alter cell death for therapeutic purposes, either for cellular protection or cell killing � processes that range from neurodegenerative disease to cancer.

�Our findings provide a new framework to understand how apoptotic proteins are regulated for cellular remodeling.� says Steller. �And now, by having a more comprehensive picture of these different pathways and how they come together, we are prepared to look much more broadly at different cell death paradigms.�

UVA researchers find important clue to immune infertility

Wed, 12 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CHARLOTTESVILLE, VA (Sept. 12, 2007) � Most of us have never heard of immune infertility, yet it prevents many prospective parents from conceiving.

Immune infertility is one of 80 autoimmune disorders, a group that includes better-known diseases like Multiple Sclerosis and Type 1 Diabetes. This reproductive disorder affects both men and women, causing their immune systems to wage war on sperm.

A recent discovery at the University of Virginia Health System may help pinpoint what molecules assist the immune system in attacking sperm. In the July 2007 issue of Gene, UVa researchers reported finding a new human protein, radial spoke protein 44 (RSP44). Exposure to RSP44 caused infertile men to produce antisperm antibodies (ASA) in their serum.

�We�ve spent several years looking for sperm molecules that evoke antibody responses in humans,� says Dr. John C. Herr, director of UVa�s Center for Research in Contraceptive and Reproductive Health. �The identification of RSP44 gives us additional insight into immune infertility and may prove useful in diagnosing the disorder in a subset of men. RSP44 will likely not be a dominant antigen in everyone.�

Researchers believe that RSP44 belongs to a highly conserved and ancient gene family. It can be found in all men, residing in the sperm tail at the center of a structure known as the axoneme. There, it clusters around microtubules involved in sperm movement. Both men and women have RSP44 in hair-like strands, called cilia, in the bronchioles of their lungs, the ventricles of their brains and the lumens of their thyroid gland.

The discovery of RSP44 also promises to broaden scientific thinking about the causes of immune infertility. Until now, researchers believed that ASA only targeted the surface of the sperm membrane.

�Because RSP44 is located in the heart of the axoneme, it doesn�t appear to be directly involved in ASA binding at the sperm membrane. Identifying RSP44 as an antigen in several individuals indicates it may serve as a useful biomarker of the anti-sperm response,� notes Dr. Jagat Shetty, lead author of the UVa paper. �There may be mechanisms underlying infertility that are yet to be discovered.�

Women with immune infertility produce ASA in their reproductive tracts. These antibodies neutralize sperm by clumping them together and poking holes in their membranes. ASA also coats over receptors involved in sperm-egg binding and fertilization.

An estimated 12 to 15 percent of unexplained infertility in women is linked to ASA. In rare cases, these antibodies have caused women to go into anaphylactic shock upon insemination.

In men, immune infertility has several causes, including vasectomies. After a vasectomy, the body can no longer release sperm and produces antibodies to help engulf and clear them. ASA persist for years in the circulation of vasectomized men and may cause reduced fertility in those who have the procedure reversed (vasovasostomy).

Several therapeutic procedures available through UVa, such as sperm washing and intra-cytoplasmic sperm injection, have proven beneficial to patients with ASA.

Scientists discover how to isolate stem cells in womb tissue

Wed, 12 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Scientists in Australia have found a way of identifying probable stem cells in the lining of women�s wombs. The finding opens up the possibility of using the stem cells for tissue engineering applications such as building up natural tissue to repair prolapsed pelvic floors. Pelvic floor prolapse is a common condition, affecting over 50% of women after childbirth; around one in ten women have surgery and a third of these women require repeated operations to correct the problem.

In research published online today (Thursday 13 September) in the journal Human Reproduction [1], Dr Caroline Gargett describes how she and her PhD student, Ms Kjiana Schwab, identified two markers, CD146 and PDGF-R�, which they were able to use to isolate mesenchymal stem-like cells (MSC) from endometrial tissue using a high speed cell sorting machine (fluorescence activated cell sorting � FACS). Only 1.5% of the endometrial cells sorted in this way expressed both markers and, therefore could be MSC.

They then investigated the properties of the MSC to discover whether they really were stem cells, capable of differentiating into a variety of different cell types. They found the cells were able to produce clones to form colonies of new cells at a rate that was 15 times greater than produced by the other endometrial cells. Furthermore, the MSC were able to differentiate into fat, bone, cartilage and smooth muscle cells in the culture dish. The MSC also appeared to be located around blood vessels in the endometrium (perivascular region).

Dr Gargett, a senior scientist at the Centre for Women�s Health Research, Monash Institute of Medical Research, Monash University, Victoria, Australia, explained: �Colony-forming ability is a property of adult stem cells, as is the ability to differentiate into different cell types. The fact that the cells expressing the two markers were located in the perivascular region strengthens our case that we have isolated mesenchymal stem cells, because mesenchymal stem cells from bone marrow and fat are found around blood vessels too. It also gives us clues as to how they might function in repairing and regenerating new endometrium each month.�

This is the first time that researchers have been able to use markers to isolate MSC from the endometrium and also the first study to show that the properties of these cells mean they are highly likely to be stem cells.

Dr Gargett said: �We had previously detected that MSC were present in the human endometrium but we were unable to isolate the MSC, which was a big drawback in studying their properties. The major finding of this study was the identification of two markers which enabled the prospective isolation of MSC-like cells from human endometrial tissue. This allows us to characterise endometrial MSC so we can understand their molecular and cellular properties better, compare them to MSC from other sources, such as bone marrow and fat, use them for tissue engineering applications, such as making constructs with biological scaffolds for pelvic floor prolapse surgery, and find where they are located in endometrium (i.e. around blood vessels); this gives us a clue as to how they might function in growing new endometrium each menstrual cycle and how they may have a role in gynaecological diseases such as endometriosis.�

The human endometrium is the only adult tissue that contains a substantial amount of the connective tissue framework (called stroma) that regularly regenerates under normal conditions when a woman menstruates. Because of its regenerative properties, Dr Gargett believed that it might contain MSC that were responsible for the monthly regeneration of the stroma and related blood vessels, and which could be an easily available source of MSC for stem cell therapy. However, until she identified CD146 and PDGF-R� as MSC markers, there were no known markers and therefore no way of isolating the endometrial MSC.

Her research, using tissue obtained from women aged between 31-49 who were having hysterectomies, indicates that the MSC are probably located mainly in the basalis layer of the endometrium, which is the layer that is not shed during a woman�s period. �We think that is where the MSC should be if they are responsible for producing the functionalis layer, which grows each month,� said Dr Gargett.

This means that, although it might be possible to collect MSC from menstrual blood, the most likely method of collection would be curettage or biopsy. �This would not be any more invasive than collecting MSC from bone marrow or surgical removal (biopsy) of fat tissue,� said Dr Gargett. �MSC could also be collected from postmenopausal women, whose endometrium is very thin. If these women are given oestrogen replacement therapy for a very short time (a week or two) their endometrium will grow to the thickness of a reproductive age woman and the MSC could be collected without harm to the woman.�

Dr Gargett believes that initial applications for endometrial MSC would be to use them on the women that they had been retrieved from (rather than on other people) for gynaecological purposes such as pelvic floor prolapse. �Pelvic floor prolapse is a common problem that significantly impacts the lives of many women and they find it embarrassing to talk about � it is a hidden disorder in need of an innovative therapy,� she explained.

�Clinicians have been using a synthetic mesh as a reinforcement material to try and reduce the high rate of recurrence of this condition. While these meshes are often successful, a significant number of complications arise due to erosion or rejection of the foreign material. Increasingly clinicians have been trying biological scaffold material, but this often fails as it lacks cells and the body breaks it down faster than the body�s cells can infiltrate and strengthen the material. We believe that using a combination of biological scaffold and a woman�s own MSC might provide a solution that would ensure a longer lasting firm natural tissue that would be a superior support for the prolapsed uterus.

�We also believe that the identification of the MSC in human endometrium gives us the opportunity to investigate their possible role in the development and pathogenesis of common gynaecological disorders associated with abnormal endometrial growth, such as endometriosis and adenomyosis.� [2]

However, it will probably be at least ten years before applications from Dr Gargett�s findings will be used in the clinic. The next stages of the research include refining the technique by looking for further markers and possibly a single marker that could do the same job as two, and testing the possible tissue-engineering applications in animal models before they are used in humans.

Low vitamin D during pregnancy linked to pre-eclampsia

Fri, 07 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) PITTSBURGH, Sept. 7 � Vitamin D deficiency early in pregnancy is associated with a five-fold increased risk of preeclampsia, according to a study from the University of Pittsburgh Schools of the Health Sciences reported this week in the Journal of Clinical Endocrinology and Metabolism.

A serious complication of pregnancy marked by soaring blood pressure and swelling of the hands and feet, preeclampsia is the leading cause of premature delivery and maternal and fetal illness and death worldwide, conservatively projected to contribute to 76,000 deaths each year. Preeclampsia, also known as toxemia, affects up to 7 percent of first pregnancies, and health care costs associated with preeclampsia are estimated at $7 billion a year in the United States alone, according to the Preeclampsia Foundation.

�Our results showed that maternal vitamin D deficiency early in pregnancy is a strong, independent risk factor for preeclampsia,� said Lisa M. Bodnar, Ph.D., M.P.H., R.D., assistant professor of epidemiology at the University of Pittsburgh Graduate School of Public Health (GSPH) and lead author of the study. �Women who developed preeclampsia had vitamin D concentrations that were significantly lower early in pregnancy compared to women whose pregnancies were normal. And even though vitamin D deficiency was common in both groups, the deficiency was more prevalent among those who went on to develop preeclampsia.�

For this investigation, Dr. Bodnar and her colleagues evaluated data and banked blood samples taken from women and newborns between 1997 and 2001 at Magee-Womens Hospital of the University of Pittsburgh Medical Center (UPMC) and affiliated private obstetrician practices. Data were analyzed for 1,198 women enrolled in the Pregnancy Exposures and Preeclampsia Prevention Study, a prospective survey designed to examine factors that may predispose women to preeclampsia. Out of this group, 55 cases of preeclampsia and 220 controls were selected for further study.

Samples of maternal blood were taken prior to 22 weeks pregnancy and again just before delivery. Samples of newborn umbilical cord blood also were tested for 25 hydroxyvitamin D, an indicator of vitamin D status.

�Low vitamin D early in pregnancy was associated with a five-fold increase in the odds of preeclampsia,� said Dr. Bodnar, who also is an assistant investigator at the university-affiliated Magee-Womens Research Institute (MWRI). �Data showed this increase risk persisted even after adjusting for other known risk factors such as race, ethnicity and pre-pregnancy body weight. Also troubling was the fact that many of the women reported taking prenatal vitamins, which typically contain 200 to 400 International Units of vitamin D,� she said.

�Even a small decline in vitamin D concentration more than doubled the risk of preeclampsia,� noted James M. Roberts, M.D., senior author of the study and MWRI founding director. �And since newborn�s vitamin D stores are completely reliant on vitamin D from the mother, low vitamin levels also were observed in the umbilical cord blood of newborns from mothers with preeclampsia.�

A vitamin closely associated with bone health, vitamin D deficiency early in life is associated with rickets � a disorder thought to have been eradicated in the United States more than 50 years ago � as well as increased risk for type 1 diabetes, asthma and schizophrenia.

In the developing world, preeclampsia accounts for up to 80 percent of maternal deaths. And while treatment is more available in developed countries, preeclampsia remains the leading cause of maternal death. Infants born to mothers with preeclampsia have a risk of mortality five times greater than those born to women with normal pregnancies. In the United States alone, nearly 15 percent of preterm deliveries are a result of preeclampsia.

MU researchers to collaborate on $20 million project

Fri, 07 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) COLUMBIA, Mo. -- More than 10 million people in the United State have cancer, and more than half of them are women. For those who could still give birth, cancer treatments might signal the end of their fertility. Now, a new $20 million, 5-year program from the National Institutes of Health is creating a national team of scientists to investigate every aspect of fertility preservation for women with cancer. Part of that effort is being led by University of Missouri-Columbia researchers.

The national research team will investigate women�s fertility preservation from all aspects including preservation of eggs, cancer treatments, current policies and practices, information available to women, and healthcare decision-making. The project, led by Teresa Woodruff, professor of obstetrics and gynecology at Northwestern University, includes more than 15 different institutions across the country.

MU researcher John Critser will receive approximately $1.25 million over five years to study cryopreservation methods of human eggs. The current methods are not efficient and there are many challenges in the cryopreservation process.

�It�s easy to freeze anything, but when biomaterial is frozen and thawed, the viability of the material is lost frequently,� said Steve Mullen, a post-doctoral researcher in veterinary pathobiology. �Most eggs in the ovaries are in the premature state, and in order to develop into mature and viable eggs, companion cells in the ovary are necessary. Therefore, freezing ovarian tissue, which is usually necessary for female fertility preservation, is very challenging because all of the different cell types must be preserved so that they can cooperate to mature the egg after the tissue is thawed.�

Critser and Mullen, along with MU colleagues Danny Schust, associate professor of obstetrics, gynecology and women�s health; James Benson, a graduate student in Department of Applied Mathematics; and Xu Han, a post-doctoral fellow in veterinary pathobiology, will collaborate with researchers from other institutions involved in the project.

�The long term goal is to allow people to have children who otherwise might not be able to do so,� said Critser, Gilbreath McLorn Professor of Comparative Medicine. �We are working to help women stay fertile and this new NIH roadmap � combining interdisciplinary groups to study a problem from all angles � will be vital to solving this problem.�

�As we become better at curing patients of diseases that would have previously been invariably fatal, we also have a responsibility to maximize the opportunities that accompany survivorship,� Schust said. �Cancer survivors put child-bearing very high on their list of post-therapy lifetime goals. This study should help us to simultaneously meet our responsibilities as health care providers and satisfy these very vital patient needs.�

As part of the project, each member institution will have a representative that sits on a Board of Governors overseeing the project. MU�s representative will be William Crist, Hugh E. and Sarah D. Stephenson Dean of the School of Medicine.

�Due to tremendous advances in medical research, millions of people who would have previously died of cancer now require care focused on improving their quality of life,� Crist said. �Preserving fertility for women has become an increasingly important aspect of cancer survivorship, and MU is proud to contribute to this national effort to enrich the lives of cancer survivors and their families.�

Drug could improve pregnancy outcomes in wider range of women with insulin resistance

Thu, 06 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) St. Louis, Sept. 6, 2007 � Women who are obese, have type 2 diabetes or a family history of type 2 diabetes could one day have more successful pregnancies because of a study at Washington University School of Medicine in St. Louis.

This study, performed in mice, suggests that Metformin, the most commonly prescribed anti-diabetes drug, could potentially improve pregnancy outcomes in women with insulin resistance.

�We found that embryos of insulin-resistant mice also have some degree of insulin resistance, and if we correct the insulin resistance in the embryo with this drug, we improve the quality of the embryo,� says Kelle Moley, M.D., lead author and professor of obstetrics and gynecology.

The finding, published online in Diabetes, suggests that Metformin could benefit women with type 2 diabetes or polycystic ovary syndrome (PCOS). About 8 percent of women trying to conceive have insulin resistance, Moley says, and even more are suspected to be borderline. In some cases, a family history of type 2 diabetes or being overweight may be the only indication that the patient may be prone to insulin resistance.

Metformin is often given to women with PCOS, an endocrine disorder that affects insulin and results in higher rates of miscarriage. These women often share the same pregnancy complications as women with type 2 diabetes and obesity.

Recent studies have shown that metformin not only aids conception in women with PCOS but also reduces the high miscarriage rates; however, how the drug does this has been unclear.

Using early-stage mouse embryos, Moley and her colleagues showed for the first time that metformin improves insulin action in insulin-resistant embryos. That allowed the embryos to absorb glucose, an important energy source, and prevented the death of cells in the embryos. As a result, the embryos were more likely to successfully implant in the uterus and to continue growing.

Moley's group also identified the molecular mechanism that accounts for metformin's positive effects. They found the drug triggers an important sensor of the energy level of cells, which sets off a chain of reactions that help insulin do its job. Previously it was not known that this sensor molecule was active in early embryos.

Moley hypothesizes that in insulin-resistant women, high levels of insulin and related factors cause their embryos to compensate by shutting down insulin signaling mechanisms. That impairs the early embryo�s ability to take in glucose at a critical stage of development and can lead to pregnancy failure.

�We found that Metformin improves glucose uptake and improves the survival of the early embryo as a result,� Moley says. �Mouse embryos in a high-insulin environment that were not exposed to Metformin did not survive.�

Most miscarriages are due to chromosomal abnormalities. But Moley says this study provides new scientific evidence that miscarriages related to insulin resistance possibly could be avoided through the use of metformin.

�This will help physicians know better how to treat these women and reassure them that they�re being correctly treated for their medical problems and that their babies will benefit from that treatment,� she says.

Choosing a mate: what we really want

Mon, 03 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) BLOOMINGTON, Ind. -- While humans may pride themselves on being highly evolved, most still behave like the stereotypical Neanderthals when it comes to choosing a mate, according to research by Indiana University cognitive scientist Peter Todd. In a new study, Todd and colleagues found that though individuals may claim otherwise, beauty is the key ingredient for men while women, the much choosier of the sexes, leverage their looks for security and commitment.

This formula has served humans throughout time, with the model of choosy females reflected in most mammals, Todd and his coauthors write in Different cognitive processes underlie human mate choices and mate preferences, which will be published the week of Sept. 4-7 in the Proceedings of the National Academy of Sciences.

Evolutionary theories in psychology suggest that men and women should trade off different traits in each other, and when we look at the actual mate choices people make, this is what we find evidence for, Todd said. Ancestral individuals who made their mate choices in this way -- women trading off their attractiveness for higher quality men and men looking for any attractive women who will accept them -- would have had an evolutionary advantage in greater numbers of successful offspring.

Not exactly politically correct Participants in Todd's study might verbally agree, though their actions said something different.

The study used a speed-dating session in Germany to compare what people say they want in a mate with whom they actually choose. Speed dating, an increasingly popular way for singles to meet, involves sessions in which men and women have numerous mini dates with up to 30 different people, each date lasting anywhere from three to five minutes. After every date, the men and women checked a box on a card noting whether they would like to see the other person again. Todd and his colleagues describe such speed-dating events as a microcosm where mate choices are made sequentially in a faster and more formalized fashion than in daily life.

For Todd's study, 46 adults in a speed-dating session were also asked to fill out a questionnaire beforehand assessing themselves and their ideal mate according to evolutionarily relevant traits, such as physical attractiveness, present and future financial status, health and parenting qualities.

Not surprisingly, Todd said, participants stated they wanted to find someone who was like themselves -- a socially acceptable answer. But once the sessions began, the men sought the more attractive women and the women were drawn to material wealth and security, setting their standards according to how attractive they viewed themselves. Furthermore, while men on average wanted to see every second woman again, the women wanted to meet only a third of the men again.

While the study's results came as no surprise to Todd, the research usefulness of the speed-dating forum did. Todd and his colleagues are conducting several other speed-dating studies that could confirm the results.

Speed dating lets us look at a large number of mate choice decisions collected in a short amount of time, Todd said. It only captures the initial stage of the extended process involved in long-term mate choice. But that initial expression of interest is crucial for launching everything else.

Auto immune response creates barrier to fertility; could be a step in speciation

Mon, 03 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Plant biologists at the Max Planck Institute of Developmental Biology and the University of North Carolina at Chapel Hill have discovered that an autoimmune response, triggered by a small number of genes, can be a barrier to producing a viable offspring.

Studying Arabidopsis thaliana, sometimes called thale cress, the researchers identified a phenotype that, when paired together from a male and female, produced plants that survived only long enough to produce a few leaves, then died � a phenomenon called hybrid necrosis; literally, death. The dead plants resembled what would result from a mortal infection, despite the absence of a pathogen.

This finding presents a new theory in the development of new species: two plants of the same species fail to reproduce not because of infestation or infection from an outside organism, nor from problems with reproductive organs.

�If two otherwise healthy members of a species cannot produce progeny, they�re on a track toward no longer being members of the same species,� said Jeff Dangl, Ph.D., John N. Couch professor of biology, microbiology and immunology and associate director of the Carolina Center for Genome Sciences. �This could be a very early event in what will, over time, lead to speciation.�

The study appears in the Sept. 4, 2007, issue of PLoS Biology.

The initial finding was serendipitous, Dangl said. Detlef Weigel, at Max Planck, shared with Dangl some photos of Arabidopsis hybrids from a project by Kirsten Bomblies, a postdoctoral fellow in Weigel�s lab that was meant to study the timing of flowering..

�I said, �those look just like autoimmune mutants,�� Dangl recalled.

Bomblies, Weigel and others at Max Planck crossed 280 genetically different strains of Arabidopsis from around the world into 881 different combinations: 2 percent of these crosses gave necrotic offspring. They all had similar gene expression profiles, a group of about 1,000 genes that would typically be expressed as during immune response following infection, or by autoimmune mutants.

Moreover, further analysis revealed that the parents carried healthy genes; their necrotic offspring were not results of genetic disorders. They were the result of a �bad luck� pairing of genetic variants for genes that are normally used to recognize pathogen attack, Dangl said.

�A normal immune system function can give rise to incompatibility in the next generation,� Dangl said. And if studies move beyond plants, �I predict it will be the same in animals.�

Dangl suggested that the necrotic plant is possibly analogous to a fertilized egg that fails to implant in the uterus. Infertility in couples might be explained by analogous auto-immune genetic profile. �How many couples can�t produce progeny, but when they separate and find another mate, they do�

The study showed �why basic research is so vital,� said Dangl, who was elected into the National Academy of Sciences earlier this year. �This was non-outcome oriented research. If we had set out to study hybrid reproduction we would not have found this fascinating system.�

Human testes may multiply mutations

Mon, 27 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The testes in humans may act as mutation multipliers that raise the odds of passing improved DNA to offspring � but that can also backfire by increasing the frequency of certain diseases.

The new theory is part of a study, appearing in PLOS Biology, that tries to explain the puzzlingly high frequency of Apert syndrome, a genetic cranial deformity found in approximately one out of every 70,000 newborns.

The study�s authors suggest that natural selection may favor �germline� cells � the precursors to sperm � carrying a mutation that causes Apert syndrome.

A competitive advantage for mutated sperm precursor cells could explain why Apert strikes 100 to 1,000 times more people than expected from a single mutation.

Useful mutations in sperm precursor cells also may be more likely to pass to the next generation, the authors suggest, �because the effective mutation frequency is elevated beyond the level that can be achieved by the molecular mutation process alone.�

Why natural selection might favor sperm precursor cells carrying a disease mutation is not yet understood.

The authors based their conclusions on an analysis of four human testes and computer models of mutation frequency.

They say their study is the first to check the location of mutant germline cells in the testes in any species. The result was surprising.

�You would expect that when a new mutation arose, it could arise virtually anywhere in the organ,� said Norman Arnheim, holder of the Ester Dornsife Chair in Biological Sciences at USC and one of the co-leaders of the project along with computational biologist Peter Calabrese.

�But when we divided the testes up, we didn�t find that. What we found were some very big clusters of precursor cells that were mutant.�

The data did not support the theory that the site of the mutation in the Apert gene is unusually prone to DNA change.

Another explanation � that the mutations arise very early in the life of a germline cell and multiply through subsequent divisions � also did not fit the data, Arnheim and Calabrese said.

But the clusters of mutant cells could be explained if the mutant cells made copies of themselves more frequently than normal cells.

If a mutant cell divided into two copies of itself every four to five years, the extra copies would be enough to explain the clusters, the researchers said.

They added that the model explains the increase in Apert risk with paternal age, while noting that other selection-based models also may be able to explain the same data.

Citing related studies along with their findings, the authors concluded that �it now seems very likely that (natural) selection can be a driving force acting to increase the mutation frequency at a number of genes in humans.�

Risk of common vaginal infection linked to preterm birth appears higher for blacks

Sat, 11 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) BOSTON, Aug. 11 Risk of a common vaginal infection linked to preterm birth appears to escalate when even one partner is African-American, according to a University of Pittsburgh School of Medicine study presented today at the 34th annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology in Boston.

When a pregnant woman has bacterial vaginosis, her risk of preterm birth goes up, said Hyagriv Simhan, M.D., M.S.C.R., assistant professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine. And now we can say that gauging risk for bacterial vaginosis is not as simple as just looking at the woman. We also should consider her partner.

Bacterial vaginosis (BV) is a common gynecological infection that affects up to 50 percent of women in some populations. BV is characterized by an increase in vaginal alkalinity and an overgrowth of abnormal bacteria. Among the infections more prominent symptoms is a milky, foul-smelling discharge.

For years, clinicians have thought of BV infection as a minor problem, but in addition to increasing the risk for preterm birth, other studies have shown that women who have BV also are more likely to get herpes and other sexually transmitted diseases, including HIV, said Dr. Simhan, a maternal-fetal medicine specialist at the Magee-Womens Hospital of the University of Pittsburgh Medical Center.

For this observational study, Dr. Simhan and his colleagues considered 325 women who were in their first trimester of pregnancy. Among these women, 129 (39.7 percent) were white female/white male partnerships, 35 (10.8 percent) were white female/black male couples, 12 (3.7 percent) were black female/white male couples, and 149 (45.9 percent) were black female/black male partnerships.

Generally, BV was less common among white women compared to black women in the group. But notably, partner race also showed an influence on BV risk, Dr. Simhan said. Our results showed that when one partner is black whether male or female risk of BV goes up two-fold.

BV infection is commonly treated with a range of antibiotics. However, in some cases treatment fails and infections become resistant. Even women whose infection clears frequently can become re-infected later.

We found that paternal race is an independent risk factor for BV during pregnancy, and that this is at least as important a risk factor as maternal race, continued Dr. Simhan. Studies on the contribution of BV to adverse pregnancy outcomes should consider paternal race as an important factor.

A recent study from the U.S. Centers for Disease Control and Prevention found that preterm birth contributed to more than a third of infant deaths twice as many as previously thought, making it the leading cause of infant deaths yet the underlying causes of premature birth are not well understood.

Reasons for the observed variance in BV rates among racial groups also are not well understood, Dr. Simhan said.

There could be genetic differences that relate to why infection rates are different, and maybe some differences in nutritional status that could play a part. But we dont even know the differences in normal vaginal flora among racial groups, he said. More study is definitely needed. What we can say now is that its just not as simple as treating the woman.

Inflammation may cause preterm labor and fetal deaths

Wed, 08 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CLEVELANDInflammation from bacterial infections is linked to preterm births and deaths, according to researchers from Case Western Reserve Universitys School of Dental Medicine and the Case School of Medicine. They found if receptors responding to the presence of dead or living bacteria in the placentas of mice can be blocked, the number of preterm deaths will decline by nearly half.

Yiping Han along with Hongqi Lui from the Case Western Reserve dental school and Raymond Redline from the Case medical school report results from their investigation, TLR4 promotes F. nucleatum-induced fetal death in mice, in the Journal of Immunology.

New findings from the mouse study holds potential to develop ways to curb the emotional and economic toll on families that lose babies to preterm labor and fetal death, said Han, a member of from the department of periodontics.

Currently antibiotic treatments are not very effective at preventing preterm births that are triggered by a bacterial infection. Mice, as well as humans, have several toll-like receptors (TLR) that sense the surface components of living or dead bacteria. TLR2 and 4 are key receptors in recognizing bacterial surfaces. The investigators concentrated their study on these two receptors as a possible link in producing the inflammatory response that is believed to have brought about the fetal death in mice.

In a prior mouse study at Case Western Reserve, the investigators noted that inflammation closely paralleled localization of bacteria. In the present study, the researchers found that mice deficient in TLR4 lacked the necro-inflammatory response to bacteria and produced healthy pups. This discovery led Han and her colleagues to attempt to block the inflammatory process by using synthetic TLR4 antagonist that prevented the receptor from sensing the bacteria.

Fusobacterium nucleatum, a common oral pathogen also found in the amniotic fluid of preterm babies, was used as the model organism for the study. Around day 16 of the gestation period for the mice (the equivalent of the third trimester for humans), F. nucleatum was injected into three groups of miceone that had TLR4 receptors, a group of TLR4-deficient mice and a group that had TLR4 receptors but were given a synthetic compound to block the receptors inflammatory response. Within eighteen hours, inflammation was present in the TLR4 mice.

The researchers wrote, F. nucleatum colonization in the mouse placenta was accompanied by inflammation, similar to intrauterine infection in humans, suggesting placental inflammatory response as an important factor in the pathogenesis of bacterial-inducted preterm birth.

The researchers found that the TLR4-deficient mice gave birth to healthy pups. The TLR4 group that was not given the synthetic compound to block TLR4 from reacting to bacteria had a 50% increase in fetal death over the mice that had TLR4 but were given the compound to block the inflammatory response. In the TLR4-deficient mice, there were very few fetal deaths.

Han said the synthetic TLR4 antagonist appears to be safe for mice mothers and their pups.

The researchers said they hope to find ways to prevent preterm labor that complicates 12% of all live deliveries and results in 70% of neonatal deaths. Preterm births affect nearly half a million babies in the U.S. each year and cost billions of dollars in health costs annually. Han added that the 30% increase in preterm births in recent decades makes it especially important to investigate novel ways of reversing this trend.

Macho men are seen as bad choice for long-term love

Tue, 07 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Women see masculine men as unsuitable long-term partners, new research suggests. Conversely, the psychologists from Durham and St Andrews Universities found that men with feminine facial features are seen as more committed and less likely to cheat on their partners.

The study, published in the current edition of Personality and Individual Differences, asked over 400 British men and women to judge digitally altered pictures of male faces made to look more masculine or feminine. The participants were asked to predict personality traits including sexual behaviour and parenting skills based on what they saw.

Men with masculine faces, with features such as a square jaw, larger nose and smaller eyes, were classed as significantly more dominant, less faithful, worse parents and as having personalities that were less warm, compared to their feminine counterparts, who had finer facial features with fuller lips, wide eyes and thinner, more curved eyebrows.

The scientists say the research, partly supported by the Medical Research Council and the Economic and Social Research Council, backs up earlier research about masculinity and perceptions of personality and gives further insight into what people see in others when choosing potential partners. It will also advance studies in areas like evolutionary biology, fertility and genetics and offer new insights for relationship counselling and psychology.

Lead author, Dr Lynda Boothroyd, a lecturer with Durham Universitys Department of Psychology, commented: This research shows a high amount of agreement between women about what they see, personality wise, when asked to judge a book by its cover.

They may well use that impression of someone to decide whether or not to engage with that person. That decision-making process all depends on what a woman is looking for in a relationship at that time of her life.

The study asked participants to complete a web-based test. Pairs of pictures which only showed the face without any hair, ears, neck, shoulders or clothing visible, were presented side by side. The participants were asked to select which face they thought was more of a particular trait and how much more so by clicking on a point of the scale. Traits selected for judgement were dominance, ambition, wealth, faithfulness, commitment, parenting, and warmth.

The survey also found that faces which appeared healthier, for instance those with better complexion, were seen as more desirable in terms of all personality traits compared to those who looked unhealthy. Similarly, older faces were generally viewed more positively compared to younger ones.

Professor David Perrett from St Andrews University adds: Our research also found that it is mens health that conveys all round good qualities for partnership and personality. Our results contradict claims that machismo denotes fitness and disease immunity. Masculinity may buy you dominance but not necessarily tip top physical condition. Instead women see a healthy guy as the source of wealth, and fit for family life.

First case of successful ovarian tissue transplantation between two, nonidentical sisters

Wed, 01 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A woman, whose ovaries had failed due to damage caused by chemotherapy and radiotherapy, has received a successful ovarian transplant from her genetically non-identical sister. The transplant restored her ovarian function, she started to menstruate and, after a year, doctors were able to recover two mature oocytes from her ovaries and fertilise them to produce two embryos.

This first case of a successful transplantation of ovarian tissue between two non-identical sisters is reported in the journal Human Reproduction today (Thursday 2 August) [1]. Professor Jacques Donnez, head of the department of gynaecology and professor and chairman at the Catholic University of Louvain in Brussels, Belgium, led the team that carried out the work [2].

In 1990, when she was 20, doctors treated Teresa Alvaro for beta-thalassemia an inherited blood disorder characterised by reduced or absent haemoglobin, which is the oxygen-carrying protein in red blood cells. She received chemotherapy and radiotherapy before having a bone marrow transplant from her 17-year-old sister, Sandra Alvaro, who had an identically matched tissue type (human leukocyte antigen (HLA) type), which meant that Teresas immune system would not recognise her sisters bone marrow as foreign and reject it.

The treatment was successful and Teresa was cured. However, in 1990 there were no procedures available for preserving her fertility before commencement of the treatment by, for instance, removing and freezing her eggs or ovarian tissue. The treatment caused complete ovarian failure, and her ovaries never recovered.

In July 2005, now aged 35, Teresa consulted Prof Donnez and his colleagues about the possibility of ovarian tissue transplantation from her sister to give her a chance of becoming pregnant.

Prof Donnez said: Having already provided bone marrow in 1990, her sister, who was now aged 32 and had never become pregnant, badly wanted to help her sister by donating some of her own ovarian tissue.

Although the option of oocyte donation from the sister to the patient was discussed, the patient refused this option. She preferred a transplant because she wanted to be responsible for the follicular maturation and considered that it was more natural than egg donation, for which her sister would have to undergo ovarian stimulation with follicle stimulating hormones and then oocyte retrieval. In addition, her sister had asked expressly to be the tissue donor and had refused to undergo ovarian stimulation for oocyte donation.

Analysis of the sisters HLA type showed that their genetically different cells coexisted successfully together (chimaerism) and that, therefore, no immuno-suppressive treatment would be required to prevent the ovarian graft being rejected. The earlier bone marrow transplant and resulting mixing of the sisters cells meant that Teresas immune system would recognise Sandras ovarian tissue as self rather than foreign.

In February 2006, Teresa and Sandra were anaesthetised together and three small sections of ovarian tissue were removed from Sandra via laparoscopy and within less than a minute were being sewn on to one of Teresas atrophied ovaries, also via laparoscopy. The sisters were discharged from hospital the day after surgery.

After six months Teresa started menstrual bleeding and this, together with differences in hormone levels, confirmed that ovarian function had been restored. Her menstrual cycles have continued ever since. A year after the transplant, the doctors retrieved two mature oocytes from her ovary and fertilised them with her husbands sperm via ICSI (intracytoplasmic sperm injection) they decided to use ICSI rather than attempting natural conception because the husband had a low sperm count. One of the resulting embryos developed to the two-cell stage and the other to the three-cell stage, but then both ceased to develop further, and so the embryos were not transferred to her uterus.

Prof Donnez said: We do not know why the embryos ceased to develop, but this also happens during normal cycles of IVF. The patient is planning more IVF attempts in the future.

He said that it was too early to say whether this procedure would ever be successful enough to enable a woman to become pregnant successfully and give birth to a live baby. However, the work did give hope to women who had not had an opportunity to freeze either their eggs or their ovarian tissue, and it emphasised the importance of leaving at least one ovary in place during any treatment because the ovary offered an excellent site for a subsequent transplant of ovarian tissue.

This method is an option for women who have not had their ovarian tissue cryopreserved, either because chemotherapy was given before 1996, or because cryopreservation was not proposed or not available in the hospital where the patient was treated, he said.

In theory, the procedure could also be used between two, unrelated women, as long as the two women were HLA compatible and if the donor had previously given bone marrow to the recipient, as in the case we are reporting here, he concluded.

Teresa Alvaro said: Early in 2005 my gynaecologist told me that the chemotherapy that I had to go through in 1990 in preparation for my bone marrow transplant had severely affected my fertility. A few months later I happened to read an article on an American woman who got pregnant after she had ovarian tissue transplanted from her twin sister. I didnt hesitate for a second and went to see Prof Donnez together with my sister. Our antigens appeared to be identical, and therefore the chances of rejection were minimal. The operation was a success. I can get pregnant the natural way. Thats something I could never have hoped for a couple of years ago.

Penn study shows lower Cesarean rates associated with preventive labor induction

Mon, 30 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) PHILADELPHIA At a time when national rates of cesarean delivery have climbed above 30%, a four-year study of patients receiving an alternative method of obstetric care experienced a significantly lower rate of cesarean births, according to a study published in the current issue of the Annals of Family Medicine. The study, conducted by researchers at the University of Pennsylvania School of Medicine, reports that a cohort of women exposed to a safe, alternative method of maternity care had a 5.3 percent cesarean delivery rate compared to a 11.8 percent of women who received more traditional care.

The new approach uses a method of pregnancy dating and risk scoring to estimate an optimal time of delivery for each pregnancy. If spontaneous labor has not occurred by this time, preventive labor induction is performed, increasing the likelihood that labor occurs before the fetus has grown too large for the maternal pelvis or before the placenta has grown too old to support the fetus during labor.

The new approach is called the Active Management of Risk in Pregnancy at Term (AMOR-IPAT). AMOR-IPAT evaluates the risk profile for each pregnancy, and uses each risk profile to estimate an optimal time of delivery. Preventive labor induction is used if a woman does not develop spontaneous labor by the upper limit of her optimal time of delivery. Within the term period, the greater the number an severity of risk factors, the earlier preventive labor induction is offered.

The findings support a preventive approach to reduce cesarean deliveries, and challenge the current belief that the use of labor induction leads to higher cesarean delivery risk. The study was conducted at a rural New England hospital and involved 1,869 women. The results of this study are similar to a 400-patient study from an urban setting, published two years ago, that reported a 4 percent cesarean delivery rate in women exposed to AMOR-IPAT.

The estimation of an optimal time of delivery, using a combination of accurate pregnancy dating and risk-factor scoring, is a concept that suggests a potentially powerful preventive approach to obstetric care, says lead researcher, James M. Nicholson, MD, Assistant Professor of Family Medicine and Community Health at Penn. By using preventive labor induction to ensure that every women enters labor during her optimal time for vaginal delivery, the AMOR-IPAT approach provides significant health benefits for mothers and babies. Dr. Nicholson also reports that the use of prostaglandin E2 gel for pre-induction cervical ripening, specifically for women scheduled for preventive labor induction who had an unripe cervix, was a key element of in the successful application of AMOR-IPAT.

Vaginal births carry with them a lower rate of morbidity than cesarean births, including decreased chances for post-partum infection and less blood loss. In addition, lower rates of C-section also correspond to lower usage rates in neo-natal intensive care units, shorter lengths of hospital stay for mother and baby, and fewer complications in subsequent pregnancies.

Sperm banking before treatment preserves fertility in young male cancer patients

Mon, 23 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A recent study at Hamilton Health Sciences proves that sperm freezing and banking is an effective way to preserve fertility in adolescents and young adult (AYA) males with cancer.

Researchers at the Centre for Reproductive Care, McMaster Childrenï¿½s Hospital and the Juravinski Cancer Centre, all members of the Hamilton Health Sciences family of health care facilities, joined forces to investigate the benefits of proactively preserving sperm prior to starting cancer treatment in order to allow male cancer patients the opportunity to father biological children in the future.

In AYA male cancer patients, surgery, radiation and chemotherapy may cause transient or permanent infertility by affecting either ejaculatory or erectile function or by impairing the generation of sperm. (ï¿½The effects of cancer and cancer treatments on male reproductive functionï¿½ by Drs Magelssen, Brydoy and Fossa).

According to a new study to be published in the September 1, 2007 issue of CANCER, a peer-reviewed journal of the American Cancer Society, and available on-line today, lead author Michael Neal, Laboratory Director at the Centre for Reproductive Care, and his co-investigators, found that even though sperm freezing is shown to be highly effective, it is an underutilized option of fertility preservation for young male cancer patients.

The study, ï¿½Effectiveness of Sperm Banking in Adolescents and Young Adults with Cancer ï¿½ A Regional Experience,ï¿½ showed that only 18 percent of the patients in the study opted to bank their sperm before cancer treatment. Those who used their frozen sperm sample after overcoming their cancer had a fertility success rate of 36 percent using intrauterine insemination (IUI ï¿½ injecting the sperm into the uterus) and 50 percent using in vitro fertilization (IVF ï¿½ fertilizing the egg in a lab and then transferring the embryo to the uterus) and intracytoplasmic sperm injection (ICSI ï¿½ injecting the sperm directly into the egg).

A vital component in the efficacy of the study was the collaborative approach taken by the different groups involved, including the Pediatric Oncology team and the Centre for Reproductive Care.

ï¿½The teams involved in the study are highly specialized and unique individually,ï¿½ said Dr. Neal. ï¿½From saving lives to creating new life, the collaboration between these two disciplines provides an exciting opportunity for improved quality of life among adolescent and young adult cancer survivors in the Hamilton region.

ï¿½Childhood cancer treatment has improved dramatically in the last decade resulting in a greater number of survivors,ï¿½ said Dr. Neal. ï¿½At the same time, improvements in the field of assisted conception are providing a great chance for male cancer survivors to father children of their own after potentially fertility-damaging treatment.ï¿½

Another important component of the study addressed the quality of life of young people affected by cancer. ï¿½When adolescents and young adults are diagnosed with cancer, every aspect of their lives is influenced, including their physical, emotional, economic, spiritual, interpersonal, psychosocial, and sexual well-being,ï¿½ said Dr. Ronald Barr, Chief of Service, Pediatric Hematology/Oncology, McMaster Childrenï¿½s Hospital and professor of pediatrics at McMaster University.

The study demonstrated that in clinical practice, the factors of sexual well-being and the effects of the treatment on reproduction might not be addressed adequately by caregivers.

The necessity for education of both health care providers and patients about this option is an essential outcome of this study. Kim Nagel, Research Nurse, Pediatric Oncology, McMaster Children's Hospital, reflects that there is a relatively small window of opportunity before young male cancer patients begin treatment, so it is essential that health care providers are prepared and diligent about providing all options available in regard to improving future fertility.

ï¿½The results of this study have demonstrated the benefits of this unique collaboration between specialties in the hospital,ï¿½ said Kim Nagel. ï¿½Consequently, more research is already in progress or in the planning stages. Given the results of this study, our goal is to improve awareness of sperm banking and future fertility treatments that may impact our patientsï¿½ quality of life.ï¿½

Vaccine trials inject hope into koala's future

Mon, 16 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The first Australian trials of a vaccine developed by Queensland University of Technology that could save Australia's iconic koala from contracting chlamydia are planned to begin later this year.

Professor Peter Timms, from QUT's Institute of Health and Biomedical Innovation, said chlamydia was a major threat to the continued survival of koalas with almost all populations affected by the disease.

The trial is planned to begin before the end of the year and will test the vaccine's ability to induce a good immune response in the koala against chlamydia, he said.

Assuming that this first trial is successful, then future trials can determine if this immune response is able to protect the koalas against chlamydial disease.

We've been able to develop the vaccine for koalas as a result of our studies on the development of human chlamydial vaccines done in the mouse model. We have identified several novel vaccine proteins that we hope will protect koalas as well.

Professor Timms said chlamydia in koalas was a significant cause of infertility, urinary tract infections, and inflammation in the lining of the eye that often led to blindness.

The numbers of koalas with chlamydia seems to be increasing, he said.

As much as 40-50 per cent of koalas coming into care in both Queensland and NSW are showing clinical signs of the disease and it seems to be getting worse.

The vaccine will be administered to a small number of koalas via an injection either under the skin or intramuscularly.

The first phase of the trial will run for between six and 12 months, he said.

We will have initial results within the first six months but we will continue to monitor the koalas for 12 months to determine how long the vaccine stimulates an immune response in the koalas and whether or not a booster shot is required.

There is no danger that a koala without chlamydia will contract the disease from the vaccine.

Professor Timms said the vaccine trial was a significant step in the right direction in fighting the threat of chlamydia in koalas.

QUT's koala vaccine team also includes Professor Ken Beagely and PhD student Asad Sukar.

While we have funding for the initial trial we are hoping to attract additional financial support for us to be able to continue this important work, he said.

We seem to be doing good science but we need more funding. We are looking for corporate or individual support to fund further research in this area.

Professor Timms said by investing in chlamydia research, people were giving hope to the future survival of koalas.

Latest WHO handbook presents family planning options for women around the world

Tue, 10 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Washington, DC The recently released Family Planning: A Global Handbook for Providers includes a chapter on fertility-awareness based methods of family planning highlighting the Standard Days Method and the TwoDay Method, two family-planning methods developed by Georgetown University Medical Centers Institute for Reproductive Health, as effective, easy-to-use and without the health risks of chemically based family planning methods such as birth control pills.

The publication, developed by the World Health Organization, Johns Hopkins University, and the United States Agency for International Development, is used by family planning providers worldwide, especially in developing countries.

With the inclusion of the Standard Days and TwoDay Methods in the WHO family planning handbook for providers, we anticipate that many more providers around the world will offer fertility awareness methods, thereby increasing womens access to these effective, easy-to-use, low-cost options, said Victoria Jennings, Ph.D., co-developer of the methods and director of the Institute for Reproductive Health. She is also professor of obstetrics and gynecology at Georgetown University Medical Center.

Utilizing data from sophisticated computer modeling of reproductive physiology and field studies, the Georgetown researchers developed the Standard Days Method and CycleBeads, the simple visual aid used by women who follow the Standard Days Method. They enable a woman to identify the 12-day fertile window of her menstrual cycle. These 12 days take into account the life span of the woman's egg (about 24 hours) and the viable life of sperm (about 5 days) as well as the variation in the actual timing of ovulation. In a clinical trial, the Standard Days Method proved to be more than 95 percent effective with correct use, similar to other user-directed methods such as the pill. Because this natural method identifies all of the fertile days, it also helps couples who want a pregnancy to achieve their goal.

To use CycleBeads to follow the Standard Days Method, a woman moves a black rubber ring over a series of color-coded beads that represent her fertile and low fertility days. The day a woman starts her period she puts the rubber ring on CycleBeads red bead. Each day she moves the ring one bead, always in the direction of the arrow. When the ring is on the red bead or a dark bead, there is very low likelihood of pregnancy. When the ring is on a glow-in-the-dark white bead - Days 8 through 19 - there is a high likelihood of getting pregnant. CycleBeads also helps a woman know if her cycle length is in the range (26-32 days long) for using this method effectively.

The TwoDay Method employs a very different approach to identifying the fertile days of a womans menstrual cycle. TwoDay Method users monitor the presence or absence of cervical secretions. Women then use a simple formula to determine whether they should consider themselves fertile on a specific day. Georgetown studies have found this method to be 96 percent effective.

Complementary therapy for infertile women may reduce chances of pregnancy

Wed, 04 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Complementary therapies in assisted reproduction may diminish the effectiveness of medical treatment for infertility in women, a scientist will tell the 23rd annual conference of the European Society of Human Reproduction and Embryology in Lyon, France, (Wednesday 4 July). Dr. Jacky Boivin, from the School of Psychology, Cardiff University, Wales, UK, will say that her research had also shown that women who used complementary therapies were more negatively affected by their fertility problems than non-users, and that this could account for the fact that they were willing to use complementary therapies that were not proven to improve fertility.

Many women use complementary or alternative therapies (CATs) to resolve fertility problems, even though there is little evidence that they are effective. However, it is not clear whether people use these to reduce stress or to increase their chances of getting pregnant. So Dr. Boivin and a colleague from the University of Copenhagen, Dr. Lone Schmidt, set out to study why women made these choices, in the hope of being able to better inform them both of their effectiveness and of other options for achieving pregnancy and reducing the stress of infertility.

They examined the psychosocial and medical profiles of 818 Danish women at the start of their IVF treatment, and then looked at which women went on to use complementary therapy in the subsequent 12 months. The study was the first large scale prospective evaluation of CAT use in an infertile population.

We found that women who went on to use complementary therapies for example reflexology and nutritional supplements during their treatments were more distressed and emotionally affected by their fertility problems than non-users, says Dr. Boivin. This difference in stress may mean that women used CATs for stress reduction, and if this were the case it would be important for future research to establish whether CATs achieve this goal more effectively than conventional psychological therapies.

So far, research shows that psychological therapies are more effective in achieving stress reduction. But women may be reluctant to ask for this because of the stigma attached, or perhaps simply because they are not aware of the research, she says We hope that our study will provide a good basis for women to make a decision on whether or not to use CATs as compared with other available options. We are currently developing brief coping interventions that may be more appealing to people who do not want to use conventional one or one or group counselling.

The study also found that women who used CAT had a 20% lower pregnancy success rate over the 12-month treatment period. Our findings do not allow us to make a direct causal link between CAT use and pregnancy rate, says Dr. Boivin. It may be that complementary therapies diminish the effectiveness of medical interventions, as has been shown in previous research. Or it may simply be that persistent treatment failure encourages women to seek out CATs because they are more willing to try anything to get pregnant.

The next step for the researchers is to study the same group over a five year period and see how many become pregnant in the longer term. It is important to do this because we are concerned that, with persistent treatment failure, women might become more and more susceptible to deceptive advertising about ineffective CATs or other unproven treatments, says Dr. Boivin.

Germany's embryo protection law is 'killing embryos rather than protecting them'

Wed, 04 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lyon, France: Instead of preserving life, Germanys embryo protection law has had the unintended consequence of increasing the number of foetuses killed after fertility treatment according to new figures presented at the European Society of Human Reproduction and Embryology today (Wednesday). A representative of the German IVF registry has called for the law to be changed urgently to ensure that this situation does not continue.

The German embryo protection law, passed in 1991, stipulates that no more than three embryos can be created per cycle of IVF and all three, regardless of their quality, must be transferred to the patients womb at one time, and cannot be frozen or discarded.

For the first time, figures for 2004 from the ESHRE European IVF monitoring consortium show that out of 8,500 deliveries in Germany in 2004 there were 222 foetal reductions performed (representing 2.6%). Foetal reductions are performed when a woman has a multiple pregnancy and doctors consider it necessary to reduce the number of foetuses she is carrying in order to increase the chances of the remaining ones surviving. It is also performed when doctors discover that foetuses are abnormal.

Professor Ricardo Felberbaum, from the German IVF registry and a member of the ESHRE European IVF monitoring consortium, said: Germanys embryo protection law is not in accordance with ART [artificial reproduction technology] practices now. Foetal reduction is being used in Germany much more than was expected and the German administration must face up to the situation that the 1991 law prevents optimal treatment of the patient and does not protect the embryo either. The law needs to be changed urgently to reflect the current state of the art.

It is far worse to kill embryos after they have implanted in a womans womb, than it is to take embryos before implantation, when they are no more than a collection of cells, freeze any surplus embryos and transfer no more than one or two embryos at one time. It is best that only those with the highest implantation potential are used, leading to healthy singleton pregnancies.

As the law currently stands it is killing embryos rather than protecting them, he concluded.

Other figures from the consortium show that the number of ART procedures in Germany has nearly halved since state funding for them was cut.

Professor Anders Nyboe Andersen told the conference that Germany was a stark illustration of the impact that state funding has on the availability of ART for infertile couples.

In 2003, Germany announced that it would be cutting its generous reimbursement of fertility treatment by 50% and in that year there was a sudden surge in the number of procedures from 84,819 in 2002 to 102,426 as couples rushed to take advantage of the existing funding arrangements. The following year, when the new reimbursement rules were implemented, total activity dropped by nearly 50 per cent to 60,425. Significantly, this was a persistent effect because the number of cycles remained at this lower level in 2005.

Prof Nyboe Andersen, of Rigshospitalet, Copenhagen, Denmark, was presenting data on behalf of the ESHRE European IVF monitoring consortium, which has been gathering information on ART procedures in Europe since 1997. These new figures relate to ART in Europe in 2004 the most recent year for which data are available.

The number of ART procedures has steadily increased over that time, said Prof Nyboe Andersen. In 2002 there was an overall increase of 13 per cent increase on 2002. However, in 2004 this rate of increase had slowed to just two per cent. This is almost entirely due to the drop in the number of cycles in Germany.

Prior to 2004, Germany carried out the most number of ART procedures in the whole of Europe, with France and the UK in second and third place respectively. However, in 2004 France performed the most ART procedures (nearly 70,000), followed by Germany (just over 60,000), Spain (nearly 41,000) and the UK (just over 40,000). There were 370,963 cycles in the 29 European countries reporting to the consortium in 2004. As a comparison, the USA carried out approximately 130,000 cycles.

The availability of ART as measured by number of cycles per one million inhabitants is highest in Denmark, where couples are entitled to at least three free cycles of fertility treatment, with 2,128 cycles per million in 2004. By comparison, availability in Germany dropped from 1,243 cycles per million in 2003 to 803 per million in 2004. Availability in France was 1,154 per million, in Belgium 1,974 per million and in the UK 665 per million.

The data confirms that the proportion of ICSI to IVF procedures has continued to move in favour of ICSI, with 166,711 ICSI (intracytoplasmic sperm injection) procedures (60 per cent) versus 114,512 IVF (in vitro fertilisation) procedures (40 per cent). The number of frozen embryo transfers has continued to increase, rising from around 18 per cent when the consortium first started collecting data to 26 per cent in 2004.

This is a very positive development, said Prof Nyboe Andersen. This means that patients are not having to go undergo repeated cycles of ovarian stimulation because enough eggs are being collected from the first cycle to freeze for use at a later date if the first cycle using the fresh eggs fails. This is much better for the health of the women.

The increasing use of frozen eggs has also led to improvements in the proportion of babies born after ART. In Finland, there were 4,761 ART cycles started and nearly 19 per cent resulted in births when fresh oocytes were used, but the cumulative delivery rate from both fresh and frozen oocytes was 30 per cent. By contrast, in the UK, from 30,495 cycles, 22% of the deliveries occurred after fresh oocytes were used, but the cumulative delivery rate (fresh and frozen oocytes) was only 25 per cent because there were proportionately fewer frozen embryo transfers.

Finland is the first country in the world to show at a national level that cryopreservation [freezing] is a very effective way of increasing the numbers of babies born after ART, because approximately third of all its ART deliveries were from frozen embryos, said Prof Nyboe Andersen.

Complex ART procedures more likely to lead to umbilical cord abnormality

Wed, 04 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lyon, France: The more complex the assisted reproduction procedure, the more likely the umbilical cord develops in an atypical place or have other abnormalities, a scientist told the 23rd annual conference of the European Society of Human Reproduction and Embryology today (Wednesday 4 July). Mrs. Ilse Delbaere, from Ghent University Hospital, Ghent, Belgium, said that the study, including over 4000 twin pregnancies, was the first to examine umbilical cord abnormalities in such a large population.

For many years, scientists have known that both singletons and twins conceived after fertility treatment do worse in terms of duration of pregnancy and in live birth weight. Certain umbilical cord pathologies, such as the insertion of the cord on the placental membranes instead of centrally in the placenta, or the absence of one artery in the cord, are known to correlate with an adverse outcome, said Mrs Delbaere, and we wanted to find out whether these cord anomalies were more frequent after assisted reproduction.

The team studied data from the East Flanders Prospective Twin Survey (EFPTS), containing information on all multiple births in the region since 1964. Since assisted reproduction was rather rare until the mid-eighties, said Mrs. Delbaere, we analysed twins born between 1985 and 2004. The scientists compared cord characteristics from 2119 spontaneously conceived dizygotic (non-identical) twins and 2243 dizygotic twins who had been born as a result of assisted reproduction technologies (ART). Sub analyses looked at the different types of ART according to its invasiveness and complexity.

The results showed not only that cord abnormalities occurred more frequently in ART twins, but that they varied according to the technique used.

We found an incidence of velamentous insertion, where the cord attaches to the placental membrane, of 3.6% in spontaneously conceived twins, said Mrs. Delbaere. But in twins conceived after IVF we found an incidence of 7.4%, and after intracytoplasmatic sperm injection (ICSI), where a single sperm is injected into an egg, it was 10.4%.

The scientists think that embryo implantation may be different after assisted reproduction. When an embryo is transferred to an area with poorer nourishment conditions, the placenta may migrate to more favourable areas, turning an initial central insertion of the cord into something more peripheral.

We intend to follow up this work by studying whether the birth weight of twins born after ART is still lower when we exclude twins with umbilical cord pathology, said Mrs Delbaere. We believe that this will be the first time that these two issues have been teased out in this way. We hope that our work will contribute to the understanding of how the placenta and cord develop early in pregnancy.

SNAP -- patches and stop

Wed, 04 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) 1050 pregnant women are being recruited for the most extensive trial of its kind to establish the effect of using nicotine patches during pregnancy. The £1.3m clinical trial Smoking, Nicotine and Pregnancy (SNAP) trial will investigate whether nicotine replacement therapy (NRT) is safe, effective and cost-effective for mums-to-be who want to give up smoking. It will also study the effect on the behaviour and development of the child.

Smoking during pregnancy is recognised as a major public health problem. Around 30% of pregnant women smoke and researchers say it can cause significant health problems in the unborn child. It accounts for around 4000 fetal deaths (including miscarriages) every year and it can lead to premature births, low birth weight, cot death and asthma. It is also associated with attention deficit and learning problems in childhood.

The trial, funded by the National Institute for Health Researchs Health Technology Assessment Programme, is being led by Dr Tim Coleman from the Division of Primary Care at The University of Nottingham. He says women are highly motivated to stop smoking when they are pregnant: If the SNAP trial establishes that NRT is effective and safe when used for smoking cessation by pregnant women, then greater use of NRT by pregnant smokers could have a substantial impact on their health and also on the health of their babies.

Women who attend hospital for ante-natal ultrasound scans at between 12 and 24 weeks pregnant are being offered trial participation. If they agree to take part they will receive either nicotine or placebo patches. This will be backed up with support and advice on how to deal with cravings, and what to do to avoid smoking. Their progress will be followed until their children are two years old when infants cognitive development and respiratory symptoms will be compared.

Smoking brings the fetus into contact not just with nicotine but with a long list of other harmful chemicals. Although there is expert consensus that NRT is probably safer than smoking the team have received funding to establish whether or not this is actually the case.

Research midwives are recruiting women to the SNAP trial at Nottingham City Hospital, Queens Medical Centre, Kings Mill Hospital in Mansfield, University Hospital of North Staffordshire in Stoke-on-Trent and the trial will begin in Crewe and Macclesfield in September. The team will be working closely with the local Stop Smoking services.

NRT can double a non-pregnant smokers chance of giving up, but as pregnant women metabolise nicotine a lot faster than other people it cannot be assumed that NRT will work for them and the SNAP trial will establish whether or not this is the case.

Sue Cooper, the Trial Manager, said: This is a really interesting and challenging trial to be involved with. Weve got a great team of enthusiastic research midwives who are working alongside local staff in the hospitals to recruit women to take part in the trial and to help support them to stop smoking.

Pre-implantation genetic screening reduces both ongoing pregnancy and live birth rates in over 35s

Wed, 04 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lyon, France: Preimplantation genetic screening (PGS), often considered to hold out the best chance for older women undergoing IVF to have a pregnancy and birth, does not increase on-going pregnancy or live birth rates, an embryologist told the 23rd annual conference of the European Society of Human Reproduction and Embryology today (Wednesday 4 July). The research is published simultaneously in the New England Journal of Medicine*. Sebastiaan Mastenbroek, M.Sc, from the Centre for Reproductive Medicine of the Academic Medical Centre of the University of Amsterdam, The Netherlands, said that the results of his teams research suggested that PGS should not be carried out routinely in women of advanced maternal age.

In a randomised double-blind trial, the team compared three cycles of IVF with and without PGS in women from35 to 41 years of age. Of the 408 women, 206 of whom were given PGS and 202 were not, the ongoing pregnancy rate was considerably lower in the PGS group than in those who did not have PGS. We found that, at 12 weeks, 52 or 25% of the women in the PGS group were pregnant, whereas 74 or 37% of the control group had an ongoing pregnancy, said Mr. Mastenbroek. And the women in the PGS group also had a significantly lower live birth rate 49 or 24% as opposed to 71 or 35% of the controls.

The investigators believe that there may be a number of explanations for the failure of PGS to improve IVF outcomes in older women. It is possible that the biopsy of a cell from an early embryo on day 3 after conception hampers the potential of an embryo to successfully implant, said Mr. Mastenbroek, though the effect of biopsy alone on pregnancy rates has not been studied.

Furthermore, say the investigators, the limitation on the number of chromosomes that can be analysed could lead to the transfer of embryos that appear normal but are in fact abnormal for one or more chromosomes not tested. Finally, many embryos resulting from IVF may be mosaic, where a single cell does not properly reflect the chromosomal composition of the whole, so that chromosomal analysis may not be representative of the entire embryo.

PGS is a relatively new technique that is in increasing use in IVF centres around the world. In 2003, more than 1700 IVF cycles with PGS for various indications were reported to the ESHRE preimplantation genetic diagnosis (ESHRE-PGD) consortium. This figure under-estimates the total number of IVF/PGD cycles, since only 50 centres worldwide reported their data to the consortium. In a recent survey of 415 assisted reproductive technology clinics in the US, 186 respondents (45%) reported that they had performed a total of 2197 cycles of PGS in 2005, said Mr. Mastenbroek.

The investigators are currently following up their work by investigating why PGS does not work. Even though evidence underpinning the effectiveness of PGS was lacking until now, patients as well as doctors were attracted to this technique. The idea of screening embryos for chromosomal abnormalities to increase live birth rates in IVF is very plausible, and women of advanced maternal age are willing to undergo any technique that may provide them with a baby, said Mr. Mastenbroek.

Our study was limited to older women undergoing PGS. We believe that our findings imply that the efficacy of the technique also needs to be investigated in other groups of women who are offered PGS, such as those who suffer recurrent miscarriage or repeated failure of IVF, since evidence for a benefit of PGS in these groups of women is currently still lacking, he said.

Cloning the male genome may help infertile men

Tue, 03 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lyon, France -- Artificially replicating the male genome could help men with very low sperm counts become fathers, a scientist told the 23rd annual conference of the European Society of Human Reproduction and Embryology (Tuesday 3 July). Professor Takumi Takeuchi, of Weill Medical College, Cornell University, New York, USA, said that mouse experiments by his team, led by Professor Gianpiero D. Palermo, had shown that offspring born as a result of such replication had shown a level of abnormalities consistent with that shown in cloned animals.

Where the man in a couple has problems making any significant level of sperm, doctors are often confronted with the challenge of retrieving a single viable sperm to inject into each egg. Such a sperm is therefore precious to couples wishing to conceive, said Professor Takeuchi. If we were able to propagate it, while maintaining its normal chromosomal make-up, its ability to fertilise and to participate in full-term embryo development, we would be able to enhance the number of chances of conception of many couples, and hence improve the changes of an on-going pregnancy.

Professor Takeuchi and his team injected a single healthy mouse sperm into a mouse egg from which the nucleus had been removed, and by doing so cloned the male genome. The process worked well in almost all cases and the sperm genome was found to be chromosomally identical to its originator in over 80% of the clones analysed. The resulting cells were fused with an egg that had been previously chemically activated.

The cells so derived had chromosomes from both parents and these were allowed to develop into blastocysts, where each early embryo contains between 70 and 100 cells. 64 blastocysts were transferred to 6 foster-mother mice, and so far 4 offspring have grown into normal adults, said Professor Takeuchi, therefore proving that it is possible to replicate the male genome, and that such a cloned genome has the ability to develop to term.

The team is now investigating whether they can make the procedure more efficient by enhancing the number of mouse pups obtained by a single sperm, and thus reducing embryo wastage. We believe that replication of the male genome, in addition to providing hope for infertile couples, could also provide the opportunity to use replicates of the sperm nucleus for diagnostic purposes. If you only have one healthy sperm you would be reluctant to use it for anything but fertilisation. But with this technique it should be possible to create enough to be sure that the embryo which is implanted is healthy.

Since this work aims at preserving the contribution of both parents to the generation of embryos, I feel that, when it is further developed and refined, it should elicit a favourable response from those involved in ethical issues, said Professor Takeuchi. But we are a long way from the time when this will be able to be used in humans. There is much work still to be done to understand why impaired development and abnormalities in the embryo occur, and to take steps to avoid that occurrence.

New research holds promise for protecting cancer patients against infertility

Tue, 03 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lyon, France: A promising new therapy for protecting the fertility of women with cancer and auto-immune diseases such as lupus was revealed at the 23rd annual conference of the European Society of Human Reproduction and Embryology today (Tuesday 3 July 2007). Dr. Kate Stern, Research Director of the Royal Womens Hospital, Melbourne, Australia, told the conference that her pilot study had shown gonadotropin-releasing hormone (GnRH) antagonists were likely to be able to protect the ovary in women receiving potentially toxic doses of chemotherapy. We are now hoping to carry out a randomised controlled trial to assess the long term protective effect of this treatment, she said

GnRH analogues are commonly used in the management of womens disorders that are dependent on oestrogen production, and in IVF therapies. Dr. Stern and her team studied women between the ages of 18 and 35 years who were due to receive high doses of cyclophosphamide, a chemotherapy drug. They knew that GnHR analogues were already used for the temporary suppression of ovulation in infertility treatment, so reasoned that it would be possible to use it to shut down the ovaries temporarily during the time that chemotherapy was administered, and hence protect them from the effect of the drugs.

The women were given the GnRH antagonist cetrorelix by 3 subcutaneous injections, each of them four days apart, concurrently with their chemotherapy. The scientists observed that there was evidence that ovarian function was suppressed, but that this returned to normal after chemotherapy stopped. Follicle stimulating hormone levels were up in 73% of the patients, but these also subsequently returned to normal. 94% of the patients resumed spontaneous ovulation and menses within 12 months.

We believe that using GnRH antagonists in this way could reduce the side effects of chemotherapy over a long period, said Dr. Stern. Other studies have tried to analyse whether similar treatments work, but the medications used have been long-acting and therefore cause shutdown for the whole time the patient is in chemo. This means that patients get unpleasant side effects related to having low oestrogen levels, such as hot flushes, and can also lead to loss of bone mass.

The side effects associated with the cyclical use of GnRH antagonists were minimal, she said. 19% of patients did not experience any at all, and only 6% reported persistent side effects, none of which were dangerous or serious.

Dr. Stern and her team are currently completing a five year follow up of the pilot study. We are optimistic that this will prove to be an effective way of protecting fertility for women without the problems that have been associated with GnRH agonists in the past, she said. The medical community needs to acknowledge the importance of future fertility for young people having cancer treatment. Not all patients who are having cancer treatment have the opportunity to talk with a fertility specialist before beginning treatment, and yet there are already several options for protecting the ovaries and even preserving eggs, embryos, or ovarian tissue. In addition to raising awareness among the medical profession, more support is needed for research in this important area.

Risk-taking in infertility treatment correlates with women's negative moods

Tue, 03 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lyon, France -- A study of womens moods during IVF has found a strong relationship between negative mood and multiple embryo transfer, a scientist told the 23rd annual conference of the European Society of Human Reproduction and Embryology (Tuesday 3 July). Dr Christopher Newton of the University Hospital at London Health Sciences Centre, London, Canada, said that his work could lead to better understanding of the importance of couples emotional health during IVF treatment, and the effect this has on their decision-making.

A reduction in the incidence of multiple pregnancies with IVF requires the transfer of fewer, and ideally only one, embryo (single embryo transfer, or SET). However, many women resist SET because they either favour a multiple pregnancy, or prefer to accept the risk rather than take the chance of not getting pregnant. Research quite unrelated to infertility for example, in gambling or playing the lottery - had shown that decision-making could be influenced by particular mood states and by the individual tendencies of some people to engage in greater risk taking behaviour, said Dr Newton. We decided to see whether this was equally applicable in assisted reproduction.

The team asked 129 female infertility patients to undertake a standardised questionnaire, the Profile of Mood States (POMS), one month before hospital UVF treatment. POMS measures such transient moods as anxiety, depression, anger and fatigue, and provides a total score of overall distress. The women also completed a Fertility Problem Inventory (FPI), that assesses and measures infertility-specific social, sexual, and relationship stress. Finally, the women were asked to rate the desirability of having a twin or triplet versus a singleton pregnancy; the perceived likelihood or a twin or singleton pregnancy; and the desirability of SET.

Risk taking behaviour was measured by asking women to make a graded endorsement of a lower risk versus a higher risk option SET versus two embryo transfer (2ET), and 2ET versus three embryo transfer (3ET), and then rating the riskiness of each choice, said Dr. Newton. We found a significant association between womens mood states and their perceptions of the likelihood of a multiple pregnancy. Women estimated their chance of having a multiple pregnancy as lower when they were experiencing more negative moods. When asked to choose between SET and 2ET, women with more negative moods also rated their choices as more risky. One possible explanation is that negative moods lead women to knowingly make more risky choices.

In a follow up study, Dr. Newton and his team plan to determine whether providing women with accurate risk information will influence their decisions about how many embryos to transfer. If infertility patients were to gain a better understanding or the risks and benefits of transferring more or fewer embryos, and the acceptability of SET were to increase, there could be huge benefits, not just emotional and physically to mothers and children, but also in terms of costs to healthcare systems, he said.

Male or female factor infertility -- men suffer just the same

Tue, 03 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lyon, France: Although most psychosocial research into infertility is centred round the unhappiness it causes women, men suffer just as much, a scientist will tell the 23rd annual conference of the European Society of Human Reproduction and Embryology today (Wednesday 4 July). Ms Laura Peronace, from the School of Psychology, Cardiff University, Wales, UK, will say that, as compared to the use of formal counselling, the development of appropriate support networks for infertile patients is more likely to be used by couples and therefore lessen their unhappiness.

Ms Peronace and her team set out to see whether men with male factor infertility, for example through sperm deficiencies, suffer more than men where the couples infertility comes from the woman. There is a common belief that being unable to father a child is shameful and emasculating, she says, and it is thought that if the man is the source of the couples failure to conceive he is likely to suffer more emotionally than if the problem lies with the woman. However, she says, most studies have focused on men shortly after their infertility was diagnosed, and few have looked at their well-being during the course of treatment.

The scientists selected 256 men from the Copenhagen Multi-Centre Psychosocial Aspects of Infertility (COMPI) research programme. Most men were in the mid thirties, and had been married, on average, for almost 8 years. They had known that they were infertile for over 4 years, and the majority of couples had no children either together, or from previous relationships. Participants completed a series of questionnaires that included measures assessing physical health, support, and psychological and social stress. They completed the questionnaire before the start of treatment, and again after 12 months of treatment, only if their partners had not become pregnant during this time. The men were divided into four categories; unexplained infertility; female infertility; male infertility; or mixed.We found that social stress, marital stress, coping effort, and physical stress increased over time, whereas mental health decreased, says Ms Peronace. Perhaps surprisingly, though, we found that men in all four groups suffered equally. Infertile people appear to rely particularly on their social environment for support, and this seems to deteriorate over time. Couples should be made aware of the possible decline in their social support network and encouraged to organise support systems that no not solely include close friends and family.

Counselling in the early stages of infertility is not often a desirable option for couples, and especially for men, say the scientists. Couples should be encouraged to focus on their partnership and communicate with each other in a mutually supportive way. They might also be directed to online support services, and given the chance to speak to other couples with fertility problems

But psychosocial counselling may be beneficial and more readily accepted in the later stages of treatment, when social networks are at their weakest, and also after repeated treatment failure, says Ms Peronace. Men who are particularly affected by fertility problems should be considered for counselling, since this may improve their mental well-being as well as their perception of their social environment. Given the level of suffering we found among men, it is important to continue to research into their needs.

Europe struggles to meet the challenges posed by PGD patients travelling abroad

Mon, 02 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lyon, France -- A new study has shown that increasing numbers of couples are travelling abroad for preimplantation genetic diagnosis (PGD), and that the main reason for this cross-border movement is the legal position in patients countries of origin.

Mr James Lawford Davies, a solicitor specialising in reproductive and genetic technologies, told the 23rd annual meeting of the European Society of Human Reproduction and Embryology today (Monday 2 July) that the main reason couples travelled to other countries was because PGD was banned in their own. However, this led to concerns over how referrals were made, whether or not the referral itself might be unlawful, and the quality (or even the existence) of counselling, medical advice, support, monitoring and follow-up for families and their children. Other reasons for travelling abroad included the quality of the treatment, test availability, expertise in certain diseases, cost and length of waiting lists in their home countries.

This is the first EU-wide study of provision and regulation of PGD, a technique for testing embryos fertilised in the laboratory for specific genetic or sex-linked disorders such as cystic fibrosis or Duchenne muscular dystrophy. Only unaffected embryos are transferred to the womans uterus, thus avoiding the possible need for a pregnancy termination when the defect is picked up at a later stage.

The study [1] was launched by the European Commission after a workshop organised jointly by the Institute for Prospective Technological Studies (IPTS) of the European Commission's Joint Research Centre (JRC), ESHRE and the European Society of Human Genetics (ESHG) revealed that little was know about the extent to which couples crossed national boundaries to gain access to treatment and what different regulatory frameworks for PGD existed in Member States. Mr Lawford Davies, who lectures in law and medicine at the Institute for Human Genetics at Newcastle University and is a visiting research fellow at Durham University Law School, UK, is a co-author of the report and he focused on the legal, ethical and regulatory aspects of the research in his presentation to the ESHRE conference.

Reproductive and genetic technologies are regulated in a wide variety of ways across Europe, he said. The free movement of people and goods around the EU is a welcome development, but there are disadvantages to such cross-border flow in relation to PGD where such treatment is prohibited in the familys country of origin.

The evidence provided in this study suggests that doctors in Ireland, Switzerland and Germany where PGD is prohibited are concerned about providing information to patients about suitable PGD clinics in other countries. Formal referral is said to be prohibited in Germany and at least one Swiss clinic feared that even informing patients about PGD might be illegal. In Ireland, doctors fears about potential prosecution has led to a peculiar inverted referral process whereby patients must contact PGD clinics in other countries themselves and these clinics then approach the Irish clinic for the relevant patient information. In situations where patients are left to identify clinics themselves, they are deprived of the benefit of medical advice, counselling and support at a vulnerable time.

Secondly, the prohibition of PGD in their own country may complicate monitoring and follow-up. Self-referred patients, who may have identified clinics via the Internet or other means, may go unnoticed and clinics in their home countries could be reluctant to get involved in following up families and children born as a result of prohibited treatment. The evidence indicates some clinics are not deterred, whilst others do not see it as their responsibility.

Our research also revealed an apparent inconsistency in countries such as Germany, Switzerland and Ireland where, on one hand PGD is prohibited, but on the other hand, prenatal testing and pregnancy termination for serious genetic disorders is permitted although the latter is not allowed in Ireland.

The reports authors sent an on-line questionnaire to PGD and IVF clinics in Europe, and then conducted a more in-depth analysis of PGD practice and provision in 11 countries, which had been chosen to include countries with different approaches to regulation: Belgium, Czech Republic, France, Germany, Greece, Ireland, The Netherlands, Slovak Republic, Spain, Switzerland and the UK. The survey identified 53 centres offering PGD, most of them located in Spain, Belgium, The Czech Republic, Greece and the UK. Seventeen centres confirmed that they received tissue samples and 36 treated patients from abroad. The countries that received the most numbers of couples from elsewhere were Spain (332), Belgium (127), the Czech Republic (110), and Cyprus (150).

Mr Lawford Davies said that the survey highlighted other areas of concern:

First baby is born after oocytes were matured in the lab and frozen

Mon, 02 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lyon, France: The first baby to be created from an egg that had been matured in the laboratory, frozen, thawed and then fertilised, has been born in Canada. Three other women are pregnant by the same process. The research was presented to the 23rd annual meeting of the European Society of Human Reproduction and Embryology today (Monday 2 July).

The baby girl was born to one of 20 patients with polycystic ovarian syndrome (PCOS) or with ovaries that had been detected to be polycystic by ultrasound (U/S), who took part in the trial at McGill Reproductive Center, Montreal, Canada. The baby is progressing well.

Dr Hananel Holzer, who led the team, is an assistant professor at the Center and coordinates the fertility preservation programme there [1]. He said: Freezing a womans eggs (or oocytes) has become an important and integral part of fertility treatment, and the introduction of new freezing techniques such as oocyte vitrification has increased significantly both oocyte survival and resulting pregnancy rates. However, to date, the pregnancies reported have been the result of fertilisation of frozen or vitrified and then thawed oocytes that had been collected after ovarian stimulation. Unfortunately, some patients seeking fertility preservation may not have enough time to undergo ovarian simulation, or may suffer from a medical condition deemed by some oncologists as a relative contraindication to hormonal stimulation, such as oestrogen-receptor-positive breast cancer.

In these circumstances, oocytes can be collected from the ovaries without hormonal stimulation, and the immature oocytes can be matured in the laboratory before being frozen or vitrified. But, until now, it was not known whether oocytes collected from unstimulated ovaries, matured in vitro and then vitrified, could survive thawing, be fertilised successfully and result in a viable pregnancy after embryo transfer.

We have demonstrated for the first time that it is possible to do this and, so far, we have achieved four successful pregnancies, one of which has resulted in a live birth. The other three pregnancies are ongoing. These results are preliminary and the pregnancy rate is probably associated with a learning curve; indeed three of the pregnancies were achieved in the last five patients.

Dr Holzer warned that the research was still in its early stages and that it had not yet been proven in cancer patients. It has the potential to become one of the main options for fertility preservation, especially for patients who cannot have ovarian stimulation and all patients who do not have enough time to undergo ovarian stimulation, he said. However, we have to remember that these are only preliminary results from a small number of patients who were not cancer patients themselves. As for all methods for fertility preservation, they should be looked at as preliminary and experimental. We need to inform the patients about the early stage of these treatments without giving any false hopes.

Women who have been diagnosed with cancer face the prospect that the treatment they receive for their disease might make them infertile by destroying their ovarian reserve of oocytes. At present, there is the still experimental option of having the ovarian tissue removed, frozen and then transplanted back at a later date; however, there is the theoretical risk that this could re-introduce metastatic cancer into the woman. For women who are infertile due to PCOS, the administration of hormones to stimulate their ovaries to produce eggs can have the dangerous side-effect of over-stimulating their ovaries, resulting in the potentially life-threatening ovarian hyperstimulation syndrome (OHSS). Therefore, being able to obtain successful pregnancies after retrieving immature eggs from unstimulated ovaries is an important step forward for women in these situations.

The researchers selected 20 patients, with an average age of about 30, who were infertile, had polycystic ovaries and had agreed to have their eggs frozen as part of their in vitro maturation (IVM) treatment. A total of 296 oocytes were collected from the patients, of which 290 were immature. The oocytes were matured in the laboratory for 24-48 hours and then 215 were frozen using the Cryoleaf oocyte vitrification kit developed at McGill. They remained frozen for no longer than a few months, and then were thawed. From these, 148 oocytes survived the thawing process and were fertilised via ICSI (intra-cytoplasmic sperm injection); 64 embryos were transferred to the women. More than one embryo was transferred to each patient because IVM is known to have lower rates of implantation. The resulting pregnancies were singleton pregnancies, with the exception of one, which started as twins but became a singleton pregnancy due to spontaneous reduction.

Dr Holzer said he believed that adjusting the media in which the immature oocytes were matured in the laboratory was probably responsible for the improved success rate as the trial progressed.

Fertility preservation is of the utmost importance to patients undergoing treatments that have the potential of making them infertile. Our research shows that it is possible to collect immature oocytes from unstimulated ovaries, mature them in vitro, freeze and thaw them and then achieve pregnancies and live births, without the risk of aggravating the patients hormone-sensitive disease, delaying their treatment for cancer or re-instituting a metastatic malignant disease, he concluded.

Time-lapse recordings reveal why IVF embryos are more likely to develop into twins

Mon, 02 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lyon, France: Evidence gathered from time-lapse recordings of the formation of early embryos (blastocysts) in the laboratory has revealed why embryos created via IVF and undergoing extended culture are more likely to develop into twins than those created via natural conception. Furthermore, the research has shown that the culture in which the IVF embryos are formed is possibly responsible for the embryos dividing into twins.

Dianna Payne, a visiting research fellow at the Mio Fertility Clinic, Yonago, Japan, told the 23rd annual meeting of the European Society of Human Reproduction and Embryology today (Monday 2 July) that about three pairs of twins per thousand deliveries occurred as a result of natural conception, but many more were born after IVF, even when only one embryo had been transferred to the mother (approximately 21 pairs per thousand deliveries). However, it was not known why this happened.

Using 33 surplus frozen-thawed embryos that had been donated for research, Ms Payne and her colleagues used computer software called MetaMorph [1], which creates a free-running film from single images taken every two minutes with a digital camera attached to a microscope. They then used the software to analyse data from the film.

After thawing, 26 of the 33 embryos (most of which were composed of between two and ten cells) developed to blastocyst stage in which the blastocoele is formed. This is a fluid-filled cavity in the blastocyst and is formed on about day four or five when the embryo forms tight junctions between the cells around its periphery. These outer cells (the trophectoderm) begin to pump fluid into the blastocoelic cavity where a micro-environment is formed in which the cells that will go on to develop into the body of the embryo (the inner cell mass or ICM) develop.

The time-lapse recording showed that at this stage the blastocoele collapsed at least once in 25 of the 26 embryos (96%). The frequency and degree of collapse varied, but the embryos that died tended to be those that had bigger and more frequent collapses, said Ms Payne.

She explained the mechanism that underlies blastocoelic collapse and re-expansion. The fluid in the cavity must be under positive pressure as this pressure is the motive force for expansion of the blastocyst. The trophectoderm maintains the pressure by pumping the fluid into the cavity. I believe that the collapses occur when some of the junctions between the cells fail possibly due to localised cell death, or maybe due to a structural weakness in the junction itself and the blastocoelic fluid leaks out. These collapses occur quite quickly far more quickly than a pump could manage. The magnitude of the collapses is determined by the number of failed junctions. The greater the number of failed junctions, the more severe the collapse. In some cases the embryo cannot re-establish the junctions and the blastocyst is unable to re-expand and thus dies.

Seventeen of the 33 embryos went on to become fully formed blastocysts and 11 either started to hatch or hatched completely from the zona pellucida (the gelatinous protective coating around the blastocyst).

Fifteen embryos degenerated during culture and 11 of them did not re-expand after a collapse and subsequently degenerated. There was no evidence of embryo splitting during the hatching which was one of the theories as to how twins were formed from a single blastocyst. However, two of the 26 embryos (8%) had two distinct ICMs and a third had a possible second ICM. The most common form of monozygotic twinning (identical twins resulting from the dividing of one embryo fertilised by a single sperm) is monochorionic/diamniotic, when two ICMs form before hatching.

Ms Payne said: The second ICM was evident early in blastocyst formation in both embryos, and appeared to be the result of some ICM cells relocating and adhering to the opposite trophectoderm wall, seeded during an early collapse of the blastocyst. Both these embryos with two ICMs hatched completely.

She continued: Up until now, blastocyst collapse in the laboratory was thought to be a normal feature of blastocyst development. However, our findings that collapse was associated with degeneration of blastocysts as well as the formation of the second ICM suggest that these episodes in which blastocoele volume cannot be maintained may be an artefact of culture. Furthermore, our findings suggest that the formation of two ICMs during blastocyst development may be the cause of the high monozygotic rate after extended culture. This hypothesis fits well with the long established cause of the most common form of natural monozygotic twins.

This research is, to Ms Paynes knowledge, the first systematic study by time-lapse recording of blastocyst formation. It was time-consuming, with each recording taking up to five days, and required specialist equipment and knowledge. However, she said it should enable embryologists to work towards avoiding twin pregnancies during IVF. This could be another tool in their armoury, she said. Those embryos that are at risk of twinning could be easily identified by counting the number of ICMs. Then, either a decision could be made about whether to transfer those embryos that are likely to give rise to twins, or, if the choice of embryos is limited, the mother could be prepared for the likelihood of twins and given appropriate clinical advice.

In addition, more information about the cause of monozygotic twins could be collected in the future by a straightforward check of the numbers of placentas and sacs when the babies are born. The chorion and amnion are foetal membranes that contribute to the placenta and the foetal sac respectively. When twinning has occurred because two ICMs have developed (monochorionic/diamniotic twins) there is one placenta and two sacs, and these can be counted at birth.

Careful recording of chorionicity and amnioticity of monozygotic twins at birth should shed further light on the effects of culture on embryos, she concluded.

Endometriosis increases the risk of certain cancers

Mon, 02 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lyon, France -- Doctors in Sweden have shown for the first time that although endometriosis is associated with an increased risk of various cancers, this risk does not depend on the number of times women with the condition have given birth.

Dr Anna-Sofia Melin, told the 23rd annual meeting of the European Society of Human Reproduction and Embryology today (Monday 2 July): Several epidemiological studies have shown an increased cancer risk among women with endometriosis, especially ovarian cancer. Infertility and never having given birth (nulliparity) are also known risk factors for different types of cancer, such as breast and endometrial cancer. However, as far as we know, this is the first study to investigate cancer risk among women with endometriosis that also stratifies for parity.

Dr Melin, a specialist doctor in the department of obstetrics and gynaecology at the Karolinska University Hospital in Stockholm, Sweden, and epidemiologists at the Karolinska Institute looked at data from 63,630 women who had been discharged from hospital with a diagnosis of endometriosis between 1969 and 2002. They were identified and followed up via the National Swedish Inpatient Register, the National Swedish Cancer Register and the Swedish Multi-Generation Register.

The researchers identified 3,822 cases of cancer amongst the women with endometriosis. While they found no overall increased risk of cancer, they did find that the women had an elevated risk of certain types of cancer, but that there was no significant difference in risk between women who had never given birth and those who had.

We found that, contrary to what one might expect, endometriosis and nulliparity did not combine to give a higher risk of cancer, said Dr Melin.

The researchers found that endometriosis increased the risk of developing ovarian cancer by more than a third (37%) above the risk for the normal population of women without endometriosis. There were similar increases in risk for endocrine tumours (38%), kidney cancer (36%) and thyroid cancer (33%). Slightly lower increases were found for brain tumours (27%) and malignant melanoma (23%), and there was a small increased risk of breast cancer (8%). Interestingly, women with endometriosis had a reduced risk of cervical cancer of just under a third (29%).

There was no significant difference between nulliparous and parous women with endometriosis regarding cancer risk for any of the cancer types. We found a non-significant decrease in ovarian cancer risk the more children a woman had had, said Dr Melin.

Little is known about the possible mechanisms involved in the increased risk of cancer from endometriosis (or decreased risk, in the case of cervical cancer).

Dr Melin said: The fact that our study did not show an association between cancer risk and parity increases the possibility that it is the endometriosis disease in itself that causes the cancer and not the infertility issue.

Various theories have been suggested. For ovarian cancer it might be the exposure of the ovaries to the hostile endometrium cells that invade the ovary during the course of the endometriosis disease. Or it could be defects in the immune system that allow the endometriosis to grow and also might allow cancer cells to grow in different parts of the body. Maybe the treatment of endometriosis, hormonal or surgical, can influence cancer development. We do not know yet.

Dr Melin plans to investigate whether hormonal or surgical treatment of endometriosis might be involved in the increased cancer risk, and she also wants to identify which women are more at risk of developing cancer than others.

But she said that it was too early to use the results of her study to give advice to doctors about improved treatments for women with endometriosis.

Our hope is that doctors in general start to view the endometriosis disease as a serious disease that causes a lot of suffering to the patient and also may lead to cancer. We hope that in the future we will be able to identify those women with endometriosis that may have a more aggressive form of disease with more atypical cells, for instance, and that this may lead to better care for the patient and, hopefully, to a early diagnosis if cancer should occur, she concluded.

Personalized approach to ovarian stimulation achieves high ART pregnancy rates

Mon, 02 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lyon, France -- An international group of fertility specialists has developed an easy-to use mathematical formula that allows a personalised approach to ovarian stimulation therapy for women seeking fertility treatment. Clinical tests demonstrated that when clinicians used the formula (or algorithm) to calculate the best starting dose for each patient, both the number of oocytes retrieved and pregnancy rates rose.

Professor François Olivennes told the 23rd annual meeting of the European Society of Human Reproduction and Embryology today (Monday 2 July) that the algorithm was based on four factors that predicted ovarian response and that were measured routinely when women were evaluated for fertility treatment: normal (or basal) levels of follicle stimulating hormone (FSH), body mass index, age and the number of small growing (antral) follicles in the ovary detected during screening.

This FSH dose algorithm is simple and easy to use and utilises readily available patient characteristics, said Prof Olivennes, coordinator of the Centre de FIV Eylau La Muette, Paris, France. It is the first to be tested in a prospective multi-national clinical study and it provided each patient with an individualised starting dose of FSH, which could be maintained throughout treatment and resulted in an excellent treatment outcome as testified by the number of oocytes retrieved and the high pregnancy rates.

This approach should enable us to improve patient management, treatment outcomes and safety by reducing the chances of having to either cancel cycles because the ovaries have not been stimulated enough or of ovarian hyperstimulation syndrome (OHSS) developing because the ovaries have been over-stimulated.

Moderate or severe OHSS can occur in 3-8% of IVF cycles [1]. Moderate OHSS can be accompanied by nausea and vomiting. Severe OHSS, which is an uncommon event, can be accompanied by ovarian enlargement and fluid imbalances, sometimes resulting in thrombosis and, very rarely, in death.

Prof Olivennes was presenting the research on behalf of a multi-national team, the CONSORT Study Group (CONsistency in r-FSH Starting dOses for individualised tReatmenT). The group treated 161 ART patients, younger than 35, in 18 centres around the world. The doctors used the algorithm to allocate the women to receive one of five different doses of a follicle stimulating hormone called recombinant human follicle stimulating hormone, filled by mass (r-hFSH FbM or GONAL-f FbM). [2]

The doses, measured in international units (IU), were 75, 112.5, 150, 187.5 and 225. The women were treated for an average of 11 days. Oocytes were retrieved from 84.4% of women, and 80.9% of the women subsequently underwent embryo transfer. Pregnancies per cycle were 31.3%, 31.1%, 35.3%, 50% and 20% per starting dose of 75IU, 112.5IU, 150IU, 187.5IU and 225IU respectively, with an average pregnancy rate of 34.2%. There were two cases of severe OHSS associated with pregnancy. One case of severe OHSS occurred in a patient allocated to the 75 IU dose group but who received a higher starting dose of FSH from the attending physician.

Prof Olivennes said: The results of the CONSORT clinical study to validate a simple FSH starting dose calculator are very promising, with a high clinical pregnancy rate. It represents an important step forward in aiding clinicians using GONAL-f FbM to individualise the starting dose based upon four easily measured patient characteristics: basal level of FSH in early spontaneous cycle, age (less than 35 years old), body mass index and antral follicle count in early spontaneous cycle.

However, we still have more work to do before the algorithm can be used for all patients in the clinic. Firstly, the FSH dose calculator has only been validated for GONAL-f FbM there are other types of FSH in use. Secondly, we have demonstrated its usefulness in women younger than 35 undergoing ART; further work is required to extend its use in other patient groups.

The results of this clinical study will provide us with an opportunity to fine-tune the model so as to allow us to further improve its usefulness before making it more generally available. One of the next steps that we are considering is to make the CONSORT FSH dose calculator available to fertility specialists through a dedicated web site, with an appropriate follow-up procedure.

At present, reproductive medicine specialists determine starting doses so as to induce multiple follicle development based upon some of the characteristics used to develop our model, other tests of ovarian reserve, and their previous clinical experience. We hope that this research will represent a move towards an evidence-based approach to the use of FSH.

New approaches to endometriosis treatment -- mouse experiments point the way

Mon, 02 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lyon, France -- Possible new directions for the treatment of endometriosis, a painful condition associated with infertility that affects up to 15% of women of reproductive age, will be outlined in the presentation of two experimental studies at the 23rd annual conference of the European Society of Human Reproduction and Embryology (Tuesday July 3). Both concern targeting angiogenesis the formation of new blood vessels which is encourages endometriosis by providing a rich blood supply.

Dr. Edurne Novella-Maestre and colleagues from the Valencia Infertility Institute (IVI), Spain, studied Vascular Endometrial Growth Factor (VEGF), which is known to be particularly involved in the angiogenesis process and therefore in the development of endometriosis. They created an experimental model of endometriosis in nude mice in order to test whether dopamine agonists, much used in other infertility treatment such as the prevention of ovarian hyper-stimulation syndrome, could be a new strategy for inhibiting endometrial lesions. We know that dopamine agonists are a safe treatment, and that they have been used for many years in order to stop breastfeeding, for example, without any major side effects, says Dr. Novella-Maestre, so we decided to see what effect they would have on the experimental mice.

The scientists found that the blood vessel formation in the lesions was significantly decreased. The percentage of new blood vessels in the two treatment groups was reduced in comparison to the control group, and we also found that the percentage of old blood vessels in these groups were higher, says Dr. Novella-Maestre. The total number of the blood vessels was not dissimilar in the treatment and control groups, but the ratio of new/old blood vessels, the numbers of cells growing in the endometrial area, and the area lesions were totally different, suggesting that there was inhibition of blood vessel replacement in the treatment group.

The team now intends to follow up the work in humans. Our initial experiments have confirmed the presence of the dopamine receptor in human endometriosis, and therefore we believe that treatment with dopamine agonists will have the same effect on humans as it does on mice, she says. This is encouraging, since current therapies are still associated with a high recurrence rate, and many of them can only be used for a limited time due to unacceptable side effects and/or osteoporosis. For women with pain, surgery can provide a temporary relief, although symptoms recur in up to 75% of women within two years. A long-term, safe, and non-invasive solution is badly needed.

An additional advantage of such a treatment, say the scientists, is that it is likely that women with endometriosis also have an increased risk of various cancers. The simultaneous occurrence of endometriosis with ovarian cancer, for example, suggests that endometriosis constituents may transfer into tumour cells. If we are able to inhibit angiogenesis in the ectopic human endometrium with a dopamine agonist, says Dr. Novella-Maestre, we may be able to decrease the cancer risk for these patients.

In another presentation to the conference, Dr. Ofer Fainaru, from Harvard Medical School and Childrens Hospital Boston, in Boston, Mass., USA, will announce that his team has found that dendritic cells highly specialised immune cells support angiogenesis by enhancing blood vessel growth. Using a mouse model of endometriosis, they found that these cells incorporate into the endometriosis lesions and enhance their growth. We also found that these cells have a similar effect on intra-abdominal tumours, he said.

We therefore believe that targeting dendritic cells may prove to be a promising strategy for treating conditions dependent on angiogenesis, such as endometriosis and cancer, says Dr. Fainaru. Our next step will be to look for specific dendritic cell inhibitors that could have the potential to decrease angiogenesis in these conditions.

The team hopes that in the future it may be able to develop cell-specific therapy for angiogenesis-dependent diseases that will be more effective and less toxic than current treatments.

Extracting eggs from pre-pubertal cancer patients brings hope for future fertility

Sun, 01 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lyon, France -- Scientists in Israel have been able to obtain and freeze eggs from the ovarian tissue of girls as young as 5 years old, the 23rd annual conference of the European Society of Human Reproduction and Embryology will hear on Tuesday (3 July). Dr. Ariel Revel, from the Department of Obstetrics and Gynaecology, Hadassah University Hospital, Jerusalem, Israel, said that the growing number of survivors of childhood cancers meant that such techniques would become increasingly important in preserving fertility in young patients.

Childhood cancers usually result in cure rates of between 70% and 90%, and are generally more responsive to therapy than adult cancers. However, the aggressive chemotherapy which is often necessary usually means that children will be sterile in later life. In adult women, the ovaries are stimulated to produce eggs which are removed, fertilised and frozen.

In younger girls this is not possible, and the method normally used is to freeze the ovarian cortex, which contains the egg-producing follicles, for transplantation at a later date. But the cortex is often damaged by freezing, and collecting and freezing individual eggs from the follicles, which are more resistant to the damage caused by extreme cold, offers a better chance of restoring fertility in adulthood.

To their surprise, Dr. Revel and his team found eggs in the follicles of girls between 5 and 10 years old who had not reached puberty. We were able to extract oocytes using needle aspiration from very young girls, he said. For example, we found 7 eggs in a girl of 5 years old with Wilms tumour, 8 in an 8 year old with Ewings sarcoma, and 17 in a ten year old, also with Ewings sarcoma. We were then able to mature the eggs in vitro and freeze them for use in the future.

The median age in the study group was 16, and eggs were found in all but one patient, herself aged 16. A total of 167 eggs were found, with an average of 8.5 per patient. Excluding one patient who asked that the oocytes we had found in her ovaries should be frozen immediately, we matured the 130 others in vitro, said Dr. Revel. 41 were successfully matured, a 32% success rate.

No eggs have yet been thawed, said Dr.Revel, so we do not know whether pregnancies will result. But we are encouraged by our results so far, particularly the young ages of the patients from which we have been able to collect eggs. We believe that no younger patients have ever undergone egg collection, in vitro maturation, and egg freezing. We are hopeful that the mature eggs can offer these girls a realistic possibility of preserving their fertility.

Key to male infertility

Fri, 29 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A factor in immune cells regulates human semen and seems to determine whether a man will be fertile, according to a new study.

Yousef Al-Abed, PhD, and his colleagues at The Feinstein Institute for Medical Research have isolated an immune substance called macrophage migration inhibitory factor (MIF) in semen samples from infertile and reproductively healthy men. MIF is key to helping sperm mature, which is necessary for its union with an egg. The finding could lead to a diagnostic test to determine fertility status.

The study appears in the latest issue of Molecular Medicine. The semen samples were collected from men three to five days after a period of sexual abstinence. The scientists had no idea when analyzing levels of MIF whether the sample came from any of the 68 men who had problems conceiving or from the 27 healthy controls. The findings have a Goldilocks kind of quality: Those with infertility problems had MIF levels that were either too high or too low. Those who had no problems conceiving had levels that were just right.

When the scientists added MIF into lab dishes filled with healthy sperm, it decreased the count and impaired their motility.

If MIF has a role in infertility, Dr. Al-Abed and his colleagues are wondering whether it might just work as a form of male contraception. In the meantime, the scientists have a patent on an assay that can be used to analyze MIF levels to help determine whether a man will have problems conceiving. About 15 percent of couples attempting to get pregnant for the first time have problems conceiving. About 40 percent of infertility problems are due to disorders in the male.

MIF is a key player of the immune system. MIF was identified 40 years ago but it was only recently that scientists discovered its role as a pro-inflammatory substance. MIF has now been linked to many autoimmune and inflammatory diseases - such as diabetes and sepsis - and Al-Abed, an organic chemist by training, has been trying to identify and design small molecules that would block MIF activity.

The Feinstein researchers recently identified a critical area on the MIF protein surface that is crucial for the inflammatory response. Such a substance designed to target this area could be used to treat a variety of conditions, including septic shock, sepsis, rheumatoid arthritis and diabetes. The team designed a specific inhibitor called ISO-1 to fit into this pro-inflammatory site. In an animal model of sepsis, ISO-1 abolishes MIFs potent inflammatory abilities and the animals respond dramatically. They lived through the once-fatal sepsis.

In patients in the throes of sepsis - an over-reactive and potentially fatal immune response to a bacterial infection - MIF concentrations are 10 to 20 times higher than normal. If MIF goes down, the chance that patients will survive sepsis is increased dramatically. The idea is to suppress inflammation so that cells stop producing MIF, said Dr. Al-Abed.

Every year, 215,000 Americans die of sepsis, a systemic inflammatory reaction to infection. Another 500,000 survive the infection, and scientists are still trying to figure out why these patients survive and others dont. There are no treatments for this massive all-out war on the body. Those who survive often face serious cardiovascular problems. Scientists examining cardiac function during sepsis have identified macrophage migration inhibitory factor (MIF) as a key factor in heart damage. And antibodies targeted to MIF, so-called anti-MIF antibodies, significantly improves cardiac performance during septic shock.

MIF levels are also two times higher in autoimmune diseases like rheumatoid arthritis and diabetes. In the laboratory, Al-Abed and his colleagues found that having MIF on board in high amounts in animals prone to diabetes set the disease process in motion weeks earlier than expected. The team is now trying to design a clinical study to look at MIF levels in type 1, or juvenile, diabetes.

One thing has become clear about the MIF molecule: It needs a network. To act as a pro-inflammatory soldier, it relies on other substances to help. MIF on its own is not toxic, Dr. Al-Abed said. They are now trying to figure out what substances MIF partners with to do its dirty work.

Researchers find gene that spurs development of the epididymis

Wed, 27 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Human sperm cells travel up to 6 meters in their transit from testes to penis, and most of that journey occurs in the epididymis, a tightly coiled tube that primes the cells for their ultimate task: fertilization. In a paper released this week in the Proceedings of the National Academy of Sciences, researchers at the University of Illinois report that they have discovered a gene and related mechanism essential to the embryonic development of the epididymis.

The findings are the result of a serendipitous discovery, said professor of veterinary biosciences Humphrey Hung-Chang Yao. His graduate student, Jessica Tomaszewski, was examining the testes of mouse embryos when she noticed something odd: In one specimen the normally convoluted coil of the epididymis was instead a stunted, straight tube.

The lack of coiling had serious implications for the fertility of the mouse, Yao said.

If you take sperm directly from the testis and put it into the female reproductive tract, it wont swim. It wont be able to fertilize the egg, he said. Going through the epididymis changes the biochemical properties of the sperm and helps it develop the energy-generating machinery that allows it to swim. So without this structure, under normal circumstances a male cannot be fertile.

The researchers first thought that the abnormality was due to a lack of the male hormone, testosterone. Decades of research had shown that the development and maintenance of male reproductive structures depend on an increase in testosterone levels that begins in the latter half of the life of an embryo.

But all the normal indicators of adequate testosterone levels (its production and other physiological characteristics) were present in the mutant embryos.

Tomaszewski looked at younger mouse embryos from the same parents, to see how early in their development the abnormality appeared. She found the earliest evidence of a lack of proper coiling in the epididymis between days 15.5 and 17.5. (Mouse gestation is about 19 days.)

Before it is formed in the embryo, the epididymis is part of a structure called the Wolffian duct. When the male mouse embryo is about 13 days old, the Wolffian duct begins to grow and differentiate into the plumbing system connecting testes and vas deferens. This normally occurs in males shortly after testosterone levels begin their increase. But in the embryos Tomaszewski had found, the epididymis did not follow the standard path, even though testosterone production was normal.

From his earlier work, Yao knew that the gene for one component of a growth factor, inhibin beta A, is highly expressed in the part of the Wolffian duct that eventually becomes the epididymis. He also knew that expression of this gene increases in response to a rise in testosterone. Inhibin beta A forms part of a protein, activin, that spurs a cascade of activity in certain cells.

By staining the cells of the developing epididymis for inhibin beta A and for a marker of activin activation Yaos team was able to show that inhibin beta A was spurring activity in the cells that form the walls of epididymal tube.

Further study showed that a lack of inhibin beta A led to stasis in these cells. Without it, the cells divided too slowly to adequately lengthen the tube.

This research adds to the evidence that while testosterone is the master switch that triggers the development of male reproductive structures, it doesnt work alone, Yao said. Other studies had shown that testosterone works with other regionally specific factors to spur the development of structures such as the prostate gland or seminal vesicles. Inhibin beta A is the first such factor shown to contribute to epididymal coiling, he said.

The identification of inhibin beta A in the development of the epididymis is important for understanding the basic biology of male sexual development, Yao said. But it also provides new insight into male infertility.

SSRI antidepressants do not pose major birth defect risk

Wed, 27 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Boston, MA -- Researchers from Boston Universitys Slone Epidemiology Center have found that certain selective serotonin reuptake inhibitors antidepressants do not appear to increase the risk for most kinds of birth defects. The findings, to be published in the June 28, issue of the New England Journal of Medicine, suggest that individual SSRIs may increase the risk for some specific defects, but these are rare and the absolute risks are small.

The risk of birth defects following antenatal exposure to SSRIs remains controversial. Early studies demonstrated that SSRIs didnt increase risks of birth defects when such defects were studied as a group. However, birth defects are not a single entity and individual defects have distinct causes. And, more recent studies have reported elevated risks for some birth defects.

Using data from the Slone Epidemiology Centers Birth Defects Study, an ongoing program of case-control surveillance of medication use in relation to birth defects, the researchers considered relationships between first trimester SSRI use and the risk of various birth defects among mothers of 9,849 infants with birth defects and 5,860 infants without defects.

The researchers analyzed defects previously linked to SSRI use and found overall SSRI use was not associated with significantly increased risks of craniosynostosis (where connections between skull bones close prematurely), omphalocele (intestines or other abdominal organs protrude from the naval) or heart defects overall.

Analysis of individual SSRIs and specific defects showed significant associations between setraline (e.g. Zoloft) and omphalocele and septal defects (defects in the walls that separate the chambers of the heart) and between the paroxetine (e.g. Paxil) and certain heart defects that interfere with blood flow to the lungs. This last association was also reported in another paper, from the CDCs National Birth Defects Prevention Study, in this weeks NEJM. However, the BU researchers stress that even if a specific SSRI increased rates four-fold, as was observed for some of these associations, the risk of having an affected child would be less than one percent.

Our analyses did not confirm previously reported associations between overall use of SSRIs and a number of birth defects, said lead author Carol Louik, ScD, an assistant professor at the Slone Epidemiology Center at Boston University. Rather our study suggests that risks are limited to specific SSRIs in relation to specific birth defects. Still, it is important to keep in perspective that the baseline risks for these rare defects are small, so even if the modest increased risks we observed are correct, the chances of having a child with such a defect are quite small, she added.

Children born after PGD as healthy as those born after conventional IVF treatment

Sat, 16 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Nice, France: Children born after embryo biopsy for preimplantation genetic diagnosis (PGD) do not show any more major malformations than those born after artificial reproduction technologies (ART) without PGD, a scientist will tell the annual conference of the European Society of Human Genetics today. Professor Ingeborg Liebaers, from the Research Centre for Reproductive Genetics, Free University of Brussels, Brussels, Belgium, will say that the results of her study of 583 children born after PGD was reassuring.

PGD is a new option for couples at risk of transmitting genetic diseases. Instead of carrying out a prenatal diagnosis followed by a termination of pregnancy, in vitro fertilisation (IVF) with intracytoplasmic sperm injection (where a sperm is injected directly into an egg) is performed, followed by genetic testing of the embryos. Only unaffected embryos are subsequently transferred to the womb.

Because embryos are biopsied in PGD procedures, and this constitutes an additional manipulation of a delicate organism, we set out to study whether this had any effect on the health of children who were born as a result of this procedure, says Professor Liebaers. The scientists first collected data on the pregnancies by giving questionnaires to patients on the day of the embryo transfer. Additional questionnaires were sent during pregnancy, at delivery, and later on to the patients, their gynaecologists, and paediatricians. Children were examined at 2 months and 2 years old.

After embryo transfer, 563 children of the 583 were liveborn, 20 were stillborn, and 9 died neonatally. It seems that the perinatal death rate is higher, especially in multiple pregnancies, then in IVF and ICSi children. We need to further investigate these perinatal death rates, says Professor Liebaers, but we were encouraged to find that the major malformation rate was only 3.6%, or no higher than that which is found in children born after conventional IVF and ICSI.

The average length of the pregnancies of singleton births was 38.8 weeks and the mean birthweight 3.268 kg, comparable to those of IVF and ICSI children, she says.

The study is the first of a large series of PGD children from one centre, Professor Liebaers will tell the conference, and we will be carrying out further follow-up as these children grow older. But we feel that results to date are reassuring; it is good to know that a procedure that can offer patients hope of having a baby unaffected by serious disease is also safe in the longer-term.

Noninvasive screening in early pregnancy reduces Down's births by 50 percent

Sat, 16 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Nice, France: Non-invasive screening of pregnant women with ultrasound early in pregnancy, combined with maternal blood analysis, has reduced the number of children born in Denmark with Down Syndrome by 50%, a scientist will tell the annual conference of the European Society of Human Genetics today. Professor Karen Brøndum-Nielsen, of the Kennedy Institute, Glostrup, Denmark, will say that another benefit of the introduction of this procedure in her country was a drop in the number of invasive pre-natal diagnostic procedures from 11% to approx. 6% of pregnancies.

In September 2004, Professor Brøndum-Nielsen will tell the conference, the National Board of Health in Denmark recommended new guidelines for prenatal diagnosis. Previously this was restricted to pregnant women over 35 years of age, but since the implementation of the new guidelines it has been available to any woman who wants it.

The women were offered a measurement of nuchal translucency in the fetus by ultrasound. This test looks at thickness of the black space (fluid) in the neck area of the fetus. If there is more than the normal amount of fluid the risk of Down syndrome is increased. Likewise if there is a certain combination of serum markers in the maternal blood test, taken at the same time, there is the possibility of an increased risk of a chromosomal abnormality. The combined screening is carried out at 11 to 14 weeks of gestation.

Professor Brøndum-Nielsen and her team looked at the effects of the new guidelines in 2004, 2005, and 2006, in 3 counties in Denmark with a total population of 1.1 million inhabitants, or about one-fifth of the population of the country. They compared these findings with national figures obtained from the Central Cytogenetic Registry, which confirmed the reduction in invasive procedures and the number of children born with Down syndrome at national level. When we looked further at the history of children born with Down Syndrome, we found that their mothers had declined the offer of screening, or had taken it up too late in pregnancy, she says. Another group had risk assessment that did not lead to invasive procedures

Women whose test results showed an elevated risk were offered an invasive procedure (chorionic villus sampling or amniocentesis) to definitely confirm or exclude the diagnosis of Down syndrome by chromosome analysis. We found that making non-invasive screening available to all pregnant women meant that the numbers of invasive procedures decreased by 40% between 2004 and 2006, says Professor Brøndum-Nielsen. Although we have not yet studied the whole of the population, these numbers are significant enough to show that the new guidelines have been accepted by a great majority of Danish parents. However, there is a need for analysis of the psychosocial aspects, both as to the pre-test counselling and the women´s attitudes, she says.

Studies to find better ways to preserve human eggs, ovarian tissue under way

Wed, 06 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The goal is to make human eggs, ovarian tissue, blood vessels, even whole organs available when needed.

To get there, researchers are directly comparing slow-freezing techniques, used successfully for decades to preserve sperm and embryos, to a more rapid method of cryopreservation that transforms tissues into durable glass-like structures.

Phase I trials under way at the Medical College of Georgia are comparing the two approaches in human ovarian tissue and eggs, or oocytes, as well as human-like cow ovarian tissue and eggs.

They start with reproductive tissues because young women with cancer produce a compelling need and are a good model for other tissues and organs.

What we tell patients is that right now the standard of care for people who are going through cancer therapy is to use egg donors later on, says Dr. Adelina M. Emmi, reproductive endocrinologist and medical director of MCG Reproductive Laboratories of Augusta.

Treatment for leukemia and cervical, ovarian, breast or other cancers often leaves women infertile because systemic chemotherapy and more focused radiation therapy, designed to kill rapidly spreading cancer cells, also can destroy dynamic reproductive tissue.

I dont think when you are faced with the reality that you may die, your fertility is the most important thing you are thinking or talking about, but there are a lot of women interested in talking about it, says Dr. Emmi. She hopes her work with Dr. Ying C. Song, cryobiologist, will one day give her more to say.

They are collecting ovarian tissue from volunteers age 16 to 37 who need the tissue taken for some reason other than cancer, such as a hysterectomy for benign disease, says Dr. Song, MCG clinical associate professor at MCG and director of research for Augusta-based Xytex Research/Xytex International. Collaborators at the University of Texas Health Science Center and M.D. Anderson Cancer Center are doing the same.

With some of the tissue, they are using conventional cryopreservation. Chemicals to protect cells from the hazards of freezing are added before taking tissue from the refrigerator temperature of 4 degrees Celsius to minus 80 degrees Celsius over two- and one-half hours. Later, liquid nitrogen takes it to minus 196 degrees

You put it in a control-rate freezer that takes down the temperature one degree centigrade per minute so it drops the temperature very, very slowly, says Dr. Song.

Slow cooling works well for simple tissue, such as sperm or even embryos, and for blood. In blood, for example, conventional cryopreservation freezes the liquid part but not the cells inside. Liquid freezes and the water inside the cells moves out gradually so they dehydrate, Dr. Song explains.

But, for more complex structures, such as a human egg or ovarian tissue, resulting ice formation can be destructive. Ice crystals break up your inside organelles. That is what hurts eggs, which are very delicate, he says.

When you trigger ovulation with a hormone or naturally, you get the last separation of the chromosomes, from 46 to 23, says Dr. Emmi. That separation enables a future baby to get half his chromosomes from mom and half from dad. Fragile spindles, which line up chromosomes for division, are easily broken during freezing so chromosomes cant properly divide. Typically the resulting embryo dies. Plus, fertilization is unlikely since freezing often hardens the eggs outer shell that sperm must penetrate.

That is why we have tried to develop technology without freezing, says Dr. Song, who has pioneered use of vitrification in blood vessels, cartilage and heart valves.

Vitrification, which takes tissue from room temperature to minus-100 degrees Celsius in 20 minutes, solidifies tissue into a clear, glass-like structure minus the opacity of ice cubes and frozen meats, a tell-tale sign of ice crystals within.

Dr. Song, whose research lab is in MCGs biotech incubator, has developed cryoprotectants that can be used safely in higher doses as well as agents to help protect tissue during the ultra-rapid process of de-vitrification.

People use low concentrations of cryoprotection because they are toxic, he says. The problem is, if you use lower concentrations, you cannot get true vitrification. The agents are needed to intercept water so it wont form ice. Interestingly if small ice crystals form during cooling, they can get larger during de-vitrification, which takes place in seconds.

We developed a solution where we can warm up tissue in under five minutes and still get no ice formation, says Dr. Song, adding that ice formation aside, it is difficult to thaw rock-solid tissue at room temperature in a matter of seconds, meaning the current approach could have extremely limited use.

A study he published in March 2000 in Nature Biotechnology showed the approach he uses works well, at least in blood vessels. Now we want to try this on eggs and ovarian tissue and see if we can develop a robust technology and improve outcomes, Dr. Song says.

Later, researchers will put ovarian tissue preserved both ways into mice to see if it survives and starts making proper connections.

The reason for using ovaries is when you have cancer, if you need chemotherapy, you often dont have time to go through stimulation cycles to get oocytes, says Dr. Emmi. You are concentrating on getting rid of cancer cells. Also, if a woman has breast cancer, for example, hormones needed to induce ovulation could be problematic because many breast cancer cells have estrogen receptors.

As pieces of a puzzle come together, Dr. Song notes scientists already are developing methods to stimulate ovarian tissue to produce eggs outside the body, a process that could also make in vitro fertilization a lot more affordable. Others are looking for ways to ensure there are no cancer germ cells in salvaged tissue.

If all goes as hoped with this study, the next step will have Drs. Song and Emmi taking ovarian tissue from cancer patients, vitrifying it then, after they are sure its cancer-free, re-implanting it when the woman is ready.

A concurrent phase I study is comparing standard cryopreservation to vitrification in eggs. They are using eggs from 60 women age 18-42 that would be discarded because they are not adequate for in vitro fertilization. They also are retrieving and maturing eggs from cow ovaries donated by a local slaughterhouse. Bull sperm will be used to test the viability of cow eggs afterward but human eggs will not be fertilized.

Standard cryopreservation has been tried and largely failed in human eggs, says Dr. Emmi, who believes some version of vitrification likely offers a better option for ovarian tissue and eggs. In fact, many in vitro fertilization programs, including the one she directs at MCG Health System, are moving toward vitrification, which also seems to work faster, better and cheaper in embryos.

They pursue the potential of egg preservation as well to really find out which is the best option: ovarian tissue or pure eggs. Also, a better way to preserve eggs which last about 24 hours outside the body without preservation would reduce the cost and logistical issues of coordinating donor eggs.

The long-term goal is organ banking, says Dr. Song, because even though there are insufficient numbers of donors for those on transplant lists today, another piece of the puzzle is developing techniques for growing organs. In fact, he is collaborating with scientists at Yale University and the Georgia Institute of Technology to regenerate blood vessels and pancreatic substitutes, noting studies published in Tissue Engineering and Cell Transplantation.

Regenerative medicine will help supplement the shortage of organs in the future, and we need technology to preserve those we make.

Cigarette smoke alters DNA in sperm, genetic damage could pass to offspring

Sat, 02 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The science has long been clear that smoking causes cancer, but new research shows that children could inherit genetic damage from a father who smokes.

Canadian researchers have demonstrated in mice that smoking can cause changes in the DNA sequence of sperm cells, alterations that could potentially be inherited by offspring. The results of their study are published in the June 1 issue of Cancer Research, a journal of the American Association for Cancer Research.

?Here we are looking at male germline mutations, which are mutations in the DNA of sperm. If inherited, these mutations persist as irreversible changes in the genetic composition of off-spring.? said Carole Yauk, Ph.D., lead author of the study and research scientist in the Mutagenesis Section of Health Canada?s Environmental and Occupational Toxicology Division. ?We have known that mothers who smoke can harm their fetuses, and here we show evidence that fathers can potentially damage offspring long before they may even meet their future mate.?

Males, whether they are mouse or man, generate a constant supply of new sperm from self-renewing spermatogonial stem cells. Yauk, along with colleagues at Health Canada and McMaster University, studied the spermatogonial stem cells of mature mice that had been exposed to cigarette smoke for either six or 12 weeks to look for alterations in a specific stretch of repeated portions of DNA, called Ms6-hm, which does not contain any known genes. The ?smoking? mice were exposed to two cigarettes per day, the equivalent ? based on blood levels of tobacco by-products ? of an average human smoker, according to research previously published by one of the study's co-authors.

Yauk and her colleagues found that the rate of Ms6-hm mutations in the smoking mice were 1.4 times higher than that of non-smoking mice at six weeks, and 1.7 times that of non-smoking mice at 12 weeks. ?This suggests that damage is related to the duration of exposure, so the longer you smoke the more mutations accumulate and the more likely a potential effect may arise in the offspring,? Yauk said.

According to Yauk, previous studies have shown that Ms6-hm and similar locations of non-coding DNA are sensitive to damage from radiation, mutagenic chemicals and intense industrial air particulate pollution. While the researchers did not specifically study the protein-coding regions of DNA where genes reside, Yauk notes that previous studies correlate mutations in non-coding regions with those in coding regions, and that some repetitive regions of DNA (not exam-ined in this study) are associated with genes.

?It stands to reason that mutations could also interfere with genes, but our ongoing research looks to clarify the severity of DNA damage throughout the genome,? said Yauk. ?So, while some men say they?ll quit smoking after their child is born, this represents a good reason to quit well in advance of trying to conceive.?

Among the next steps in gaining a better understanding of the germline genetic health conse-quences of smoking, Yauk and her colleagues plan to study how altered DNA manifests itself in the children and grandchildren of male mice that are exposed to firsthand smoke. They also plan to study the effects of secondhand smoke on male mice as well the possibility that the eggs of females are affected by smoke.

No-scalpel vasectomies by skilled surgeons may speed recovery

Tue, 17 Apr 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Although no-scalpel vasectomies are becoming more popular among physicians and patients, there are no definitive statistics to confirm the superiority of this choice, and a new review's main conclusion is to underline the importance of training.

Yet training is not always available or sought, said lead reviewer Dr. Lynley Cook, a public health physician and clinical senior lecturer at the University of Otago in Christchurch, New Zealand.

She said, Training may not be available in all places in the world and surgeons who learned how to do vasectomies using the standard incision method may not be interested in learning a new technique.

Vasectomy, a surgical form of birth control in which a duct known as the vas is cut or tied, has traditionally been performed by making an incision in the skin of the scrotum. Cutting or tying the vas, which carries sperm from the testicles, leaves a man infertile.

Instead of making an incision, the no-scalpel technique uses a sharp instrument to puncture the skin. Advantages of puncturing rather than cutting the skin of the scrotum include less bleeding, bruising, infection and pain. Also, the puncture is usually so small that it does not require stitches.

The review looked at two studies that compared the no-scalpel method of vasectomy to the traditional method. The studies arrived at conflicting results.

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates research in all aspects of health care. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing trials on a topic.

The larger study, conducted in 1999, included 1,429 men in five countries: Brazil, Guatemala, Indonesia, Sri Lanka and Thailand. All eight physicians general surgeons and urologists had experience with the standard vasectomy technique and three had experience with the no-scalpel method. Inexperienced surgeons received training in the no-scalpel technique.

In this study, men who received no-scalpel vasectomies had less bleeding, bruising, infection and pain during surgery and follow-up. Doctors using the no-scalpel method had more surgical difficulties than those who used the incision method primarily locating the vas. Even so, the no-scalpel method resulted in a shorter operation. The patients also had a shorter recovery with a quicker resumption of postoperative sexual activity.

The smaller trial included 100 participants treated at a single site in Denmark. None of the eight doctors had substantial experience in the no-scalpel technique. Training was limited to an instructional video and one supervised procedure. Only one surgeon performed more than 10 no-scalpel vasectomies in the trial.

The smaller study showed no difference in postoperative results between the two techniques, but this, review authors say, could have been due to the small numbers of participants. Another important factor was the lack of experience that participating doctors had in the no-scalpel technique.

Both studies found the two techniques to be equally effective in terms of providing permanent fertility control. Although the larger study seemed to demonstrate many advantages to the no-scalpel method, the reviewers found the results inconclusive, largely because results from the studies could not be pooled for analysis.

From the results of the review, we would agree that the no-scalpel methodology is the preferable method to use, as it has lower rate of adverse events, Cook said. But the no-scalpel technique requires more training and a higher level of skill. One of the most important issues for men seeking a vasectomy is the experience of the surgeon with that particular method.

The no-scalpel vasectomy is much more difficult to learn than the conventional one and requires more hands-on training, said Dr. Marc Goldstein, executive director of the Men's Service Center, Cornell University, Weill Medical College. Adequate training is key. Goldstein was not involved with the review.

Despite the lack of documented evidence, men are increasingly asking their doctors about this method. Goldstein said that one-third of the vasectomies now done in the United States use the no-scalpel method.

Goldstein recommends that a patient considering a no-scalpel vasectomy ask his doctor where he received his training and how many of these surgeries he has done. More studies would help: Informed patients will benefit from data showing that it is a technique associated with less pain and fewer complications.

Researchers find gene mutation that causes infertility in male mice

Tue, 10 Apr 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Up to 15 percent of couples of childbearing age struggle with the heartache of infertility. Now there is the promise of new hope with Cornell researchers' identification of a mutation in a gene that causes male infertility in mice. Because this is the first time that a dominant mutation that leads specifically to infertility in a mammal has been discovered, the researchers say they can now look for similar mutations in the DNA of infertile men.

If you consider infertility a disease, you can't study it like you would other diseases, because the affected people can't reproduce, said John Schimenti, director of Cornell's Center for Vertebrate Genomics and senior author of the paper published in the current issue of the Public Library of Science journal PLoS Biology. Laura Bannister, a research associate in Schimenti's laboratory, is the paper's lead author.

Consequently, we know very little about the genetic causes of infertility in humans, said Schimenti, a Cornell professor of genetics.

The gene, called Dmc1, provides the code for a key protein involved in meiosis, the process that produces sperm and egg cells for reproduction. These sex cells contain only one set of chromosomes that combine during conception and create an embryonic cell with two chromosome sets, one from each parent.

The mutation leads to a change in an amino acid in Dmc1 that blocks meiosis in its tracks, preventing sperm production. The mutant allele (one version of the pair of genes we inherit from each parent) is dominant; females who carry it remain fertile but carry the defect and pass the mutation on to future generations.

However, female carriers show higher rates of abnormalities during meiosis, which can potentially cause chromosome imbalances and birth defects, the researchers discovered. In addition, the researchers found that female mice with the Dmc1 mutation are born with fewer egg cells and can run out of eggs prematurely -- resulting in early menopause (or mousapause as the researchers humorously refer to the condition).

To get their results, the researchers randomly induced mutations in the mouse genome and then looked for infertility in the resulting mice. They then analyzed the DNA of the sterile males and identified the allele that caused the infertility. While most studies on the genetics of fertility stem from analyses of mice that have had a custom gene knockout, this is the first to reveal a dominant mutation that leads specifically to infertility in a mammal. The researchers believe this kind of dominant effect is closer to how real-life infertility occurs in humans.

People have been sequencing genes in humans, including the Dmc1 gene, to try and associate changes in gene sequences with infertility, said Schimenti. There have been occasional reports that in some patients, a sequence change in this or other meiosis genes might cause a dominant defect in function, but until now there has been no definitive proof.

Mouse models, he said, will be critical in distinguishing between those DNA sequence changes that are benign in humans versus those that disrupt sperm or egg production. The researchers are engaged in a project to identify ultimately all the genes needed for fertility in mice and apply this information to the human situation.

Too much weight spells double trouble for couples trying to conceive

Tue, 06 Mar 2007 04:59:37 PST

( from http://www.rxpgnews.com ) If both partners in a couple are overweight or obese, they are more likely to have to wait longer before successfully conceiving a child, according to new research published online in Europes leading reproductive medicine journal, Human Reproduction, today (Wednesday 7 March). [1]

Researchers in Denmark studied 47,835 Danish couples between 1996 and 2002 and found that if both partners were obese the chances of the couple having to wait for more than a year before the woman became pregnant were nearly three times higher (2.74) than for a normal weight couple. If both partners were overweight, the likelihood they would have to wait longer than a year was 1.4 times higher. [2]

Cecilia Ramlau-Hansen, who led the study, warned that if further research supported the findings of the study that too much weight could make couples less fertile, this would have major implications for population levels, particularly in parts of the world where obesity and low fertility were, or would become, more common.

If overweight and obesity actually is a cause of subfecundity, and if the obesity epidemic continues, this reduced capacity to reproduce could become a serious public health problem. Further research in this area is needed, she said.

Sub-fertility (or subfecundity) is normally defined as a waiting time to pregnancy of more than 12 months from the time a couple starts to have unprotected sex with an intention to conceive.

Earlier research has already shown that weight can affect fertility in both women and men, individually. However, this is the first study to look at the effect on fertility of overweight and obesity in couples. Ms Ramlau-Hansen, a doctoral student in the Department of Occupational Medicine, Aarhus University Hospital, Denmark, who is on a visiting scholarship to the University of California Los Angeles School of Public Health, USA, said: Since it is quite common to have couples where both partners are overweight or obese, it is important to have risk estimates for couples rather than individuals.

The researchers obtained data from the Danish National Birth Cohort, a nationwide study of pregnant women and their offspring, which enrolled more than 100,000 women between 1996 and 2002. The women completed four interviews over a period of two years, giving information for both themselves and their partners on weight, height, previous pregnancies, smoking habits and socioeconomic groups. After excluding all couples where the information was incomplete, where a disease might be affecting the womans weight and fertility, or where donated sperm was used, the researchers were left with data on 47,835 couples.

Ms Ramlau-Hansen said: In this cohort, we had 6.8% obese men, 8.2% obese women and 1.4% couples where both were obese. The percentages of persons with normal weight were 53% for men and 68% for women.

We found there was a relationship between the BMI of the couple and their fertility among the men and women in different BMI combinations. We found a higher risk of sub-fertility related to overweight and obesity for both men and women, particularly for couples where both were overweight. Underweight combined with obese partners, especially underweight men, seemed to cause additional pregnancy delays. The combination of an underweight man and obese woman was associated with a risk of sub-fertility nearly four times higher (3.79) compared to a normal weight couple, although we have to treat this figure with caution as there were only 22 couples in this category.

The researchers also looked more closely at 2,374 couples where the women had had more than one pregnancy, and where the womens initial BMI was 18.5 or more. They converted the womens waiting times to pregnancy into days and found that on average, every 1kg gained in weight added an extra 2.84 days to the waiting time. A further analysis of this group found that among 365 couples where the woman was overweight or obese before her first pregnancy (BMI of 25 and above) and either lost weight or maintained the same weight in the time up to the next pregnancy, for every 1kg of weight lost, the waiting time to pregnancy reduced by an average of 5.5 days.

These findings indicate a causal association between BMI and fertility, said Ms Ramlau-Hansen. In addition, for underweight women in this group, we saw a tendency for the time to pregnancy to decrease if the women gained weight, when compared to the first pregnancy. This is in line with earlier studies that show that being underweight can adversely affect a womans fertility.

Since the study only included couples where the woman had become pregnant, it could not be used to detect an association between high BMI and sterility. We believe that if BMI is a cause of sub-fertility, the effect is quantitative rather than qualitative in other words, that couples have to wait longer to conceive the heavier they become, but there is not a threshold weight beyond which they become sterile. This is supported by all existing studies. A high BMI probably leads to sterility only in people with additional fertility problems, said Ms Ramlau-Hansen.

She continued: Our results indicate that overweight and obesity is a cause of sub-fertility, but from this study we cannot say that for sure. There might be an unknown underlying factor, such as a disease or genetic factors, that causes both the overweight/obesity and the sub-fertility, and this could only be established in a randomised trial. A randomised trial could also establish whether losing weight might bring fertility back to normal values for overweight and obese couples. Our study indicates that it may be the case. In the meantime, our advice to overweight and obese couples that want to have a child would be that losing weight might decrease their waiting time to pregnancy.

Previous studies have shown that mens BMI is associated with semen quality and levels of reproductive hormones, and that, in women, obesity can adversely affect ovulation, conception, implantation and early foetal development. Since reliable data on frequency and timing of sexual intercourse were not available, we cannot exclude the possibility that infrequent intercourse has delayed conception in overweight and obese couples, added Ms Ramlau-Hansen.

Pregnant smokers raise their child's risk of stroke, heart attack

Fri, 02 Mar 2007 04:59:37 PST

( from http://www.rxpgnews.com ) ORLANDO, Fla., March 2 -- Women who smoke during pregnancy can cause permanent vascular damage in their children increasing their risk for stroke and heart attack, researchers said today at the American Heart Associations 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention.

The Netherlands Atherosclerosis Risk in Young Adults (ARYA) study showed that participants who were exposed to smoke when their mothers were pregnant resulted in permanent cardiovascular damage that could be detected in young adulthood.

This is the first report to demonstrate this association, said Cuno S. Uiterwaal, M.D., Ph.D., lead researcher and associate professor of clinical epidemiology at the University Medical Center Utrecht in The Netherlands. This is a preventable risk factor. Women need to stop smoking, especially in pregnancy, not only for their own health, but for their unborn child.

Smoking during pregnancy can result in intrauterine growth retardation and low birth weight. Active and passive smoking in young adults also is associated with cardiovascular disease. But until the Dutch study, researchers were unsure whether this is due to a cumulative effect of smoke or whether children are vulnerable at specific periods, such as during gestation.

The studys 732 participants were born in 1970-73 and vascular risk measurements were performed in 1999-2000. Uiterwaal and colleagues found that adult offspring of the 215 mothers who smoked during pregnancy had thicker walls of the carotid arteries in the neck. The carotid artery intima-media thickness (CIMT), an ultrasound measurement of the thickness of the inner walls of the neck arteries, is used to determine the level of atherosclerosis. Offspring whose pregnant mothers were exposed to smoke had 13.4 micrometers thicker CIMT by young adulthood when compared to the offspring of mothers who did not smoke in pregnancy, researchers reported.

Even after the researchers adjusted for other risk factors in the young adults such as age, gender, body mass index, pulse pressure and cholesterol levels, the CIMT remained 9.4 micrometers thicker in children of mothers who smoked. Adjustment for current smoking by both mothers and fathers or the number of pack years (one pack year is 20 cigarettes smoked/day for one year) smoked by study participants also did not change this association.

While it is difficult to separate the problem of current smoking and smoking during pregnancy, this study indicates that smoking in pregnancy has an independent effect, Uiterwaal said.

If both parents smoked during pregnancy, the children as young adults had thicker CIMT than other participants with either one smoking parent or parents who didnt smoke. Offspring of mothers who smoked the highest number of cigarettes during pregnancy had thicker CIMT than those born to mothers smoking less than the average or those who did not smoke.

Our findings suggest that both smoking by mothers themselves in pregnancy and exposure to passive smoking are important, he said. More exposure leads to more vascular damage in the offspring.

The researchers found that pregnancy was a critical period for damage from smoke exposure. They compared the children of mothers who didnt smoke during pregnancy and were currently not smoking to the children of mothers who didnt smoke in pregnancy but smoked now. They found no difference in CIMT. However, children from mothers who smoked in pregnancy, but who didnt currently smoke had significantly thicker CIMT compared to offspring of abstaining mothers.There is the possibility that the compounds in tobacco smoke go through the placenta and directly damage the cardiovascular system of the fetus, Uiterwaal said. The damage appears to be permanent and stays with the children.

When study participants were born, about 30 percent of the mothers smoked during pregnancy. But the current rate has dropped to between 5 percent and 7 percent due to health warnings, Uiterwaal said.

There are still substantial numbers of mothers who smoke during pregnancy, he said. This is just another reason for expectant mothers not to smoke.This is the first study in which researchers have dealt with this issue. Uiterwaal said further evidence should come from additional studies that show similar results.

Steroid use fails to boost pregnancy rates in infertility treatments

Thu, 01 Mar 2007 04:59:37 PST

( from http://www.rxpgnews.com ) There is no clear benefit from a hormone commonly prescribed to enhance the effectiveness of infertility treatments, according to a new review of studies.

The steroid hormones called glucocorticoids have potent effects on the bodys inflammatory and immune responses, so many fertility specialists prescribe them in hopes of making the lining of the uterus more receptive to embryo implantation. But lead review author Carolien Boomsma says that routine practice should stop.

This meta-analysis shows that empirical use of glucocorticoids is not supported by evidence from studies, she said. Moreover, we dont know enough about the possible adverse effects of glucocorticoids in early pregnancy. Therefore, at present, glucocorticoids should not be prescribed in this way, said Boomsma, a researcher at the University Medical Centre Utrecht in the Netherlands.

The review appears in the most recent issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The review compares success rates between would-be mothers who took glucocorticoids around the time of embryo implantation and those who did not. All of the women underwent one of two types of assisted reproductive technology. In vitro fertilization (IVF) involves removing mature eggs from a womans ovary, mixing them with sperm in the laboratory, and placing the embryos in the womans reproductive tract. Intracytoplasmic sperm injection (ICSI) is another in vitro fertilization practice where a single sperm is injected directly into a harvested egg.

The meta-analysis pooled data from 13 studies including 1,759 couples. Every study was a randomized controlled trial, which is considered the most reliable form of scientific evidence.

The review found no overall improvement in pregnancy rates when the assisted reproductive technologies were combined with glucocorticoid treatment. However, six of the studies of 650 women undergoing IVF revealed a slightly higher pregnancy rate among women who took the hormones. The review authors say the difference barely exceeds that which could be attributed to mere chance.

At present, glucocorticoids should not be offered as a routine procedure in women undergoing ART (assisted reproductive technologies), except in the context of well-designed studies, the reviewers conclude.

Glucocorticoids can bring on problems such as infections or premature births. Though the available studies reported no significant increases in these negative outcomes, they were poorly and inconsistently reported, the review said. Further research is needed to clarify both benefits and harms, Boomsma and colleagues said.

Only three of the studies in the review continued long enough to report actual birth rates rather than simply pregnancy rates. Trials should be of sufficient duration to have live birth as their primary outcome, the authors say.

Despite substantial improvements in IVF and ICSI techniques, only 20 percent to 30 percent of couples go home with a healthy baby after each treatment cycle. That tantalizing hint of benefit may nevertheless encourage some practitioners to continue routine use of glucocorticoids for their IVF patients, said Randall Hines, M.D., director of the division of reproductive endocrinology and infertility at the University of Mississippi Medical Center.

When you have a therapy that doesnt have significant risk and doesnt impose significant burden on the patient in terms of cost or inconvenience, its hard for people to let go of it, said Hines, who was not involved in the review and does not prescribe glucocorticoids routinely in his practice.

The compiled studies included couples who were infertile due to a wide variety of problems in either the woman, man or both partners.

Future research may reveal that glucocorticoids do help specific subsets of these patients, the authors say. For example, women with unexplained infertility, endometriosis, recurrent implantation failure or certain immunological issues may benefit from the hormonal effects on uterine receptivity. None of the studies included in the review focused specifically on these patient groups.

Treating male infertility with stem cells

Thu, 01 Mar 2007 04:59:37 PST

( from http://www.rxpgnews.com ) Los Angeles, CA -- New research has examined the usefulness of bone marrow stem cells for treating male infertility, with promising results. The related report by Lue et al, Fate of bone marrow stem cells transplanted into the testis: potential implication for men with testicular failure, appears in the March issue of The American Journal of Pathology.

When a couple experiences infertility, the man is just as likely as the woman to be the cause. Male infertility may arise from failed proliferation and differentiation of the germ cells (precursors of sperm) or from dysfunction of the supporting cells. New research is looking to stem cells as a means of replacing nonfunctioning cells, whether germ cells or supporting cells.

Researchers, directed by Dr. Ronald S. Swerdloff of the Harbor-UCLA Medical Center, collected bone marrow stem cells from mice expressing the green fluorescent protein (GFP). These green cells, which could be easily tracked in recipient mice, were injected into the testes of infertile mice, in which infertility was induced either chemically or genetically (via mutations in a gene required for sperm production).

The donor GFP-expressing cells took up residence in the testes and survived within the recipient mice for the entire 12-week study period. The donor stem cells displayed the characteristic shape of either germ cells or supporting cells, suggesting that the stem cells had differentiated. These differentiated donor (green) cells were also found near the native recipient cells of the same type, demonstrating that the local cellular environment likely influenced the fate of the donor stem cells.

As further confirmation of the differentiation status of the donor cells, the expression of specific proteins on the cell surface was examined. Both germ and supporting cells expressed marker proteins known to be found only on the differentiated cells, not on stem cells.

These data demonstrate that bone marrow stem cells have the potential to differentiate into cells of the testes involved in sperm production, both germ cells and supporting cells. Interestingly, the germ cells did not differentiate fully into sperm, suggesting that additional factors or cellular signals are needed.

Future studies will characterize the other factors, such as hormones, required to complete sperm production in this transplant model. In addition, since the bone marrow cells used here represent a mixed population of stem cells, further studies will determine which specific stem cell type was able to colonize and differentiate in the testes. The results of future studies could have dramatic implications for treating male infertility or testosterone deficiency.

Eating ice cream may help women to conceive, but low-fat dairy foods may increase infertility risk

Tue, 27 Feb 2007 04:59:37 PST

( from http://www.rxpgnews.com ) Drinking whole fat milk and eating ice cream appears to be better for women trying to become pregnant than a diet consisting of low-fat dairy products such as skimmed milk and yoghurt, according to new research published in Europe's leading reproductive medicine journal, Human Reproduction, today (28 February). [1]

Researchers in the United States have found a link between a low-fat dairy diet and increased risk of infertility due to lack of ovulation (anovulatory infertility). Their study showed that if women ate two or more servings of low-fat dairy foods a day, they increased their risk of ovulation-related infertility by more than four fifths (85%) compared to women who ate less than one serving of low-fat dairy food a week. On the other hand, if women ate at least one serving of high-fat dairy food a day, they reduced their risk of anovulatory infertility by more than a quarter (27%) compared to women who consumed one or fewer high-fat dairy serving a week.

Lead author of the study, Dr Jorge Chavarro, who is a research fellow in the Department of Nutrition at Harvard School of Public Health, Boston, Massachusetts, USA, said that, given the scarcity of information in this area, it was important that more research should be carried out into the association between low-fat dairy foods and anovulatory infertility in order to confirm or refute the findings.

Clarifying the role of dairy foods intake on fertility is particularly important since the current Dietary Guidelines for Americans recommend that adults consume three or more daily servings of low-fat milk or equivalent dairy products: a strategy that may well be deleterious for women planning to become pregnant as it would give them an 85% higher risk of anovulatory infertility according to our findings.

In the meantime, he said that his advice to women wanting to conceive would be to change their diet. They should consider changing low-fat dairy foods for high-fat dairy foods; for instance, by swapping skimmed milk for whole milk and eating ice cream, not low fat yoghurt. However, he said that it was important that women did this within the constraints of maintaining their normal calorie intake and limiting their overall consumption of saturated fats in order to maintain general good health. Once they have become pregnant, then they should probably switch back to low-fat dairy foods as it is easier to limit intake of saturated fat by consuming low-fat dairy foods, he said.

In their prospective study, Dr Chavarro and his colleagues identified 18,555 women, aged between 24 and 42, without a history of infertility, who had tried to become pregnant or had became pregnant between 1991 and 1999. The women were part of a much larger study of 116,000 women in The Nurses' Health Study II.

Every two years the women completed a questionnaire that asked if they had tried to become pregnant for more than a year without success, and what the cause was if they had been unable to conceive. The women also supplied information on how often, on average, they had consumed certain foods and drinks during the previous year. During the eight years, 438 healthy women reported infertility due to an ovulatory disorder.

After adjusting for various factors such as age, parity, body mass index, total calorie intake, physical activity, smoking, drinking and contraceptive use, the researchers found an 85% increased risk of anovulatory infertility in women eating two or more servings of low-fat dairy food a day compared to women eating one or fewer servings a week, and a 27% decreased risk of infertility for women eating high-fat dairy food one or more times a day compared to women eating a serving one or fewer times a week.

Dr Chavarro said: Intake of total dairy foods was not associated with the risk of anovulatory infertility, but when the low-fat and high-fat foods were considered separately, we found a positive association between low-fat dairy food intake above five servings a week and risk of anovulatory infertility, and an inverse association between high-fat dairy food intake and risk of developing this condition.

Further analysis of the findings in which specific foods were investigated, showed that an extra serving per day of a low-fat dairy food such as yoghurt, appeared to increase the risk of anovulatory infertility by 11%, if the total daily intake of calories was unchanged. In contrast, an extra daily serving of a high-fat dairy food such as whole fat milk was associated with a 22% lower risk (with an unchanged calorie intake). The study showed that the more ice cream the women ate, the lower was their risk, so that a woman eating ice cream two or more times a week had a 38% lower risk compared to a woman who consumed ice cream less than once a week.

The researchers believe that the presence of a fat-soluble substance, which improves ovarian function, might explain the lower risk of infertility from high-fat dairy foods. The intake of dairy fat, or a fat-soluble substance present in dairy foods, may partly explain the inverse association between high-fat dairy foods and anovulatory infertility, said Dr Chavarro.

Previous studies had suggested that lactose (a sugar found in milk) might be associated with anovulatory infertility, but Dr Chavarro's study found neither a positive nor negative association for this, and nor was there any association between intake of calcium, phosphorus or vitamin D and anovulatory infertility.

New research finds that a natural family planning method is as effective as the contraceptive pill

Tue, 20 Feb 2007 04:59:37 PST

( from http://www.rxpgnews.com ) Researchers have found that a method of natural family planning that uses two indicators to identify the fertile phase in a womans menstrual cycle is as effective as the contraceptive pill for avoiding unplanned pregnancies if used correctly, according to a report published online in Europes leading reproductive medicine journal Human Reproduction today (21 February). [1]

The symptothermal method (STM) is a form of natural family planning (NFP) that enables couples to identify accurately the time of the womans fertile phase by measuring her temperature and observing cervical secretions. In the largest, prospective study of STM, the researchers found that if the couples then either abstained from sex or used a barrier method during the fertile period, the rate of unplanned pregnancies per year was 0.4% and 0.6% respectively. Out of all the 900 women who took part in the study, including those who had unprotected sex during their fertile period, 1.8 per 100 became unintentionally pregnant.

The lead author of the report, Petra Frank-Herrmann, assistant professor and managing director of the natural fertility section in the Department of Gynaecological Endocrinology at the University of Heidelberg, Germany, said: For a contraceptive method to be rated as highly efficient as the hormonal pill, there should be less than one pregnancy per 100 women per year when the method is used correctly. The pregnancy rate for women who used the STM method correctly in our study was 0.4%, which can be interpreted as one pregnancy occurring per 250 women per year. Therefore, we maintain that the effectiveness of STM is comparable to the effectiveness of modern contraceptive methods such as oral contraceptives, and is an effective and acceptable method of family planning.

A number of fertility awareness based (FAB) methods of family planning have been advocated over the years, but comparisons between different methods and studies of their effectiveness have been limited and hampered by problems such as differences in cultural backgrounds, different ways to measure the effectiveness of a FAB method, different ways of classifying unintended pregnancies and other methodological problems.

To be able to make an informed choice when selecting a family planning method, couples need to know the efficacy of a method when used both perfectly and imperfectly, said Prof Frank-Herrmann. We believe that this is a significant prospective cohort study that clearly defines STM and perfect and imperfect use, and which defines intended and unintended pregnancies, classifying them according to the couples intentions before conception.

The researchers selected data from a cohort of 900 women who were part of a much larger study of 1,599 women using STM, which was conducted by the German Natural Family Planning study centre between 1985 and 2005. The 900 women provided data on 17,638 cycles to Prof Frank-Herrmann and her colleagues.

STM identifies the beginning and end of a womans fertile period using two measurements (body temperature and cervical secretions) in order to have a double-check system. The first fertile day is when the woman first identifies either: 1) first appearance or change of appearance of cervical secretion, or 2) the sixth day of the cycle. After 12 cycles, this second guideline is replaced by a calculation that subtracts seven days from the earliest day to show a temperature rise in the preceding 12 cycles, in order to identify the first fertile day. The woman is then in her fertile period. The fertile phase ends after the woman has identified: 1) the evening of the third day after the cervical secretion peak day, and 2) the evening when the woman measures the third higher temperature reading, with all three being higher than the previous six readings and the last one being 0.2 degrees C higher than the previous six.

Prof Frank-Herrmann said: The women or couples who want to learn the method have to buy a book, or attend an NFP course, or get some teaching by a qualified NFP teacher. Learning STM is usually no problem. There are precise rules that work. However, in contrast to the oral contraceptive pill or other family planning methods, STM needs more engagement and time to learn it.

Every month the women in the study sent charts to the researchers that showed their cycles, their observations of temperature and cervical secretions, and that recorded their sexual behaviour and family planning intentions for the next cycle.

Of the 900 women, 322 used only STM and 509 women used STM with occasional barriers during the fertile time. Sixty-nine women did not document their sexual behaviour. Out of the women who documented their sexual behaviour and abstained from sex during their fertile period (perfect use) the unintended pregnancy rate was 0.4 per 100 women and 13 cycles [2], and 0.6 for women who used STM plus a barrier if they had sex during their fertile period. For cycles in which couples had unprotected sex during the fertile phase, the pregnancy rates rose to 7.5 per 100 women and 13 cycles. The drop-out rate from using STM for reasons such as dissatisfaction or difficulties with the method was 9.2 per 100 women and 13 cycles, and compared well with the drop-out rates from other methods of family planning, which can be as high as 30%, although direct comparisons are difficult due to methodological problems. This demonstrates a fairly good acceptability for this particular FAB method, said Prof Frank-Herrmann.

The authors were surprised by the relatively low rate of unintended pregnancies (7.5%) among women who had unprotected sex during their fertile period. If people are trying for pregnancy you expect a pregnancy rate of 28% per cycle, said Prof Frank-Herrmann. Therefore, we think that some of the couples were practising conscious, intelligent risk-taking, and were having no unprotected sex during the few highly fertile days, but had unprotected intercourse on the days at the margins of the fertile time when the risk of pregnancy was lower.

Some studies have suggested that womens libido is higher during their fertile period, and this could be one of the reasons why NFP methods traditionally have had a reputation for being less effective than other methods of family planning. However, Prof Frank-Herrmann said: There are studies that suggest that this is only the case for a small proportion of women, and that, in fact, women also identify other parts of their cycle with increased sexual desire. Most women who use FAB do not find this a problem. Its possible that the increased libido may be one of the reasons that some of the couples in our study used a barrier, such as a condom, in the fertile phase.

This is the first time that a large, prospective STM database has been established with sufficient detailed information on sexual behaviour. It enables the true method effectiveness for STM to be calculated and we found this was 0.4% per year when there was no intercourse during the fertile phase. The user-effectiveness of STM, in other words the total number of unintended pregnancies that were due to both method and user failure, was 1.8% after 13 cycles of use, and this compares very well with results from other European studies of FAB methods of family planning. The markedly good user-effectiveness rate may be explained partly by the motivation of the couples and their teachers who agreed to participate in the study, she concluded.

Vasectomy may put men at risk for type of dementia

Mon, 12 Feb 2007 04:59:37 PST

( from http://www.rxpgnews.com ) CHICAGO --- Northwestern University researchers have discovered men with an unusual form of dementia have a higher rate of vasectomy than men the same age who are cognitively normal.

The dementia is Primary Progressive Aphasia (PPA), a neurological disease in which people have trouble recalling and understanding words. In PPA, people lose the ability to express themselves and understand speech. It differs from typical Alzheimer's disease in which a person's memory becomes impaired.

Sandra Weintraub, principal investigator and professor of psychiatry and behavioral sciences and of neurology at Northwestern's Feinberg School of Medicine, began investigating a possible link between the surgery and PPA when one of her male patients connected the onset of his language problem at age 43 to the period after his vasectomy.

At a twice-yearly Chicago support group for PPA patients Weintraub sees from around the country, the male patient rushed into the room and asked the men sitting there, OK, guys, how many of you have PPA? Nine hands went up.

How many of you had a vasectomy? he demanded next. Eight hands shot up.

Weintraub and her team of researchers surveyed 47 men with PPA who were being treated at Northwestern's Cognitive Neurology and Alzheimer's Disease Center and 57 men with no cognitive impairment who were community volunteers. They ranged from 55 to 80 years old.

Of the non-impaired men, 16 percent had undergone a vasectomy. In contrast, 40 percent of the men with PPA had had the surgery.

That's a huge difference, said Weintraub, director of neuropsychology in the Cognitive Neurology and Alzheimer's Disease Center. It doesn't mean having a vasectomy will give you this disease, but it may be a risk factor to increase your chance of getting it.

In addition, the men who had undergone a vasectomy developed PPA at a younger age (58 years) than men with PPA who hadn't had one (62 years.)

While PPA robs people of their ability to speak and understand language, an unusual twist of the disease is patients are still able to maintain their hobbies and perform other complicated tasks for a number of years before other symptoms develop. Some people garden, build cabinets and even navigate a city subway system. By contrast, Alzheimer's patients lose interest in their hobbies, family life and may become idle. As PPA progresses over a number of years, however, patients eventually lose their ability to function independently.

Preliminary evidence from the study also seemed to connect another form of dementia to a vasectomy. In a smaller group of 30 men with a dementia called frontotemporal dementia (FTD,) 37 percent had undergone a vasectomy. The earliest symptoms of FTD are personality changes, lack of judgment and bizarre behavior. As in PPA, FTD usually starts at an earlier age, in the 40s and 50s.

One of Weintraub's patients with FTD was eating lunch in a restaurant with his family and excused himself to go to the bathroom. When he hadn't returned after 10 minutes, his sons went to investigate. They found him doing pushups on the bathroom floor. Other FTD patients begin shoplifting, compulsively gambling, misspending large amounts of money or become sexually demanding.

The most common form of dementia caused by brain deterioration in individuals over age 65 is Alzheimer's disease. Weintraub did not find an increased rate of vasectomy in patients with Alzheimer's.

Many patients with FTD and PPA share a common brain disease that is completely different from Alzheimer's. Whether a patient will get the behavioral or language problems depends on where the disease causes the most destruction in the brain. In FTD, most of the damage is in the frontal lobes; in PPA, it's in the language centers of the left hemisphere of the brain.

Weintraub theorizes a vasectomy may raise the risk of PPA (and possibly FTD) because the surgery breeches the protective barrier between the blood and the testes, called the blood-testis barrier.

Certain organs including the testes and the brain exist in what is the equivalent of a gated community in the body. Tiny tubes within the testes (in which sperm are produced) are protected by a physical barrier of Sertoli cells. The tight connections between these cells prevent blood-borne infections and poisonous molecules from entering the semen.

After a vasectomy, however, the protective barrier is broken and semen mixes into the blood. The immune system recognizes the sperm as invading foreign agents and produces anti-sperm antibodies in 60 to 70 percent of men.

Weintraub said these antibodies might cross the blood-brain-barrier and cause damage resulting in dementia. There are other neurological models of disease which you can use as a parallel, Weintraub said. Certain malignant tumors produce antibodies that reach the brain and cause an illness similar to encephalitis, she noted.

The next step in Weintraub's research will be to launch a national study to see if her results will be confirmed in a larger population.

I don't want to scare anyone away from getting a vasectomy, Weintraub stressed. It's obviously a major birth control alternative. This is just a correlational observation, she said of the dementia connection. We need to do more research to find out.

Standard treatment more effective than diabetes drug for achieving pregnancy in fertility disorder

Wed, 07 Feb 2007 04:59:37 PST

( from http://www.rxpgnews.com ) Metformin, a drug used to treat diabetes and thought to hold great promise at overcoming the infertility associated with polycystic ovary syndrome (PCOS), is less useful for helping women with the condition achieve pregnancy than is the standard treatment with the infertility drug clomiphene, report researchers in an NIH research network.

This study is the largest, most comprehensive effort yet to compare the two drugs in helping women with PCOS achieve successful pregnancy.

The finding appears in the February 8, 2007 issue of the New England Journal of Medicine.

The results of this study underscore the need to test any new treatment rigorously, no matter how promising it may seem initially, said Duane Alexander, M.D., Director of the National Institute of Child Health and Human Development, which supported the study, along with the National Center for Research Resources. Both NICHD and NCRR are part of NIH.

Polycystic ovary syndrome (PCOS) affects seven to eight percent of women in the United States and may be the most common cause of female infertility, the study authors wrote. With PCOS, an excess of male hormones interferes with ovulation. The ovaries become enlarged and fill with cysts. In addition to infertility, PCOS symptoms include irregular menstrual periods, excessive body and facial hair, acne, and obesity.

Women with PCOS frequently experience insulin resistance, a prediabetic condition in which higher-than-normal amounts of insulin are required to allow glucose to enter tissues. Earlier studies had shown that drugs such as metformin, which make the body more sensitive to insulin, could increase ovulation in PCOS patients. Similarly, several smaller studies had suggested that metformin, alone or when taken together with the drug clomiphene, could result in greater fertility rates for PCOS patients than could clomiphene taken alone. Clomiphene fosters ovulation by stimulating the release of hormones needed for ovulation to occur.

To conduct the study, the researchers randomly assigned 626 infertile women with PCOS to one of three groups, explained the study's lead investigator, Richard. S. Legro, M.D., of the Department of Obstetrics and Gynecology at Penn State College of Medicine in Hershey, Pennsylvania. The first group received clomiphene and a placebo, the second group received metformin and a placebo, and the third group received both metformin and clomiphene. The women took the treatments for up to six months. The researchers tested the women's levels of the hormone progesterone to gauge when the women were ovulating.

The researchers found that fewer women in the metformin only group had given birth than had women in either of the clomiphene groups. In the metformin only group, 15 out of 208 women had given birth, or 7.2 percent. In the clomiphene only group, 47 out of 209 women had given birth, or 22.5 percent. In the combined clomiphene-metformin group, 56 out of 209 women had given birth (26.8 percent). The difference in the number of births between the clomiphene only group and the combined clomiphene-metformin group was not statistically significant. The researchers also found that, compared to the other women in the study, obese women were less likely to conceive during the course of the study and less likely to ovulate in response to metformin.

The researchers noted that women in the combination therapy group ovulated more frequently than did the women in either the clomiphene-alone or the metformin-alone groups. However, the tendency to ovulate more frequently did not translate into a significantly greater number of pregnancies for the combination group.

Dr. Legro said that these findings were consistent with earlier studies that also reported an increase in ovulation from the combined therapy and that these early observations had led to researchers' initial enthusiasm for metformin as a potential treatment for PCOS. He theorized that although the combination of the two drugs might stimulate more cycles of ovulation than clomiphene alone, these extra cycles might result in a higher number of eggs that are not capable of fertilization or development.

Our results show that you can't use ovulation as a surrogate for pregnancy, Dr. Legro said An ovulation on clomiphene treatment is twice as likely to result in pregnancy as an ovulation on metformin, thus all ovulations are not alike.

The researchers also reported that women in the clomiphene groups had more occurrences of multiple pregnancy: 6.4 percent for the clomiphene-only group, 3.3 percent for the combination group and 0 percent for the metformin group. Clomiphene is known to stimulate the release of more than one egg at a time. Dr. Legro noted that the rate of multiple pregnancy seen in the study for women treated with clomphene was less than the multiple pregnancy rate after in vitro fertilization, which averages about 33 percent.

The study authors noted that while metformin alone did not improve the chances for pregnancy, it was useful for lowering the high blood testosterone levels that occur with PCOS.

In summary, our study supports the use of clomiphene citrate alone as first-line therapy for infertility in women with PCOS, the study authors wrote.

Brain's reward circuit activity ebbs and flows with a woman's hormonal cycle

Fri, 02 Feb 2007 04:59:37 PST

( from http://www.rxpgnews.com ) Fluctuations in sex hormone levels during women's menstrual cycles affect the responsiveness of their brains' reward circuitry, an imaging study at the National Institute of Mental Health (NIMH), a component of the National Institutes of Health (NIH), has revealed. While women were winning rewards, their circuitry was more active if they were in a menstrual phase preceding ovulation and dominated by estrogen, compared to a phase when estrogen and progesterone are present.

These first pictures of sex hormones influencing reward-evoked brain activity in humans may provide insights into menstrual-related mood disorders, women's higher rates of mood and anxiety disorders, and their later onset and less severe course in schizophrenia, said Karen Berman, M.D., chief of the NIMH Section on Integrative Neuroimaging. The study may also shed light on why women are more vulnerable to addictive drugs during the pre-ovulation phase of the cycle.

Berman, Drs. Jean-Claude Dreher, Peter Schmidt and colleagues in the NIMH Intramural Research Program report on their functional magnetic resonance imaging (fMRI) study online during the week of January 29, 2007 in the Proceedings of the National Academy of Sciences.

Reward system circuitry includes: the prefrontal cortex, seat of thinking and planning; the amygdala, a fear center; the hippocampus, a learning and memory hub; and the striatum, which relays signals from these areas to the cortex. Reward circuit neurons harbor receptors for estrogen and progesterone. However, how these hormones influence reward circuit activity in humans has remained unclear.

To pinpoint hormone effects on the reward circuit, Berman and colleagues scanned the brain activity of 13 women and 13 men while they performed a task involving simulated slot machines. The women were scanned before and after ovulation.

The fMRI pictures showed that when the women were anticipating a reward, they activated the amygdala and a cortex area behind the eyes that regulates emotion and reward-related planning behavior more during the pre-ovulation phase (four to eight days after their period began) than in the post-ovulatory phase.

When they hit the jackpot and actually won a reward, women in the pre-ovulatory phase activated the striatum and circuit areas linked to pleasure and reward more than when in the post-ovulatory phase.

The researchers also confirmed that the reward-related brain activity was directly linked to levels of sex hormones. Activity in the amygdala and hippocampus was in lockstep with estrogen levels regardless of cycle phase; activity in these areas was also triggered by progesterone levels while women were anticipating rewards during the post-ovulatory phase. Activity patterns that emerged when rewards were delivered during the post-ovulatory phase suggested that estrogen's effect on the reward circuit might be altered by the presence of progesterone during that period.

Men showed a different activation profile than women during both anticipation and delivery of rewards. For example, men had more activity in a striatum (signal relay station) area during anticipation compared to women and women had more activity in a frontal cortex (executive hub) area at the time of reward delivery compared to men.

Topical anaesthetic spray delays ejaculation by five times as long says new study

Wed, 24 Jan 2007 04:59:37 PST

( from http://www.rxpgnews.com ) Patients with premature ejaculation who used a topical anaesthetic spray were able to delay ejaculation for five times as long, according to a study in the February issue of the urology journal BJU International.

Researchers from the UK and Netherlands studied 54 men with premature ejaculation, randomly assigning them to a treatment and control group. Both groups reported that without any therapy they normally ejaculated an average of one minute after vaginal penetration.

The men who were prescribed the TEMPE spray, which delivers a combination of lidocaine and prilocaine, managed to delay ejaculation by just under an extra four minutes after using the product reports Professor Wallace Dinsmore from the Royal Victoria Hospital, Belfast.

Meanwhile the control group, who were prescribed a placebo (dummy) spray, increased their penetration to ejaculation time by just over 40 seconds.

Overall, the TEMPE spray was 2.4 times more effective than the placebo.

The study focussed on heterosexual couples who had been in a stable monogamous relationship for at least three months and were willing to attempt sexual intercourse on at least seven occasions during the ten-week study period.

Recruited from six hospitals and medical centres across the UK Sheffield, Manchester, Durham, Plymouth, Belfast and London and one in The Hague, the men were aged from 18 to 75, with an average age of 39.

Time since diagnosis ranged from seven months to just under 35 years, with an average of nine and a half years.

The men in the TEMPE group (Topical Eutectic Mixture for Premature Ejaculation) administered three metered sprays of the local anaesthetic preparation to the glans of their penis 15 minutes before intercourse. This delivered a total of 22.5mg of lidocaine and 7.5mg of prilocaine.

The placebo group were issued with an identical container that delivered a spray without any active ingredients. Both groups were advised not to use the spray more than once in any 24-hour period to avoid possible bias resulting from too frequent ejaculation.

Participants were also issued with a stopwatch so that they, or their partner, could measure the time lapse between penetration and ejaculation.

20 TEMPE users and 23 placebo users completed the study and 83 per cent of all users found the spray easy to use.

The majority of the TEMPE users and their partners tolerated the spray well. Three men reported numbness in their penis, one said he was unable to get an erection and one partner reported a mild burning sensation each time the spray was used, but continued with the treatment.

No adverse effects were found during patient safety checks, which included vital signs, physical findings, electrocardiograms, haematology, biochemistry and urine analysis.

At the moment, only a small number of men with premature ejaculation seek or receive treatment from a healthcare professional and the lack of effective pharmacological treatment is a contributory factor concludes co-author Dr Michael Wyllie from Plethora Solutions Ltd, which manufactures the TEMPE spray.

The encouraging data from this phase two study suggests that TEMPE has the potential to offer a convenient, novel treatment for men with premature ejaculation and might be useful as a first-line treatment for the condition.

Young single men are more likely to bank sperm before testicular cancer treatment

Mon, 08 Jan 2007 04:59:37 PST

( from http://www.rxpgnews.com ) A quarter of men with testicular cancer banked their sperm before treatment, but only six per cent of those actually used the sperm to father a child, according to a study published in the January issue of the urology journal BJU International.

Researchers from the Vanderbilt University Medical Centre in Nashville, USA, surveyed 129 males treated at the institution over a ten-year period.

They discovered that 31 of the men (24 per cent) chose to bank their sperm before treatment, at an average cost of US $358. Maintenance fees added an average of US $243.86 a year.

Despite the cost, only two of the men use their banked sperm to father a child, one said he might use it in the future and a further 12 had children naturally.

Men who banked their sperm had an average age of 26 - ten years younger than those who didn't. They were less likely to have children at the time of diagnosis and more likely to have children after treatment.

And single men were twice as likely to bank their sperm (44 per cent) as married men (21 per cent).

The most common reasons given for not banking sperm were that they didn't want to have children, or more children, that they or their partner were infertile or they had already had a vasectomy.

38 per cent of all the men who took part in the survey hadn't had children at the time of diagnosis. 45 per cent of the men who had banked their sperm had children after treatment, compared with 14 per cent of the men who hadn't banked their sperm.

As most men treated for testicular cancer are young and the survival rate exceeds 90 per cent, the issue of after-treatment fertility is important says lead author Christopher R Girasole.

Revolutionary techniques such as in vitro fertilisation and intracytoplasmic sperm injection make pregnancy possible with even the lowest quality of sperm.

However, up to a quarter of men don't produce usable sperm after treatment.

These factors probably explain why most urologists, radiation oncologists and medical oncologists offer sperm banking before therapy for testicular cancer.

However, our survey shows that sperm banking costs are relatively high and usage is relatively low. We feel that patients should be counselled on both the costs and benefits of sperm banking before they receive treatment for testicular cancer.

The males who took part in the survey ranged from 14 to 76 years of age. The youngest man to bank his sperm was 18 and the oldest was 43.

Sex ends as seasons shift and kisspeptin levels plummet

Thu, 28 Dec 2006 04:59:37 PST

( from http://www.rxpgnews.com ) BLOOMINGTON, Ind. -- A hormone implicated in the onset of human puberty also appears to control reproductive activity in seasonally breeding rodents, report Indiana University Bloomington and University of California at Berkeley scientists in the March 2007 issue of Endocrinology. The paper is now accessible online via the journal's rapid electronic publication service.

The researchers present evidence that kisspeptin, a recently discovered neuropeptide encoded by the KiSS-1 gene, mediates the decline of male Siberian hamsters' libido and reproduction as winter approaches and daylight hours wane.

Ours isn't the first study to link the peptide to reproduction, but it is the first to connect kisspeptin to how animals interpret seasonal cues, including day length, said IUB biologist Gregory Demas. Kisspeptin likely plays an integral role in coordinating seasonal reproduction in a wide range of animals.

Kisspeptin joins a select few proteins believed to act as switches that connect environmental changes to a physiological response.

This peptide is poised to act as an integrator of environmental information to allow for the optimal neuroendocrine control of reproduction in vertebrates, including humans, said UC Berkeley neuroscientist Lance Kriegsfeld. In humans and other species, if the environment is not satisfactory, sex drive will decline; kisspeptin is likely part of the pathway responsible for this regulation.

The scientists divided a population of male Siberian hamsters (Phodopus sungorus) into treatment groups: those housed in long, summer-like photoperiods and those in short, winter-like photoperiods. In a separate experiment hamsters were also treated with exogenous injections of kisspeptin after eight weeks of either short- or long-day photoperiod exposure. At the conclusion of the experimental period, scientists analyzed the hamsters' reproductive system status, blood levels of reproductive hormones, as well as the number of kisspeptin-expressing cells in the brain.

They found hamsters in wintry conditions experienced marked reductions of kisspeptin in a critical brain region important for regulating reproduction and sex behavior compared to hamsters in simulated summer conditions.

Winter hamsters, however, were just as responsive to kisspeptin, elevating a key hormone -- luteinizing hormone -- as much as hamsters in simulated summers. This finding indicates the ability of this hormone to turn on the reproductive switch even in the presence of cues signaling a winter, non-breeding environment.

What is really striking is the disappearance of kisspeptin in animals experiencing winter-like days, yet the ability to respond to kisspeptin when we provide it, said Timothy Greives, lead author of the study. These data show that the disappearance of kisspeptin in the brain is likely critical in turning off reproduction during winter.

Recent research by scientists in the U.K. and France have shown human kisspeptin triggers the release of gonadotropin-releasing hormone and luteinizing hormone, both of which are important to puberty and other sex-related functions.

Studies in humans have shown that individuals with deficits in the receptor for kisspeptin have severe reproductive impairments, Demas said.

Kisspeptin's role in seasonal human reproduction, however, is unknown -- that is, if it even has one. It is interesting to note the CDC reports fertility rates in the United States decrease rapidly in autumn. The phenomenon is particularly clear-cut among Caucasians, believed to have originated in more temperate climes.

KiSS-1 and kisspeptin were not named whimsically. They were originally associated with metastatic tumor suppression (the SS in KiSS-1 stands for suppressor sequence). The subsequent connection of KiSS-1 and kisspeptin to reproductive function was entirely fortuitous.

Durable critters providing insight for human egg preservation

Mon, 18 Dec 2006 04:59:37 PST

( from http://www.rxpgnews.com ) A tiny, six-legged critter that suspends all biological activity when the going gets tough may hold answers to a better way to cryopreserve human eggs, researchers say.

Tardigrades, also called water bears, can survive Himalayan heights or ocean depths as long as they have moisture.

When they dont, they produce a sugar, trehalose, slowly dehydrate and essentially cease functioning until the rain comes, says Dr. Ali Eroglu, reproductive biologist and cryobiologist at the Medical College of Georgia.

Tardigrades are not alone in their amazing ability to outlast adverse conditions. A type of brine shrimp, often called a sea monkey, comes back to life with water. The Bakers yeast Dr. Eroglu uses when he bakes bread with his children does as well. Similarly arctic wood frogs use the sugar, glucose, to tolerate frigid temperatures until the summer thaw.

While humans dont naturally produce trehalose, researchers think they can use it to safely preserve human eggs and those of endangered species giving better options to young women facing cancer therapies that may leave them infertile and others who simply want to delay reproduction.

Our hypothesis is when we introduce sugars into cells and into oocytes, we can protect them against freezing-associated stresses, says Dr. Eroglu, who received a $1.2 million grant from the National Institute of Child Health and Human Development to continue pursuing his hypothesis. We also hypothesized if we used trehalose, we also could use conventional cryoprotectants, which can be toxic, in lower concentrations to minimize their toxicity while maximizing overall protection.

Pilot data show it works like a charm, at least in mouse eggs. Researchers injected eggs with trehalose, cooled them to liquid nitrogen temperature, thawed them and exposed them to sperm. They got healthy babies at a similar rate to unfrozen controls.

We were very excited, says Dr. Eroglu, whose work has prompted desperate calls from young cancer patients wanting to preserve their eggs. We got very good development rates, then we transferred the embryos to foster mothers and got pups that were completely healthy. In fact, those pups had healthy pups. His limited testing in human eggs indicates they also can be preserved and thawed safely using this approach, however further research is needed to pursue clinical applications.

The NIH grant enables him to use monkey eggs, which are similar to human eggs, to find the optimal mix of sugar, conventional cryprotectants and freezing to maximize egg preservation. Collaborators at Emory University are providing the eggs and at the Georgia Institute of Technology are developing a mathematical model to predict cooling rates while avoiding destructive intracellular ice formation. Dr. Eroglu also is working with the MCG Section of Reproductive Endocrinology, Infertility and Genetics In vitro Fertilization Program to obtain discarded eggs that failed to fertilize.

Dr. Eroglu looks for a better way because current approaches are fraught with problems. Scientists have been freezing human eggs for about two decades but not very successfully. Embryo cryopreservation is relatively successful, but to freeze oocytes, we have to overcome many hurdles, he says. A major problem is the protective, exterior jelly coat of an egg doesnt freeze well. The jelly coat protects the egg from mechanical stress and serves as a receptor for sperm. Sperm must pass through the coat then penetrate the interior plasma membrane. As soon as a single sperm penetrates, it triggers intracellular signaling that transforms the coat into a hard, impermeable structure and with good reason: if multiple sperm penetrate, chromosomal abnormalities result. Interestingly, traditional freezing, even with cryopreservatives, can cause these problems and more. The jelly coat hardens, making it impossible for sperm to get through the traditional way. You dont have this issue with an embryo because fertilization already has occurred, Dr. Eroglu says.

Intracytoplasmic sperm injection came into use in 1997 to help overcome the hardened jelly coat but other problems persist. Chemical stress, freezing or warming can disrupt the eggs mechanism for dividing chromosomes babies get half their chromosomes from mom and half from dad so they dont line up as they should. In addition to hardening the jelly coat, cold stress can change intracellular signaling resulting from sperm penetration. Lipids or fats in the egg can fuse and the membrane can become leaky.

The bottom line is only about 1-5 percent of eggs develop to term after standard cryopreservation techniques, which include a combination of slow freezing in conjunction with low levels of cryoprotectants such as dimethyl sulfoxide, or rapid freezing with more cryoprotectants.

Dr. Eroglu says the sugars, which help protect the natural structure of proteins, enable use of warmer temperatures and fewer cryoprotectants. He uses the tried and true intracytoplasmic sperm injection approach to deliver sugar instead of sperm - to eggs before cooling. One of his ultimate goals is to design sugars that can easily penetrate the eggs membrane, but at least for now, tardigrade sugars seems to work just fine in mice.

One of his many hopes is that freezing embryos wont always be necessary, whether its a human or an endangered species. Rather, eggs and sperm which have been frozen successfully for decades can be kept apart until fertilization is desirable. This could preclude the controversy of destroying unused embryos and perhaps the debate over embryonic stem cells, he says.

Eggs, which can reprogram cell function by turning genes off and on, can produce cells that can become essentially anything, Dr. Eroglu says. If he can better understand how they do this, regular body cells might be reprogrammed in a test tube to embryonic-like stem cells for therapeutic use.

Binghamton University researcher to study declining US fertility rates

Tue, 12 Dec 2006 04:59:37 PST

( from http://www.rxpgnews.com ) In the United States, the total fertility rate the number of children a woman has in her lifetime fell from seven or eight in 1800 to slightly more than two today, says J. David Hacker, assistant professor of history at Binghamton University. And with a five-year $667,237 grant from the National Institute of Child Health and Human Development, Hacker hopes to find out why.

It's one of the most profound social revolutions of the period, he said. It has all kinds of ramifications for the social and economic history of the United States, including women's ability to participate in the paid labor force, parental resources available for children's education, the age structure of the population and even the future of the social welfare state.

Declining fertility in that period was a major factor in the aging of the population. The median age of Americans rose from less than 16 years in 1850 to older than 35 in 2000, Hacker said. It is projected to reach 39.1 years in 2035.

What's interesting about the fertility decline is that the vast majority of it takes place before there's modern contraceptive technology, Hacker said. It's kind of ironic. Our best source of data on fertility the U.S. birth registration system was not in place until 1933, but at that point we've had almost 100 years of continuous decline in the birth rate.

For that reason, Hacker's quantitative study will rely primarily on data from the U.S. Census Bureau. He will describe the fertility decline in greater detail than previously possible, looking at differentials such as race, ethnicity, region and occupation. He will also explain the decline using multi-level empirical models.

The census is quite rich, he said. I am employing a method of analysis called Own Child Fertility Methods, which allows me to look at women's childbearing experience and correlate that with individual and household-level data that's available in the population census and with county-level data available in the agriculture and manufacturing censuses.

There's a split in the literature about the fertility decline, Hacker notes. Economists argue that factors such as a decrease in available farmland, industrialization, urbanization and the rising costs of children are key causes. Social historians point more to culture and women's status and role in the household. Hacker's study is designed to address both of those viewpoints.

Hacker has pioneered the creation of cultural variables in the census to correlate with the fertility decline. He tracks child-naming practices as a proxy measure of parental religiosity, for instance. During the 19th century, he notes, there was an amazing secularization of the naming pool. Three-quarters of all children's names had biblical origins in 1800, while by 1920 just a fifth had such origins.

What I've shown, Hacker said, is that parents who rely on biblical names for their children have much larger families than parents who rely on secular names, controlling for economic and other factors.

The 15 census microdata samples Hacker will examine include records for some 18 million individuals. Computer technology has really aided the kind of research I conduct, Hacker said. There's no way you could have analyzed 18 million cases just 10 years ago it would've been difficult.

According to Hacker, many countries have experienced or are experiencing a demographic transition from high birth rates and high death rates to low birth rates and low death rates.

The United States is in some ways an ideal laboratory to study this both because it appears to be quite early in the adoption of conscious family-limitation practices and because of the heterogeneity of the population and its large-scale immigration.

Incontinence a common postnatal problem

Tue, 12 Dec 2006 04:59:37 PST

( from http://www.rxpgnews.com ) Almost a quarter of all mothers have problems with exertion incontinence one year after childbirth, according to a new doctoral thesis from Karolinska Institutet. However, despite many physical ailments, new mothers have better self-rated health than other women in the same age group.

In her thesis, Womens health after childbirth, postgraduate student and midwife Erica Schytt takes an all-inclusive approach to the question of how childbirth affects mothers physical health. Her survey included some 2,500 Swedish women, who were asked to complete a series of questionnaires on physical symptoms and rate their health on a scale of one to five, from the start of their pregnancy until after the delivery.

The thesis shows that most of the women were troubled by at least one symptom for their entire first year, and that a quarter of them had five or more symptoms. The most common complaint was exertion incontinence, which no less than 22% of the women suffered a year after childbirth.

This is serious, as its often a chronic problem, says Dr Schytt.

Women who suffer from obesity or constipation, who have already had a child, or who are older than 35 are at particular risk of developing exertion incontinence, while the chances were lower for those who had had a caesarean. However, Dr Schytt stresses that this is not to be taken as an argument for opting for a caesarean, as the operation has its own dangers.

Other common complaints after delivery were fatigue, headaches, and neck, shoulder or lower back pain. Pain from the caesarean operation, pain during intercourse and haemorrhoids were common after two months, but for most women these problems had ceased after a year.

Despite a number of physical complaints, most of the women described themselves as feeling well. To the question: All in all, how would you describe your present state of health, 91% responded good or very good two months after childbirth. When the question was asked again after one year, the number had dropped slightly to 86%.

According to Dr Schytt, these figures are better than for women of the same age in the normal population.

Either giving birth makes you healthy, or healthy women have babies, she says. Its probably the latter, but I daresay its also the case that women experience powerful elation after giving birth that takes their mind off any ailments that they might also expect to be only temporary.

Dr Schytt thinks that her results can be of use in postnatal care.

Most women recover after childbirth, but there are those who dont, and its these we need to get to, she says. The two-month postnatal check up is an important opportunity for midwives and doctors to identify and deal with womens physical problems and other risk-factors of poor self-rated health.

World-class Biomedical Research Center to be in West London

Sun, 10 Dec 2006 04:59:37 PST

( from http://www.rxpgnews.com ) An international team of experts has judged the biomedical research conducted at The Hammersmith Hospitals NHS Trust, St Mary's NHS Trust and Imperial College London to be amongst the very best in the country.

Health Secretary Patricia Hewitt announced last week (8 December) the creation of eleven Biomedical Research Centres (BRC) and awarded BRC status to the two hospitals in partnership with Imperial College. BRCs will be leaders in translating scientific research into benefits for patients. Imperial's academic clinicians will work with their NHS colleagues to take research from the bench to the bedside, enabling the adoption of new technologies, techniques and treatments.

The award guarantees the partners research funding of Â£19.5 million per annum for the next five years, and makes the West London BRC the leading centre for the UK.

Trust Chief Executives Derek Smith and Julian Nettel, and Rector of Imperial College London Sir Richard Sykes said, We are delighted to be recognised for the innovative research which is carried out through our partnership to advance healthcare and medical research around the world. Our research is at the forefront of biomedical invention with the primary goal of improving patient care.â

Awarding BRC status to the Trusts in academic partnership with Imperial is an endorsement of their intention to become the UK's first Academic Health Science Centre. (AHSC). The AHSC will be a healthcare organisation that integrates governance and management for service delivery, teaching and research, based on tried and tested models around the world. This concept represents a future that has captured the imagination and support of clinical leaders and senior management of all organisations and will enable West London to compete on a global stage.

The AHSC will be a magnet for investment and for clinical leaders who champion the creation and delivery of new diagnostic and treatment options to improve the lives and welfare of patients.

Staff, patients and local communities will be involved in designing and planning the AHSC as well as being formally consulted about it in 2007.

Between them the hospitals can already boast the best breast cancer survival rates; the best lung cancer survival rates; and the third and fourth fewest deaths during coronary artery by-pass operations. They have achieved this record by employing the very latest thinking, technology and treatments.

Imperial College is the UK's leading clinical academic university with 140 clinical academic fellows and 53 clinical lecturers. It recently had its world-class reputation confirmed by the Times Higher Educational 2006 World University Rankings, which placed the university fourth in the world for biomedicine and ninth in the world overall.

Further endorsement was received in the Chancellor's pre-budget statement this week (6 December). Gordon Brown announced that the government accepted the findings of a new report into UK Health Research funding, which included a statement of support for the AHSC model. The Cooksey report states: Universities and Trusts might follow the US Academic Medical Centre model, as Imperial College and St. Mary's and Hammersmith NHS Trusts are doing with their plan to create the UK's first Academic Health Sciences Centre. This proposal, which promises to deliver greater integration of not only research strategies, but vital underpinning human resources and capital assets, should make for a more effective approach to health research and patient care at these institutions.â

Rochester study rolls out RU-486 to treat uterine fibroids

Wed, 06 Dec 2006 04:59:37 PST

( from http://www.rxpgnews.com ) Low doses of the drug mifepristone shrink uterine fibroid tumors and greatly improve the quality of life in women who suffer from pain and heavy bleeding, according to a University of Rochester study published in the December Obstetrics and Gynecology journal.

Leiomyoma, the medical term for uterine fibroids, affects roughly half of all women aged 35 to 49. The non-cancerous tumors cause iron-deficiency anemia due to excessive menstrual bleeding, and deeply impact the quality of life for women who have this condition. Thousands of women annually opt for hysterectomies or have the tumors removed surgically because no other medical treatment has been proven effective, the study said.

With no approved treatment for symptomatic fibroids, this study and its findings are very significant, said corresponding author Kevin Fiscella, M.D., M.P.H., of the Department of Family Medicine Research Program at the University of Rochester Medical Center. Interestingly, this is the same drug that was recently shown to prevent breast cancer in a rat model. Federal funding for research related to mifepristone should be given a high priority.

Doctors have known from prior data that mifepristone, an antiprogestin, might help uterine fibroids. But the benefits had not been confirmed until now. The University of Rochester study is the first randomized, double blind, placebo-controlled trial of mifepristone, also known as RU-486, to establish that it can be safely used at low doses to treat uterine fibroids. Forty-two premenopausal women from western New York volunteered to participate in the clinical trial from March 2004 to March 2005.

Of the total, 22 women received mifepristone at 5 mg daily, and 20 women received an identical looking placebo pill daily, for six months. Doctors sought to evaluate physical changes as well as quality of life improvements. To assess the latter, they used a survey with a 100-point scale that asked questions such as: During the past month, how distressed were you by: heavy bleeding during your menstrual period, feeling tightness or pressure in your pelvic area, or feeling fatigued

Researchers assessed bleeding with a daily log and hemoglobin tests, and administered ultrasound and other tests to assess uterine volume and tumor size. Safety monitoring was conducted throughout the trial. The National Institute of Child Health and Human Development funded the study.

Results were dramatic. By the end of the study, for example, virtually every woman in the mifepristone group was certain she had been receiving the drug because of so many improvements -- despite the studys intentional design to keep everyone blind to the data and outcomes.

Here are some statistics cited by the study authors:n Although quality of life measurements were the same for both groups at the start of the study, the women on mifepristone reported a 135-percent improvement in quality of life after six months, compared to a 41-percent improvement in the placebo group. Symptoms decreased in both groups, but severity was significantly less in the mifepristone group.

n Blood loss also improved among women taking mifepristone. For example, hemoglobin levels went up in the treatment group from 12.0 to 13.5 g/DL, compared to a decrease in hemoglobin levels in the placebo group. At the start of the study, 11 of 22 women (50 percent) in the mifepristone group were anemic, but after six months of treatment only 2 or 22 women (9 percent) were anemic. In the placebo group anemia rose, with 9 of 22 women (45 percent) anemic at the start of the study, and 12 of 22 women (60 percent) anemic after six months.

These very promising findings warrant replication through a large multicenter study, the authors wrote. Further studies should evaluate whether the drug can be safely taken for longer periods, and how long after stopping the drug would regrowth of fibroids occur. Side effects to the drug were uncommon during the University of Rochester study, but the authors noted that adverse events should be carefully monitored during follow-up studies.

A few deaths have been reported among women taking mifepristone at much higher doses (200-600 mg.) for pregnancy termination. However, medical authorities have not established a causal relationship between mifepristone and the deaths.

Synthetic cannabinoid may aid fertility in smokers

Fri, 01 Dec 2006 04:59:37 PST

( from http://www.rxpgnews.com ) BUFFALO, N.Y. -- A reproductive medicine specialist at the University at Buffalo has shown that a new compound may improve the fertility of tobacco smokers who have low sperm count and low percentage sperm motility.

The sperm from male smokers were washed with a synthetic chemical called AM-1346. After incubation, there was a doubling in the fertilizing capacity of sperm from poor quality semen, results showed.

Lani Burkman, Ph.D., and colleagues presented the findings at the 2006 meeting of the American Society of Reproductive Medicine held recently in New Orleans. Based on our previous data and published literature, it is clear that most tobacco smokers will exhibit a small or a significant decline in fertility, she stated. Nicotine addiction is quite powerful. The best solution is to stop smoking and then wean yourself off of all nicotine products. But for smokers who cant quit, the in vitro use of AM-1346 may significantly improve their fertilizing capacity.

Burkman, associate professor in the departments of gynecology/obstetrics and urology and head of the Section on Andrology in the UB School of Medicine and Biomedical Sciences, previously demonstrated that sperm functions critical for fertilization are altered by nicotine exposure, whether in vitro, or through long-term tobacco use. Two-thirds of the male smokers studied had decreased fertility; some showed a serious loss.

The new study involved nine selected smokers (22 experiments) who had been evaluated previously for sperm fertilizing potential using the outside cover of a human egg, called the zona pellucida. Four men had a high number of sperm attaching to the zona (normal, Group I), while five other smokers had sperm with poor egg binding (poor fertilizing potential, Group II).

The new experiments were designed to evaluate whether sperm with poor fertilizing capacity from smokers could be treated so that egg binding was improved. Specifically, the researchers studied a potential interaction between two chemical systems that control sperm.

Human sperm carry the cholinergic receptor, which responds to the neurotransmitter acetylcholine, noted Burkman. Nicotine mimics acetylcholine and binds to the cholinergic receptor. In earlier research, Burkman and colleagues also showed that human sperm contain cannabinoid receptors, which respond to marijuana, as well as natural cannabinoids occurring in the body.

Research from other scientists indicates that the cholinergic system and the cannabinoid system naturally regulate human sperm and help prepare them for fertilizing an egg, she said. Our research suggests that this natural regulation is out of balance for the majority of smokers when sperm are continuously exposed to nicotine.

We think there is an important communication between the cannabinoid and cholinergic receptor systems in human sperm, said Burkman. No one has shown this interaction before when looking at human tissue. AM-1346, the drug that we tested, is a synthetic version of a natural cannabinoid found in the body.

In 22 Hemizona tests, we showed that the response to AM-1346 depended on the initial fertility of the tobacco smoker, and if his semen showed poor quality, meaning low sperm count and low percentage motility.

The sperm from Group II volunteers were incubated with AM-1346 for several hours and then retested in the Hemizona Assay. Six experiments in Group II started with semen of low quality and all six resulted in stimulation of sperm binding to the zona ranging from 133 percent to 330 percent, with a mean of 201 percent, when compared to their own untreated sperm, results showed.

In contrast, said Burkman, samples from Group I (normal fertility, normal semen quality) reacted in the opposite manner. This two-way, or biphasic, response is common for cannabinoid action. With Group I, the drug AM-1346 caused a substantial decrease in sperm binding to the zona for eight out of nine samples.

This opposite response must be studied further, Burkman said. It might be tied to early-versus-late steps in fertilization, where it is expected that one process is slowed down while another process is stimulated.

It does appear that sperm functioning in tobacco smokers with low fertility and low semen quality is quite different when compared to smokers with higher fertility and good semen quality. Nicotine appears to change the sperm membranes and sperm receptors. It also raises the question of why sperm from some smokers are protected from the effects of tobacco and nicotine.

US teen pregnancy rates decline as result of improved contraceptive use

Fri, 01 Dec 2006 04:59:37 PST

( from http://www.rxpgnews.com ) Eighty-six percent of the recent decline in U.S. teen pregnancy rates is the result of improved contraceptive use, while a small proportion of the decline (14%) can be attributed to teens waiting longer to start having sex, according to a report by John Santelli, MD, MPH, department chair and professor of Clinical Population and Family Health at the Mailman School of Public Health and published in the January issue of the American Journal of Public Health. The scientific findings indicate that abstinence promotion, in itself, is insufficient to help adolescents prevent unintended pregnancies.

Data from the report, Explaining Recent Declines in Adolescent Pregnancy in the United States: The Contribution of Abstinence and Improved Contraceptive Use suggest that the United States is following patterns seen in other developed countries where increased availability and increased use of modern contraceptives have been primarily responsible for declines in teenage pregnancy rates. The study by Dr. Santelli of the Mailman School in conjunction with researchers at the Guttmacher Institute examines information from the National Survey of Family Growth, a nationally representative household survey that provides comprehensive coverage of female adolescents.

Between 1995 and 2002, U.S. teen pregnancy rates declined by almost one-quarter (24%). The new study examines the data to determine the relative contributions of abstinence and contraceptive use to this decline. According to the analysis, most of the decline (86%) was due to more sexually active teens using contraceptives, using more effective methods (e.g., condoms and birth control pills) and using multiple methods (e.g., the pill together with condoms) in 2002 than in 1995. When broken down by age, delays in sexual activity played a greater role for younger teens aged 1517 (23% of the decline). Among 1819-year-olds, the decline in the risk of teen pregnancy was entirely attributable to improved contraceptive use.

The United States seems to be following the recent patterns in other developed countries where increased availability and use of modern contraceptives and condoms have led to remarkable declines in teen pregnancy, said Dr. Santelli. If most of the progress in reducing teen pregnancy rates is due to improved contraceptive use, national policy needs to catch up with those realities.

The authors conclude that this study raises serious questions about the value of the federal government's funding of abstinence-only education programs that prohibit information about the benefits of condoms and contraception. They suggest that public policies and programs in the United States and elsewhere should vigorously promote provision of accurate information on contraception and on sexual behavior and relationships, support increased availability and accessibility of contraceptive services and supplies for adolescents, and promote the value of responsible and protective behaviors, including condom and contraceptive use and pregnancy planning.

Program to freeze women's ovaries to preserve fertility after cancer

Wed, 29 Nov 2006 04:59:37 PST

( from http://www.rxpgnews.com ) CHICAGO --- The Center for Reproductive Research at Northwestern University is launching a new, experimental research program for young women who may be at risk to lose their ovarian function and fertility following treatment for cancer.

The program, in which a woman's ovary is removed and frozen for possible future use, is being led by Teresa Woodruff, Ph.D., associate director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and executive director of the Institute for Women's Health Research at Northwestern's Feinberg School of Medicine. The long-term goal of the program is to be able to extract and mature eggs from cryopreserved (frozen) ovarian tissues to initiate pregnancies once cancer treatment has been completed.

This breakthrough may permit not only the potential preservation of fertility options for women and girls with cancer, but also can be applied to normal in vitro fertilization patients. This procedure, when developed, could radically change the way infertility is viewed, reduce and eliminate embryo storage and provide better options for women who do not respond to hormonal therapy, said Woodruff.

In recognition of the Cancer Center's commitment to providing fertility options to women and men with cancer, it has been recognized as a Fertile Hope Center of Excellence, the fifth medical center in the country to receive this designation. Fertile Hope is a non-profit organization that assists cancer patients faced with infertility.

Woodruff's research involves developing new techniques for the long- term preservation of human ovarian tissue. Scientists are exploring ways to remove immature eggs from this tissue and to mature them in the laboratory so that they can potentially be fertilized at a later date.

At this time, the only pregnancies resulting from this research are in mice. Eligible participants will have one ovary surgically removed at Northwestern Memorial Hospital in an outpatient procedure called a laparoscopy before starting cancer treatment. Eighty percent of the ovary will be preserved for the patient's future use and 20 percent will be used by researchers to explore ways to extract and develop immature eggs.

Scientists and physicians from Northwestern are developing a new discipline described as oncofertility and are organizing a collaboration of national experts that include biophysicists, biomaterials biologists, clinical oncologists, reproductive biologists, psychologists, ethicists and legal scholars. The objectives of oncofertility are to better understand the impact of cancer treatment on fertility, to identify new technologies to preserve fertility and to explore the psychosocial role fertility has on survivorship.

Minimally invasive treatment helps infertile couples conceive

Tue, 28 Nov 2006 04:59:37 PST

( from http://www.rxpgnews.com ) CHICAGO -- Couples struggling with infertility face uncertain odds when considering various treatment options. But a new study reveals that embolization, a minimally invasive treatment for arguably the most common cause of infertility in men, can significantly improve a couples chances for pregnancy. Furthermore, the study identified the level of sperm motility (movement) prior to treatment as a key predictor of a successful pregnancy. The findings were presented today at the annual meeting of the Radiological Society of North America.

We found that spermatic vein embolization combined with anti-inflammatory treatment improves sperm motility and sperm count in infertile men with varicoceles, said Sebastian Flacke, M.D., assistant professor of radiology at the University of Bonn in Germany. Six months after treatment, 26 percent of couples had achieved a pregnancy.

Normally, blood flows to the testicles and returns to the heart via a network of tiny veins that have a series of one-way valves to prevent the blood from flowing backward to the testicles. If the valves that regulate the blood flow from these veins become defective, blood does not properly circulate out of the testicles, causing swelling and a network of tangled blood vessels in the scrotum called a varicocele, or varicose vein.

Varicoceles are relatively common, affecting approximately 10 percent to 15 percent of the adult male population in the United States. According to the National Institutes of Health, most cases occur in young men between the ages of 15 and 25. Many varicoceles cause no symptoms and are harmless. But sometimes a varicocele can cause pain, shrinkage or fertility problems.

Varicoceles have long been regarded as key contributors to infertility in men. Common belief held that the warm blood pooling in the varicocele increased scrotum temperature and reduced sperm count and motility. However, some recent studies have argued that varicoceles are not a factor and that treating them will not increase male fertility.

The traditional treatment for problematic varicoceles has been open surgery, but recently varicocele embolization has emerged as a minimally invasive outpatient alternative. In the procedure, an interventional radiologist inserts a small catheter through a nick in the skin at the groin and uses x-ray guidance to steer it into the varicocele. A tiny platinum coil and a few milliliters of a sclerosing agent to ensure the occlusion of the gonadic vein are then inserted through the catheter. Recovery time is minimal, and patients typically can return to work the next day.

Dr. Flacke and colleagues set out to identify predictors of pregnancy after embolization of varicoceles in infertile men. The study included 223 infertile men, ages 18-50, with at least one varicocele. All of the men had healthy partners with whom they were trying to achieve a pregnancy.

In the study, 226 of the patients 228 varicoceles were successfully treated with embolization. Anti-inflammatory treatment and hormone substitution was initiated if required.

A semen analysis performed on 173 patients three months after the procedure showed that on average, sperm motility and sperm count had significantly improved. Six months later, 45 couples, or 26 percent, reported a pregnancy. A high level of sperm motility before the procedure was identified as the only significant pre-treatment factor associated with increasing the odds of successful post-treatment pregnancy.

This study confirms that varicocele repair can significantly improve sperm count and motility, Dr. Flacke said.

Pregnant women with lupus face higher risk of complications and death

Sat, 11 Nov 2006 04:59:37 PST

( from http://www.rxpgnews.com ) DURHAM, N.C. -- Women with systemic lupus who become pregnant are at significantly greater risk for death or other medical complications than are pregnant women without lupus, Duke University Medical Center researchers have found in a nationwide study of more than 18 million women.

The study, believed to be largest of its kind, suggests that pregnant women with systemic lupus should be considered a high-risk population and should be monitored closely by both a rheumatologist and an obstetrician who specializes in caring for high-risk patients, the researchers said.

Pregnant women with lupus should never try to go through their pregnancy alone and simply hope for the best, said study leader Megan Clowse, M.D., M.P.H., assistant professor in the Division of Rheumatology. They should stay in close contact with their doctors and report any problems immediately.

Clowse presented the findings on Sunday, Nov. 12, at the annual meeting of the American College of Rheumatology, in Washington, D.C. The study was funded by the National Institutes of Health's Building Interdisciplinary Research Careers in Women's Health program.

Lupus is an autoimmune disease in which the immune system loses its ability to distinguish between self and foreign substances and thus relentlessly attacks the body's own tissues and cells. Individuals with lupus often exhibit many different symptoms, including arthritis, kidney disease, rashes, fevers, anemia and sensitivity to light, among other problems.

Approximately 1.5 million Americans -- roughly 90 percent of them women -- have some type of lupus. Most patients are diagnosed during their reproductive years. Seventy percent of patients have systemic lupus, the most severe form of the disease.

All women with systemic lupus, pregnant or not, are at increased risk for death and medical complications compared to a healthy population, Clowse said. Other studies report that each year, between 0.8 percent and 3 percent of lupus patients die from the disease.

Previous research also has shown that pregnancy can increase the activity level of lupus, increasing the danger to the woman and sometimes causing problems in her fetus, according to Clowse. What was not certain, she said, is how much lupus increased a woman's health risk.

To help answer this question, Clowse's team analyzed data from more than 18 million pregnancy-related hospital admissions and discharges in the United States from 2000 to 2002. The study found that slightly more than 13,500 women with systemic lupus gave birth during this time, and 44 of the women -- 0.3 percent -- died, Clowse said.

Overall, women with systemic lupus showed a more than 20-fold greater risk of pregnancy-related death, compared with women without the disease, she said. Extrapolating this observed increase in risk to the general population suggests that for every 100,000 women with systemic lupus who would deliver a baby, approximately 325 of them would die, compared with approximately 14 deaths for every 100,000 women without the disease who would give birth, Clowse said.

We don't want these results to scare women with lupus away from getting pregnant, especially if they have a mild form of the disease, Clowse said. But these women really must plan their pregnancies. They may need to change their medications before they get pregnant, and they really shouldn't conceive when their lupus is active.

Clowse said patients whose lupus has been dormant for at least six months before conception are at low risk for developing active systemic lupus during pregnancy and therefore are at least somewhat less likely than women whose disease is active to experience health complications.

However, all women with systemic lupus do face elevated risks for pregnancy complications, she said. In the study population, women with systemic lupus, compared to women without the disease, were nearly six times more likely to suffer from deep vein thrombosis -- a blood clot -- and 3.5 times more likely to develop sepsis, a severe illness caused by an extreme infection of the bloodstream. Many women with lupus also were anemic or had low blood platelet counts at delivery and were three times more likely to need transfusions.

Additionally, almost 37 percent of women with lupus gave birth via cesarean section -- 15 percent higher than the national average of 22 percent. Women with lupus also were 2.5 times more likely to experience preterm labor and three times more likely to develop preeclampsia, or pregnancy-related high blood pressure, than women without lupus.

Clowse said the study's results are highly suggestive and should be taken seriously within the health care community, but she added that the study did have certain limitations.

On the plus side, the study examined a large number of patients, including patients from a variety of clinical environments, and it compared pregnancy results among women with and without lupus, she said.

However, she added, the study relied on analyzing hospital admission and discharge data, rather than on analyzing individual patient records or on examining the patients themselves.