RxPG News : Gynaecology

Anaesthesia not harmful for babies during birth

Tue, 28 Jul 2009 13:08:33 PST

( from http://www.rxpgnews.com ) Babies exposed to anaesthesia during caesarean deliveries are not at any higher risk of developing learning disabilities than children delivered normally.

'We found that the incidence of learning disabilities was equal between children who were delivered vaginally and those who were delivered via C-section but with general anaesthesia,' says Juraj Sprung, Mayo Clinic anaesthesiologist who led the study.

'It's reassuring that the anaesthetics required for caesarean delivery do not appear to cause long-term brain problems,' Sprung adds.

The study was conducted with data from the Rochester Epidemiology Project. Researchers analysed the medical records of 5,320 children born between 1976 and 1982 to mothers living in Olmsted County.

They compared birth records with scholastic achievement and IQ tests administered to the children later in life as part of their schooling.

The study builds on a previous project, reported in March, which found that children exposed to a single dose of anaesthesia during the first three years of life had no increased risk for learning disabilities, but those exposed multiple times had an almost doubled risk of learning disabilities.

Prolonged exposure to anaesthetics has been shown to cause brain abnormalities in young animals, which was the impetus behind these two studies.

Not only did the researchers find that the use of anaesthesia during delivery was not harmful to the baby, they found that babies delivered by caesarean using an epidural anaesthetic - had a substantially reduced risk for learning disabilities later in life.

'The risk was reduced by about 40 percent compared to children delivered vaginally and those delivered via caesarean section but with general anaesthesia,' says Sprung, according to a Mayo Clinic release.

Study co-author and Mayo Clinic anaesthesiologist Randall Flick cautions that because

this study is preliminary, changes to medical practice should not be considered at this point. 'What we've found is an association between two things,' he says.

These findings are reported in the current issue of Anaesthesiology.

New technique could sustain cancer patients' fertility

Tue, 14 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Researchers funded by the National Institutes of Health have completed a critical first step in the eventual development of a technique to retain fertility in women with cancer who require treatments that might otherwise make them unable to have children.

The researchers have developed a method to advance undeveloped human eggs to near maturity, in laboratory cultures maintained outside the body. The technique focuses on the follicle, a tiny sac within the ovary that contains the immature egg. The researchers were able to grow human follicles in the laboratory for 30 days, until the eggs they contained were nearly mature.

The research seeks to provide women who require a fertility-ending treatment with options for reproduction after their treatment is complete. Men facing such treatments can freeze their sperm for use at a later date. Female cancer patients have fewer options. Unlike sperm, eggs rarely survive freezing and thawing.

The accomplishment represents the successful completion of the first of three steps needed to preserve a woman's fertility after radiation treatments or chemotherapy. For the next step, researchers will need to induce the egg's final division, so that it contains only half the genetic material of its precursors. Finally, the researchers will have to demonstrate that they can freeze and thaw human follicles before growing them in culture.

The new technique could provide an option for women and girls who have cancer and are not yet ready to start families, said Duane Alexander, M.D., director of NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), which funded the research as part of the NIH Roadmap Interdisciplinary Research Consortium program. An additional benefit is that it will allow researchers to more closely follow the process by which immature eggs grow and mature. In turn, these observations may lead to new advances for treating other forms of infertility.

The best option currently for a female cancer patient to preserve fertility is to collect eggs, fertilize them with sperm, and freeze the resulting embryos. But that technique may not be acceptable to all female cancer patients.

Researchers have already identified experimental methods to freeze entire ovaries or strips of ovarian tissue and implant them in a woman's body when she is ready to have children. This is a good option for some patients, but it is possible that some cancer cells may hitch hike on the ovarian tissue and result in a new cancer after treatment is completed.

Developed by Teresa K. Woodruff, Ph.D. and Lonnie D. Shea, Ph.D., of Northwestern University's Feinberg School of Medicine, and their colleagues, the new technique would avoid both concerns.

The findings were published online in

New technique could sustain cancer patients' fertility

Tue, 14 Jul 2009 03:59:36 PST

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.

Polycystic ovarian syndrome: New light on its causes and its effect on brothers

Tue, 30 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Amsterdam, The Netherlands: Researchers have found evidence that chronic disease in either a mother or father can create unfavourable conditions in the womb that are associated with the development of polycystic ovarian syndrome (PCOS) in daughters. In another study, researchers found that brothers of women with PCOS and insulin resistance are themselves at greater risk of developing insulin resistance or diabetes, suggesting that factors associated with the condition can be passed down to sons as well as daughters.

The two studies were presented to the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam heard today (Tuesday).

Associate Professor Michael Davies told a news briefing: We already know from clinical studies of women with reproductive problems that foetal growth restriction is associated with the development of PCOS symptoms in daughters, and that problems during pregnancy and in the way the mother adapts to the metabolic challenge of pregnancy can indicate the future cardiovascular health of both the mother and the child. What we don't know is whether giving birth to a daughter who later develops PCOS is associated with increased, long term cardiovascular disease risk in the mother. Nor do we know whether conditions underlying chronic disease in the father increases the risk of PCOS in the daughter.

Prof Davies, co-director of the Research Centre for the Early Origins of Health and Disease at the University of Adelaide (Australia), looked at records for all female babies who were born and survived between 1973-1976 at The Queen Elizabeth Hospital in Adelaide. He and his colleagues interviewed the daughters to build up a picture of their health and any history of chronic disease in their parents. So far, 998 (63%) have responded, and Prof Davies reported preliminary data up to mid-1975 to the conference.

Sixty-two daughters (6.2% of the group) had a pre-existing diagnosis of PCOS. Mothers of these women tended to have elevated blood pressure during pregnancy. Daughters were nearly eight times as likely to have PCOS if their mothers had it, and they had a slightly higher risk if their mothers smoked during pregnancy. Mothers were 1.6 times as likely to have high blood pressure in later life if their daughters developed PCOS. If their fathers had heart disease or stroke, the daughters also had a higher risk of PCOS: double and three times the risk respectively. A history of diabetes in either parent was not significant.

Prof Davies said: These findings suggest a new pathway for the development of PCOS. We think that factors associated with the pre-existence of cardiovascular dysfunction in the mother or the father, and which operate during pregnancy, may create adverse conditions for the foetus, which alter the metabolic profile of offspring, leading to insulin resistance and reproductive consequences, such as PCOS, for daughters. A family history of diabetes is, therefore, not essential to observe an insulin resistance-related disease in offspring.

He said it was still unclear exactly how the cardiovascular risk in the father affected the daughter. We firstly need to consider the potential role of a common environment; for instance, that families with high levels of obesity (and therefore cardiovascular disease) will also tend to have heavy daughters who are thereby more likely to be affected by PCOS. However, the paternal effect that we saw was independent of the daughter's weight, maternal age, socioeconomic status, maternal smoking, and country of birth, which suggests either a direct genetic effect on the daughter, or an effect of paternal genetic factors that are expressed during pregnancy.

Dr Verena Mattle told the news briefing that her study was the first to show that brothers of women who had PCOS and insulin resistance were themselves more likely to develop insulin resistance or even diabetes or dyslipidaemia (a disruption in the levels of lipids (or fats) in the blood).

Until now, it was not clear whether the male relatives of women with PCOS were at increased risk for the metabolic disorders associated with PCOS, said Dr Mattle, who is chief resident at the University Clinic of Gynecological Endocrinology and Reproduction Medicine in Innsbruck (Austria).

Dr Mattle and her colleagues conducted oral glucose tolerance tests on 15 brothers of sisters with PCOS and insulin resistance (group 1). They also performed a serum analysis to determine lipid levels. As a control, nine brothers of sisters with PCOS but without insulin resistance were included in the study (group 2).

The researchers found that in the first group eight brothers showed an insulin resistance, one was diagnosed with diabetes and six had a normal glucose tolerance test. All nine affected brothers had a body mass index (BMI) between 19-31 kg/m2 and had elevated cholesterol and triglyceride levels. The six unaffected brothers had a BMI between 23-29, and none had high levels of cholesterol or triglycerides. In the second group, no insulin resistance was diagnosed. BMI was between 18-27 and two brothers had elevated cholesterol levels. Although there was a trend towards higher BMI in the first group, Dr Mattle said there was no statistically significant difference in BMIs between the two groups.

Dr Mattle said: These results mean that we should pay attention to the health not only of women with PCOS but also to their brothers as they seem to have an increased risk for the medical problems that make up the metabolic syndrome, such as insulin resistance, diabetes and cardiovascular disease. Our findings are also in accordance with the hypothesis that not only is PCOS is a heritable disease, but that factors associated with it, such as insulin resistance, can be passed down to the next generation of either sex.

She said that it could not be the case that the high BMI by itself could have caused the insulin resistance and diabetes in the affected brothers. There must be a correlation between PCOS and insulin resistance because we could only find brothers with insulin resistance in the group that had sisters with PCOS and insulin resistance, but we couldn't find brothers with insulin resistance in the group that had sisters with PCOS and no insulin resistance. It is known that about 50% of women with PCOS are insulin resistant and also that lean PCOS patients are insulin resistant. The BMI of insulin-resistant and non-resistant brothers were not statistically different.

Dr Mattle and her colleagues are continuing to test brothers of women with PCOS for insulin resistance and lipid levels to collect more data from a larger group. At this stage we would hesitate to say that a genetic inheritance is definitely playing a role in the increased risk of insulin resistance and other, related conditions in these brothers. We need to explore the possible effect of conditions in the womb and also the role of the environment. However, we think our data strongly support the view that brothers of women with PCOS and insulin resistance may have an increased risk of insulin resistance, diabetes and other, adverse metabolic conditions, she concluded

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 suggests obese women should not gain weight

Fri, 29 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) For years, doctors and other health-care providers have managed pregnant patients according to guidelines issued by the American College of Obstetricians and Gynecologists (ACOG). In 1986, ACOG stated, Regardless of how much women weigh before they become pregnant, gaining between 26-35 pounds during pregnancy can improve the outcome of pregnancy and reduce their chances of having the pregnancy end in fetal death. Until its revised guidelines were released yesterday, the Institute of Medicine (IOM) had recommended that overweight women should gain about 15 pounds during pregnancy.

The current study was undertaken to test whether these guidelines make a difference in maternal-fetal outcomes among obese women. In the study, conducted at several hospitals, the researchers followed 232 obese pregnant women, all of whom had a body mass index (BMI) of 30 or greater. Half of the women followed conventional prenatal nutritional guidelines, which is essentially eat to appetite (control group). The other half were placed on a well-balanced, nutritionally monitored program, which included a daily food diary (study group). The average weight gain in the control group was 31 pounds, compared to 11 pounds in the study group. Twenty-three extremely obese patients lost weight during their pregnancy.

The findings showed that there were no fetal deaths and no growth-restricted infants in the study group. Also, there were fewer babies weighing more than 10 pounds in the study group than in the control group. (A birth weight over 10 pounds poses significant hazards to both infants and mothers.) Moreover, women in the study group gained less weight, had fewer cesarean deliveries, were less likely to develop gestational diabetes, and retained less weight after they delivered than women in the control group.

The researchers concluded that obese pregnant women may be placed on a healthy, well balanced, monitored nutritional program without adverse maternal-fetal outcomes.

Women who are obese when beginning a pregnancy are, by definition, unhealthy, says study leader Yvonne S. Thornton, MD, MPH, a clinical professor of obstetrics and gynecology and board-certified specialist in maternal-fetal medicine at New York Medical College. To say that they should gain even more weight is counter-intuitive, and our study bears that out. Rather than focusing on numerical endpoints with respect to weight gain, we need to focus on making these women healthier by getting them to eat a well-balanced diet.

The study grew out of Dr. Thornton's personal experience with obesity and pregnancy. Despite being overweight, she gained a substantial amount of weight during her first pregnancy, exacerbating her life-long battle with obesity. During her second pregnancy, she followed a well-balanced diet and gained little weight, with no adverse consequences for mother or baby.

Dr. Thornton observed the same pattern in her own clinical practice, leading her to question prevailing guidelines for weight gain during pregnancy. Adding to her skepticism was the fact that women who develop gestational diabetes are routinely put on diets that effectively limit weight gain, with no ill effects.

It is the mindset of our specialty, and our society, that we need to have round, chubby pregnant women in order make sure they are healthy, adds Dr. Thornton. Pregnancy has become a license to eat. We talk about 'eating for two,' but it's really more like eating for 1 and 1/20th.

These attitudes have contributed to the obesity epidemic in the U.S., where 35 percent of women are considered obese, says the researcher. The situation is even worse among African-American women, four out of five of whom are overweight or obese.

Gaining weight during pregnancy contributes to obesity, and it makes it that much harder for overweight women to return to their normal weight after pregnancy, says Dr. Thornton.

Identification of genetic variants affecting age at menopause could help improve fertility treatment

Mon, 25 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Vienna, Austria: For the first time, scientists have been able to identify genetic factors that influence the age at which natural menopause occurs in women. Ms Lisette Stolk, a researcher from Erasmus MC, Rotterdam, The Netherlands, told the annual conference of the European Society of Human Genetics today ( Monday 25 May) that a greater understanding of the factors influencing age at menopause might eventually help to improve the clinical treatment of infertile women.

Ms Stolk and her team performed a Genome-Wide Association Study (GWAS) in 10,339 menopausal women. The data analysed were taken from 9 different studies undertaken in The Netherlands (the Rotterdam Study 1 and 2), the UK (the TwinsUK study), USA (the Framingham study, the Cardiovascular Health Study, the ARIC study, the HAPI Heart Study), Iceland (AGES-Reykjavik) and Italy (the InCHIANTI study). The scientists found 20 single nucleotide polymorphisms (SNPs) in four different places on chromosomes 19 and 20. SNPs are common genetic variants that influence how humans look, behave, develop disease or react to pathogens. In genetics they are used to compare regions of the genome between different groups of individuals and to identify those regions that are associated with a particular disease or characteristic. The SNPs the researchers found had not been identified before, and the part of the body where they might have an effect has yet to be identified, though the researchers speculate that this is likely to be in the ovaries or brain.

We found that the 20 SNPs were all related to a slightly earlier menopause, said Ms Stolk, and women who had one of them experienced menopause nearly a year earlier than others. We know that ten years before menopause women are much less fertile, and five years before many are infertile. In Western countries, where women tend to have children later in life and closer to menopause, age at menopause can be an important factor in whether or not a particular woman is able to become a mother.

In addition to its effect on fertility, earlier menopause has other deleterious effects on women such as an increased risk for osteoporosis, osteoarthritis and cardiovascular disease, while it has a protective effect on the risk of breast cancer. The age of menopause varies greatly among Caucasian women, ranging between 40 and 60 year of age, with an average at around 50. The reasons for this variation are unknown, but there is evidence from studies of twins that this could be due to inheritable genetic factors. However, until now, GWAS had not been used to study the effect of genetic variants on age at menopause.

The scientists intend to follow up their work with an even larger sample of menopausal women to identify more chromosomal loci. GWAS gives you SNPs connected with menopausal age, and a possible indication of the gene involved, but not a total proof of function, said Ms Stolk. When we have a larger group of loci we intend to perform functional studies to study the exact biology and effect of this association.

The scientists say that it may be several year before they have enough information to make genotyping for earlier menopause available to patients, and even then this may not be helpful to all women with fertility problems. However, if these studies give us a better understanding of the function of the genetic variants involved in early menopause, we might one day be able to screen women who have problems getting pregnant to see if they have one or more of these variants which might relate to their sub-fertility, and perhaps interfere with the relevant physiological pathways in order to delay their total infertility, said Ms Stolk.

Two genes involved with determining time of menarche identified

Sun, 17 May 2009 11:16:42 PST

( from http://www.rxpgnews.com ) Researchers from the Peninsula Medical School, along with collaborators from research institutions across Europe and the United States, have for the first time identified two genes that are involved in determining when girls begin menstruation. The work will be published in Nature Genetics.

The findings of the study could have ramifications for normal human growth and weight too, because early-age menstruation is also associated with shorter stature and increased body weight. In general, girls who achieve menstruation earlier in life tend to have greater body mass index (BMI) and a higher ratio of fat compared to those who begin menstruation later.

The study carried out an analysis of 17,510 women across eight different international population-based sources. This number included women of European descent who reported the age at which they reached menstruation of between nine and 17 years.

The two genes identified were on chromosomes nine and six. One in 20 females carry two copies of each of the gene variations which result in menstruation starting earlier, and they will start menstruating approximately four and half months earlier than those with no copies of the gene variants.

Dr Anna Murray from the Peninsula Medical School, commented: "This study provides the first evidence that common genetic variants influence the time at which women reach sexual maturation. Our findings also indicate a genetic basis for the associations between early menstruation and both height and BMI."

She added: "The study takes us nearer to understanding the biology of the processes involved in puberty and early growth and to understand what constitutes 'normal' in growth and development."

Fellow author John Perry, also from the Peninsula Medical School, added: "Understanding the biological mechanisms behind reproductive lifespan may also help inform us about associated diseases that affect a lot of women as they get older, including diabetes, heart disease and breast cancer."

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.

Penn State professor investigates estrogen, heart disease connection in women

Mon, 04 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) A new study on old rats by a Penn State researcher will shed light on the connection between estrogen deficiency, heart disease and aging in women.

Heart disease is the leading cause of death in women over the age of 75. After menopause, women lose their ability to produce the hormone estrogen and researchers believe that low estrogen levels somehow make women more vulnerable to heart disease and heart attack.

Donna Korzick, associate professor of physiology and kinesiology in Penn State's College of Health and Human Development, has a $1.8 million, five-year project funded by the National Heart, Lung and Blood Institute of the National Institutes of Health to figure out why estrogen deficiency puts women in danger for heart disease.

Korzick will identify proteins in heart cells that might be affected by both aging and low estrogen levels. She will work with Bruce Stanley, director of scientific programs, Penn State Milton S. Hershey Medical Center, to identify these proteins.

Proteins are the work horses of the cells, said Korzick. When they become activated, they can trigger different functions within the cell. Some are even responsible for cell death as we age.

Proteins can become 'activated' in a variety of ways, including by low estrogen levels.

Korzick will analyze the proteins within one segment of heart cells, the mitochondria. These are the gate keepers of cell survival, says Korzick. The mitochondria play a significant role in whether or not a cell lives or dies as we age, especially while experiencing a heart attack.

Cell death is a natural process, explained Korzick But when heart cells die, it means that the remaining cells have to do more work. In this way, cell death is directly linked to how well the heart can withstand a stress like a heart attack.

After identifying the heart cell's proteins, Korzick will determine which proteins respond to low-estrogen environments. She will then use protein-targeting drugs that can activate or inhibit specific proteins in the heart cells to change what is happening inside the cells. Korzick hopes that these experimental results will provide the missing piece to the estrogen deficiency -- heart disease puzzle.

Because of their short life span -- only two years, Korzick will look primarily at rats. According to Korzick, this short life span allows for a true model of aging. Additionally, other researchers have already completed a large body of work involving aged rats so she will have a comprehensive knowledge base with which to work.

At the very least, we'll be learning about heart disease in older females, says Korzick. Right now, most of the estrogen-specific research is based on males, or young rats. Our research focuses on females, both young and old.

With the assistance of Tim Lancaster, who received his master's degree in kinesiology in 2008, Korzick has already identified nearly 600 proteins within the mitochondria of a rat heart cell.

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.

Clinical trial finds microbicide promising as HIV prevention method for women

Thu, 05 Mar 2009 04:59:36 PST

( from http://www.rxpgnews.com ) March 5, 2009 -- A clinical trial involving more than 3,000 women in the U.S. and southern Africa demonstrates for the first time the promise of a vaginal microbicide gel for preventing HIV infection in women. According to findings presented at the Conference on Retroviruses and Opportunistic Infections (CROI), one 0.5 % dose of a microbicide designed to prevent HIV from attaching to cells in the genital tract, was 30% effective. While the results are encouraging, researchers on the study, known as HPTN 035, report that additional evidence is needed to determine more definitively its effectiveness.

These findings provide the first signal that a microbicide gel may be able to prevent women from HIV infection, says Salim S. Abdool Karim, MD, PhD, professor of clinical Epidemiology at Columbia University Mailman School of Public Health, pro vice-chancellor (research) at the University of KwaZulu-Natal in Durban, South Africa, and director the Center for the AIDS Program of Research in South Africa, who led the multi-center study for the U.S.-based Microbicide Trials Network (MTN). Indeed, for the millions of women at risk for HIV, especially young women in Africa, there is now a glimmer of hope. But these findings also indicate that more research is needed; we can't yet say that we have an effective microbicide.

Microbicides are substances intended to reduce or prevent the sexual transmission of HIV and other sexually transmitted infections when applied topically. Several candidate microbicides are being tested in clinical trials, although none is yet approved or available for use. Earlier trials have yielded disappointing results or were stopped prematurely.

Currently, women comprise half of all people worldwide living with HIV. In sub-Saharan Africa, women represent nearly 60 % of adults living with HIV, and in several southern African countries young women are at least three times more likely to be HIV-positive than young men. In most cases, women become infected with HIV through sexual intercourse with an infected male partner. Although correct and consistent use of male condoms has been shown to prevent HIV infection, women often cannot negotiate condom use with their male partners. An effective microbicide could provide women with an HIV prevention method they initiate.

HPTN 035 evaluated the safety and effectiveness of two candidate microbicides for preventing male-to-female sexual transmission of HIV. The study was conducted between February 2005 and September 2008 and involved 3,099 women at six sites in Africa and one in the United States. In Africa, the sites were located in Durban and Hlabisa, KwaZulu-Natal, South Africa; Harare, Zimbabwe; Lusaka, Zambia; Blantyre, Malawi; and Lilongwe, Malawi. The U.S. site was in Philadelphia.

I am particularly impressed by and grateful to the women who took part in HPTN 035, commented Sharon Hillier, PhD, vice chairman and professor, department of obstetrics and gynecology and reproductive sciences at the University of Pittsburgh School of Medicine, and MTN principal investigator. We have reached an important milestone in HIV prevention research, and these women deserve credit for the success of the study.

MRI and PET/CT improve cervical cancer patient's chances for optimal treatment

Wed, 04 Mar 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Pretreatment MRI and PET/CT for cervical cancer may direct more women to optimal therapy choices and spare many women potential long-term morbidity and complications of trimodality therapy (surgery followed by chemoradiation), according to a study performed at the Institute for Technology Assessment in Boston, MA.

An interdisciplinary team of investigators developed a decision-analytic model to determine the value of pretreatment imaging with MRI and/or PET/CT in patients with FIGO Stage IB cervical cancer. Stage IB cervical cancer, in the absence of pre-treatment imaging, is treated with surgery. As surgery cannot completely resect the cancer in many of these patients, they receive post-surgical chemoradiation, i.e. trimodality therapy, said Pari Pandharipande, MD, lead author of the study. The goal of pre-treatment imaging is to identify these patients noninvasively, spare them surgery and have them treated with chemoradiation alone, she said. Study results showed that while imaging does not improve survival, PET/CT resulted in the highest percentage of patients receiving correct primary therapy (89%) and use of both MRI and PET/CT spared the most patients of trimodality therapy (95%).

Pretreatment imaging can triage patients to optimal primary treatment choices that minimize the risk of long-term complications and morbidity while preserving chances for survival, said Dr. Pandharipande. Because both over- and underestimation of disease extent can result in adverse patient outcomes, determining the extent of disease accurately up front is critical. For example, when patients are subjected to pelvic surgery, and then are radiated in the same operative field, complication rates can increase by a substantial percentage, as compared to if they were simply treated with surgery alone or chemoradiation alone. Our study shows how pre-treatment imaging may improve chances of correctly receiving surgery or chemoradiation instead of both, said Dr. Pandharipande.

MRI and PET/CT are expensive, but long-term consequences of trimodality therapy can severely affect long-term quality of life and are also expensive. Further study of these long-term consequences is needed to more precisely consider the cost implications of upfront MRI and PET/CT, she said.

Currently there are no specific guidelines that prescribe MRI or PET/CT for determining a plan of action for the treatment of stage IB cervical cancer patients. It remains important for patients to make imaging and treatment decisions with their gynecologic-oncologist on a case-by-case basis, said Dr. Pandharipande.

My goal as a researcher in radiology is to continue to objectively look at what we do and how it impacts patient care. A better understanding of what happens to people after they receive imaging tests both improves patient care directly and focuses further research efforts in areas most influential to patient outcomes, she said.

New data show periodontal treatment doesn't reduce preterm birth risk

Thu, 29 Jan 2009 04:59:36 PST

( from http://www.rxpgnews.com ) The study, involving researchers from Duke University Medical Center and the University of North Carolina at Chapel Hill, is one of the largest randomized trials to date to look at the link between the two conditions.

Previous research had suggested that gum disease was associated with very preterm deliveries (defined as less than 32 weeks gestation). That led insurance policies and healthcare providers to recommend scaling and root planing, sometimes referred to as deep cleaning, in pregnant women. It was thought that such care had the potential to reduce preterm delivery risk.

These new findings, based on a randomized trial of 1,800 pregnant women with periodontal disease, indicate that routine gum treatments do not reduce the risk of early delivery.

I'm always asked whether we should mandate dental treatment for all pregnant women, said Amy Murtha, MD, director of obstetrics research at Duke University Medical Center in Durham, NC, who presented the findings at the annual meeting of the Society for Maternal-Fetal Medicine in San Diego. The biggest implication of this study is that this level of standard periodontal care will not affect the birth outcome.

That's not to say pregnant women should not get dental exams and treatment as needed; they should, Murtha added. Our study emphasizes that treating periodontal disease during pregnancy is safe, but that standard periodontal care is not enough.

Progression, or worsening of periodontal disease occurs in about 25 percent of pregnancies, said Steven Offenbacher, DDS, PhD, the study's lead investigator and director of the UNC-Chapel Hill School of Dentistry-based Center for Oral and Systemic Diseases. The bacterial infection attacks the teeth-supporting tissues below the gum line. Left untreated, it can lead to tooth loss as well as a host of other problems.

This study, conducted at Duke, the University of Alabama at Birmingham and the University of Texas at San Antonio, was overseen by the UNC-Chapel Hill School of Dentistry. Pregnant women with periodontal disease were randomly assigned to two groups: one received periodontal treatment before 23 weeks gestation; the other did not. Overall, no significant differences were reported regarding obstetric or neonatal outcomes when the two groups were compared.

Despite the findings, Murtha said much remains unknown about the relationship between the two conditions. Periodontal disease and poor pregnancy outcomes travel together, but we don't know why.

Nor do researchers understand how or why pregnancy appears to jumpstart the onset and progression of the disease. Murtha said it may be that preterm birth and periodontal disease share a common underlying trait, such as an exaggerated inflammatory response, but more studies are needed to fully explain the connection.

Additional research is also needed to determine whether more intensive periodontal care during pregnancy might make a difference. Although we did not reduce the risk of preterm births, the level of periodontal care provided in this study was not as effective as compared to earlier studies, Offenbacher said. It may be that a more aggressive approach to periodontal disease management could have a different outcome, he added.

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.

Testosterone perks up libido in post-menopausal women

Tue, 11 Nov 2008 14:52:19 PST

( from http://www.rxpgnews.com ) Washington, Nov 7 - Testosterone perks up libido in post-menopausal women, according to a new study.

The study of over 800 women from the US, Canada, Australia, Britain and Sweden is the first to show that testosterone administered by a skin patch can boost the sex drive of post-menopausal women.

Previous studies have shown testosterone treatment for low libido is beneficial for women undergoing oestrogen therapy. However, this study shows testosterone by itself could be a good alternative for women who do not want to take oestrogen, according to a Cedars-Sinai press release.

Cedars-Sinai Medical Centre experts co-authored the study that appeared in Thursday's edition of the New England Journal of Medicine.

A reversal of thinking: How women with lupus can increase chance for healthy pregnancies

Sat, 25 Oct 2008 03:59:37 PST

( from http://www.rxpgnews.com ) In the not so distant past, women with systemic lupus erythematosus (SLE), an autoimmune disease, were advised not to have children, and if they became pregnant, to have therapeutic abortions to prevent severe flares of their lupus. Research by rheumatologists at Hospital for Special Surgery in New York, in patients with lupus who have had successful pregnancies is yielding insights that support a reversal of that thinking.

The research effort, a multi-center research initiative lead by Jane Salmon, M.D., attending physician at Hospital for Special Surgery, is known as the PROMISSE (Predictors of pRegnancy Outcome: bioMarkers In antiphospholipid antibody Syndrome and Systemic lupus Erythematosus) Study.

Two research projects will be presented at this year's American College of Rheumatology meeting in San Francisco on October 24-29 by Dr. Salmon, based on data gathered from the PROMISSE Study. She and her collaborators identified factors that help a woman and her doctor plan for a healthy pregnancy.

Patients with lupus can live free of symptoms for long periods of time and then experience a disease flare, when symptoms such as a red rash across the nose and cheeks, painful or swollen joints, swollen legs or extreme fatigue suddenly appear. The first presentation will examine whether problems during pregnancy can be correlated to the severity, frequency and timing of disease flares. Dr. Salmon and her colleagues followed 198 pregnant patients with lupus. The investigators found that women who conceived while their disease was stable or only mildly active had relatively infrequent flares during their pregnancies and delivered healthy babies. This held true regardless of past disease severity or past kidney disease (a frequent consequence of lupus). The findings inform women with lupus on how to plan when to conceive to have a low risk pregnancy.

Lupus patients, as well as other patients with the antiphospholipid syndrome, produce special types of proteins called antiphospholipid antibodies that can attack their own tissues and cause pregnancy complications. The second study to be presented by Dr. Salmon showed that the presence of a specific subset of these autoantibodies is highly associated with poor pregnancy outcomes. Specifically, the researchers found that women who tested positive for an autoantibody called lupus anticoagulant were more likely to have complications such as miscarriage or preeclampsia during pregnancy.

These results can help doctors identify patients at high risk for complications by obtaining a blood test to determine if they are positive or negative for the lupus anticoagulant autoantibody. While women with lupus or the antiphospholipid syndrome who are positive for this protein can still have successful pregnancies, their doctors should monitor them more closely for early signs of pregnancy complications.

Based on our new data, we believe we are in a position to help doctors counsel and care for their patients, says Dr. Salmon, Collette Kean Research Chair and co-director, Mary Kirkland Center for Lupus Research at HSS. In the past, women were discouraged from becoming pregnant because of a very high risk to the mother and the baby. Our findings from the PROMISSE study show that women with lupus can have normal pregnancies when they work together with their doctors, beginning with the decision of when it is safe to conceive and continuing with close follow-up to anticipate potential problems.

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.

$4.8M NIH grant aids interstitial cystitis research

Fri, 26 Sep 2008 03:59:37 PST

( from http://www.rxpgnews.com ) University of Iowa researchers are ready to find the causes of interstitial cystitis, thanks to a five-year, $4.8 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health. The grant is the largest ever received by the University of Iowa Department of Urology.

Interstitial cystitis is a painful bladder condition that causes excessively frequent urination and associated pain. An estimated 1.3 million Americans have the condition, more than one million of them women, according to an NIH report published in 2007.

Some people with interstitial cystitis can't work because their symptoms are so severe. The condition has been difficult to treat because we don't know the causes, said the grant's principal investigator Karl Kreder, M.D., professor of urology at the University of Iowa Carver College of Medicine.

This NIH grant will allow us to explore inflammatory factors in the bladder and, as some recent evidence suggests, whether interstitial cystitis is a total body condition, said Kreder, who also is director of urodynamics, female and reconstructive urology in the Department of Urology at University of Iowa Hospitals and Clinics.

The funding makes the UI a Discovery Site for the NIH's Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network. In particular, the UI researchers will explore the roles of the pituitary gland and sympathetic nervous system in the inflammatory process. Kreder said the project involves five different, but interrelated, projects and will draw on the UI's Institute for Clinical and Translational Science.

One project, led by Susan Lutgendorf, Ph.D., professor of psychology in the UI College of Liberal Arts and Sciences, examines the hypothalamic pituitary-adrenal axis, which helps regulate temperature, the immune system, mood, sexuality, and energy, as well as reactions to stress and injury.

A second project examining brain pathways that may govern painful syndromes is led by Satish Rao, M.D., Ph.D., UI professor of internal medicine.

Catherine Bradley, M.D., UI associate professor of obstetrics and gynecology, leads a third project that is focused on the epidemiology of interstitial cystitis and categorizes it by pain mapping.

The research is rounded out by two basic sciences projects -- one to develop animal models that mimic the disorder, led by Yi Luo, Ph.D., UI assistant professor of urology, and one, led by Michael O'Donnell, M.D., UI professor of urology, that examines how certain bladder factors may predispose a person to interstitial cystitis.

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.

Chronic exposure to estradiol diminishes some cognitive functions

Sun, 03 Aug 2008 01:27:51 PST

( from http://www.rxpgnews.com ) University of Illinois researchers report this week that chronic exposure to estradiol, the main estrogen in the body, diminishes some cognitive functions. Rats exposed to a steady dose of estradiol were impaired on tasks involving working memory and response inhibition, the researchers found.

Their report appears this week in the journal Behavioral Neuroscience.

The researchers made the discovery when studying the effects of estradiol on activities mediated by the prefrontal cortex, a brain region that is vital to working memory and to the ability to plan, respond to changing conditions and moderate or control one's behavior.

Working memory is the ability to briefly remember information needed for a particular task, said Susan Schantz, a U. of I. professor of veterinary biosciences and principal investigator on the study. An example in humans is a phone number that is forgotten soon after the number is dialed.

"With working memory you're just keeping it active until you use it," she said.

In the new study, rats were trained to press one of two levers to obtain a food reward. Those that alternated between the levers (which were withdrawn from the rat enclosure for a few seconds between trials) received a reward. Those that hit the same lever twice in a row got no reward. Rats exposed to estradiol performed worse than their counterparts on this task, earning significantly fewer rewards.

A second set of tests measured the rats' ability to wait before responding to a stimulus. The rats had to wait 15 seconds before pushing a lever to get a reward. Those exposed to estradiol performed worse on this task than those that were not exposed.

"That's the test where we really saw the most striking effects with estradiol," Schantz said. The estradiol-treated rats "were not as good at waiting," she said.

"Rats treated with estradiol are definitely a lot more active and make a lot more lever presses," said neuroscience graduate student Victor Wang, the lead author on the study. "That's not conducive toward being rewarded."

The researchers had not expected to see such pronounced results. In fact, the study had been designed to give them baseline information for a separate inquiry into the effects of soybean estrogens on cognitive function. They planned to compare the effects of chronic estradiol exposure to the effects of chronic exposure to genistein, a phytoestrogen found in soybeans. Genistein is believed to have similar effects in the body as natural or synthetic estrogens, although no study has definitively proven that it does.

Schantz and her colleagues had focused on the prefrontal cortex because it is rich in estrogen receptor beta (ER-beta), a protein that spurs gene expression and other activities in the cell when it binds to estradiol. Genistein also activates ER-beta.

Some women take genistein supplements or eat soy-based foods to reduce hot flashes or other symptoms of menopause, Schantz said.

"Women take them thinking they'll be a safe alternative to hormone-replacement therapy and they might help hot flashes," she said.

Those who have heard that hormone replacement can improve cardiac or brain function also hope that eating soy or taking genistein supplements will have the same effects, she said.

The effects of hormone replacement therapy (HRT) are more complex – and problematic – than once thought. A recent large-scale study of HRT in post-menopausal women was stopped because of an increased risk of stroke and blood clots in women taking estrogen alone, and a higher than average incidence of breast cancer, cardiovascular disease, blood clots and stroke in women taking estrogen and progesterone.

Studies of estrogen's effects on cognition have also had mixed results. In earlier studies, for example, psychology professor Donna Korol, a collaborator on the current project, found that estradiol enhances some abilities, such as place or spatial learning, while hindering others, such as learning that relies on stimulus-response associations, considered by some to be akin to "habit" and not fluid thought.

Performance in these tasks involves brain structures outside the prefrontal cortex.

The research indicates that multiple factors influence the effects of estradiol on the brain, Schantz said. The timing of the exposure, the types of brain functions or structures studied and the age of the test subjects can all generate different results, she said.

Inheritance of hormonal disorder marked by excessive insulin in daughters

Mon, 28 Jul 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Elevated levels of insulin could be an early sign that girls whose mothers suffer from polycystic ovary syndrome -- or PCOS -- may also be susceptible to the disease, according to gynecologists who have found evidence of insulin resistance in young children.

The findings could help determine whether daughters of women suffering from PCOS are at a higher risk of developing the disease, compared to girls whose mothers do not have the disease.

Polycystic ovary syndrome is a common hormonal disorder that affects women of reproductive age, and sometimes causes inability to become pregnant. Symptoms include hairiness due to excessive amounts of male hormones, irregular periods, and insulin resistance.

We found insulin resistance in children who had entered puberty, and whose mothers had PCOS, said Richard Legro, M.D., professor of obstetrics and gynecology, Penn State College of Medicine and lead author. We did not find it in the youngest children, which suggests that the disease is triggered by puberty.

Legro and his colleagues were interested in finding out whether metabolic and reproductive abnormalities associated with the inheritable disease, are more likely to show up in children whose mothers have PCOS, and how parents could find out whether their child was at risk.

The researchers designed a study to compare 38 children -- boys and girls aged 4 to 14 -- whose mothers had PCOS with 32 children in a control group. They specifically looked for the early onset of androgen -- male hormones -- production, and production of excess insulin.

We collected samples of saliva and urine to analyze levels of insulin and sex steroids respectively, explained Legro. But we also looked for gonadotropins, hormones that stimulate sex steroids and provide the earliest sign of puberty.

Results from the test indicate that older girls, but not boys, of PCOS mothers had significantly higher concentrations of salivary insulin. Compared to the control group, the girls also had lower levels of urinary hormones.

According to Legro, the key finding of the study is that insulin levels appear to be elevated in daughters of PCOS mothers, which becomes more pronounced as they pass through puberty. Since the androgen levels were comparatively normal throughout puberty, and insulin resistance was only found in girls who had undergone puberty, Legro argues that insulin is the primary problem, while male hormones are a secondary problem.

Insulin is the real culprit in terms of stimulating the ovary, more so than gonadotropins, said Legro, whose findings appeared in a recent issue of

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!

Cancer incidence and mortality in young people decreases with increasing deprivation

Mon, 09 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) London, UK: Results of research into the associations between cancer and socio-economic deprivation and affluence have shown that, in contrast to cancers in older people, the numbers of new cases and deaths from the disease in teenagers and young adults (TYAs) decrease with increasing deprivation.

Professor Jillian Birch told Teenage Cancer Trust's Fifth International Conference on Teenage and Young Adult Cancer Medicine today (Monday) that research by her group also showed increases in the incidence of a number of cancers, including two potentially preventable cancers among younger people: cervical cancer and melanoma.

Prof Birch, Director of the Cancer Research UK Paediatric and Familial Cancer Research group, University of Manchester (UK), explained: Strong associations with socio-economic deprivation and affluence are seen for many diseases. Overall cancer incidence and mortality increase with increasing deprivation. However, different cancers and age groups show different patterns. Geographical variations in incidence, trends over time, and associations with deprivation and affluence can point to lifestyle or other environmental factors as possible causes. Until recently, very little was known about the detailed patterns of cancer in TYAs, but my group has carried out a series of studies to rectify this. The most recent studies have looked at geographical variations, time trends and associations with deprivation.

Results show that in contrast to cancers in older people, in TYAs incidence and mortality decreases with increasing deprivation. This is because the more common types of cancers that occur in young people are associated with affluence, including lymphomas, brain tumours, germ cell tumours and melanoma. These cancers also show significant regional variations in incidence and are increasing over time. However, carcinoma of the cervix, which is one of the more common cancers seen in young women, shows increasing rates with increasing deprivation and an upward trend in incidence over time.

Prof Birch's team showed that the incidence of cervical cancer in TYAs had increased by 1.6% per year during 1979-2003. However, national data show that across all ages, incidence is falling. We therefore analysed trends in 15-39 year olds to look at the changing pattern with age. We found that in 15-19 year olds, rates were increasing by 6.8% per year and by 1.4% per year in 20-24 year olds, but rates were decreasing among those aged 25 and over, she said.

Similar analyses for melanoma showed increasing rates at all ages but a greater rate of increase in 20-29 year olds than at older ages. In 20-24 year olds the annual percentage change was 4.1 and 4.0 in 25-29 year olds, but declined to 3.3 in 30-34 year olds and 2.5 in 35-39 year olds.

Overall, the research showed that cancer incidence rates between 1979-2001, varied from 173 per million person years (per mpyr) in the North East to 208 per mpyr in the South East and South West [1]. National rates have increased during this time period by 1.5% per year. For the whole period, melanoma incidence varied from 12 per mpyr in the East Midlands and London, to 20 per mpyr in the South West. Incidence of melanoma increased nationally by 3.8% per year but the trend was strikingly different in different regions. During 1979-1983 highest rates of around 15 per mpyr were seen in the South and West of England but the rates increased over time more rapidly in the North, so that during 1999-2003 highest rates of between 22 and 32 per mpyr were seen in Northern regions.

Prof Birch said: It is important that public health messages about these two mainly preventable cancers are targeted appropriately. For other TYA cancers, the results of our analyses provide a basis for designing studies to look at possible causes.

Simon Davies, CEO at Teenage Cancer Trust said: It is worrying that cervical cancer and melanoma, two preventable cancers, are increasing in teenagers faster than in other groups. More education is desperately needed so young people can change their behaviour before it's too late. This is why Teenage Cancer Trust funds an education programme for teenagers and young adults throughout schools and colleges in the UK. We are targeting hundreds of thousands of teenagers this summer in our sun safety campaign, fronted by Leona Lewis.

Prenatal biochemical screening only detects half of chromosomal abnormalities

Sun, 01 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Barcelona, Spain: Prenatal biochemical screening tests are widely used to look for chromosomal abnormalities in the fetus which can lead to serious handicap, or even death during gestation or in the first few days after birth. But these tests are only able to detect fewer than half of the total chromosomal abnormalities in the fetus, a scientist will tell the annual conference of the European Society of Human Genetics tomorrow (Monday 2 June) Dr. Francesca R. Grati, of the TOMA Laboratory, Busto Arsizio, Italy, says that these findings mean that women should be better informed on the limitations of such diagnostic tests.

The researchers studied 115,576 prenatal diagnoses carried out during the last fourteen years. 84,847 were amniocenteses, usually carried out around the 16th week of pregnancy, and 30,729 chorionic villus samplings, which can be undertaken from 12 weeks into the pregnancy. Both these tests carry an increased risk of miscarriage, so the decision on whether or not to undertake them can be difficult to weigh up. Since our sample included a large number of women aged less than 35 who underwent invasive prenatal diagnosis without any pathological indication to do so, we felt that the results could be useful in helping to inform pre-test counselling of such women, says Dr. Grati. Up until now, the information we had came from smaller studies which only looked at the performance of these tests in detecting a limited number of chromosomal abnormalities.

After analysing the results of the chromosomal abnormalities from their own dataset, the researchers combined them with the official detection rates for these abnormalities published by SURUSS and FASTER consortia. These are multi-centre research groups involved in the investigation of screening and diagnostic tests performed in pregnancy, whose results are being used to optimise prenatal care for pregnant patients. They found that current screening procedures were only able to detect half the total chromosomal abnormalities in women both younger and older than 35.

The TOMA laboratory is particularly suited to carry out this kind of research, says Dr. Grati, because it was among the first in the world to deal with prenatal diagnosis, and has a vast number of prenatal diagnostic samples at its disposal.

Current tests do not detect all fetal chromosomal abnormalities, but only trisomies 21 (Down syndrome), 18 (Edward's syndrome), and 13 (Patau syndrome), monosomy X (Turner syndrome), and triploids (conceptuses with 69 chromosomes instead of 46). These are common vital chromosomal abnormalities, but there are many others which are not picked up by these tests, says Dr. Grati. And the tests do not even detect 100% of the common abnormalities.

At conception, 23 chromosomes from each parent combine to create a fetus with 46 chromosomes in all its cells. Trisomy occurs when the fetus has one additional chromosome (47 instead 46). The extra genetic material from the additional chromosome causes a range of problems of varying severity.

In Down syndrome, for example, where the fetus has three copies of chromosome 21, babies are usually born with impaired cognitive ability and physical growth, cardiac defects and a characteristic facial appearance. Unlike many other such abnormalities, however, babies born with Down syndrome are able to lead relatively normal lives and their life expectancy is around 50 years.

Other than trisomy, the fetus can also have the loss of genetic material (deletions) or chromosomal abnormalities in a non-homogeneous form, where there is a mixture of two cell lines, one normal and the other abnormal. Some of these disorders are relatively common in the fetus, which may have as much chance of surviving as children who are born with Down syndrome, and it is worrying that current biochemical tests are not always able to detect them says Dr. Grati. Our research confirms that it is fundamental for doctors to counsel patients about the limitations of current screening methods, so that they can make an informed decision on whether or not to undergo invasive diagnostic testing.

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.

Hormone replacement therapy linked to cancer recurrence

Wed, 26 Mar 2008 10:31:44 PST

( from http://www.rxpgnews.com ) London, March 26 - Hormone replacement therapy - for pre and post menopausal women increases the chances of recurrence in breast cancer survivors, according to a study.

Previous studies have shown that HRT increases the incidence of breast cancer in healthy women, but its impact on survivors had remained obscure. Other studies had suggested that HRT had no effect or even might reduce recurrence.

However, a two-year follow-up trial has indicated that survivors taking HRT were more likely to suffer disease recurrence than those who did not take HRT.

Lars Holmberg of King's College, London, and his colleagues examined the breast cancer rates in the trial after a median follow-up of four years.

The study found that 39 out of the 221 women in the HRT treatment arm had developed breast cancer recurrence or a new breast cancer malignancy, compared with 17 of 221 women in the control arm.

Findings of the study have been published in the latest issue of the journal of the National Cancer Institute.

The estimated five-year cumulative rate for disease recurrence was 22.2 percent for the HRT arm and 9.5 percent in the control arm, for an absolute increase in risk of 14.2 percent.

'The results of the trial indicate a substantial risk for a new breast cancer event among survivors using HRT.

'The risk elevation is in line with the evidence from observational studies and randomised trials that - increases the risk of breast cancer in healthy women,' said the authors.

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.

Oregon study raises questions on synthetic progestins

Sun, 09 Mar 2008 04:59:37 PST

( from http://www.rxpgnews.com ) The widely used synthetic progestin medroxyprogesterone acetate (MPA) decreased endothelial function in premenopausal women in a study done at the University of Oregon. The finding, researchers said, raises concerns about long-term effects of MPA and possibly other synthetic hormones on vascular health in young women.

The vascular endothelium lines the inside of blood vessels. In recent years, it has been found to be a dynamic organ that serves an important role in the prevention of atherosclerosis.

The logical conclusion of this study is that over a long period of time it would not be good to have exposure to an agent that is reducing blood vessel flexibility, because it could be associated with the development of heart disease or related problems, said co-author Dr. Paul F. Kaplan, a long-time Eugene gynecologist and senior researcher in the UO's human physiology department. He stressed, however, that a longer, larger study is needed.

MPA is the progestin that was used in the Women's Health Initiative (WHI), including a clinical study on hormone-replacement therapy halted because of health concerns in postmenopausal women. MPA is the active ingredient of Provera, which is used to treat abnormal uterine bleeding, induce menstrual cycles and relieve symptoms of the menopause.

It's also a component in Depo/Provera, an injectible long-lasting contraceptive used by many young women. Millions of women use various hormone therapies with a variety of progestin types for contraception. In the U.S. alone, 80 percent of women have used oral contraceptives.

The UO study, appearing online ahead of regular publication by the journal Heart and Circulatory Physiology, is among the first to focus on the impact of MPA in premenopausal women. Fourteen women, 19-27 years old, took part in the study after passing thorough medical exams to screen out numerous health conditions.

The five-member UO team -- led by Jessica R. Meendering, a former UO doctoral student now a professor of exercise science at the University of Nebraska in Omaha -- studied the effects of the sex hormone estradiol by itself and in combination with MPA on endothelial function of the brachial artery. The health of the endothelium in this artery has been shown to be a telling proxy for the coronary arteries and a good predictor of cardiovascular risk.

When researchers gave an oral version of MPA to determine its impact, they found that it wiped out the positive effects on endothelial function that estradiol had provided. MPA reduced the function by reducing the brachial artery's ability to dilate -- grow bigger in diameter -- in response to the stress of changing blood flow, Kaplan said.

UO researchers also found that MPA had an effect on concentrations of endothelin-1, a peptide that promotes cell division and serves as a mediator of inflammation. It also acts as a constricting factor for blood vessels. When peptide levels rise, endothelin-1 is suspected to play a key role in many diseases of the airways, pulmonary circulation, inflammatory lung diseases and vasoconstriction of blood vessels. UO researchers saw levels decline with estradiol alone, but increase substantially with the addition of MPA, negating the benefits of the estrogen.

There is an overwhelming amount of evidence to suggest that estrogen is beneficial to arterial vascular health of women, Meendering said. Since the WHI found either no benefit or a slight increase in adverse cardiovascular events in postmenopausal women taking combination hormone-replacement therapy containing estrogen and MPA, many have questioned the vascular effects MPA and its use in postmenopausal women. This led our group to question how MPA affects the vasculature in young women.

We need to be taking the time to find out if different synthetic hormones have different effects on vascular health in young women, she said. It's not a big health concern right now, because there are no obvious short-term effects raising health concerns. But we don't know how these synthetic hormones taken by young women affect their long-term cardiovascular health. Maybe effects aren't being noticed while women are young, but maybe they are adding to the fact that rates of cardiovascular disease are so high in women.

Kaplan stressed that this project was a starting point of major basic science research, so this study does not say women should change what they are doing.

We can say that we saw vascular changes in the arteries of the arm that have been shown in previous studies involving coronary arteries, he added. This study does let us say that whatever changes we are seeing are important not just for the arm but probably for most of the major arteries in the body, and this is important for cardiac disease.

WHI follow-up study: Risks of long-term hormone therapy continue to outweigh benefits

Tue, 04 Mar 2008 04:59:37 PST

( from http://www.rxpgnews.com ) New results from the Women's Health Initiative (WHI) confirm that the health risks of long-term use of combination (estrogen plus progestin) hormone therapy in healthy, postmenopausal women persist even a few years after stopping the drugs and clearly outweigh the benefits. Researchers report that about three years after women stopped taking combination hormone therapy, many of the health effects of hormones such as increased risk of heart disease are diminished, but overall risks, including risks of stroke, blood clots, and cancer, remain high. The WHI is sponsored by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH).

Results of the WHI three-year follow-up study of the estrogen-plus-progestin clinical trial are published in the March 5, 2008, issue of the Journal of the American Medical Association.

The good news is that after women stop taking combination hormone therapy, their risk of heart disease appears to decrease, noted Elizabeth G. Nabel, M.D., NHLBI director. However, these findings also indicate that women who take estrogen plus progestin continue to be at increased risk of breast cancer, even years after stopping therapy. Today's report confirms the study's primary conclusion that combination hormone therapy should not be used to prevent disease in healthy, postmenopausal women.

The FDA recommends that hormone therapy never be used to prevent heart disease, and, when hormone therapy is used for menopausal symptoms, it should only be taken at the smallest dose and for the shortest time possible.

The new findings are from a follow-up study of 15,730 postmenopausal women with an intact uterus, ages 50 to 79 years (average age of 63) at enrollment, who participated in the WHI estrogen-plus-progestin clinical trial. Participants were randomly assigned to receive a combination of estrogen (0.625 milligrams of conjugated equine estrogens per day) plus progestin (2.5 mg of medroxyprogesterone acetate) or placebo (inactive pill). The main estrogen-plus-progestin study was stopped in 2002 after an average of 5.6 years of treatment due to an increase in breast cancer. Women on combination hormone therapy were also at increased risk of stroke, blood clots, and heart disease, while their risk of colorectal cancer and hip fractures was lower, compared to women who did not take hormone therapy.

The follow-up study began in July 2002 after women in the study were instructed to stop taking combination hormone therapy, and continued through March 2005, with participants followed for an average of 2.4 years. All study participants were examined at least once a year by a WHI clinician and received an annual breast examination and mammogram, with biopsies performed as needed. During the follow-up study, the numbers of heart attacks, strokes, and blood clots were not significantly different between the two groups (overall, 343 cardiovascular events among those who initially received hormone therapy versus 323 among those who did not). In addition, the number of deaths was not significantly different (233 women who had been in the hormone therapy group died, versus 196 women who had been in the placebo group).

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.

Women aren't men

Mon, 19 Nov 2007 04:59:37 PST

( from http://www.rxpgnews.com ) CHICAGO --- Women's bodies and medical needs are vastly different than men's way beyond their reproductive systems. Women wake sooner from anesthesia, have less familiar symptoms of cardiovascular disease and are more likely to suffer from depression and sleep problems-- just to name a few of the differences.

Yet, there's a cavernous void in research based on sex and gender. Historically, most studies have been done on men and the findings applied to women.

Northwestern University's Feinberg School of Medicine has launched the Institute for Women's Health Research to spur much needed research on health issues that affect women throughout their lifespan. Some topics on the ambitious research agenda: cancer, autoimmune disease, anesthesia, cardiovascular disease, depression, sleeping disorders, osteoporosis, osteoarthritis and menopause.

Another mission of the institute will be to create an Illinois Women's Health Registry to provide a large pool of potential study subjects for researchers, who often have trouble recruiting enough participants for their studies. Scientists at the institute also will identify gender-based guidelines for the treatment and prevention of disease in women. For example, do women need a differently designed knee joint than men in replacement surgery or do women need to be given anesthesia differently The institute will link physicians to these guidelines as they are developed.

We should look at every research study with a sex and gender lens and see what applies to women as opposed to men, said Teresa Woodruff, executive director of the new Institute for Women's Health Research and the Thomas J. Watkins Professor of Obstetrics and Gynecology at the Feinberg School. What are the differences between women and men that need further exploration What does gender mean in development of disease throughout the lifespan What is the influence of hormones We have many questions, but we don't have concrete answers.

Our goal is to deepen the medical and research community's understanding of women's health, Woodruff added. The knowledge we gain through fundamental research will be translated into improved sex and gender-specific clinical care.

Vivian Pinn, M.D., director of the Office of Research on Women's Health for the National Institutes of Health, came to Chicago to speak at the recent inauguration of the Institute for Women's Health Research.

It's rare to see this kind of commitment to research in women's health. I can count the institutions on my fingers, Pinn said. The issues Northwestern is working on will hopefully unlock the answers for many of these health issues. The results will have implications for the health of women worldwide. To improve women's health care, it's important to generate new knowledge.

To produce that knowledge, Woodruff is reaching out to researchers at the university and its clinical affiliates with grants to encourage them to incorporate gender differences into their studies. We are trying to instill the premise that biological sex matters in everybody's thought processes, she said, noting many scientists have never considered gender in their research.

One such physician was Melina Kibbe, M.D., assistant professor of surgery at the Feinberg School and a vascular surgeon at Northwestern Memorial Hospital and the Jesse Brown VA Medical Center. Kibbe researches how to extend the effectiveness of such vascular procedures as balloon angioplasty and stenting, bypass grafting and other vascular procedures with limited durability.

Kibbe wasn't doing any gender-based research until Woodruff met with her a few months ago and asked if she would include a cohort of women in her research. Thus, Kibbe began a new study with funding from the new institute to see whether her therapy -- which extends the effectiveness of the vascular procedures with nitric oxide-- produced different results in male and female animals. To her surprise, preliminary findings showed it did.

Kibbe's early results reveal male animals respond better to the nitric-oxide-based therapy better than females. If we actually see gender differences in our therapy when the study is complete, it may mean that we have to tailor our therapy so that it could be equally effective in both genders, she said. This could lead me down a whole new research path.

In cardiovascular therapies, gender research is in its infancy, Kibbe noted. Right now very few investigators are looking at the differences between men and women with respect to these cardiovascular therapies, she said.

A common obstacle for most researchers is recruiting enough participants for their studies. To address this challenge, the institute will develop the Illinois Women's Health Registry to provide a vast pool of potential study subjects with diverse backgrounds. This registry will be a critical tool for researchers who don't necessarily have the staff or the marketing skills to go out and recruit people.

The registry will tap the 12,000 women who come through Prentice Women's Hospital each year as well as the community at large, so all women will have an opportunity to participate. Woodruff hopes this registry will encourage researchers to do more gender studies.

One reason researchers have shied away from using women in studies is their fluctuating hormones. Hormones are complex, but they can be taught, Woodruff said.

Mice help researchers understand chlamydia

Mon, 29 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Genetically engineered mice may hold the key to helping scientists from Queensland University of Technology and Harvard hasten the development of a vaccine to protect adolescent girls against the most common sexually transmitted disease, Chlamydia.

Dr Michael Starnbach from Harvard Medical School is in Australia to work with QUT on a joint research project using a mouse model to study how the immune system responds to infections such as Chlamydia.

Ultimately the idea is to understand enough about how Chlamydia interacts with cells and how the immune system responds to those infected cells, to be able to understand which components of the immune system need to be stimulated to fight the Chlamydia infection, Dr Starnbach said.

At Harvard we have been working on the basic biology of how the immune fighter cells known as T-cells respond to infection.

When a person is infected with Chlamydia, the organism enters into the outermost cells of the genital tract and stays there and replicates within those cells.

Once they're hidden within the cells, only the T-cells can recognise that the cells are infected.

T-cells are able to recognise cells that are infected and destroy those cells, ultimately eliminating the organism from the body.

Dr Starnbach said the mouse model being developed by QUT and Harvard would see mice genetically engineered with T-cells that were specifically directed to protect against the mouse strain of Chlamydia.

In doing this we will be able to learn things about what is involved in protecting mice against Chlamydia infection and then mimic those responses with vaccines, he said.

Professor Peter Timms along with Professor Ken Beagley, from QUT's Institute of Health and Biomedical Innovation, are heading a QUT research team working with Dr Starnbach.

QUT has already identified certain proteins that may be able to be incorporated into vaccines to protect against Chlamydia infection, Professor Timms said.

We've been testing these proteins and, by working with Harvard, we hope to build on this research.

Professor Timms said, with rates of Chlamydia infection in some Australian communities as high as 12 per cent of the female population, there was a real need to develop a vaccine.

Chlamydia is the most common sexually transmitted disease in the world and results in infertility in women and long-term chronic pelvic pain, he said.

There are antibiotics to treat Chlamydia, but there's no vaccine to prevent it. In many cases women don't know they are infected because there are not really any physical signs or symptoms, so by and large they don't get treatment.

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.

MacArthur commits $11 million to further UCSF work in maternal safety

Fri, 19 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The John D. and Catherine T. MacArthur Foundation has promised $10.75 million to extend a ground-breaking UCSF project to help combat maternal mortality in Nigeria and India � two countries that comprise one-third of all maternal deaths worldwide.

MacArthur Foundation President Jonathan Fanton announced the grant today in London at the Women Deliver conference.

The funding will go to the nongovernmental organization Pathfinder International, which will use the grant to implement a spectrum of interventions developed and tested by UCSF researchers to treat women suffering from post-partum hemorrhaging. UCSF will continue to advise the group on the roll-out, including development of a plan for monitoring and evaluating the project�s outcomes.

The centerpiece of the program is the non-pneumatic anti-shock garment, or NASG, a low-cost and reusable body suit made of lightweight neoprene that was originally designed for battlefield use. When the suit's five Velcro closures are tightened around the patient's body, the compression stops blood from flowing to the lower extremities and forces it back to the heart, lungs, and brain to counteract shock.

The suit has now been shown to effectively stem hemorrhaging after childbirth, according to Suellen Miller, CNM, PhD, who proposed the garment�s use as a maternal life-saver and pilot-tested the project in Egypt over the past four years with Egyptian colleagues Mohammed Mourad Yousiff, MD, from El Galaa Maternity Hospital, in Cairo; and Mohamed Fathalla, MD, from the Assiut Teaching Hospital, in Assiut.

�It is tremendously gratifying to see this work being expanded by Pathfinder,� said Miller, an associate professor in the UCSF Department of Obstetrics, Gynecology and Reproductive Services and director of the Safe Motherhood Programs of the UCSF Women�s Global Health Imperative.

�Hundreds of thousands of new mothers die needlessly every year due to hemorrhaging, simply because they don�t have access to a hospital,� she said. �This simple garment appears extremely promising in pilot studies and could potentially have a huge impact on the lives of both the women and their families.�

In the pilot study, 158 obstetrical hemorrhage patients underwent standard hemorrhage treatment and 206 patients with obstetrical hemorrhaging underwent standard treatment plus the anti-shock garment.

Study results showed a 50 percent decrease in blood loss among women treated with the garment, which is statistically significant, Miller said. Pilot results, which were published in the April 2006 issue of the �British Journal of Obstetrics and Gynecology,� showed a 69 percent decrease in death and severe illness.

�In our research, women who appeared clinically dead, with no blood pressure and no palpable pulse, were resuscitated and kept alive for up to two days until they could be transported to a hospital,� said Miller.

The World Health Organization estimates that 529,000 women died in pregnancy or childbirth in the year 2000. More than 99 percent of these deaths occurred in developing countries, where Miller said the majority of women give birth at home, with poorly trained or untrained attendants. Of the risks, postpartum hemorrhage is the most common cause of maternal mortality, accounting for approximately 25-30 percent of all maternal deaths.

Pathfinder will use the MacArthur grant to introduce a package of low-tech interventions at several hundred health facilities in seven Indian states and eight states in Nigeria. Those interventions, called the Continuum of Care for PPH (post partum hemorrhage), were developed by Miller and Stacie Geller, PhD, an associate professor at the University of Illinois College of Medicine.

The package of interventions includes the anti-shock garment, a uterus-contracting drug to prevent bleeding, a calibrated blood collection drape to diagnose postpartum hemorrhage, and a community-developed communication and transportation plan to get patients to a health facility for assessment and emergency obstetrical treatment.

�It is important to address postpartum hemorrhage wherever there is the potential for it to occur, from the community up through the health system,� said Dan Pellegrom, president of Pathfinder International. �Prevention and management starts in homes and communities, so it is important to cultivate informed and engaged communities that are aware of the danger signs of hemorrhaging and can transport women to skilled service providers.�

The current funding builds upon nearly $2 million in previous MacArthur grants to UCSF for preliminary pilot studies of the anti-shock garment in Egypt, Mexico and Nigeria. Fanton, from MacArthur, said the introduction of the garment on a large-scale could help save hundreds of thousands of lives and help strengthen national health care systems.

�No other major cause of maternal death can be prevented as easily as postpartum hemorrhage,� Fanton said. �Our hope is that the anti-shock garment will eventually become part of a standard package of care for postpartum hemorrhage in developing countries.�

Miller and her team will continue a rigorous NIH funded randomized cluster trial of the garment in Zambia and Zimbabwe.

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.

Media availability: low-fat dietary pattern may lower risk of ovarian cancer

Tue, 09 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A diet low in fat could reduce the risk of ovarian cancer in healthy postmenopausal women, according to new results from the Women�s Health Initiative (WHI) Dietary Modification Trial. Researchers found that after four years, women who decreased the amount of dietary fat they consumed were 40 percent less likely to develop ovarian cancer than women who followed normal dietary patterns. As expected, no effect was found during the first four years because preventive benefits on cancer often take many years to develop. Ovarian cancer affects about 1 in 60 U.S. women in their lifetimes and has the highest mortality of all cancers of the female reproductive system.

Low-Fat Dietary Pattern and Invasive Cancer Incidence: Further Results from the Women�s Health Initiative Dietary Modification Trial, is published online October 9 by the Journal of the National Cancer Institute. The WHI Dietary Modification Trial was conducted in 40 clinical centers throughout the United States and is funded by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health.

The WHI Dietary Modification clinical trial followed 48,835 healthy, postmenopausal women for an average of 8.1 years to test whether a low-fat diet would reduce the risk of cancer and cardiovascular disease. Nearly 20,000 women in the intervention group were counseled to decrease fat intake to 20 percent of calories and to replace calories from fat with calories from vegetables, fruits, and grains. The control group (nearly 30,000 women) received diet-related education materials only.

Women in both groups started with average consumption of more than 35 percent of calories from fat when they joined the study. By the end of the first year, the low-fat diet group reduced average total fat intakes to 24 percent of calories from fat, about 11 percent less than the women in the usual diet group. By the end of the study, women in the low-fat diet group averaged 29 percent calories from fat, compared to 37 percent calories from fat in the usual diet group. The low-fat diet group also increased their consumption of vegetables, fruits, and grains.

Researchers found that women who started with the highest fat intake and who reduced their fat intake the most during the study lowered their risk of ovarian cancer the most. In addition, although no effect on rates of endometrial cancer were found, the new results suggest a small reduction in overall risk of cancer among the women who ate less fat, but this finding was not statistically significant.

In the study's primary findings published in the February 8, 2006, issue of the Journal of the American Medical Association, women in the low-fat diet group had a tendency toward reduced risk of breast cancer, heart disease, and stroke, and no reduction in risk of colorectal cancer. The overall 9 percent reduction in breast cancer was not statistically significant; however, like the results for ovarian cancer, the study found that women who started with the highest fat intake lowered their risk of breast cancer more markedly.

The WHI is the most comprehensive study to date of the causes and prevention of the major diseases affecting the health of older women. Over 15 years, the study�s findings on heart disease, breast and colorectal cancer, and osteoporosis have stimulated many changes in clinical practice. The WHI is also one of the largest studies of its kind ever undertaken in the United States and is considered a model for future studies of women�s health.

This study of low-fat dietary pattern is one of the three randomized clinical trials that make up the WHI. The others included trials of hormone therapy (estrogen plus progestin and estrogen alone). Both trials were stopped early because of increased risk of diseases like stroke, blood clots, and breast cancer, and because the hormones failed to reduce risk of heart disease. The third clinical trial studied the effects of calcium and Vitamin D supplementation on osteoporosis-related bone fractures and on colorectal cancer. As reported in February 2006, the study found that calcium and vitamin D supplements provide a modest benefit in preserving bone mass and prevent hip fractures in certain groups of healthy postmenopausal women, especially those over age 60, but do not prevent other types of fractures or colorectal cancer.

David Grimes, FHI physician, inducted into Institute of Medicine

Mon, 08 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Research Triangle Park, NC -- David Grimes, MD, of Family Health International (FHI) was publicly welcomed into the National Academy of Sciences� prestigious Institute of Medicine (IOM) today. Dr. Grimes is the second IOM member from FHI.

The Washington-based IOM is a nonprofit component of the National Academy of Sciences that works outside the framework of government to provide unbiased, evidence-based, and authoritative information and advice about health and science policy. Each year, 65 individuals are inducted into the IOM, which has about 1,700 members.

�We are so fortunate to have someone with David�s world class talents working with us at FHI,� said Willard Cates, Jr., MD, MPH, president of research for the organization and FHI�s other IOM member. �I have been privileged to work alongside David for more than three decades. He represents the essential core values of excellence, integrity, and passion for providing reproductive health services to women in the most resource-poor areas. David has inspired and mentored generations of colleagues at the US Centers for Disease Control and Prevention, four medical schools, and now FHI.�

Dr. Grimes has been a leader in developing the field of evidence-based medicine, which involves systematically searching for the best available evidence to answer clinical questions. Through his leadership, FHI has led more than half of the literature reviews on fertility regulation published in the Cochrane Library (an international effort to identify, analyze, and disseminate findings from the world�s most rigorous clinical trials). These reviews focus on the safety and effectiveness of different methods of family planning and serve as the foundation for the World Health Organization�s international guidelines on contraceptive use.

An inspiring role model, Dr. Grimes has won numerous awards for training medical students and residents to make clinical decisions based on scientific evidence. Beginning in 2002, he also coauthored with FHI�s Kenneth Schulz, PhD, MBA, a popular series of articles on research methodology in The Lancet, with the goal of preparing clinicians to read the medical literature more critically.

Before joining FHI in 1988, Dr. Grimes worked as an epidemiologist for nine years at the U.S. Centers for Disease Control and Prevention, and was on the faculty at three medical schools. Currently, he serves on the faculty of the Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, where he received his medical degree. He is one of a small number of physicians in the United States who are board certified in both obstetrics/gynecology and preventive medicine.

Dr. Grimes was inducted with other class members into the IOM during the institute�s 37th annual meeting, held today in the historic National Academy of Sciences Building in Washington. He received his certificate of membership and was personally welcomed into the institute by current IOM President Dr. Harvey V. Fineberg during a private ceremony last night.

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.

Mutation of the COX2 gene can double or treble a woman's risk of ovarian cancer

Tue, 25 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Barcelona, Spain: Researchers in Portugal have discovered that a specific mutation of the COX2 gene seems to play a role in the onset of ovarian cancer, increasing women�s susceptibility to developing the disease.

The discovery raises the possibility that, if the findings are confirmed by further studies, it might be possible to use non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, which are used already for other conditions, to prevent ovarian cancer developing in women with the COX2 mutation.

Dr Ana Carina Pereira told the European Cancer Conference (ECCO 14) in Barcelona, today (Tuesday) that the COX2 gene is responsible for the production of the enzyme COX-2, which plays a crucial role in prostaglandins production; prostaglandins cause inflammation, pain and fever, as well as mediating a wide range of other physiological processes. �Although the causes of ovarian cancer are not fully understood yet, inflammation is known to play an important role in the onset of both ovarian and invasive cervical cancer,� she said. �COX-2 has an important role in the inflammatory process, as well as in key steps in tumour development.�

Dr Pereira, who is a junior scientist in the molecular oncology group at the Portuguese Institute of Oncology, Oporto, Portugal, said that one mutation, the -765G>C COX2 polymorphism, had been associated with the development of a number of diseases such as cancers of the stomach, oesophagus and prostate, and asthma, heart attacks and stroke. So she and her colleagues decided to investigate the role it played in ovarian and invasive cervical cancer.

They analysed the DNA in blood samples from 727 women; 150 had ovarian cancer, 351 had cervical lesions, including 291 with cervical cancer, and the remaining 226 women had no cancer and were the control group.

Although they found no evidence that the -765G>C COX2 polymorphism played a role in cervical cancer, they found that particular versions of it doubled the risk of developing ovarian cancer and, in women aged 53 or younger, it trebled the risk.

Dr Pereira looked at the distribution and frequency of three different types (genotypes) of the -765G>C COX2 polymorphism: the GG, GC and CC genotypes. An individual genotype is composed of two distinct parts, the inherited sequences from the maternal and paternal genomes. Therefore, for every genotype, there are two copies of the sequence and these copies are called alleles. Alleles may be identical or different.

Dr Pereira explained: �The C and G are alleles that can be inherited, one from each parent. As everyone carries two alleles, their genotypes could be a CC, GC or GG genotype. The G allele is the most common, while the CC genotype is rare; therefore, it is usual to pool the GC and CC genotypes together and we call people with these genotypes C allele carriers.

�Our results demonstrated that C allele carriers had a nearly two-fold (1.8) increased risk of developing ovarian cancer. This was even more evident when we stratified our analysis into two groups based on the average age of the patients; the women aged 53 or under had a nearly three-fold (2.8) increased risk of developing ovarian cancer.�

She said the polymorphism could enhance the expression of the COX2 gene, thereby inhibiting apoptosis (programmed cell death) and promoting tumour proliferation, metastasis and angiogenesis (the formation of new blood vessels needed to supply a growing tumour). The reason why the same effect was not observed in cervical cancer was probably due to the different causes of the two cancers.

�The biological mechanism involved in the carcinogenesis of different organs is not always similar. In the case of cervical cancer we know that the trigger mechanism is an oncogenic virus, HPV (human papillomavirus) and that in ovarian cancer, although not as clearly understood, inflammation and hormonal regulation are credited with playing a role in its development.�

She continued: �Although our findings are very interesting and this polymorphism seems to play an important role in cancer development, these are only preliminary results which need to be confirmed with more complete studies, nor only in the Portuguese population but also in other populations.

�The interesting clue from these results is the importance of this COX-2 enzyme and the therapeutic drugs that may inhibit its activity (such as aspirin and other NSAIDs). Former studies involving NSAIDs and risk for ovarian cancer were not strongly conclusive because the individual variability in the response to preventive drugs was not taken into account. Now we need studies that will confirm whether giving NSAIDs to women with this polymorphism might be of value in both preventing and treating ovarian cancer.

�Identifying the molecular epidemiologic profile of individuals may open new windows for the development of preventive strategies and for the individualisation of therapies for patients. It would be possible to anticipate the patient�s response to therapy, increasing treatment efficacy and decreasing the incidence of adverse reactions to drugs.�

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.

'Fruity vegetables' and fish reduce asthma and allergies

Tue, 11 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Giving children a diet rich in fish and �fruity vegetables� can reduce asthma and allergies, according to a seven-year study of 460 Spanish children, published in the September issue of Pediatric Allergy and Immunology.

The findings also reinforce the researchers� earlier findings that a fish-rich diet in pregnancy can help to protect children from asthma and allergies.

�We believe that this is the first study that has assessed the impact of a child�s diet on asthma and allergies and also taken into account the food their mother ate during pregnancy� says lead author Dr Leda Chatzi from the Department of Social Medicine at the University of Crete, Greece.

�Because we studied the children from pregnancy to childhood, we were able to include a wide range of elements in our analysis, including maternal diet during pregnancy, breastfeeding, smoking, the mother�s health history, parental education and social class.�

Researchers followed the progress of the children, on the Spanish island of Menorca, at regular intervals from before they were born until they were six-and-a-half.

They discovered that children who consumed more than 40 grams of �fruity vegetables� a day � namely tomatoes, eggplants (aubergines), cucumber, green beans and zucchini (courgettes) - were much less likely to suffer from childhood asthma.

And children who consumed more than 60 grams of fish a day also suffered less childhood allergies, echoing the protective effects they experienced when their mothers ate fish during pregnancy.

However the researchers noted that the dietary effects were quite specific and that other fruits and vegetables examined did not provide the same protective effect. Nor did other food groups included in the study, such as dairy products, meat, poultry and bread.

The mothers of 232 boys and 228 girls, who had been recruited during antenatal classes, completed detailed questionnaires on their children�s health, weight, diet and any breathing problems every year until their child was six-and-a-half.

90 per cent of the children also underwent allergy testing � skin prick tests were used to check their response to the six most common allergens, including grass pollen and cats.

The researchers found that just under nine per cent of the children suffered from some degree of wheezing, including six per cent with an allergy-related wheeze. And 17 per cent reacted to at least one of the allergens in the skin prick test.

�After adjusting the results for a wide range of variables, we concluded that the link between symptom-free children and a diet rich in fruity vegetables and fish was statistically significant� says Dr Chatzi.

�The biological mechanisms that underlie the protective affect of these foods is not fully understood, but we believe that the fruity vegetables and fish reduce the inflammation associated with asthma and allergies.

�The interesting thing about this study is that it followed a large number of children from the womb to the age of six-and-a-half and incorporated a wide range of dietary, social and health factors� says the Journal�s Editor, Professor John Warner, Head of the Department of Paediatrics at Imperial College London.

�It provides parents with specific advice about the health promotion benefits of including fish and fruity vegetables as part of a balanced diet for both their children and the rest of the family.�

Common misdiagnosis: most women believe they have a yeast infection when they don't

Mon, 10 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) ST. LOUIS -- Most women who think they have a vaginal yeast infection are wrong and may be doing more harm than good in treating their problem, says a Saint Louis University researcher who presented her findings recently.

�Everything that itches isn�t a yeast infection,� said Susan Hoffstetter, Ph.D., assistant professor of obstetrics, gynecology and women�s health at Saint Louis University School of Medicine and a SLUCare women�s health nurse practitioner.

�People keep treating themselves. They buy over-the-counter medicines for yeast infections or they call the doctor to get a prescription for medicine over and over again.�

Nearly three times out of four, they�re treating themselves or calling a doctor for a medicine to treat a problem they don�t have, said Hoffstetter, who co-directs the SLUCare Vulvar and Vaginal Disease Clinic, which specializes in treating women who have chronic pain, unhealthy discharges or skin problems in their vaginal area.

�If you treat yourself and it never goes away, you shouldn�t continue to treat yourself,� Hoffstetter said. �You�re making a situation worse and you can get into cyclic episodes where you think you have a yeast infection all of the time.�

Vaginal yeast infections are common; three out of four women have had one at some point during their lives. Symptoms include pain or discomfort during sex; burning, redness and swelling of the vaginal area; a thick, white cottage cheese-like discharge that doesn�t smell bad; and pain during urination.

Hoffstetter analyzed the records of more than 150 new patients of the SLUCare Vulvar and Vaginal Disease Clinic, a specialty practice that sees women with recurrent vaginitis problems. These women thought they had yeast infections, however only 26 percent actually did.

�Their symptoms didn�t correlate with the clinical evidence of a yeast infection,� she said.

The women reported itching and a vaginal discharge, which also could indicate an inflammation, dry skin tissues or a sexually transmitted infection. These problems require a different treatment than the anti-fungal medicine given for a yeast infection.

Her advice to women who think they have a yeast infection is to call their doctor or women�s health nurse practitioner for an appointment. The physician or nurse practitioner will do a pelvic exam to detect swelling and unhealthy discharge. The health professional also may take a swab to get a specimen for a lab test or to be examined under the microscope to see if yeast is the true culprit.

�Women shouldn�t just run to the drugstore if they think they have a yeast infection. The optimal thing would be to be evaluated,� Hoffstetter says.

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.�

Removing ovaries before menopause leads to memory and movement problems

Wed, 29 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) ST. PAUL, Minn. � Women who have their ovaries removed before menopause are at an increased risk of developing memory problems or dementia and movement disorders such as Parkinson�s disease, according to two studies published August 29, 2007, in the online edition of Neurology�, the medical journal of the American Academy of Neurology.

The study on dementia involved approximately 1,500 women who underwent the removal of one or both ovaries for non-cancer-related reasons, such as ovarian cysts, endometriosis, or for the prevention of ovarian cancer. The women were compared to an equal number of women who still had both ovaries at the beginning of the study. All participants were followed for a median of 27 years and were interviewed about their memory. If the women could not be interviewed directly, the investigators interviewed a family member.

Researchers found that women who had one or both ovaries removed before menopause were nearly two times more likely to develop cognitive problems or dementia compared to women who did not have the surgery. In addition, those women who were younger when their ovaries were removed were more likely to develop dementia than women who were older when their ovaries were removed.

�It�s possible that estrogen has a protective effect on the brain and that a lack of estrogen due to ovary removal may increase a woman�s risk of developing memory problems,� said study author Walter A. Rocca, MD, MPH, with the Mayo Clinic in Rochester, MN, and member of the American Academy of Neurology.

Rocca says this is one of the first studies to show there may be a critical age window for the protective effect of estrogen on the brain in women. Before this study, knowledge was based almost exclusively on animal experiments. �For example, the study found women who had both ovaries removed before age 49, but were given estrogen treatment until at least age 50, did not have an increased risk of developing memory problems. These findings suggest that estrogen is protective for these women in this age window. By contrast, past studies from the Women�s Health Initiative have shown that estrogen use started at age 65 years or later may have a negative effect on memory and may increase the risk of developing dementia,� said Rocca.

Rocca says these findings have important clinical implications and should prompt physicians to reassess removing ovaries before menopause and the use of estrogen treatment following such surgery. �Although almost 60 percent of women received some estrogen treatment after both of their ovaries were removed, only 20 percent of them received estrogen treatment until at least age 50. Age 50 is the median age when women reach natural menopause.�

Many of the women involved in the dementia study were also included in a larger study that found women who had one or more ovaries removed before menopause were nearly two times more likely to develop Parkinsonism, a syndrome involving tremor at rest, muscle rigidity, and slowness of movements. The most common form of this syndrome is Parkinson�s disease. The risk for Parkinsonism increased with younger age at ovary removal. �Similar to the findings for dementia, these findings may be explained by a premature loss of estrogen and decreased neuroprotection,� said Rocca.

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.�

Study sheds new light on intimate lives of older Americans

Wed, 22 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The first comprehensive, nationally representative survey on the prevalence of sexual activity among older Americans provides a portrait of the intimate lives of people ages 57 to 85.

A majority of older Americans are sexually active and view intimacy as an important part of life, despite a high rate of �bothersome� sexual problems, according to a new report in the Aug. 23, 2007, issue of The New England Journal of Medicine. The findings come from the National Social Life, Health and Aging Project, research supported by the National Institutes of Health (NIH). The findings shed new light on the intimate social relationships and health of people ages 57 to 85, informing health care providers and patients about sexual norms in the older U.S. population.

The project is the first comprehensive, nationally representative survey to assess the prevalence of sexual activity, behaviors and problems in relation to health status among people in their late 50s and beyond. The study provides information about a number of important aspects of health and sexuality with age, including sexual problems in relation to specific chronic health conditions such as arthritis, diabetes and hypertension; relationships between physical health problems or limitations generally and sexual activity; and physician communication about sexuality at older ages. Physical health, the researchers found, was more strongly associated with many sexual problems than age alone.

The study has implications for health education efforts to prevent sexually transmitted disease in older people. Although data from the Centers for Disease Control and Prevention suggests stability in HIV diagnoses among Americans aged 50 and older, the number of older people diagnosed with AIDS and living with HIV is increasing, as individuals who were infected with HIV at younger ages are living longer before progressing to AIDS. However, sexual activity among older adults poses risks for new cases of HIV, as approximately 15 percent of newly diagnosed HIV infections are among Americans over age 50.

Led by Stacy Tessler Lindau, M.D., who conducted the study with Linda Waite, Ph.D., and others at the University of Chicago, the research was funded primarily by the National Institute on Aging (NIA), a component of NIH. Additional funding came from NIH�s Office of Research on Women�s Health, Office of AIDS Research and Office of Behavioral and Social Sciences Research and from private-sector sources. Data collection was supported by the National Opinion Research Center at the University of Chicago. Georgeanne E. Patmios of NIA�s Behavioral and Social Research Program is program officer for the project.

�Despite the aging of the population, little had been known about the intimate lives of older adults,� said NIA Director Richard J. Hodes, M.D. �This study expands our knowledge by reporting, on a national scale, data about sexual functioning and health among older adults.�

Dr. Lindau expects the study to help open a dialogue between older patients and their doctors as older Americans were very receptive to the survey and its questions. This openness suggests that, when asked, many older people want to talk about this part of their lives. �We found, despite the high prevalence of problems, that most older adults have never discussed sex with a physician. From a medical and a public health perspective, we have an opportunity and an obligation to do better patient education and counseling about health-related and potentially preventable and treatable sexual problems,� Dr. Lindau said.

The researchers gathered information from a nationally representative sample of 3,005 men and women ages 57 to 85 years, asking about each person�s marital or other relationship status, frequency and types of sexual activity during the past 12 months, physical health, and communication with a physician about sex. They also queried sexually active respondents about the presence of sexual problems.

�This study breaks new ground in social and behavioral research,� said Richard Suzman, Ph.D., director of NIA�s Behavioral and Social Research Program. �Its portrait of this aspect of older Americans� lives suggests a previously uncharacterized vitality and interest in sexuality that carries well into advanced age, which perhaps has not been appreciated as an important part of late life.�

The study found that many older adults are sexually active, but about half of the men and women surveyed reported at least one sexual problem and about a third report at least two problems. Specifically:

Early cord clamping could be harmful for baby

Fri, 17 Aug 2007 11:57:49 PST

( from http://www.rxpgnews.com ) London, Aug 17 - A British expert has said that clamping the umbilical cord right after birth could be harmful for babies.

The umbilical cord connects the developing foetus with placenta. The expert said that leaving the cord for around three minutes can boost the baby's iron stores, cutting the risk of anaemia.

Early cord clamping is a common practice in several countries. It is widely used as part of active birth management guidelines, which have been shown to prevent the mother haemorrhaging immediately after birth.

But Andrew Weeks, a lecturer in obstetrics at the University of Liverpool, said there was no evidence that clamping the cord immediately had any benefit for the mother.

In the baby, evidence has shown that allowing the cord blood to keep flowing for a few minutes increases the iron stores, reported the online edition of BBC News.

In the developing world, where anaemia is a major problem, practices have now changed to delay clamping. The World Health Organization - has dropped early clamping from its guidelines.

Weeks recommended waiting three minutes in healthy babies but said the issue was more complicated in babies born prematurely or by caesarean section even though they would perhaps benefit the most.

'For them a policy of 'wait a minute' would be pragmatic,' he said.

There have been concerns that delaying clamping in healthy babies could increase the risk of jaundice, but a recent study in the US suggested this was not the case.

$6M NIH grant to fund U-M research on childbirth-related prolapse, incontinence

Thu, 16 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) ANN ARBOR, Mich. A group of researchers from the University of Michigan Health System has been awarded a $6 million federal grant to study the serious injuries that afflict millions of women as a result of childbirth. More than 300,000 women require surgery each year for problems such as incontinence and pelvic organ prolapse that arise from injuries sustained during vaginal birth.

A team that includes a unique multidisciplinary team of U-M gynecologists, engineers, nurses and other researchers will use the grant from the Office of Research on Womens Health part of the National Institutes of Health to examine the damage that can be done to pelvic muscles during vaginal deliveries. The Specialized Centers of Research (SCOR) grant is funded for five years.

Of the 3 to 4 million women who give birth each year, about 10 percent (300,000 per year) eventually will require surgery for a problem attributable to the birth. These injuries are known as pelvic floor disorders, and they include urinary incontinence and pelvic organ prolapse conditions that can be debilitating for women.

Twice as many women suffer a major injury to the muscles near the birth canal per hour of labor as women suffer injuries in major college athletics. Despite this high number of injuries, preventive strategies to reduce the injury rate have not been previously developed, says John O.L. DeLancey, M.D., director of Pelvic Floor Research, Norman F. Miller Professor of Obstetrics and Gynecology, and principal investigator on the SCOR grant.

Although the process of labor is well-studied, the mechanical changes that must take place that allows the baby to emerge from a womans body have, until recently, escaped scientific study.

U-M is at the forefront nationally in the research and treatment of pelvic floor disorders with its Pelvic Floor Research and Pelvic Floor Disorders Clinic. With the SCOR grant, the researchers will advance the knowledge about these conditions by studying the changes that muscles undergo in preparation for birth, how they are injured, and how they either recover or do not.

This unique effort couples the knowledge of obstetrician-gynecologists with the expertise of biomechanical engineers, who use complex three-dimensional computer simulations to study the changes in birth.

The research also will include new state-of-the-art MRI technology for the purpose of studying birth injuries and structural mechanics of the problems that arise later in life. Simulating birth in advanced biomechanical models will allow the research team to isolate specific situations that may increase the chances of a woman being injured, says DeLancey.

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.

Postpartum hospital discharges -- when is the 'right time?'

Mon, 06 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) LEBANON, N.H. A landmark nationwide study, published today in the journal Pediatrics, is the first ever to prospectively examine the decision-making process of over 4,000 mothers and their physicians around the readiness of mothers and their infants to leave the hospital after childbirth.

The study, led by Dr. Henry Hank Bernstein M.D., Professor of Pediatrics at Dartmouth Medical School, and Chief of General Academic Pediatrics at Children's Hospital at Dartmouth (CHaD), is known as the Life Around Newborn Discharge or LAND study. It looked specifically at postpartum decision-making, with results showing that 17 percent of all mother-infant pairs were identified as not ready.

This study also identified those factors most related to the unreadiness of mother-infant pairs to leave the hospital. These included: being a first-time mother, being black and non-Hispanic, the mothers history of chronic disease, inadequate prenatal care, delivering during non-routine hours, the newborn having problems while in the hospital, the mothers intent to breastfeed, and whether or not there was adequate in-hospital education.

Clinical decision-making regarding maternal and infant discharge is a subjective and contextual process that must take into account the perspectives of each person involved in the mothers and infants health care experience, Bernstein says. This suggests that the mother and the clinicians caring for her and her infant must make the postpartum discharge decision jointly.

Hospital affiliates and offices of 451 practitioners from 112 Pediatric Research in Office Settings (PROS) practices conducted the LAND study nationwide. The aim was to address the lack of information regarding the postpartum decision-making process for healthy term newborns and its consequences during the neonatal period. Data were collected through self-administered questionnaires completed by the mother, pediatrician and obstetrician on the day of discharge. A mother-infant dyad was determined unready for postpartum discharge if at least one of the three informants perceived that either the mother or infant should stay longer.

Federal legislation The Newborns and Mothers Health Protection Act of 1996 requires insurance plans offering maternity coverage to pay for at least a 48-hour hospital stay following childbirth, or a 96-hour stay in the case of a cesarean section. While Bernstein says he understands the need for some agreed upon minimum length of stay, he cautions against a one-size-fits-all approach to readiness.

A customized reflection of both the mothers and her babys needs and concerns is required, Bernstein says. The length of postpartum stay is not the actual determinant of outcome, and the chronological clock is not necessarily what is important. The debate regarding postpartum hospital stays must be refocused toward a broadened scope of policy and clinical care considerations.

Progesterone treatment does not prevent preterm birth in twin pregnancy

Wed, 01 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Progesterone therapy does not reduce the chances of preterm birth in women pregnant with twins, reported researchers in a network sponsored by the National Institutes of Health.

An earlier study showed progesterone therapy reduced the risk for preterm birth in another category of high risk pregnant womenthose carrying a single baby who had delivered a single baby prematurely in the past.

This study shows that progesterone therapy is not beneficial for all women at risk for giving birth prematurely, said Duane Alexander, M.D., Director of the NICHD, the NIH institute that supported the research network. So far, the evidence supports progesterone therapy as a means to reduce preterm birth only in women pregnant with a single baby who are at risk for premature delivery because of a prior preterm birth.

After the initial study showed progesterone therapy could reduce the likelihood of preterm birth in women carrying a single baby and who had previously given birth prematurely, many physicians began prescribing the therapy for women pregnant with twins and for other categories of women at risk for preterm birth as well. In addition to women carrying two or more babies, and those who have delivered prematurely before, also at risk for preterm delivery are pregnant women having a shortened cervix (the lower part of the uterus) and certain infections of the reproductive tract.

The study appears in the August 2, 2007 issue of The New England Journal of Medicine.

A large team of researchers from the NICHD Maternal-Fetal Medicine Units Network, led by Dwight J. Rouse, M.D., Professor of Obstetrics and Gynecology at the University of Alabama at Birmingham School of Medicine, conducted the study.

In the study, 655 women pregnant with twins were randomly assigned to receive weekly injections of a placebo or the form of progesterone known as 17-alpha hydroxyprogesterone caproate (17-OHPC), explained Catherine Y. Spong, M.D., Branch Chief of NICHDs Pregnancy and Perinatology Branch, and the NICHD author of the study.

Progesterone is a female hormone that is produced in large quantities during pregnancy. Researchers with the Maternal Fetal Medicine Units Network reported in 2003 that weekly injections of progesterone reduced the risk of preterm birth by 34 percent among pregnant women who had given birth prematurely in an earlier pregnancy.

Women in the current study were randomly assigned to groups receiving weekly injections of either 250 mg of progesterone or a placebo. The injections started when the women were 16-20 weeks pregnant and continued until the 35th week of pregnancy or until the woman gave birth. Women in both groups had similar characteristics such as age, race, and marital status.

The researchers found that the use of progesterone did not reduce premature birth in twin pregnancies when compared with the placebo group: 41.5 percent of women on progesterone treatments delivered prematurely (before 35 weeks) or experienced fetal loss vs. 37.3 percent of women receiving placebo injections. Fetal loss describes the loss of the baby because of such factors as stillbirth or miscarriage, said Dr. Spong.

There was no difference between the two groups in the amount of time the baby spent in the womb before it was delivered. Progesterone treatment did not affect the proportion of deliveries before 37 weeks or before 32 or 28 weeks, when compared to the placebo group.

Whether the child was conceived using assisted reproductive methods or conceived spontaneously did not affect these results, nor did the type of placentation (whether the babies shared a placenta or had two separate placentas). The study could not determine whether progesterone therapy could reduce the chances of preterm birth in women pregnant with twins who had delivered prematurely in a previous pregnancy. Fewer than 10 percent of women participating in the current study had experienced a prior preterm deliverya number too small to allow a reliable estimate of the effect of treatment in this group of women.

Premature infants are often very small and at greater risk for life-threatening infections, blindness, breathing problems, learning and developmental disabilities, and cerebral palsy. Premature babies are also more likely to die from SIDS (sudden infant death syndrome) than full-term infants. Premature birth is one of the leading causes of infant death.

Women pregnant with twins are at higher risk for preterm birth than are other pregnant women, with more than half delivering prematurely, said Dr. Spong. Over one quarter of all very low birth weight infants (less than 1500 grams or 3.3 pounds) are the result of a multiple pregnancy. Multiple pregnancy accounts for one in seven infant deaths, she said.

Overall, the number of twin births has increased in recent years. Between 1980 and 2004, the rate of twin birth rose from 18.9 to 32.2 per 1000 live births, the study authors wrote, citing data from the National Center for Health Statistics.

Dr. Spong added that NIH-funded researchers are testing progesterone in other groups of women who are at risk for preterm birth, such as women with shortened cervixes and women pregnant with triplets.

Progesterone injections do not prevent preterm birth in twin pregnancies

Wed, 01 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CHAPEL HILL -- Weekly progesterone injections do not prevent premature births in women pregnant with twins, a University of North Carolina at Chapel Hill study has found.

The result came as a surprise to the researchers, who previously discovered that weekly injections of the naturally occurring hormone, called 17 alpha-hydroxyprogesterone or 17-OHPC, reduced additional preterm births by one-third in women whose previous babies were born prematurely.

Based on the results of the first study, which showed that 17-OHPC reduced preterm birth in the group with the highest risk, we were hopeful that it would also prevent preterm birth in twin pregnancies, which represents an intermediate level of risk, said John Thorp, M.D., a study co-author and professor of obstetrics and gynecology UNC-Chapel Hill. The mechanisms that lead to preterm birth are complex, and I think our current study shows they may not be amenable to a single solution.

The study results are published in the Aug. 2 issue of The New England Journal of Medicine. The lead author is Dwight J. Rouse, M.D., of the University of Alabama at Birmingham. 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. It took place at 14 sites across the United States, including UNC-Chapel Hill, WakeMed and the Wake County Health Department.

For the study, 655 healthy women with twin pregnancies and no prior preterm births received weekly injections of either 17-OHPC or placebo, starting at 16 to 20 weeks into their pregnancies and ending at 35 weeks. The results showed no meaningful difference between the 17-OHPC and placebo groups. Birth or miscarriage before 35 weeks gestation occurred in 41.5 percent of the 17-OHPC group and in 37.3 percent of the placebo group.

The researchers concluded that treatment with 17-OHPC did not reduce the rate of preterm birth in women with twins.

Why 17-OHPC is effective in reducing the rate of preterm birth in women with a prior spontaneous preterm birth, but not in women carrying twins is a question that will be answered only when the mechanisms underlying preterm birth and the actions of 17-OHPC are better understood, they wrote, adding that additional research is needed to see whether 17-OHPC is effective in other conditions in which the risk of preterm birth is increased.

Thorp said the same research network is currently working on two other 17-OHPC studies. One involves women with triplets while the other focuses on women with a short cervix. Both groups are considered to have an intermediate risk of preterm birth.

Another question for future research, Thorp said, is whether or not injections are the best method for administering 17-OHPC. Its worth investigating whether other methods, such as daily vaginal suppositories, might be more effective, he said.

A commercial formulation of the drug, marketed under the name Gestiva, has been granted orphan drug status by the Food and Drug Administration and an application for full FDA approval is pending.

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.

Fluctuating weight during pregnancy could affect babies

Mon, 30 Jul 2007 13:59:12 PST

( from http://www.rxpgnews.com ) London, July 30 - Scientists have warned that fluctuating weight of women during pregnancy could affect their unborn babies.

The findings have emerged from two studies. The first found that weight gain between pregnancies was strongly associated with major complications for the mother and child in the months proceeding, during and just after childbirth, reported health portal News Medical.

This was independent of whether a woman was, by definition, overweight.

The second study found that women whose Body Mass Index -, a marker of body weight, fell during pregnancies had a higher risk of giving birth prematurely than women whose weight remained stable or increased.

Gaining or losing weight in between pregnancies can have major health implications for an unborn baby, senior obstetricians Jennifer Walsh and Deirdre Murphy wrote in the British Medical Journal.

While weight and obesity have long concerned women in relation to body image and lifestyle issues, few are aware of the possible risks that fluctuating weight could have on their unborn child, the obstetricians said.

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.

Breast cancer and hormone therapy -- A looking-glass mirror?

Tue, 24 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The medical community has been debating for many years whether, and to what extent, postmenopausal hormone therapy (HT) use is associated with a higher risk of breast cancer, says Professor Amos Pines, President of the International Menopause Society. Although it is agreed that long-term HT slightly increases that risk, the definition of long-term use is still unclear, particularly in view of data showing that it may vary significantly by type of HT (estrogen-alone vs. estrogenprogestin, brand of progestin, dosage). A new study from the Kaiser Permanente health plan[1] raises the question whether trends in breast cancer incidence and use of HT over the past 25 years may be directly linked.

The Womens Health Initiative (WHI) trial was a landmark in menopause medicine since it provided information based on the best available study methodology[2]. By adopting its results as the ultimate source of information, many organizations, medical societies and health authorities actually declared that data derived from observations in the postmenopausal population are less valuable. Nevertheless, during the past few months, several studies have used databases on the incidence of breast cancer, on the one hand, and sales of HT on the other hand, in order to suggest a direct link between trends of hormone use and the number of newly diagnosed breast cancer patients. While such information, by itself, is very important and interesting, conclusions must be drawn with great caution. It is tempting to simplify the observed year-by-year figures on HT use and breast cancer incidence and establish a mirror glass equation: the more postmenopausal hormone use, the more breast cancer, and vice versa. But human biology is far too complicated and the pathophysiology of breast cancer is far too complex to adopt such a mechanistic approach, as the authors of those studies and related Editorials rightly say.

The mere fact that the incidence of lung cancer is higher among people carrying a lighter in their pocket does not mean that lighters cause lung cancer. Thus, having two parallel time trends, for breast cancer incidence and for hormone use, still makes it necessary to investigate further in order to better understand if and how those trends could be linked. For example, a third important player has now been added, namely the rate of mammography screening, which has proved to have similar fluctuations as HT use and breast cancer incidence1. According to the Kaiser Permanente registry[1], the rate of women aged 4559 undergoing screening mammography in 20022004 (post-WHI period) decreased from 48% to 44%. Thus, awareness of the need for periodic breast examinations may ease, and the likelihood of women coming to be examined may decrease in a population that uses HT less frequently, which could lead to under-diagnosis of breast cancer.

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.

Nearly 90 percent of babies receive recommended newborn screening tests

Tue, 10 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) WHITE PLAINS, N.Y., JULY 11, 2007 Nearly 90 percent of all babies born in the United States more than double the percentage in 2005 live in states that require screening for at least 21 life-threatening disorders, according to the latest March of Dimes Newborn Screening Report Card.

The March of Dimes endorsed the 2004 report of the American College of Medical Genetics (ACMG) that calls for every baby born in the U.S. to be screened for 29 genetic or functional disorders. If diagnosed early, all of these devastating conditions can be successfully managed or treated to prevent severe consequences.

Two years ago, only 38 percent of infants were born in states that required screening for at least 21 of these 29 core conditions. As a result of four years of intensive advocacy efforts by March of Dimes chapters and their partners, that percentage has increased to 87.5, or about 3.6 million babies.

While this important expansion of newborn screening is very good news for families, the lives of 500,000 newborns who still arent tested hang in the balance, said Dr. Jennifer L. Howse, president of the March of Dimes. Despite the pleas of parents, clinicians and advocacy groups the United States still lacks consistent federal guidelines for newborn screening. Babies must be screened, to receive immediate treatment necessary to survive and lead healthy lives. The lack of federal guidelines makes it difficult for states to get support for needed legislation.

In states that do not follow the ACMG recommendations, the March of Dimes staff and volunteers continue to work with governors, legislatures, and parent groups to advocate for expanded newborn screening on a state-by-state basis.

In Pennsylvania, newborn screening is offered at most hospitals, but it is not required by law. Therefore it is not a guarantee and, potentially, screening could be eliminated or reduced.

Massachusetts had been a leader in newborn screening when, in the early 1960s, it became the first state to routinely screen all newborns for PKU (phenylketonuria), an inherited metabolic disorder that, if untreated, causes severe mental retardation. But today Massachusetts requires screening for only 12 of the 29 core conditions.

Nationwide, a discouraging 6.1 percent of babies are born in states that required screening for only 10 to 20 of the core conditions and 6.2 percent of newborns will get screening for fewer than 10 conditions. Disparities in state newborn screening programs mean some babies may die or develop brain damage or other severe complications because they are not identified in time for effective treatment, said Dr. Howse.

All babies across America should receive the benefits of being screened for all of these 29 treatable conditions, said Dr. Howse.

At present, 13 states and the District of Columbia require screening for all 29 core, treatable, conditions. While most states are working to meet that goal, Montana, Kansas and West Virginia, enacted legislation this year requiring all babies be screened for all of the core conditions. Their programs will be implemented next year.

Other states overcame remarkable challenges in order to provide for the health of their smallest citizens. For example, Louisiana, which still is recovering from the devastating hurricanes of 2005, requires screening for 28 of the core conditions.

This is the fifth consecutive year the March of Dimes has analyzed state-by-state newborn screening requirements, creating a snapshot of the nations progress toward improving the health of newborns. The March of Dimes contracted with the National Newborn Screening and Genetics Resource Center to survey each states newborn screening requirements.

The snapshot shows that the nation is on target to meet the March of Dimes goal of having all babies screened for 20 or more of the recommended panel of genetic disorders by 2008.

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.