RxPG News : Gynaecology

Yale researchers pinpoint reasons for dramatic rise in cesarean births

Wed, 22 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) In one of the first studies to examine the reasons for the rising number of women delivering their babies by cesarean section, Yale School of Medicine researchers found that while half of the increase was attributable to a rise in repeat cesarean delivery in women with a prior cesarean birth, an equal proportion was due to a rise in first time cesarean delivery. Among these deliveries, factors such as slowly progressing labor and fetal heart rate concerns were the largest contributors.

The U.S. cesarean delivery rate has increased dramatically over the past decade, with some of the highest increases noted in Connecticut and Rhode Island. Much of the previous research on the reasons for this increase is limited to birth certificate data, which does not record the specific indication or reason for cesarean delivery.

Pre-released online and published in the July issue of Obstetrics & Gynecology, the study was led by Yale researcher Jessica Illuzzi, M.D., of the Department of Obstetrics, Gynecology & Reproductive Sciences. Illuzzi and her co-authors analyzed indications for cesarean delivery on prospectively collected data from over 30,000 births at Yale-New Haven Hospital from 2003 to 2009.

"We found that more objective reasons, such as the baby being in a breech position and placenta previa, remained stable over time, while less objective reasons, such as slow progress in labor and concerns about fetal heart tracings contributed large proportions (>50%) to the increasing primary cesarean delivery rate," said Illuzzi.

In addition, suspected large infants, twin pregnancies, and preeclampsia contributed to the increase despite relatively stable rates of these conditions in the population during the seven-year study. "This suggests that the use of cesarean for these indications is increasing," said Illuzzi.

The researchers also examined some of the commonly cited reasons for increasing cesarean rates. "Despite speculation that the decreasing use of forceps and vacuum-assisted vaginal delivery have led to increasing cesarean delivery rates, our data shows that since 2003 the increase in cesarean for labor arrest disorders was manifested in the first stage of labor prior to full dilation when forceps or vacuum are not appropriate." In addition, maternal-choice cesarean births, often cited as another factor, contributed only a small proportion (8%) to the total increase in primary cesarean delivery in the study.

"Elucidating the reasons for the rise in cesarean delivery can help us consider if the benefits of the surgery based on indication appropriately outweigh the known risks, costs and longer recovery time," said Illuzzi.

New male infertility test could 'bring hope to millions'

Thu, 09 Jun 2011 15:24:14 PST

( from http://www.rxpgnews.com ) A groundbreaking new test for male infertility, which will save time, money and heartache for couples around the world, has been developed by Northern Ireland's Queen's University Belfast.

The medical breakthrough, known as the SpermComet, has resulted from more than a decade's research by Professor Sheena Lewis, who leads the Reproductive Medicine research group at Queen's.

The SpermComet provides unique information that no other test offers.

By measuring damaged DNA in individual sperm, it can predict the success of infertility treatments and fast-track couples to the treatment most likely to succeed, leading to significantly reduced waiting times and improved chances of conception.

Lewis said according to a Belfast statement: 'One in six couples has difficulty in having a family. In 40 percent of cases, the problems are related to the man. Until now, there have been few accurate ways of measuring a man's fertility.'

'Traditionally, the diagnosis of male infertility has relied on semen analysis. This provides the basic information on which fertility specialists base their initial diagnosis.'

'However, its clinical value in predicting male fertility or success with infertility treatment is limited, particularly if the semen analysis results are normal,' he added.

'The SpermComet test is so called because it looks just like a comet in the sky. The head of the 'Comet' is undamaged DNA and the tail is damaged DNA.

'Good quality sperm DNA is closely associated with getting pregnant and having a healthy baby, and the SpermComet Test is the most sensitive test available for sperm DNA testing,' concluded Lewis.

Lewis, in partnership with Queen's venture spinout company, QUBIS, has now set up a new company to market the test, which is already available through a number of fertility clinics in Britain.

The pill does not lead to weight gain

Tue, 07 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Many young women do not want to start taking the contraceptive pill because they are worried that they will put on weight, or come off it because they think that they have gained weight because of it. However, a thesis from the University of Gothenburg, Sweden, has demonstrated that the combined contraceptive pill does not cause weight increase.

In her thesis, Ingela Lindh reports on a long-term study of 1,749 women born in 1962, 1972 and 1982 who answered questions about matters such as contraception, pregnancies, height/weight and smoking habits every five years from the age of 19 to 44.

The women who were on the pill and were monitored from their teenage years until the age of 34 didn't put on any more weight than their peers who had never taken the pill at all, says Lindh, a registered midwife and researcher at the Sahlgrenska Academy.

The study also showed that the combined pill is the most widely used contraceptive up to the age of 29, after which condoms are most common. From the age of 32 onwards the coil proved most popular.

There were lots of reasons why women came off the pill, including a fear of side-effects, weight gain and mood swings, and these gradually increased over time and were more common in the youngest group, says Lindh.

Despite women's concerns about weight gain, the researchers did not find any link between being on the pill and putting on weight. The only factors that affected weight were ageing and smoking. The number of smokers among the 19-year-olds born in 1962 was on average of 42%, compared with 29% among those born in 1982. At the same time, average weight rose by 3.2 kilos between these two groups. In the youngest group, women from low socioeconomic status areas were heavier than their peers. By following the same women from the age of 19 to 44, the researchers were able to calculate that they gained an average of 10.6 kilos, which works out at around 0.45 kg a year.

Lindh would like this new knowledge to increase the use of the combined pill and thus reduce the risk of unwanted pregnancies.

It's important to let women know that the pill doesn't affect their weight, as there's a real fear that they will put on weight, especially among young women, and this can be one of the reasons why they don't want to go on the pill. When giving advice about different types of contraception, we should also tell young women about the importance of lifestyle factors such as diet and exercise so that we can break this trend of heavier teenagers.

Researchers discover biochemical weakness of malaria parasite -- vaccine to be developed

Tue, 07 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Every year, 10,000 pregnant women and up to 200,000 newborn babies are killed by the malaria parasite. Doctors all around the globe have for years been looking in vain for a medical protection, and now researchers from the University of Copenhagen have found the biochemically weakness of the lethal malaria parasite, and will now start developing a vaccine to combat pregnancy related malaria.

The malaria parasite travels via the spit of an infected mosquito to the liver of the new host, where it spreads to the red blood corpuscles and starts to reproduce itself.

Pregnant women and children below the age of five years are particularly vulnerable to malaria because of the parasite's survival mechanisms. The parasite has a protein hook designed to attach it to the placenta and this leads to amnesia of the mother who in worst case can die or deliver prematurely. This increases the maternal mortality - and infant mortality, explains Associate Professor Ali Salanti from the University of Copenhagen's Centre for Medical Parasitology who manages the project.

The body's immune system normally attacks any foreign body but since our spleen constantly filters our blood and removes ruined or deform blood cells, the body's natural defense does not need to check the blood. And the malaria parasite exploits this fact.

An infected red blood corpuscle is more stiff than in its normal state and this would usually trigger the spleen to destroy the cell and parasite, but the malaria parasite has an advanced arsenal of protein hooks. With these hooks the parasite attaches itself to the inner side of the blood vessel and even if our immune system succeeds in defeating one hook, the parasite has 60 different hooks, which again differ from one malaria parasite to another.

Researchers have for years been looking for a vaccine which can attack the malaria parasite's specific placenta hook. This is tricky not least due to the fact that the parasite's hooks are long proteins which are difficult to produce artificially in the lab when developing of a vaccine.

After intensive research efforts, the researchers have now succeeded in identifying a fragment of the placenta hook (VAR2CSA) which not only is crucial for the parasite's ability to attach itself to the placenta, but also is possible to produce artificially for a vaccine.

A vaccine must stimulate the immune system to quickly attack something foreign in the body. Therefore, it was a matter of finding the part of the placenta hook, which the parasite cannot manage without and which we could target a vaccine against, says Associate Professor Ali Salanti.

With a grant of 15 million DKK (approximately 3 million USD) from the Danish National Advanced Technology Foundation and close corporation with two Danish biotech companies, the researchers can now start developing the vaccine and take it through the first trials to test its safety.

Ali Salanti and his colleagues will collaborate with the biotech companies ExpreS2ion Biotechnologies and CMC Biologics A/S to develop a method for mass production of the vaccine.

Once this has fallen into place, the researchers can start up the clinical trials on animals and human beings. If the trials are successful the parasistologists from the University of Copenhagen and their partners will make a significant contribution in reaching the UN's Millennium Development goal number 4 and 5. These two goals encourage every country in the world to work on lowering global child mortality with two thirds and maternal mortality with three quarters.

Hormone test predicts ovarian function after chemotherapy for breast cancer

Sun, 05 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A test that shows how many eggs a woman has in her ovaries may help young women with breast cancer know what their reproductive function will be after chemotherapy, a new study finds. The results will be presented Sunday at The Endocrine Society's 93rd Annual Meeting in Boston.

Called the anti-Mullerian hormone (AMH) test, this blood test measures levels of an ovarian hormone that reflects the size of the ovarian reserve, or remaining egg supply. Currently, doctors use it to quantify a woman's ovarian reserve before in vitro fertilization treatments. Now researchers from Scotland have found that measurement of AMH indicates how likely it will be for a woman to still have eggs in her ovaries after chemotherapy, which can often damage a woman's eggs and cause infertility.

Future reproductive function is a concern for many young women with cancer, said lead investigator Richard Anderson, MD, PhD, professor of clinical reproductive science at the University of Edinburgh. This test will be of benefit to women with newly diagnosed cancer to help decide whether they need to take steps to preserve their fertility.

In the U.S. alone, breast cancer is diagnosed in more than 25,000 women younger than 45 each year, according to the American Cancer Society.

For this study, Anderson and his colleagues recruited 50 premenopausal women, ages 29 to 51, who had just received a diagnosis of early breast cancer. All women had normal menstrual cycles and were asked to keep a daily record of their menstrual cycle, as an index of ovarian activity, during the two years of the study. Before the women started chemotherapy, they gave blood samples for AMH testing. They again had AMH tests one and two years after starting treatment.

Before chemotherapy the median AMH level was 0.4 nanograms per milliliter (ng/mL). After cancer treatment the AMH level fell rapidly, becoming undetectable (below 0.16 ng/mL) in 68 percent of the women after one cycle of chemotherapy, the authors reported. By one-year follow-up, 11 women withdrew from the study, mostly because of cancer recurrence, Anderson said. Menstrual records were available for 39 women at one year and for 29 women at two years.

A low AMH measurement before treatment correlated well with amenorrhea, or absence of menstruation, after treatment. Women whose AMH before treatment was low (below 0.4 ng/mL) were 16 times likelier to have stopped menstruating after chemotherapy than women with a high pretreatment AMH value, Anderson said. The odds of losing ovarian function remained higher even after statistical analysis controlled for increasing age, which tends to lower AMH levels. Women whose AMH before chemotherapy exceeded 0.92 ng/mL were reportedly almost five times more likely to continue menstruating after treatment.

Our data suggest that the AMH test, taken before cancer treatment, can help individualize a woman's infertility risk after chemotherapy for breast cancer, Anderson said.

He added that results of this study, which was funded by the U.K. Medical Research Council, are likely to apply to other types of cancer as well.

New mothers can learn a lot from watching their babies

Mon, 02 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) The best teacher for a young mother is her baby, contend experts who train social workers to interact with first-time moms.

We like to think of babies as 'ordinary miracles,' said Victor Bernstein, a research associate at the School of Social Service Administration at the University of Chicago. But adjusting to a baby can take work, and the task of social workers often is to help young mothers learn to focus on an infant's needs, say Bernstein and other SSA experts. Mothers are not only important to their kids, but kids are really important to their mothers, Bernstein said.

For instance, a social worker may ask permission to pick up a newborn, ask the mother to call out the child's name, and then watch as the baby turns to her voice, Bernstein said. This hands-on experience can show a young mother the importance of talking to her infant, much more vividly than any discussion could.

Bernstein and others at the school have done extensive research on the needs of young mothers, particularly unwed teens. Their work shows that a wide variety of parenting styles can be effective in rearing children, but helping a mother focus on her baby and make the baby a priority is key. SSA is the only school of social work in the country that prepares students specifically to work with infants.

Early attention to children's needs is becoming an increasingly important part of the work of social workers, said Sydney Hans, the Samuel Deutsch Professor at SSA. The health care act that President Obama signed into law in 2010 funds home visits to new parents and their infants through programs that research has proven effective, Hans pointed out.

Work at SSA helps prepare students to be effective in home visits. Bernstein is teaching a class this spring titled Strategies for Working with Infants, Toddlers and their Parents, in which he helps students understand the interaction between mothers and their babies so that they might help in the nurturing process. The students videotape and later discuss interactions between mothers and children.

Bernstein's clinical work shows that videos taken of teen mothers interacting with their children are an effective part of the home visiting program. A central component of the home visitor's role is to help the parent interpret the meaning of the child's behavior, said Bernstein. His teaching and training, along with Hans' research, have been supported by the Irving B. Harris Foundation in Chicago.

Making and viewing the video is fun for parents and provides a concrete and lasting means of showing parents how they and their babies grow together, Bernstein points out in Strengthening Families through Strengthening Relationships: Supporting the Parent-child Relationship through Home Visiting, published by the Infant Mental Health Promotion Project.

Heart drugs could cut blood pressure risks in pregnancy

Wed, 20 Apr 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Pregnant women could benefit from a pioneering trial that will test whether heart disease drugs can be used to treat pre-eclampsia.

Researchers are investigating if a class of drugs - known as statins - can prevent the potentially fatal condition, which affects up to eight per cent of pregnant women in the UK.

The world's first trial on statins in pregnancy follows on from research showing that statins, which are prescribed to lower heart disease, could also help to decrease amounts of two proteins linked to inducing pre-eclampsia.

Statins act on an enzyme that suppresses the production of these proteins - soluble FLt-1 and soluble endoglin.

The trial, funded by the Medical Research Council and led by the University of Edinburgh, will involve pregnant women in the UK diagnosed with very early-onset pre-eclampsia, which occurs in women who are less than 32 weeks pregnant.

It will also involve researchers from the University of Birmingham, University College London Hospital and Queen Mary, University of London.

The study follows on from previous research that shows the enzyme involved - heme oxygenase 1 - produces carbon monoxide within cells. This could explain why female smokers, who have higher levels of carbon monoxide in their blood, have a lower risk of pre-eclampsia.

The condition, which is responsible for around four million premature births worldwide each year, causes high blood pressure, inflammation of the lining of blood vessels and can also cause kidney and liver damage. In extreme cases, when unmanaged, it can also lead to convulsions and death.

Early onset pre-eclampsia affects one in 100 expectant mothers in Britain. The condition carries greater risk than pre-eclampsia occurring later in the pregnancy because the only treatment for the condition is to deliver babies prematurely.

Professor Asif Ahmed, who is leading the study, stressed that until the results were available, pregnant women who think they may be susceptible to pre-eclampsia should not ask their doctor to prescribe statins.

Professor Asif Ahmed, of the University of Edinburgh's Centre for Cardiovascular Science, said: This is the first stage, but we are confident that taking a scientific approach to find a way to alleviate pre-eclampsia would enable us to prolong affected pregnancies, improving the outcome for both the baby and the expectant mother. If successful this could help provide cheap, widely available therapy against pre-eclampsia which could help reduce maternal and infant deaths across the world.

The study is known as StAmP - statins to ameliorate early onset pre-eclampsia.

Professor Max Parmar, Director of the Medical Research Council's Clinical Trials Unit, said: The MRC supports trials which drive the translation of discoveries made in the lab into real benefits for public health. The design of the StAmP study means that it should provide important evidence on whether statins, which are already widely used in other conditions, could be exploited even further. Pre-eclampsia is a major problem area in women's health, so it would be a key step forward if this trial provides a positive outcome.

Genetic errors linked to life-threatening pregnancy disorder

Tue, 22 Mar 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Scientists have identified genetic errors in women with autoimmune diseases that increase the risk of preeclampsia, a potentially life-threatening condition that occurs in 10 percent of all pregnancies.

The researchers also found the same mutations in some women with preeclampsia who don't have underlying autoimmune diseases. Their findings provide genetic targets for new treatments and suggest that screening tests could one day identify women at risk of the condition, which accounts for 15 percent of all preterm births.

We're going to need to confirm these links in a larger study, but if they are validated it may be possible to develop better ways to identify and treat women at risk, says senior author John P. Atkinson, MD, of Washington University School of Medicine in St. Louis.

Preeclampsia typically develops after the 20th week of pregnancy. It causes dangerously high blood pressure, protein in the urine, headaches and swelling of a mother's hands and face. The only treatment is to induce delivery, which can be fatal to the baby if preeclampsia strikes too early in pregnancy.

The research, published March 22 in PLoS: Medicine, is an international collaboration among researchers at Washington University, Weill Cornell Medical College, the University of Utah at Salt Lake City, Newcastle University in the United Kingdom and the Georges-Pompidou Hospital of Paris.

Preeclampsia results from a breakdown of the placenta, which delivers oxygen and nutrients to the baby. If the condition is not treated, preeclampsia can lead to seizures, strokes, kidney and liver damage and breathing problems that threaten the lives of both mother and baby.

Scientists have suspected that problems with the immune system provoke many cases of preeclampsia because women with lupus and certain other autoimmune diseases have an increased risk of the disorder.

Preeclampsia seems to involve multiple hits, says Atkinson, the Samuel B. Grant Professor of Medicine. First you may have a genetic predisposition for small blood vessels, which can worsen problems with inflammation. Then maybe you have lupus or another autoimmune condition. Then along comes pregnancy, which is a major source of stress on the organs.

For the new study, researchers studied 250 pregnant women with lupus and/or a related condition, antiphospholipid antibody syndrome. Thirty of the women developed preeclampsia during the study, and 10 had suffered from the condition in previous pregnancies.

In these 40 women, researchers looked at three genes involved in the body's immune response to injury and infection. They found seven women had mutations in at least one of these genes.

The scientists also found the mutations in five of 59 pregnant women with preeclampsia who did not have an underlying autoimmune disease.

Researchers zeroed in on the three genes because of their link to atypical hemolytic uremic syndrome, a rare, but potentially fatal disorder that triggers an out-of-control immune response.

A drug treatment for atypical hemolytic uremic syndrome that suppresses the immune response is now in clinical trials. According to Atkinson, if further research confirms the links between immune system dysfunction and preeclampsia, it may be possible to adapt the drug, called eculizumab, to treat preeclampsia in at-risk mothers.

The researchers now plan to study additional pregnant women and other genes known to play a role in regulating immune response to further understand the genetic links to preeclampsia.

Surgical technique helps adult male survivors of childhood cancer regain fertility

Mon, 14 Mar 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A new study has shown that a surgical technique called microdissection testicular sperm extraction (TESE) can effectively locate and extract viable sperm in more than one-third of adult male childhood cancer survivors who were previously considered sterile due to prior chemotherapy treatment. As a result, many of the men were subsequently able to father children with the help of in vitro fertilization. The findings offer a new option for many cancer survivors who want to have children but were thought infertile because of earlier cancer treatment.

It was previously assumed that most male survivors of childhood cancer whose semen contained little to no viable sperm were incapable of fathering children. This study demonstrates that some of these men do in fact still produce healthy sperm, and that this technique can help men experience parenthood, said senior author Peter Schlegel, MD, chairman of the Department of Urology at Weill Cornell Medical College and urologist-in-chief at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York.

Most adult men who received certain types of chemotherapy in childhood or adolescence have traditionally been considered infertile. Although some will regain their fertility up to several years after treatment, as many as two-thirds will be permanently left with very low sperm counts, a condition known as azoospermia.

Microdissection TESE enables doctors to identify small areas in the testicles where sperm are made and then carefully extract these healthy sperm cells, even in men whose testicles have been severely damaged by chemotherapy. In this study, 1,072 TESE procedures were performed between 1995 and 2009 on 892 patients with azoospermia. This group included a subgroup of 73 former cancer patients an average of 19 years after receiving chemotherapy.

Researchers were able to retrieve sperm in 37 percent (27 of 73) of male cancer survivors and in 42.9 percent of individual procedures. They subsequently applied an in vitro fertilization technique, called intracytoplasmic sperm injection (ICSI), to fertilize an egg with a single sperm. This resulted in slightly more than a 57 percent fertilization rate, a pregnancy rate of 50 percent (18 of 36), and the births of 20 children. Schlegel and his co-authors believe this is the largest group of men who have had microdissection TESE-ICSI after chemotherapy to date.

The investigators found that sperm retrieval rates differed according to the type of chemotherapy the men received. Men who received platinum drugs, such as those who were treated for testicular cancer, had the highest rate of sperm retrieval at 85 percent. Men treated with alkylating agents such as cyclophosphamide, had lower sperm retrieval rates ranging from 26 percent to 36 percent; this group mainly consisted of men treated for lymphoma. Men treated for sarcoma had the lowest retrieval rate, at only 14 percent.

When we started this study, we thought sperm retrieval rates would be close to zero among the group of cancer survivors, but we were surprised to discover that in many cases small areas of testicular tissue survived and resumed sperm production over a period of several years, Schlegel said. Even in this situation where we thought sperm production had ceased, there still may be an opportunity for fertility with the use of assisted reproductive techniques like this one.

Schlegel noted that freezing and preserving sperm prior to chemotherapy for later use � sperm banking � is an important and frequently possible option for males diagnosed with cancer. However, it remains underused for a number of reasons, including poor sperm quality, young age, cost and a desire to promptly start chemotherapy treatment. The investigators recommend that doctors offer the option to adolescents and men before starting chemotherapy, even if the chance of the treatment affecting sperm production appears small. In addition, male cancer survivors who have had chemotherapy may also become fathers through adoption and the use of sperm donors.

Intrafamilial medically assisted reproduction

Thu, 20 Jan 2011 05:00:00 PST

( from http://www.rxpgnews.com ) The ESHRE Task Force on Ethics and Law acknowledges the benefits that IMAR may bring to those choosing this approach and concludes that certain forms of IMAR are morally acceptable under certain conditions. The group advises to evaluate each request for IMAR individually, based on four ethical principles in health care: the respect for autonomy, beneficence and non-maleficence and justice.

The Task Force explains that the right for individual autonomy is elementary: any individual should have the principle of choice with whom to reproduce. It is understandable that couples wish to preserve some sort of genetic identity with the child, and hence may wish to choose a donor in the family. IMAR may facilitate a child's access to its biological roots and enable it to have contact with the donor or the surrogate mother. Often faced with no realistic alternatives due to long waiting times or lack of donors, IMAR may also be the only option available to these patients.

The ESHRE group recommends that fertility doctors should take into account the relevant regulations in their country when they assist a couple with IMAR. In some countries IMAR is illegal and the relevant laws against incest and consanguinity apply to protect the offspring from genetic risks and to avoid possible social disruptions and conflicts.

Doctors should assess any possible psychosocial and medical risks related to the treatment, says Dr. Wybo Dondorp, deputy coordinator of the Task Force. Doctors must therefore consider the principles of beneficence and non-maleficence together and aim at producing net benefit over harm for all parties involved.

Potential risks may affect several parties, including the future child. These risks can arise from intrafamilial conflict if parents feel threatened in their parental role or if they have different views from the collaborators on how the child should be informed of its genetic origins. Especially in cases of intergenerational IMAR, there are concerns that the child may be confused about his role in the family. The possible pressure on the donor or surrogate to collaborate can also lead to psychological problems. Adequate information on possible risks should be given to all parties. This includes both combined and separate counseling of recipients and collaborators to assess the voluntariness of the donation and to reduce potential conflict situations.

According to the principle of justice, doctors should treat similar cases in the same way. So if sister-to-sister oocyte donation is accepted so should brother-to-brother sperm donation. The justice principle also applies where IMAR may circumvent unjust exclusion if waiting times for donors are long or the treatment costs are too high without intrafamilial donors.

It is of paramount importance that recipients and collaborators give their informed consent. The ESHRE group is in favour of disclosure of information to the child if other relatives are aware of the familial collaboration. The counselor should offer support in any case and various strategies may be equally justified; while some would give priority to the child's right to know, others would be more concerned about the risk of confusion and accept a parental preference for secrecy.

Doctors should not accept a minor relative as a gamete donor or a surrogate. In the case of intended surrogacy the Task Force considers parenthood by the surrogate to be a precondition in order to collaborate in IMAR.

The paper gives special attention to (rare) cases of consanguineous IMAR, involving the mixing of gametes of persons that are genetically closely related. The Task Force considers consanguineous IMAR between up to third degree relatives as acceptable in principle, subject to additional counseling and risk-reduction, says Professor Guido de Wert, coordinator of the ESHRE Task Force. Here, genetic counseling is appropriate to assess the increased risk of conceiving a child affected by a serious recessive disease.

Part of adequate genetic counseling and good clinical practice in such cases is to offer carrier screening for those disorders that are more prevalent in the particular ethnic group. Given that fertility specialists have a co-responsibility for the welfare of the child, it may be morally justified to offer such genetic testing as a condition for access to assisted reproduction.

The group concludes that in some situations IMAR is morally acceptable as long as counseling of recipients and collaborators is applied in order to reduce potential psychosocial and medical risks. First-degree intergenerational IMAR needs special scrutiny, also in view of the increased risk of undermining autonomous choice. First- and second degree consanguineous IMAR is at odds with the spirit of anti-consanguinity and anti-incest legislation in most countries and should not be offered. The group encourages more research into the psychosocial implications of IMAR to contribute to adequate and moral guidance.

Preventing pre-menstrual syndrome with essential oil pill

Mon, 17 Jan 2011 08:10:30 PST

( from http://www.rxpgnews.com ) A pill containing a mix of essential oils has been shown to significantly reduce the symptoms of premenstrual syndrome (PMS). Researchers writing in BioMed Central's open access journal Reproductive Health tested the tablets by carrying out a randomised, controlled trial in 120 women.

Edilberto Rocha Filho worked with a team of researchers from the Federal University of Pernambuco, Brazil, to conduct the tests. He said, "The administration of 1 or 2 grams of essential fatty acids to patients with PMS resulted in a significant decrease in symptom scores. Furthermore, the administration of the dietary supplement did not result in any changes in the total cholesterol in the patients evaluated".

Women who were given capsules containing 2 grams of a combination of gamma linolenic acid, oleic acid, linoleic acid, other polyunsaturated acids and vitamin E reported significantly eased PMS symptoms at both 3 and 6 months after they began the treatment. Few adverse events were recorded and these were mild, insignificant and did not appear to be directly related to the medication. Speaking about the results, Rocha Filho said, "The negative effect of PMS on a woman's routine activities and quality of life may be significant, in addition to the repercussions on economic costs resulting predominantly from a reduction in productivity. Essential oil capsules can now be said to show much promise as a treatment".

UCSF study identifies chemicals in pregnant women

Fri, 14 Jan 2011 05:00:00 PST

( from http://www.rxpgnews.com ) The bodies of virtually all U.S. pregnant women carry multiple chemicals, including some banned since the 1970s and others used in common products such as non-stick cookware, processed foods and personal care products, according to a new study from UCSF. The study marks the first time that the number of chemicals to which pregnant women are exposed has been counted.

Analyzing data for 163 chemicals, researchers detected polychlorinated biphenyls (PCBs), organochlorine pesticides, perfluorinated compounds (PFCs), phenols, polybrominated diphenyl ethers (PBDEs), phthalates, polycyclic aromatic hydrocarbons (PAHs) and perchlorate in 99 to 100 percent of pregnant women. Among the chemicals found in the study group were PBDEs, compounds used as flame retardants now banned in many states including California, and dichlorodiphenyltrichloroethane ( DDT), an organochlorine pesticide banned in the United States in 1972.

Bisphenol A (BPA), which makes plastic hard and clear, and is found in epoxy resins that are used to line the inside of metal food and beverage cans, was identified in 96 percent of the women surveyed. Prenatal exposure to BPA has been linked to adverse health outcomes, affecting brain development and increasing susceptibility to cancer later in life, according to the researchers.

Findings will be published in Environmental Health Perspectives on Jan. 14, and now are available on an embargoed basis.

The study was not designed to identify direct connections to adverse health outcomes.

It was surprising and concerning to find so many chemicals in pregnant women without fully knowing the implications for pregnancy, said lead author Tracey Woodruff, PhD, MPH, director of the UCSF Program on Reproductive Health and the Environment.

Several of these chemicals in pregnant women were at the same concentrations that have been associated with negative effects in children from other studies. In addition, exposure to multiple chemicals that can increase the risk of the same adverse health outcome can have a greater impact than exposure to just one chemical, said Woodruff, an associate professor in the UCSF Department of Obstetrics and Gynecology and Reproductive Sciences.

Exposure to chemicals during fetal development has been shown to increase the risk of adverse health consequences, including preterm birth and birth defects, childhood morbidity, and adult disease and mortality according to the research team. In addition, chemicals can cross the placenta and enter the fetus, and in other studies, a number of chemicals measured in maternal urine and serum have been found in amniotic fluid, cord blood and meconium, they state.

The researchers analyzed data for 268 pregnant women from the National Health and Nutritional Examination Survey (NHANES) 2003-2004, a nationally representative sample of the U.S. population.

Our findings indicate several courses of action. First, additional research is needed to identify dominant sources of exposure to chemicals and how they influence our health, especially in reproduction, said Woodruff. Second, while individuals can take actions in their everyday lives to protect themselves from toxins, significant, long-lasting change only will result from a systemic approach that includes proactive government policies.

Widespread vitamin D deficiency a concern in Asia

Mon, 13 Dec 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Bone health experts attending the 1st Asia-Pacific Osteoporosis Meeting in Singapore this week have flagged vitamin D deficiency as a major concern in the region, particularly in South Asia where the problem is especially severe and widespread across the entire population.

Dr. Nikhil Tandon, Professor of Endocrinology and Metabolism at the All India Institute of Medical Sciences of New Delhi, India highlighted the results of various studies which show severe deficiency across India and Pakistan in all age groups, as well as insufficiency in populations of South-East and East Asia. A lack of exposure to sunshine, genetic traits and dietary habits are all factors which influence vitamin D levels. In certain regions, vitamin D deficiency can also be attributed to skin pigmentation and traditional clothing, as well as air pollution and limited outdoor activity in urban populations, he stated.

Vitamin D is primarily made in the skin when it is exposed to sunlight, with limited amounts obtained from food sources. However, in people with low sunlight exposure vitamin D is principally obtained from nutritional or supplemental sources. In the elderly, vitamin D deficiency is linked to reduced physical performance and increased risk of fall-related fractures. In children, severe vitamin D deficiency results in inadequate mineralization of bone, leading to growth retardation and bone deformities known as rickets. As well, there is evidence that children born to mothers who are vitamin D deficient during pregnancy may have reduced bone mass, which could in turn be a risk factor for osteoporosis later in life.

At a Vitamin D Roundtable held in conjunction with the meeting, nutrition and bone health experts discussed the importance of encouraging further studies on vitamin D status and risk factors in countries where data are scarce. The group is developing interactive vitamin D maps based on published data of 25(OH)D serum levels, the biomarker used to measure vitamin D status in the blood. Chair of the Roundtable, Professor Robert Josse, Professor in the Departments of Medicine and Nutritional Sciences at the University of Toronto, Canada commented, The maps will track vitamin D levels by region and different population groups, giving a valuable overview of the prevalence of vitamin D deficiency around the world. The global maps are innovative tools that will help identify problem areas, encourage awareness and stimulate research studies. By facilitating global comparisons, the maps should provide an incentive for health authorities to implement strategies to improve vitamin D status in the population.

Genes link sexual maturity to body fat in women

Sun, 21 Nov 2010 05:00:00 PST

( from http://www.rxpgnews.com ) An international group of scientists, including researchers at the Medical Research Council (MRC), has discovered 30 genes that control the age at which girls reach sexual maturity. They found that many of the genes responsible for puberty also play a strong role in how the body metabolises fat, establishing new biological links between going through puberty at a young age and being at increased risk of obesity.

This knowledge will help to explain why girls in some families are more likely to go through puberty at an early age, and may eventually help to prevent chronic health problems associated with excessive weight gain.

Reaching puberty at an early age not only puts women at an increased risk of obesity, but is also associated with a number of illnesses and poorer health in later life. A study of more than 100,000 women from Europe, the US and Australia found that many of the genes identified play an important role in the regulation of body weight. The study also identified specific genes involved in hormone regulation and cell development, showing that timing of puberty is controlled by a complex range of biological processes.

Lead author Cathy Elks at the MRC Epidemiology Unit in Cambridge says:

It is interesting that several of the new genes for puberty timing have been linked in other studies to body weight gain and obesity. This suggests that females in some families may inherit a joint genetic susceptibility to weight gain and early puberty.

Senior author Dr Ken Ong at the MRC Epidemiology Unit in Cambridge says:

We know that girls who are overweight are more likely to go through puberty at younger ages. Our findings tell us that being overweight and early puberty are intricately linked. It is also important to understand that these 'common genetic factors' can be modified by changes in lifestyle. If rates of childhood obesity continue to rise we will see many more girls reach puberty at young ages. Conversely, efforts to prevent or reduce childhood obesity will help avoid early puberty.

Senior author Dr Anna Murray at the University of Exeter says:

Scientists have long been fascinated by how the body knows whether it has enough nutrient stores to launch into puberty which leads to reproductive maturation. We found that the timing of puberty is related to fatty acid metabolic pathways. There is evidence that the brain can sense these types of body fats.

The study was supported in the UK by the Medical Research Council and the Wellcome Trust.

The findings are reported in the journal

Research on the balance of bacteria in women's bodies holds key to improving women's health

Thu, 14 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Vancouver, BC-- A team of Canadian researchers are examining the delicate balance of bacteria and viruses in women's bodies in order to optimize women's health through their lives.

Dr. Deborah Money at the Women's Health Research Institute in Vancouver is leading the initiative, called the Vaginal Microbiome Project, which will examine the communities of microorganisms (bacteria and viruses) in the vagina in order to determine what a healthy bacterial balance is for women. We know that a healthy balance is critical to preventing vaginal infections, protecting against sexually transmitted infections and preventing pregnancy loss and preterm birth. says Dr. Money. To date, we have not been able to study this ecosystem adequately because it is difficult or impossible to grow some of the bacteria in the lab, and we currently have poor methods of assessing the population of microbes.

Genomics is making it possible to crack this mystery. Thanks to the latest tools, Dr. Money's team can rapidly sequence up to hundreds of thousands of the bacteria. What's important about this approach is that we are not looking at a single bacteria in isolation, says Money. We are able to look at whole communities and how they interact with each other, which is critical to understanding how a woman keeps healthy, and to identifying when something is going wrong with her reproductive system.

The project is funded by the Canadian Institutes of Health Research (CIHR), through their Canadian Microbiome Initiative, and Genome BC, each contributing $1,745,341 and $581,781 respectively for a total of $2,327,122 over five years. This project puts Canadian researchers on the forefront of microbiome research, says Dr. Alan Winter, President and CEO of Genome BC. The fact that the research team includes people from all over Canada is a testament to how effective collaboration is in addressing key health issues.

One of the major consequences of abnormal bacterial balance in the vagina is preterm birth. Preterm birth rates are increasing for Canadian women, now at rates of almost 8%, and are responsible for 70% of newborn deaths and 50% of long-term adverse health consequences for infants. This project will study the bacterial populations associated with preterm birth and develop diagnostic tests in order to prevent preterm birth. Studies to prevent preterm birth are of importance not only for Canadian women but for women worldwide where preterm birth has even more serious consequences, says Money.

The project will be lead by Dr. Money at University of British Columbia, based at the Women's Health Research Institute, with her co-leads, Drs. Janet Hill at the University of Saskatchewan, Dr. Sean Hemminsgen at the National Research Council, Dr. Gregor Reid at the University of Western Ontario, and Dr. Alan Bocking at the University of Toronto and many other collaborators across Canada.

Can Wii help control gestational diabetes?

Wed, 13 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) TORONTO, Ont., Oct. 13, 2010--Many women have trouble finding time to exercise in their busy lifestyles. That's especially true for pregnant women who live in northern climates such as Canada, where the weather can limit outdoor activity during winter months every year.

But exercise is critical to managing gestational diabetes, a growing problem that occurs in 2 to 9 per cent of pregnancies.

Researchers at St. Michael's Hospital have proposed a novel solution. They want to offer women recently diagnosed with gestational diabetes a Nintendo Wii gaming console, a Wii Fit activity platform and two activity-promoting games, Wii Sport and Wii Fit Plus. The goal is to see whether the women get more exercise and thereby lower their blood glucose levels and decrease the need for insulin.

We all know how hard it is to maintain a proper exercise regimen in the best of times. It is obviously much harder while pregnant. We thought that by combining a fun, home-based activity with a clinical goal we will be able to achieve an important health benefit for our patients with gestational diabetes, said Dr. Howard Berger, head of the high-risk pregnancy unit at St. Michael's.

Women usually have a blood test for gestational diabetes when they are 24 to 28 weeks pregnant. The treatment is diet and exercise, such as 20-30 minutes of walking a day. If that doesn't control their blood glucose levels, they have to take insulin, which happens in 15 to 66 per cent of women with gestational diabetes.

Women with gestational diabetes are at increased risk of developing diabetes and obesity later in life. They are also at increased risk of developing complications during pregnancy and delivery, including heavier babies, pre-eclampsia, premature births, higher rates of Cesareans and post-partum hemorrhage. Newborns of a diabetic mother may also suffer from metabolic complications including hypoglycemia (low blood glucose) and hyperinsulinemia, a condition also known as pre-diabetes.

Study participants will be patients at the hospital's diabetes in pregnancy clinic, part of the Women's Health Centre, which today moves back to 61 Queen St. E. following a $6.3 million renovation of their fourth- and fifth-floor offices and exam room and the building lobby.

Our new ambulatory center for women strives to treat women as a whole, offering the most appropriate care for their individual situation and incorporating the most recent advances in health care practice and technology, said Dr. Guylaine Lefebvre, chief of obstetrics and gynecology.

The renovations include bigger examining rooms, where the patient will remain while various health care professionals come to her, and bigger ultrasound rooms, with space for partners and relatives to be present. The architect for the project was from Diamond + Schmitt Architects, who also designed the hospital's new Li Ka Shing Knowledge Institute.

Fertility concerns of cancer survivors inadequately addressed, study finds

Mon, 11 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Many cancer survivors experience changes in sexual function that leave them feeling guilty and a longing for intimacy, Australian researchers told at the 35th Congress of the European Society for Medical Oncology (ESMO) in Milan, Italy. The researchers say that these sexuality and fertility concerns are often not adequately addressed by doctors.

Professor Bogda Koczwara from Flinders Medical Centre in Adelaide said that fertility concerns among cancer survivors was a growing problem, due to a combination of improved cancer treatment outcomes in young cancer survivors and the trend for people to delay having children.

Millions of people worldwide are living after treatment for cancer, many of them still of reproductive age, Prof Koczwara said. To evaluate the range of fertility and sexuality concerns among these patients, she and her colleagues interviewed 25 cancer survivors --19 women and 6 men.

Respondents perceived fertility as an important concern that was often inadequately addressed by healthcare providers, Prof Koczwara said.

The most intriguing finding was that fertility concerns were also identified by women who have already completed their family, and fertility was an important issue even for those women who had no plans for further children.

The researchers found that fertility was important for these patients' sense of identity and body image. That is important, as doctors may not raise these issues with patients who claim not to have plans for further children. As our study points out, maybe we should.

Sexuality and fertility can be affected by cancer and its treatment in a variety of ways. For some cancers, treatment may involve removal of reproductive organs. For others, the chemotherapy or radiotherapy may affect reproductive organs function either temporarily or permanently. For most patients, cancer treatment, delays reproduction and by making the patient unwell may impact on sexual desire.

In this study, sexual concerns seemed to be related to changes in body image and sexual identity, and the often discrepant sexual needs of patient and their partner. For single people, changes in sexual function resulted in anxiety about entering into future relationships.

The lack of desire attributed to cancer treatment was associated with feelings of guilt about not supporting the partner among the participants in our study, Prof Koczwara said. With time, many respondents accepted fertility loss but struggled with ongoing impact of changes in sexual function and its impact on their relationships.

Prof Koczwara said there are some good resources available for patients to help them with concerns about fertility and sexuality, but patients in the study indicated interest in more information and resources.

There appears to be a need for raising awareness of these concerns among cancer professionals and providing them with information and training regarding these concerns, she said.

Prof Ian Olver, CEO of Cancer Council Australia, commented that the presentation by Prof Koczwara highlights a major issue that impacts on the quality of life of people who survive cancer.

Up to 65% patients diagnosed with cancer are still alive in 5 years, and survival is increasing with better treatments. Until recently the emphasis was on treating the cancer but it is being increasingly recognized that a variety of psychosocial problems and late effects of treatment persist and need to be addressed in this population, Prof Olver said.

Perhaps the most surprising aspect of Prof Koczwara's study is that issues of fertility are important even to those who have completed their families, which highlights the importance of fertility to a person's identity. The call for greater awareness amongst cancer professionals of sexual and fertility issues should be translated as the need to provide the opportunity for patients to discuss these issues and then have the appropriate support to help in their resolution.

Sexual health: Computer-based approaches increase knowledge

Tue, 07 Sep 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Interactive computer packages are effective in improving knowledge about sexual health, according to a new study by Cochrane researchers. Computer-based approaches could help to tackle problems such as sexually transmitted infections and unwanted pregnancy.

Patients may be unlikely to discuss sexual health concerns with health professionals because of the sensitivity of the issues, or simply because healthcare providers have limited time. Computer-based interventions are a promising alternative and have already proved successful in the promotion of HIV-related sexual health, but there is less certainty about whether computer-based interventions can help with other sexual health concerns such as unwanted pregnancy, psychosexual difficulties or relationship problems.

The authors reviewed data from 15 trials which tested interactive computer-based interventions (ICBIs), involving a total of 3,917 people. Interactive packages require input from the user, for instance making choices that result in personalised feedback. The interactive packages in these 15 trials made imaginative use of multimedia capability, for example games, animations, scenarios, simulations and interactive characters. The authors combined the results from the trials to answer three questions: are ICBIs effective, are they as effective as face-to-face interventions, and how do they work?

According to the researchers, ICBIs moderately increased knowledge about sexual health issues and had smaller effects on increasing people's confidence in their actions to protect sexual health, and on actual sexual behaviour. In one study for instance, condom use in the previous month was increased. They also concluded that ICBIs seem as effective as face-to-face interventions for improving knowledge but were unable to draw clear conclusions about how ICBIs might work.

This review suggests interactive computer-based interventions are effective tools for learning about sexual health and could be used by people of different ages and sexuality, at least in high-income countries, said lead researcher Julia Bailey from the e-Health Unit at University College London in London, UK. We need some new ways of tackling problems such as genital Chlamydia: More and more people have access to mobile phones and the Internet, and these routes can be used to provide personally relevant health promotion.

More evidence is needed for the cost effectiveness of ICBIs, and the relative effectiveness of different designs. The latter may rely on unpicking the complexities of sexual behaviour. Knowing the main reasons for risky behaviour in a given population would help to suggest which factors a computer package should target. For example, are there particular myths that need to be addressed? Computer packages will not be a magic bullet, but people can access them anonymously and at convenient times, which is especially important for sexual health, said Bailey.

Significant advance announced in treatment of cervical cancer

Thu, 19 Aug 2010 04:00:00 PST

( from http://www.rxpgnews.com ) A medical researcher at the University of Leicester has made a significant advance in the treatment of cervical cancer.

Dr Paul Symonds from the Department of Cancer Studies and Molecular Medicine has demonstrated that the use of a particular drug in collaboration with radiotherapy gives significantly better results than radiotherapy alone.

The study used the case histories of 1,412 patients from 42 different cancer treatment centres which were collected in 2001-2 as part of an audit which Dr Symonds led for the Royal College of Radiologists. This information included not only the treatment used but also follow-up notes which continued for five years on average, indicating whether or not cancer recurred in the pelvic area.

The new research, supported by the Medical Research Council (MRC), studied the use of a drug called cisplatin, a platinum-based molecule which directly affects the DNA strands within cells to cause controlled cell death or 'apoptosis'. It was already known that a combination of radiotherapy and cisplatin was more effective than radiotherapy alone in curing cancer of the cervix but there was no reliable data on the long-term effects of the combined treatment.

Working with colleagues in London and Manchester, Dr Symonds examined the long-term survival rates of patients after the treatment was complete. Complex statistical analysis was used to eliminate variable factors in comparing radiotherapy with 'chemoradiotherapy'.

The results showed that the addition of cisplatin to radiotherapy treatment of cervical cancer reduces the likelihood of death by a full 23 per cent. This is an important breakthrough and will be featured in the September issue of the publication Clinical Oncology alongside an editorial written by patients who have recovered through the dual treatment and another editorial presenting a doctor's view.

Dr Symonds, who is also a Consultant Clinical Oncologist at Leicester Royal Infirmary, said: The addition of cisplatin to radiation has literally saved the lives of hundreds of women with locally advanced cancer in the east midlands.

What the national audit has shown is that the addition of cisplatin improves survival. The addition of cisplatin in routine UK practice reduces the odds of death by 23%. As this is curative treatment we can genuinely say that this is a reduction in the odds of death.

This audit showed a marked improvement in 5-year survival of locally advanced cervix cancer compared to the last national audit of patients who were treated in 1993. Moreover the UK results, as derived from a total of 42 centres (most district general hospitals) show that the results in the UK are now compatible with the best international practice.

Involuntary childlessness more detrimental than originally thought

Mon, 16 Aug 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Test-tube fertilisation is the reason why more couples than previously now have the chance to become biological parents. However, the path to achieving this can be laborious and, for some, the treatment is unsuccessful. A thesis from the University of Gothenburg, Sweden, indicates that people are more negatively affected than previously reported in studies of involuntary childlessness.

In the thesis, interviews have been conducted with women and men for whom test-tube fertilisation (known as in vitro fertilisation or IVF) was concluded two years previously without resulting in childbirth. All the men had a diagnosis of severe male factor infertility and in the interviews, the men and women described their experiences of involuntary childlessness.

The study shows that childlessness amongst women feels like bereavement whilst the men's perception is described as climbing a mountain one step at a time towards the summit to achieve the goal of forming a family. The men often feel frustrated by not knowing the cause of the infertility; the emphasis is often on the woman and a sense of marginalisation can arise. For the men, the driving force is forming a family and they selflessly protect their loved ones by taking on responsibility for the situation.

Furthermore, quality-of-life, wellbeing and health were studied as well as the experience of childlessness in couples who had concluded IVF treatment around five years previously without it resulting in childbirth.

We then compared this group with couples for whom the treatment had resulted in childbirth, plus a control group of parents without infertility problems who had children of the same age, says Marianne Johansson, researcher and midwife at the Institute of Health and Care Sciences.

Two hundred couples in each group were invited in to complete a questionnaire. Men and women were also studied separately and compared with each other.

The results showed that 77% of those couples concluding public sector IVF treatment after five years were living with children, just under 40% had biological children, usually after a further IVF treatment under private care, and around 35% had adopted children.

Those couples living without children, both men and women, had a significantly poorer quality of life than those for whom IVF treatment had been successful and also in comparison with the couples in the control group.

They perceived their infertility as central to their lives and above all that quality of life amongst men without children was more negatively affected than had been previously reported in studies of involuntary childlessness, confirms Johansson.

Johansson therefore considers it important that the health service should allow time for supportive discussions following the conclusion of treatment in which the emphasis is on the couple's - the man's and woman's - reactions and thoughts regarding infertility and the future.

I also believe that the health service should strive to reduce the group in which IVF treatment has not succeeded. In some cases, this can take place by offering the couple a number of further treatments, says Johansson.

Hormonal birth control alters scent communication in primates

Tue, 27 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) DURHAM, N.C. -- Hormonal contraceptives change the ways captive ring-tailed lemurs relate to one another both socially and sexually, according to a Duke University study that combined analyses of hormones, genes, scent chemicals and behavior.

Contraception alters the chemical cues these scent-reliant animals use to determine genetic fitness, relatedness and individuality. And, as a sort of double whammy to birth-control efforts, male lemurs were shown to be less interested in females that were treated with contraceptives.

Hormonal contraception is known to alter the attractiveness of scent cues in humans and the presence of fertility cues in other primates, said Christine Drea, an associate professor of evolutionary anthropology at Duke. We wanted to understand all the ways in which contraception changes scent cues and the subsequent way these animals might interact with each other.

A dozen female lemurs at the Duke Lemur Center were given monthly injections of the contraceptive Medroxyprogesterone acetate, or MPA, (marketed as Depo-Provera by Pfizer). Drea's chemical analysis found that they expressed different scent molecules than intact females, significantly altering the signals females send about themselves to social contacts and prospective partners. In other words, they smell funny.

The findings are part of a series of studies that Drea's group has done using chromatography to tease apart the chemical components of the rich stew of scents produced by lemurs. A female lemur's scent normally conveys not only her fertility status, but also information about identity, her relatedness to others and her genetic homozygosity, an indicator of in-breeding.

If all of that information is scrambled by hormonal contraception, it may in part explain changed patterns of aggression that other studies have noted when captive primates are treated with contraceptives, Drea said.

In this study, the 12 females served as both intact and contracepted females by being sampled in each condition. Under contraception, the females were found to express some scents that intact females do not, and to express scents in different proportions. The contracepted females also tended to lose their scent individuality.

There's something very different about these gals, Drea said. If animals are figuring out who their kin are by scent, she no longer smells like her brother.

In behavioral tests, the 13 males in the study showed clear preferences for the scents of intact females, spending less time investigating odor samples from contracepted females.

The bigger question is whether these findings are relevant for our own species, Drea said. Humans are known to send and receive olfactory cues about hormonal status and possible compatibility. One has to wonder if human mate choice might be affected in some of the same ways it has been in these primates, Drea said.

Air pollution doesn't increase risk of preeclampsia, early delivery, study finds

Fri, 02 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) BUFFALO, N.Y. -- While pregnant women may worry about the effects of air pollution on their health and that of their developing child, exposure to carbon monoxide and fine particles in the air during pregnancy does not appear to increase the risk of preterm delivery or preeclampsia -- a serious condition that arises only during pregnancy -- according to results of a study headed by a University at Buffalo epidemiologist.

The research was conducted in the region around Seattle, Wash., using data from 3,675 women who were enrolled in the Omega Study, an investigation of the effects of diet and environment on women's health and nutrition before and during pregnancy.

Carole Rudra, PhD, assistant professor of social and preventive medicine at UB and first author on the study, presented the results June 23 at the Society for Pediatric and Perinatal Epidemiology annual meeting held in Seattle June 22-23. Rudra studies the ways in which the human-made environment and maternal behaviors affect health during pregnancy.

There is strong evidence that air pollutants may increase risk of cardiovascular disease, says Rudra. This led me to examine air pollutants in relation to preeclampsia, which is similar to cardiovascular disease and a risk factor for the condition. Pollutants may interfere with delivery of oxygen to the placenta and increase maternal oxidative stress and inflammation. These pathways could lead to both preeclampsia and preterm delivery.

Rudra noted that carbon monoxide levels were fairly high in the Seattle area in comparison with other U.S. cities when she began this research, but have declined significantly in recent years.

Rudra and colleagues collected data from regional air-pollutant-monitoring reports on concentrations of carbon monoxide (CO) and minute airborne particles (such as dust, fumes, mist, smog and smoke) during specific exposure windows at residences of study participants.

The exposure windows were the three months before pregnancy, the total of the first four months of pregnancy, during each trimester and the last month of pregnancy.

Preeclampsia is a condition in which high blood pressure and protein in the urine develop after the 20th week (late second or third trimester) of pregnancy. Symptoms are swelling of the hands, face or eyes, and sudden weight gain. Delivery is the only cure. Preterm delivery was defined for this study as occurring less than 37 weeks of gestation.

Analysis of the data showed that the amount of air pollutant exposure at any of the collection times had no effect on either of the pregnancy problems.

In this geographic setting and population, these two air pollutant exposures do not appear to increase risks of preeclampsia and preterm delivery, notes Rudra. She now is planning to examine women's health outcomes in relation to air pollutants in Western New York.

Europe leads the world in assisted-reproduction technology

Wed, 30 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Rome, Italy: Europe leads the world in Assisted Reproduction Technology (ART) with most cycles initiated in the region, the 26th Annual Meeting of the European Society of Human Reproduction and Embryology heard today (Wednesday 30 June).

According to data presented by the European IVF Monitoring Group (EIM), 479,288 treatment cycles were reported in 32 European countries in 2007 . This compares globally with 142,435 cycles from the US and 56,817 cycles from Australia and New Zealand. The number of cycles performed in many developed countries has grown by 5-10% per annum over the last 5 years, said Dr. Jacques de Mouzon, chairman of ESHRE's EIM. The 4.5% increase we observed in Europe from 2006 to 2007 however is partly due to more clinics reporting to our database, he added.

In 28 countries where clinics reported deliveries, more than 90,000 babies were born in 2007. There were 118,667 regular IVF treatments, 246,687 intracytoplasmic sperm injection (ICSI) cycles, 74,855 frozen embryo transfer cycles (FER), 15,028 egg donor cycles (ED), 6,822 preimplantation genetic diagnosis/screening cycles (PGD/PGS) and 660 in vitro maturation cycles (IVM). The reverse trend from IVF to ICSI continues with now 67.5% of fresh cycles using the latter technology, although the efficacy of ICSI in terms of pregnancy rates is the same as standard IVF, he added.

He pointed out that the overall rate of multiple births was very similar to the previous year with European ART twin deliveries at 20.5% and triplet deliveries at 0.8%. Most countries in Europe are now recording fewer than 1% triplet deliveries, except for Italy (2.8%), Latvia (11.1%) and Serbia (3.3%). The good news is that since 1997, we have observed a decline from 30% to 21% in overall multiple birth rates and a fourfold reduction in triplet deliveries from 3.7% to 0.8%, he said.

Nordic countries like Denmark still have the highest availability of ART at 13,263 cycles per million of women aged 15-45. The lowest availabilities were recorded in the largest economies in Europe such as Germany (3,931), UK (3,794) and Italy (3,829). This is also mirrored in the number of infants born after ART with only 1.5% in Germany, 1.8% in the UK and 1.2% in Italy. In comparison in Denmark 4.9% of all children were born through IVF.

In the last 11 years since the beginnings of the EIM we have seen a gradual increase of 26% to 33% of pregnancies per transfer for IVF and ICSI, from 15% to 22% for FER and from 27% to 46% for oocyte donation, and all this despite the transfer of fewer and fewer embryos, said Dr. de Mouzon.

In order to further assess the safety of ART, the EIM has initiated a major study (MART - the Morbidity in ART study), collecting data from a large series of ART children born in Scandinavia. Funded by ESHRE and the Medical Faculty of Copenhagen University, the team will analyse data from the national ART registers in Denmark, Finland, Norway and Sweden. We estimate that we will have about 75,000 children in our database at the end. The data from Denmark and Finland are ready, the Swedish will finalise their data soon and in Norway the application to obtain these data is currently being processed, explains Prof. Anders Nyboe Andersen, past chairman of the EIM.

Due to the possibility of cross-linking ART data with data from other health registers, the researchers will be able to assess long-term morbidity in these children and compare it with appropriate control groups. It is the long-term commitment of the EIM to expand this database to other European countries, but it will be at least a year before we can present the results to the public, Prof. Nyboe Andersen concluded.

Cheap, simple, noninvasive blood test may replace invasive diagnostic techniques in early pregnancy

Tue, 29 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Rome, Italy: Researchers in The Netherlands believe they are on the verge of developing a simple, prenatal blood test that would be able to detect accurately chromosomal abnormalities in the developing foetus. At present, the only reliable way to do this is through amniocentesis or chorionic villus sampling, both of which are invasive and carry the risk of triggering a miscarriage.

Dr Suzanna Frints, a clinical geneticist at Maastricht University Medical Centre (Maastricht, The Netherlands), will tell the 26th annual meeting of the European Society of Human Reproduction and Embryology in Rome today (Tuesday), that she and her colleagues have been able to use molecular genetic probes to detect DNA belonging to the foetus in blood samples taken from pregnant women.

So far, they have been successful in identifying DNA from the Y chromosome, indicating that the foetus is a boy and therefore could be at risk of inheriting an X-linked disorder such as Duchenne's muscular dystrophy and haemophilia. [1]

The researchers believe the same method can be used to detect trisomy 21 (where an extra chromosome 21 causes Down's syndrome) and they are investigating this next, followed by trisomy 13 and 18 (responsible for causing Patau and Edward's syndromes respectively). [2]

Dr Frints and her colleagues are using the Multiplex Ligation-dependent Probe Amplification (MLPA), technique to detect foetal DNA that is present in the blood of women who have been pregnant for at least six to eight weeks. The MLPA test is part of an existing kit that is already used around the world to detect chromosomal abnormalities in invasively obtained amniotic fluid or chorionic villi samples from pregnant women. The kit is cheap and fast, delivering results within 24-62 hours, but, until now, it has only been used on samples taken during invasive procedures; it was not known whether it would work on cell free foetal DNA circulating in blood samples of pregnant women.

It is inexpensive compared to the costs of invasive prenatal diagnosis, and could easily be implemented at low cost, between 30-150 Euros per kit per person, with a small apparatus in every hospital in the world. Blood samples can be taken during routine antenatal visits, said Dr Frints.

The study started in 2009 and is expected to continue to 2012 or longer. The researchers are recruiting women who are at high risk of an abnormal pregnancy and undergoing prenatal screening and invasive diagnostic procedures. To obtain MLPA proof of principle, they have recruited 14 women who had a pregnancy termination between 14-22 weeks gestation because of trisomy 13, 18 or 21 detected by invasive prenatal diagnosis (group A), four women who had non-invasive prenatal screening at 12-14 weeks gestation (group B), three women who had invasive prenatal diagnosis because of being at least 36 years old (group C), and nine non-pregnant control women who had had up to three children (group D). A total of 20, 715, 40 and 30 women are needed in each group respectively to complete the clinical trial to test the reliability of the MLPA technique.

The MLPA test results obtained in 2009 were compared with the results of amniocentesis, chorionic villus sampling and pregnancy outcome. All but one sample correlated with the non-invasive MLPA test results, detecting foetal Y-chromosome sequences, said Dr Frints. At the moment, the reliability of the test is about 80% due to false negative results, but we are working to improve the accuracy of the MLPA probe.

Although we need to test and refine this MLPA technique further, our results so far are promising. This is innovative translational research and when we succeed in developing the MLPA procedure for use in maternal blood, we will be able to offer a safe, cheap, fast, reliable and accurate non-invasive test, which will be of immediate benefit to pregnant women, young and old, all over the world.

The researchers hope the test may be available in the clinic in two to five years' time.

Study finds why some women are sub-fertile with a poor response to ovarian stimulating hormones

Tue, 29 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Rome, Italy: Researchers have discovered that some women carry a genetic variation that makes them sub-fertile and less likely to respond to ovarian stimulating hormones during fertility treatment. The discovery opens the way to identifying these women and devising personalised fertility treatments that could bypass the problem caused by the genetic abnormality.

Dr Maria Lalioti told the 26th annual meeting of the European Society of Human Reproduction and Embryology in Rome today (Tuesday) that she and her colleagues from the Yale University Medical School, New Haven (USA), had found that some women had an abnormal hormone receptor on cells surrounding oocytes (eggs). This abnormal receptor impaired the function of normal receptors that were also present and resulted in the affected women responding less well to Follicle Stimulating Hormone (FSH), which is given to women during fertility treatment to stimulate the production of more than one oocyte.

Dr Lalioti, as assistant professor in the Department of Obstetrics Gynecology and Reproductive Sciences at Yale, said: When a woman undergoes in vitro fertilisation, she receives medication called Follicle Stimulating Hormone to produce more than one oocyte, which is the normal production each month. Cells called granulosa cells, which surround the oocyte, receive the FSH; these cells excrete other factors that 'feed' the oocyte. The granulosa cells have proteins present on their surface called FSH receptors (or FSHR) and it is these proteins that stick to the FSH and then carry signals into the cell's interior. When we looked at a portion of these granulosa cells in the laboratory we saw that in some women, who produced very few oocytes, there were some receptors that lacked a piece of the protein, although there were still other, normal FSHR in the women's cells.

The abnormal FSHR contained a deleted sequence of protein called exon 2 that is an important part of the protein that binds the FSH; FSHR with the exon 2 deletion was only detected in women younger than 35 who had a poor response to FSH and yielded less than four oocytes in a follicle stimulating cycle.

We produced the normal and abnormal protein in the lab in a different type of cell called HEK293 (Human Embryonic Kidney) which is a common cell type used in the labs to examine properties of proteins. We saw that when the abnormal receptor was present, the normal one could no longer work as well as it does when it is the only protein present, explained Dr Lalioti. The receptor is normally present on the cell surface in order to meet and bind FSH, and it needs to go through a number of cellular checkpoints inside the cell that assure the quality of the protein presented on the surface. We saw that the abnormal receptor remains longer in one of these checkpoint compartments, indicating that the cell has detected a problem and is trying to correct it. In this way the abnormal FSHR can contribute to an abnormally low response to stimulation in certain women undergoing IVF.

Dr Lalioti's discovery of the mechanism behind why some young women have a poor response to FSH has important implications for future research and treatment of these women. The importance of this finding is that it creates a link between genetic variation and sub-fertility. These women have a normal menstrual cycle and they may present to the fertility centre as patients with unexplained infertility, before their first IVF cycle that would reveal an ovarian stimulation defect, she said.

Our finding explains why these women have a lower response to FSH. Currently, FSH is the only medication used to stimulate ovarian response, but once other medications are available that can bypass the receptor for FSH, they can be tested on these women. Also, at present we cannot predict if the women would profit from having higher doses of medication, and, in fact, some preliminary data from other groups show the opposite: that lower FSH may be more beneficial.

Future research will examine the FSHR signalling mechanisms within the cell and investigate how newly developed drugs might bypass the problems created by the genetic abnormality. In the future, this could lead to personalised treatments for a sub-group of patients, said Dr Lalioti.

It is not known how many women have this particular genetic variation. Dr Lalioti found it in two out of five women that she tested. These patients are hard to recruit because most patients with a low response to FSH do not complete the IVF cycle for financial reasons, she said. We need to recruit more patients to discover how common it is. She and her colleagues will need a year to recruit and test more women, to set up collaborations with more fertility centres and to start to test new drugs that could promote oocyte production more effectively in these women.

Ovarian transplantation restores fertility to old mice and also lengthens their lives

Tue, 29 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Rome, Italy: Scientists have discovered that when they transplant ovaries from young mice into aging female mice, not only does the procedure make the mice fertile again, but also it rejuvenates their behaviour and increases their lifespan. The question now is: could ovarian transplants in women have the same effect?

Dr Noriko Kagawa will tell the 26th annual meeting of the European Society of Human Reproduction and Embryology in Rome today (Tuesday) that successful ovarian transplants increased the lifespan of the mice by more than 40%. At present ovarian transplants are performed with the aim of preserving a woman's fertility after cancer treatment for instance, or of extending her reproductive lifespan. However, the completely unexpected extra benefit of fertility-preserving procedures in our mouse studies indicates that there is a possibility that carrying out similar procedures in women could lengthen their lifespans in general, she said.

A very small number of women in the world have had ovarian transplants, and some have been more successful than others. Dr Kagawa stressed that there was still a lot of research to be carried out before it would be known whether ovarian transplants had similar, rejuvenating effects in women, particularly as it would involve waiting for many years until the patients became older.

Dr Kagawa, Associate Director for Research at the Kato Ladies' Clinic in Tokyo (Japan), told the conference that she and her colleagues had conducted two mouse experiments. In the first, both ovaries were removed from young female mice (about 140 days old), and transplanted in to six older mice (aged over 525 days) that were too old to be fertile any more. In the second experiment, only one ovary was removed from the young mice (about 170 days old) and transplanted into eight aged mice (over 540 days old). The average normal lifespan for this particular breed of mice (C57BL/6J) is 548 days, and they normally reach a mouse menopause at about 525 days old.

All the mice that received transplants in both experiments became fertile again, while control mice that had not received transplants did not. In the first experiment the mice resumed normal reproductive cycles that lasted for more than 80 days, and in the second experiment, they lasted for more that 130 days.

Dr Kagawa said: All the mice in both experiments that had received transplants resumed the normal reproductive behaviour of young mice. They showed interest in male mice, mated and some had pups. Normally, old mice stay in the corner of the cage and don't move much, but the activity of mice that had had ovarian transplants was transformed into that of younger mice and they resumed quick movements. Furthermore, the lifespan of the mice who received young ovaries was much longer than that of the control mice: the mice that had received two ovaries lived for an average of 915 days, and the mice that had received one ovary, for an average of 877 days. The newest of our data show the life span of mice that received transplants of young ovaries was increased by more than 40%.

The results show that transplanted normal ovaries from young mice can function in old, infertile mice, making them fertile again, but, in addition, extending their lifespan. Women who have ovarian tissue frozen at young ages, perhaps because they are about to embark on cancer treatment, can have their young ovarian tissue transplanted back when they are older. Normally we would be doing this simply to preserve their fertility or to expand their reproductive lifespan. However, our mice experiment suggests that this might also improve overall longevity. Further research has to be conducted before we can know whether or not this is the case.

Dr Kagawa said it was not known why the ovarian transplant increased the lifespan of the mice, but it might be because the transplants were prompting the continuation of normal hormonal functions.

She and her colleagues have been collaborating for the past six years with Dr Sherman Silber, from St Luke's Hospital, in St Louis, Missouri (USA), who has performed a number of successful ovarian transplants in women, either because they were about to be treated for cancer or because they had not yet found the right partner in life. Their future collaborative research will include investigating whether it is possible for a woman to have a transplant using an ovary that is not her own and with minimal drugs to suppress the body's natural immune response to what it perceives as a foreign body. They are also looking at culturing follicles in ovarian tissue in the laboratory in order to obtain mature eggs that can be used for IVF.

In the meantime, the researchers believe it is very important for doctors and patients to know that women have options when faced with cancer treatment that could destroy their fertility. We have been successful in getting frozen ovaries to function completely normally after thawing and transplantation, said Dr Kagawa. So this should no longer be considered an 'experimental' procedure. Ovarian transplantation is the proper and necessary accompaniment to otherwise sterilising treatment for young cancer patients. We must not neglect to freeze and save at least one of their ovaries before cancer treatment.

Studies of women's attitudes to 'social egg freezing' find reasons differ with age

Mon, 28 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Rome, Italy: Women of different ages differ in their reasons for wishing to undergo egg freezing, show two studies presented to the 26th annual meeting of the European Society of Human Reproduction and Embryology today (Monday). A large number of female university students would be prepared to undertake egg freezing in an attempt to combine career success and motherhood, said Dr. Srilatha Gorthi, a research fellow at the Leeds Centre for Reproductive Medicine, Leeds, UK, adding that her team's research emphasised the importance of educating young women about their biological clocks in order that they could take informed decisions about future reproduction.

Dr. Gorthi surveyed 98 medical students (group A) and 97 students of education and sports studies (group B) from the University of Leeds. Information regarding egg freezing was provided, including the fact that they would have to finance their own egg freezing. The average age was 21 with age range from 18-30 years in both the groups; 63.3% of the medical students were not in a relationship, as opposed to 25.8% in group B, probably reflecting the level of commitment and time needed for their courses.

While 85.7% in group A said that they would be prepared to delay starting a family, only 49.5% in group B said they would consider this. Eight out of ten from group A said they would undergo egg collection and freezing, compared with only half as many (four out of ten) from group B. In group A, 85.3% were prepared to undergo up to three cycles of egg collection to bank enough eggs to give them a realistic chance of pregnancy. In contrast, the majority (79%) of those who would bank their eggs from group B said they would be prepared to undergo only one cycle of egg collection.

Career considerations were given as the commonest reason to delay starting a family in group A, followed by financial stability and marriage or a stable relationship, said Dr. Gorthi. However, in group B, financial stability came first, followed by a stable relationship and then career reasons. We think that this is the first time that young women's attitudes to egg freezing have been studied in this way.

Egg freezing is still a relatively new technology; a woman has to go through an IVF treatment cycle, which takes two to four weeks and carries certain risks: ovarian hyperstimulation, haemorrhage, infection and a possible, albeit small, effect on future natural fertility.

Endometriosis has a significant effect on women's work productivity, first

Mon, 28 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Rome, Italy: The first worldwide study of the societal impact of endometriosis has found a significant loss of work productivity among those women who suffer from the condition, a researcher told the 26th annual meeting of the European Society of Human Reproduction and Embryology today (Monday). Dr. Kelechi Nnoaham, from the Department of Public Health, University of Oxford, UK, said that the results of this multi-centre study would help highlight the previously unrecognised plight of an estimated 176 million women around the world whose lives are affected by endometriosis.

Endometriosis is a painful inflammatory disease that, for many women, is chronic during their reproductive years. The inflammation occurs in cells similar to the endometrial cells of the uterus, which are found primarily in the pelvic cavity, on pelvic organs, and also on the bowel, bladder and (rarely) in the lungs.

Dr. Nnoaham and colleagues recruited 1459 women aged 18-45 from 14 participating centres in ten countries across five continents to the Global Study of Women's Health (GSWH). The women were all scheduled to undergo a laparoscopy because of symptoms suggestive of endometriosis. Women who had been previously diagnosed with endometriosis were excluded. The participants were asked to complete a comprehensive questionnaire about their symptoms and the impact these had on their lives. After surgical diagnosis the questionnaires were analysed according to whether the women had been diagnosed with endometriosis or other conditions. Those not diagnosed with endometriosis acted as controls.

Scientists already know that women with chronic pelvic pain report a lower quality of life. But the GSWH is the first study to assess whether women with endometriosis-related pelvic pain are affected differently than those with pelvic pain from other or no identifiable causes, which our study confirmed is indeed the case, said Dr. Nnoaham. Our research is the first ever prospective study to be undertaken in the field of endometriosis to assess the impact of the disease.

The researchers found that there were substantial differences between those with endometriosis and controls. Loss of work productivity among employed women with endometriosis averaged ten hours per week, versus seven hours per week with those who had other disorders, said Dr. Nnoaham, and this was primarily due to reduced productivity rather than absence from work. Non-work related activities, such as housework, exercising, studying, shopping and childcare were also significantly impaired by the painful symptoms of the condition.

Through its symptoms, endometriosis impairs quality of life in all the areas covered by the Short Form (36) Health Survey (SF-36), a standard tool for measuring health-related quality of life, except for physical functioning and mental health. As symptoms become more severe, quality of life worsens, said Dr. Nnoaham.

Overweight women undertaking ART twice as likely to miscarry as their slimmer counterparts

Mon, 28 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Rome, Italy: Being overweight leads to a greater risk of miscarriage for patients undergoing assisted reproductive technology (ART), the 26th annual conference of the European Society of Human Reproduction and Embryology heard today (Monday). Dr. Vivian Rittenberg, a Clinical Fellow in the Assisted Conception Unit, Guy's and St. Thomas' Hospital NHS Foundation Trust, London, UK, said that her research provided additional evidence to show that increased body mass index (BMI) was independently associated with a higher miscarriage rate after IVF or ICSI treatment. This information should be included in the counselling given to patients before they undertake ART, she said.

Dr. Rittenberg and colleagues analysed all pregnancies arising after single blastocyst (five-day embryo) transfer (SBT) performed in their clinic over a four year period, between January 2006 and December 2009. The 318 women were divided into two groups according to their BMI at the start of their treatment cycle. One group of 185 women had BMI in the normal range, from 18.5-24.9, and the other group (133 women) was made up of those who had a BMI of 25 or above. Of this group, 19 (14%) were obese, defined as having a BMI of 30 or more.

Overall, 26% of women miscarried before 20 weeks gestation. The researchers found that the miscarriage rate was significantly lower in women with normal weight (22%) compared to women who were overweight (33%). After adjusting for other variables that might have skewed the results such as age, duration of infertility, smoking and a history of previous miscarriage, they were able to show that being overweight or obese more than doubled the risk of miscarriage.

Although there is evidence that miscarriage rates are higher in overweight women who conceive spontaneously, there were conflicting views about the effect of increased weight on the outcome of pregnancies occurring after IVF and ICSI, Dr. Rittenberg said. The difficulty of interpreting the studies to date is that they are heterogeneous, their thresholds for defining obesity vary, and they assess the outcome in relation to BMI following the transfer of multiple embryos at various stages of development. Our study differs in that we transferred only one embryo at a specific stage of development, and were therefore able to provide clear evidence of the deleterious effect of being overweight on the chances of miscarriage.

Being overweight can lead to a number of other pregnancy risks including high blood pressure, pre-eclampsia, diabetes, premature delivery and post-partum bleeding. Besides the inherent medical dangers of these conditions, they can lead to lengthy hospital stays for the pregnant woman. Additionally, babies of obese mothers are more likely to have a high birth weight and thus may face an increased rate of delivery by Caesarean section, which in itself can cause complications for both mother and baby.

Overweight women wishing to get pregnant by spontaneous conception are already counselled to lose weight before trying for a baby, said Dr. Tarek El-Toukhy, Consultant in Reproductive Medicine at the Assisted Conception Unit, Guy's and St. Thomas' Hospital NHS Foundation Trust, London, UK, who led the study. Our findings have shown clearly that women undertaking ART should be strongly encouraged to heed this advice in order that they can have the best possible chance of obtaining and maintaining a pregnancy.

IUDs reduce pregnancy rates compared to hormonal contraceptives

Tue, 15 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Women who have had intrauterine devices (IUDs) fitted as contraceptives are less likely to become pregnant than those who have hormone injections, a new review by Cochrane Researchers has found. The review, which focused on women in developing countries, also found a possible link between contraceptive method and disease progression in HIV.

An IUD, sometimes known as a coil (although IUDs are no longer coil-shaped) is a plastic and copper device that sits in the womb preventing sperm from crossing it and making its lining less likely to accept a fertilised egg. There are also IUD's which contain hormones rather than copper, which were not evaluated in this study. In many countries IUDs are not widely used, perhaps because they can only be inserted by skilled professionals. Women often experience pain after insertion, but IUDs may be preferred long-term to other contraceptive methods because they last for five to ten years and have no hormonal effects. Hormonal contraceptives, by comparison, have been associated with side effects and require more frequent visits to the health care provider for injections or prescriptions.

The researchers reviewed data from two studies comparing IUDs and hormonal contraceptives, which together involved 967 women. The first included women attending family planning clinics in Brazil, Guatemala, Egypt and Vietnam and the second focused on HIV-positive women in Zambia. In each study, women were randomly assigned to have an IUD inserted or to receive hormonal contraceptives. Hormonal contraceptives were given only by injection in the first study, but women were allowed to switch between pills and injections in the second. Overall, fewer became pregnant in the groups receiving IUDs. Drop-out rates were higher for those using hormonal contraceptives in the first study and for those fitted with IUDs in the second study.

Lead researcher Justus Hofmeyr, of the Department of Obstetrics and Gynaecology at the University of the Witwatersrand and Eastern Cape Department of Health, South Africa, said the study highlights issues of choice in contraception. This information will be useful for counselling women regarding their choice of contraception, he said. The importance of choice is suggested by the fact that fewer women stopped taking hormonal contraceptives when they were allowed to switch between different types.

There was also some indication that progress of HIV was slower in women using IUDs, although the researchers say further analysis of this effect is required. A large, high quality study is urgently needed to shed light on these findings, said Hofmeyr. Meanwhile, HIV positive women should be given the option of using an IUD.

Exposure to nitrogen dioxide lowers in vitro fertilization success

Mon, 12 Apr 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Exposure to an increased level of air pollutants, especially nitrogen dioxide, has been associated with lower likelihoods of successful pregnancy among women undergoing in vitro fertilization, according to a team of fertility researchers.

The team examined the outcomes of the first pregnancy attempt of 7,403 women undergoing IVF at Penn State Milton S. Hershey Medical Center, Hershey, Pa.; Shady Grove Fertility, Rockville, Md.; and Columbia University College of Physicians and Surgeons, New York, N.Y. They conducted their observations over a seven-year period from 2000 to 2007.

Numerous studies have consistently shown a relationship between air pollution and human health, ranging from mortality, cardiovascular disease and other chronic conditions, said Duanping Liao, Ph.D., professor of epidemiology and vice chair department of public health sciences, Penn State College of Medicine. In the process of searching for the mechanisms responsible for the above associations, we, and others, have reported significant links between air pollution and inflammation and increased blood clotting. These intermediate factors are also associated with reproductive health.

The IVF population was chosen, as it is a well-controlled and timed process to investigate the association of air pollution and human reproductive effects.

Burning of fossil fuels and diesel engine combustion produces nitrogen dioxide and fine particles. Researchers looked at those pollutants along with ozone, the gas involved in smog formation. While the effects of declining air quality on IVF success are variable and pollutant-dependent, elevated exposures to nitrogen dioxide and fine particles were consistently associated with lower success rates of pregnancy.

Researchers looked at the effects of pollution particles both individually -- single pollutant model, and with other particles -- multi-pollutant model. For the single pollutant model, exposure to ozone appeared to have a positive association with a successful birth if the exposure was before the embryo culture or embryo transfer. Researchers theorize that higher ozone levels indicate lower nitrogen dioxide levels, which would show better pregnancy outcomes. In addition, for the multi-pollutant model, the positive effects of ozone were diminished with the addition of nitrogen dioxide. In contrast, after adjusting for ozone, higher nitrogen dioxide exposures consistently associated with the lower success rate, regardless of which indictor was used -- positive pregnancy test, clinically confirmed intrauterine pregnancy or live birth.

These findings may be useful in studying the adverse effects of air pollution on human reproduction in general.

Since IVF is a well controlled and highly timed process, we have a much better handle on the assessment of the time of exposures to elevated air pollutants in relationship to fertilization, pregnancy, and delivery, Liao said. Therefore, the IVF population coupled with detailed assessment of air pollution exposures may provide us an ideal situation to investigate the potential health effects of air quality on human reproduction.

Air pollutant concentration data for the study period came from the U.S. Environmental Protection Agency. The researchers calculated daily pollution concentrations for each patient during the entire in vitro cycle and pregnancy. They calculated varying periods of air quality exposure for average daily concentrations at the patient's home during four stages of IVF and at the IVF clinic during fertilization and embryo transfer.

Pregnant women can receive breast cancer chemotherapy without endangering health of their babies

Thu, 25 Mar 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Barcelona, Spain: Women who discover they have breast cancer while they are pregnant can be treated with chemotherapy without endangering the health of their unborn baby, according to research to be presented at the seventh European Breast Cancer Conference (EBCC7) in Barcelona today (Friday).

Dr Sibylle Loibl, Assistant Professor in Obstetrics and Gynaecology at the University of Frankfurt, Germany, and a member of the German Breast Group, will tell the conference that pregnant breast cancer patients can be treated as close as possible to standard recommendations because chemotherapy delivered while babies were in the womb did not appear to cause the babies significant problems at or after birth.

Until now, the evidence upon which we based our decisions about how to treat pregnant women with breast cancer has been largely limited to case studies and retrospective investigations. For this reason doctors have tended to be cautious in their approach to treatment because of fears about the effect it might have on the foetus, even though it meant that women did not necessarily receive the best treatment for their cancer, said Dr Loibl. Therefore, the German Breast Group set up a registry to collect data both retrospectively and prospectively from patients who have been diagnosed with breast cancer during pregnancy. It is the only international registry to focus on the outcomes of both the mother and the baby.

The researchers entered details of 235 patients prospectively (119) and retrospectively (116) to the registry between April 2003 and October 2009. The ages of the women ranged between 23 and 46 with an average (median) age of 33. Breast cancer was diagnosed, on average, at 23 weeks into the pregnancy. Not all the data are complete yet, but out of 151 women, 91 received an average of two cycles of chemotherapy while they were pregnant.

The average gestational age of the babies at the time of delivery was 36 weeks, ranging between 28 and 42 weeks. Babies that were exposed to chemotherapy during pregnancy were born slightly lighter than babies who were not: an average of 2636mg, compared to 2791mg.

Of the 91 babies exposed to chemotherapy, three were born bald (alopecia), one was small for gestational age, one had trisomia 18 (a chromosomal disorder) and died one week after birth, one had necrotic enterocolitis (a severe bacterial infection of the intestine) and died three weeks after birth, one developed sepsis (blood infection), one developed neutropenia (low white blood cell count) and two had anaemia. Of the 60 babies who were not exposed to chemotherapy, one had temporary apnoea (breathing interruption), one had an increase in C reactive protein (a protein that appears in response to inflammation or infection) and one had gastroenteritis.

Dr Loibl said: Most of the problems described in the babies exposed to chemotherapy were not related to the treatment but were most probably due to other circumstances (for instance, necrotic enterocolitis due to preterm delivery or trisomia 18). Normally, in nature, there is a risk of malformations of between one and two percent, and other problems such as infection can happen. The foetal outcomes of these babies that received chemotherapy were not significantly different from those who did not.

Therefore, this study suggests that pregnant breast cancer patients can be treated as close as possible to standard recommendations and receive chemotherapy, if it is indicated, while they are pregnant. Ideally, this should take place in the care of specialised, multidisciplinary teams. We would like to generate more robust data to confirm this and so the registry is continuing and we are updating and completing the data.

In addition to the data on outcomes for mothers and babies, Dr Loibl and her colleagues are also collecting tumour specimens and placenta material from the women who are being followed prospectively, and these are sent to the German Breast Group's biomaterial bank. The researchers hope that this will give them important information in the future about the effects of pregnancy and chemotherapy on outcomes for mothers and babies.

Panel questions 'VBAC bans,' advocates expanded delivery options for women

Wed, 10 Mar 2010 05:00:00 PST

( from http://www.rxpgnews.com ) An independent panel convened this week by the National Institutes of Health confronted a troubling fact that pregnant women currently have limited access to clinicians and facilities able and willing to offer a trial of labor after previous cesarean delivery because of so-called VBAC bans. Many, even those at low risk for complications in a trial of labor, are not offered this option. The panel affirmed that a trial of labor is a reasonable option for many women with a prior cesarean delivery. They also urged that current VBAC guidelines be revisited, malpractice concerns be addressed, and additional research undertaken to better understand the medical and non-medical factors that influence decision making for women with previous cesarean deliveries.

Declining VBAC rates and increasing cesarean delivery rates over the last 15 years would seem to indicate that planned repeat cesarean delivery is preferable to a trial of labor. But the currently available evidence suggests a very different picture: a trial of labor is worth considering and may be preferable for many women, said Dr. F. Gary Cunningham, panel chair, and chair of obstetrics and gynecology at the University of Texas Southwestern Medical Center at Dallas.

Rigorous research shows that a trial of labor is successful in nearly 75 percent of cases, and maternal mortality is actually lower for women who have a trial of labor, regardless of whether they end up delivering vaginally or by cesarean, though those women who have an unsuccessful trial of labor and undergo a repeat cesarean delivery experience higher morbidity than those who have a successful VBAC.

In light of their assessment of VBAC's relative safety, the panel urged professional societies to revisit existing VBAC guidelines, in particular, the recommendation for immediate availability of surgical and anesthesia personnel as prerequisites for offering a trial of labor; two recent surveys of hospital administrators found that 30 percent of hospitals had stopped offering trial of labor or providing VBAC services because they could not meet this standard, creating a serious barrier to that option.

The panel thus advocated for additional research to develop clear, evidence-based risk assessment tools to assist mothers and providers in the decision-making process from early pregnancy through delivery, accounting for individual risk factors, values, and preferences.

The panel also expressed concern that medico-legal considerations exacerbate other barriers to trial of labor for women with a previous cesarean delivery. They strongly recommended that policymakers and providers collaborate in the development and implementation of appropriate strategies to address malpractice concerns and mitigate this problem.

There's still a lot we don't know about which women will be successful in having a VBAC, but we believe it's essential that women's desires and preferences be respected throughout the decision making process, said Dr. Cunningham.

Safety is the chief concern for women and their providers in deciding whether to attempt a trial of labor or plan a repeat cesarean delivery. Each option carries important benefits and risks for both mother and baby. This poses a profound dilemma because benefits for the woman may come at the price of increased risks for the baby, and vice versa. For example, hysterectomy rates were comparable across both modes of delivery, but uterine rupture was higher in women who have a trial of labor. Conversely, women who had a VBAC had reduced abnormalities of placental growth and position in subsequent pregnancies. Unfortunately, the lack of high-quality evidence about many medical and non-medical factors prevents precise risk calculations that could inform the decision-making process.

Factors contributing to some women's desire to attempt a trial of labor include desire for their partner's involvement in the delivery, belief that labor and vaginal delivery can be deeply empowering, enhanced opportunity for maternal-infant bonding, greater ease in establishing breast feeding, and easier recovery. Conversely, scheduling convenience, the desire to avoid labor pain, fear of failed trial of labor, avoidance of possible emergency cesarean section, and desire for surgical sterilization at the time of delivery may all contribute to a preference for planned cesarean delivery.

Prior to 1980, VBACs were generally discouraged because of the widely held idea that once a woman had a cesarean delivery, any subsequent pregnancies would also have to be delivered by cesarean. After a 1980 consensus statement questioned routine repeat cesarean delivery, VBAC rates increased steadily until 1996 when rates began to decline again. This panel's deliberations took place in the context of this trend, in which the current overall cesarean delivery rate is 31 percent and the VBAC rate is less than 10 percent compared to 28 percent in 1996.

Changes during menopause increases risk of heart disease and stroke

Tue, 23 Feb 2010 05:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO- When women hear the word menopause, they often think about hot flashes, hormone shifts and mood swings. But what about heart disease? Studies show a woman's risk of heart disease intensifies drastically around the time of natural menopause, which for most women is around the age of 50. This news may come as a surprise, but experts explain that understanding risk factors is an important first step, and reassure women that there are ways to lower your risk.

Many women younger than 50 have not yet gone through menopause and still have high levels of the female hormone estrogen in their blood, which is thought to help protect the heart. After menopause, however, the levels of estrogen in a woman's body drop significantly and can contribute to the higher risks of cardiovascular disease, explains Vera Rigolin,MD, associate director of the Center for Women's Cardiovascular Health in the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital.

Weight gain is also a factor that may play a role in postmenopausal risk of heart disease. Maintaining a healthy weight often becomes difficult after your body experiences a change in hormone levels. Extra mass can take a toll on the body causing physical inactivity, high blood pressure, diabetes, and high cholesterol, all risk factors that can lead to heart attack and stroke.

Detecting heart disease in women can be difficult. Many women are unaware that symptoms of the disease may differ from those of men. Although women often experience chest discomfort when presenting with a heart attack, they commonly have other, more subtle symptoms, including fatigue, nausea, shortness of breath, jaw pain and general discomfort in the chest and abdominal area.

In some women, plaque can build in the smallest blood vessels called the microvascular circulation. These blockages do not show up in an angiogram, says Rigolin. In these cases, we often use Magnetic Resonance Imaging (MRI) with medication to visualize blood flow within the small blood vessels when other standard tests do not provide us answers.

Women, especially those who are menopausal can reduce the risk of heart disease by adopting a healthy lifestyle.

If you are a smoker, quit immediately and avoid second hand smoke. Eat a diet rich in fruits and vegetables and exercise at least three times per week to maintain a healthy body weight, says Rigolin.

Rigolin also recommends visiting your health care provider at least once per year to have your blood pressure, blood sugar and cholesterol levels checked.

In vitro pregnancy rates improve with new device that mimics motions in the body

Mon, 18 Jan 2010 05:00:00 PST

( from http://www.rxpgnews.com ) The University of MichiganNews Service412 MaynardAnn Arbor, MI 48109-1399

Jan. 18, 2009Contact: Nicole Casal Moore, (734) 647-1838 or (734) 647-7087, ncmoore@umich.edu

EDITORS: Watch and link to a video about this research at: http://www.youtube.com/watch?v=ZnNS_yUFTDg

Images are available at: http://umich.edu/news/index.html?Releases/2010/Jan10/oviduct

In vitro pregnancy rates improve with new device that mimics motions in the body

ANN ARBOR, Mich.---Gently rocking embryos while they grow during in vitro fertilization (IVF) improves pregnancy rates in mice by 22 percent, new University of Michigan research shows. The procedure could one day lead to significantly higher IVF success rates in humans.

Researchers built a device that imitates the motion that embryos experience in the body as they make their way down a mammal's oviduct (a woman's Fallopian tube) to the uterus. Currently in IVF, eggs are fertilized with sperm and left to grow for several days in a culture dish that remains still. Then the embryos are transferred to the uterus.

By making the cells feel more at home, we get better cells, which is key to having better infertility treatment, said Shu Takayama, an associate professor in the Department of Biomedical Engineering and in macromolecular science and engineering.

Takayama and Gary Smith, associate professor in the Department of Obstetrics and Gynecology at the U-M Medical Center, are co-authors of a paper detailing the findings published online in the journal Human Reproduction.

Their device holds early-stage embryos, which are about half the size of the period at the end of this sentence, in a thimble-sized funnel. The bottom of the funnel is lined with microscopic channels that allow fresh nutrient-rich fluid to flow in and waste products out. The funnel sits on rows of Braille pins that are programmed to pulse up and down, pushing the fluids in and out of the channels.

The current the Braille pins generate simulates flows that occurs in the body due to muscle contractions and the motion of hair-like projections called cilia that line the oviducts. In the body, these motions help to push fertilized eggs to the uterus and flush out eggs' waste products.

Compared with mouse embryos grown in a static dish, those incubated in the new dynamic device were healthier and more robust after four days. Those grown in static dishes contained an average of 67 cells. Those grown in the new device had an average of 109. Control embryos that had matured in the bodies of mice for the same amount of time had an average of 144 cells.

Approximately 77 percent of the rocked mouse embryos led to ongoing pregnancies, compared with 55 percent of the statically-grown embryos. In a control group of mouse embryos conceived naturally and grown within the oviduct, 83 percent led to ongoing pregnancies.

One of our goals for years now has been to modify how we grow embryos in the lab to be more like how they grow in the human body, because we know that the human body grows them most efficiently, Smith said.

Infertility affects one in six couples, Smith said. Many of them turn to IVF, which can cost $15,000 per cycle and is often not covered by insurance. Currently, it has a success rate of about 35 percent.

If we could increase that, even just to 45 percent, that's significant, Smith said. We're making healthier embryos, which not only can improve pregnancy rates, but also could allow us to transfer fewer embryos per cycle and reduce the incidence of twins and triplets.

Through the company Takayama and Smith founded, Incept Biosystems, human clinical trials have begun.

Smith is also an associate professor in the departments of Molecular and Integrative Physiology and Urology, as well as director of the Reproductive Sciences Program.

The paper is called Dynamic Microfunnel Culture Enhances Embryo Development and Pregnancy Rates. The research is funded by the National Institutes of Health, the U.S. Department of Agriculture, the Michigan Economic Development Corp., the U.S. Army Research Laboratory and the Coulter Foundation.

For more information:

Shuichi Takayama: http://www.bme.umich.edu/labs/takayama/index.html

Gary Smith: http://www2.med.umich.edu/healthcenters/provider_profile.cfm?individual_id=76912

Full text of Dynamic Microfunnel Culture Enhances Embryo Development and Pregnancy Rates: http://humrep.oxfordjournals.org/cgi/reprint/dep449

Michigan Engineering:The University of Michigan College of Engineering is ranked among the top engineering schools in the country. At more than $130 million annually, its engineering research budget is one of the largest of any public university. Michigan Engineering is home to 11 academic departments and a National Science Foundation Engineering Research Center. The college plays a leading role in the Michigan Memorial Phoenix Energy Institute and hosts the world class Lurie Nanofabrication Facility. Find out more at http://www.engin.umich.edu/.

3 IVF attempts double chances

Mon, 09 Nov 2009 05:00:00 PST

( from http://www.rxpgnews.com ) Just one in three women gives birth after a single IVF attempt, but the cumulative chance of a live birth increases with each cycle - where women are offered three cycles nearly two thirds go on to have babies, reveals a thesis from the Sahlgrenska Academy at the University of Gothenburg in Sweden.

Around three per cent of all children born in Sweden are test-tube babies resulting from IVF (in vitro fertilisation).

There are considerable discrepancies between the number of cycles offered by the various regional councils, says physician Catharina Olivius, author of the thesis. Some councils, primarily in northern Sweden , offer just one free attempt, but this study shows that a couple's chances of having a baby increase considerably over three cycles.

The study followed almost a thousand women during their IVF treatment at Sahlgrenska University Hospital . The probability of having a baby was 35 per cent after one treatment, 52 per cent after two treatments and 63 per cent after three treatments. It was slightly higher for women under the age of 35.

Half of the couples who did not have a baby dropped out of IVF before three attempts. The most common reasons were that the treatment was felt to be too psychologically stressful, and that the chances of having a baby were considered to be very slim.

My conclusion is that we need to get better at looking after patients' mental welfare during treatment, says Olivius. A greater sense of wellbeing among patients would not only benefit them psychologically, but could also mean that fewer abandon treatment, which in turn could result in more couples having babies.

The risk of having twins means that these days a single fertilised egg is generally implanted in the woman's womb. A follow-up study of a previous controlled trial where 661 women were randomly assigned the implantation of one or two embryos looked at the overall birth rate after all the frozen embryos had been used. The follow-up study shows that the single-embryo transfer method results in almost as high a chance of having a baby as the double-embryo transfer method, if we include the birth rate from the frozen embryos. 44 per cent of women had a baby in the single-embryo group, and 51 per cent in the double embryo group.

Just over a quarter of the women in the double-embryo group had twins, which was unusual in the other group, says Olivius. Multiple pregnancies increase the risk of premature delivery, which can result in complications. Given that the results from the single-embryo transfer are almost as good, this is, in most cases, a better method.

Anaesthesia not harmful for babies during birth

Tue, 28 Jul 2009 13:08:57 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 04:00:00 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 04:00:00 PST

Probiotics can increase effectiveness of some antibiotic therapies

Thu, 09 Jul 2009 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 11:17:06 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 05:00:00 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 05:00:00 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 05:00:00 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 04:44:22 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 14:52:42 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 01:28:14 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 10:32:07 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 16:03:51 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 04:00:00 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 05:00:00 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 05:00:00 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 17:00:00 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 13:30:00 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 05:00:00 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 05:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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.�