Testosterone Offers New Hope For IVF Success

Many women have the frustrating experience of pursuing costly IVF only to have their cycles cancelled and their hopes dashed when poor ovarian response to stimulation eventuates in them being diagnosed as a ‘poor responder.’

Even when massive doses of gonadotropin stimulants are used, some women's ovaries seem recalcitrant to stimulation and do not produce follicles as expected. Many strategies have been pursued to find novel ways of boosting the ovarian response of poor responders, testosterone is one such strategy that may give such women new hope.

Historically, a number of studies have been performed on the benefits of giving poor responders testosterone prior to IVF as a means of improving IVF response. The results have been very positive thus far.

In a 2011 South Korean study, poor responder women were given a transdermal testosterone gel before ovarian stimulation began. In this study poor responders were defined as women who had failed during previous IVFs to produce more that 3 follicles over 16 mm diameter, despite high gonadotropin stimulation.

The 110 women were randomized to receive either transdermal testosterone pretreatment with 12.5 mg daily for 21 days in the cycle preceding the IVF or a placebo. The results of the study showed that the women who received testosterone pretreatment needed less gonadotropin stimulation and had a significantly higher number of oocytes retrieved. They also had more mature oocytes that fertilized and more high quality embryos.

The testosterone pretreated women also had a higher pregnancy rate and there were no adverse effects from the male hormone treatment. The researchers concluded that;

"TTG pretreatment might be beneficial in improving both response to COS and IVF outcome in low responders undergoing IVF/ICSI."

This study echoes the findings of previous studies that have likewise found that pretreatment with testosterone can offer poor responder women a novel, inexpensive and low-risk way to up the odds of IVF succeeding.

Reference:
Fertil Steril. 2011 Feb;95(2):679-83.
The effect of transdermal testosterone gel pretreatment on controlled ovarian stimulation and IVF outcome in low responders. Kim CH, Howles CM, Lee HA.

Clowning helps IVF patients become pregnant: study

Dr. Shevach Friedler an infertility doctor with the Infertility and IVF unit at Assaf Harofeh Medical Center, in Zrifin, Israel, led a study of the effects of a bedside encounter with a professional medical clown on the pregnancy rate of women undergoing in-vitro fertilization (IVF).
Dr. Friedler and colleagues tracked 219 women undergoing IVF treatment at the medical center and, over a period of a year, treated half of them to a medical clown's 15-minute routine of jokes, magic tricks and other clowning immediately after their embryos were implanted. The clown’s routine was created especially for the study by Friedler and a colleague.
The results showed 36.4 percent of women exposed to clowning immediately after embryo transfer became pregnant, while only 20.2 percent of the controls became pregnant. Dr. Friedler said the reason was probably because the clowning reduced the stress of what for many was many years of grueling IVF treatments, but this is not certain. It is also unclear what role, if any, stress may play in the success of IVF treatments.
Dr. Friedler, who is also trained in movement and mime, originally thought of the research after reading about laughter as an anti-stress mechanism. He realized that IVF patients are often extremely stressed, and wondered if relieving that stress through clowning at a crucial moment in the treatment could help.
Dr. Friedler and colleagues conclude that medical clowning may be a beneficial adjunct to IVF treatments and it deserves further investigation. Medical clowning is already used to good effect in hospitals in Europe, Australia, North America and Israel, particularly in children’s hospitals.
Dr. Friedler also pointed out that clowning is “one of the least hazardous interventions in our field.” Other methods of reducing stress could also be investigated. The findings are reported in the journal Fertility and Sterility.
More information: The effect of medical clowning on pregnancy rates after in vitro fertilization and embryo transfer (IVF-ET), Shevach Friedler, M.D et al., Fertility and Sterility, published online 06 January 2011, doi:10.1016/j.fertnstert.2010.12.016

Women using IVF more likely to conceive when stressed

Women who are stressed out when undergoing IVF may have a higher chance of falling pregnant, research suggests.
Those reporting higher stress levels had up to double the chance of a positive pregnancy test when compared with those who were more relaxed, according to a study on 217 women.
They were asked on their first appointment how much fertility-related stress they were experiencing on a scale from 1 to 10.
Those who scored 1 to 3 on the scale had a pregnancy rate of 30 per cent while those who scored 7 to 10 had a rate of 50 to 60 per cent.
Dr Robert Hunter, from Staten Island University Hospital in New York, which carried out the study, said previous research had found a similar finding. However, other studies have discovered that stress can negatively affect IVF.
'We were a little surprised by the outcome of the study - we were expecting the opposite result,' Dr Hunter said.
'It highlights the complexity of stress. There's a very complex relationship between stress pathways and the reproductive pathways.
'This is something that we're still struggling to understand and more work needs to be done.'
Dr Hunter said there was good evidence, however, that stress could actually improve how the body functions, such as the 'fight or flight' response.
Levels of key hormones rise when a person is under stress, including the adrenal hormones adrenaline and cortisol.
The team are now planning further studies, including looking at these markers of stress in the body.
Co-researcher Dr Eric Knochenhauer said questions also need to be asked about sources of stress, such as coming from a partner, worries about the costs of IVF and pressure from parents, in-laws or friends.
'Fertility-related discussions used to be something that nobody had with friends but now it's much more common,' he said.
'I think that causes stress for some patients.'
Another one of the researchers, Dr Michael Traub, said one interesting finding from the study related to older women, who reported being less stressed.
'If they are older and they think their chances of becoming a parent are very low, they might have less stress because their expectations are lower.'
All the findings held true even when factors such as depression, smoking status, age and alcohol intake were taken into account.
Tony Rutherford, chair of the British Fertility Society, said: 'This study used a questionnaire to assess stress rather than looking for biochemical markers.
'There is some evidence that increasing stress might be of benefit to patients undergoing IVF.
'In the UK we are pushing for a national trial on whether steroids improve IVF.
'It's an interesting relationship.'

IVF success usually peaks early

More tries aren't necessarily better when it comes to in vitro fertilization. New research found that about 1 in 3 women had a baby the first time they tried a test tube embryo, and that improved to nearly 1 in 2 with a second try.
However, undergoing a third cycle boosted success rates very little and leveled off with subsequent attempts.
"Don't quit if the first cycle isn't successful. Your chances go up with the second cycle," said lead researcher Barbara Luke of Michigan State University. But "if you haven't gotten pregnant by the third, the chances are slim to continue."
In vitro fertilization involves mixing egg and sperm in a laboratory dish. The resulting embryo is then transferred into the womb to grow into a baby. Earlier last month, British researcher Robert Edwards won the medicine Nobel Prize for pioneering the technique that has led to 4 million test tube babies.
Infertility treatment is expensive. The average cost for an IVF cycle is about $12,400, according to the American Society of Reproductive Medicine. Some insurance companies cover it.
Desperate couples often try over and over to conceive, and there are no ethics standards on when doctors should stop helping them try. Fertility clinics report success rates based on the number of cycles attempted, but that doesn't indicate how likely an individual woman is to get pregnant with each IVF cycle she undergoes.
The new study is the first to examine that nationally. It looked at in vitro procedures around the country between 2004 and 2008.
Over the five-year period, some 300,000 women had more than half a million IVF cycles that resulted in 171,327 first-time deliveries. The live birth rate was 36% on the first IVF try, 48% with a second cycle and 53% with a third attempt.
Among those who tried seven or more times, the chance of success was 56% -- hardly any better than the 53% after three tries.
The findings show "diminishing returns" after three IVF cycles, said lead researcher Luke. "The results are not going to be much better."

Assessing Embryo Metabolism May Aid IVF Success

Examining the metabolism of embryos may help determine which ones offer the best chance of success with in vitro fertilization (IVF), a new study finds.

Currently, the process of selecting embryos for implantation in the mother's womb is highly subjective.

"It's a guessing game that can end in IVF failure or multiple pregnancies," Dr. Emre Seli, an associate professor in the obstetrics, gynecology and reproductive sciences department at Yale School of Medicine, said in a school news release. "Our goal is to find a way to pinpoint the embryos with the best chance of success, so that we can transfer fewer embryos and cut down on the possibility of multiple pregnancies without reducing the pregnancy rate."

Seli and colleagues have studied the metabolomic profiles of spent embryo cultures. A metabolomic profile is a unique chemical signature of the activity of embryos in culture.

The Yale team found that a viability score based on a noninvasive metabolomic assessment of embryo culture media affected pregnancy outcomes in women treated at four centers in Europe and Australia. The research, performed in collaboration with Molecular Biometrics Inc., was presented this week at the American Society for Reproductive Medicine annual meeting, in Atlanta.

"These findings have important implications for the more than 125,000 IVF cycles performed yearly in the United States," Seli said. "The high multiple pregnancy rates associated with IVF have significant public health consequences, such as decreased survival and increased risk of lifelong disability associated with severe prematurity."

You cannot beat age

A report published by the US Centers for Disease Control and Prevention (CDC) shows that the younger a woman is when she uses assisted reproductive technology (ART), the more likely she is to become pregnant and have a live birth using her own eggs. The report defines ART as procedures in which both egg and sperm are handled in a laboratory, and says the majority of ART treatments its data include refers to IVF. The CDC's annual report,used data for the year 2002 collected from 391 of the 428 fertility clinics in the US. The report, called '2002 Assisted Reproductive Technology Success Rates', showed that, in 2002, 45,751 live births were achieved from 115,392 ART procedures performed in the US. This was an increase from the previous year's figures, when there were 40,687 live births from 107,758 treatments. Overall, the per-cycle ART success rate in 2002 was 35 per cent, compared to 28 per cent in 1996.The 2002 data show that 37 per cent of women who undergo ART using their own, fresh eggs when they are below the age of 35, had a live birth. This is compared with 31 per cent of women aged between 35 and 37; 21 per cent of women aged between 38 and 40; 11 per cent of women aged between 41 and 42 and just four per cent for women older than 42. However, the report also showed that the age of the woman undergoing ART had 'little effect' on success rates if donated eggs were used. In 2002, the live birth rate for all ART procedures where donated eggs were used was 50 per cent, with the success rate varying only slightly between age groups.
Victoria Wright, one of the authors of the CDC report, said that the data show that 'women in their 20s and early 30s who used ART had the most success with pregnancies, and single live births'. But, she added, 'success rates declined steadily once a woman reached her mid-30s'. She said the figures should act as 'a reminder that age remains a primary factor with respect to pregnancy success, and younger women have greater success than older women, even with technology'