Weight-loss surgery may improve IVF outcomes

Preliminary findings from patients who underwent obesity surgery, also known as bariatric surgery, at Washington University in St. Louis, indicate that this procedure used to induce weight loss may improve the ability of morbidly obese women to conceive after undergoing in vitro fertilisation (IVF).

Meanwhile, a second study conducted at Albert Einstein College of Medicine in Bronx, New York, suggests that reproductive hormone levels are reduced in obese women and are only partially restored to normal within six months following weight-reduction surgery.

Both studies were presented at the 64th annual meeting of the American Society for Reproductive Medicine in San Francisco.

"Some studies have shown that women who are obese and undergoing fertility treatment have less success, require higher doses of medication to help get them to ovulate, as well as higher miscarriage rates," Washington University's Dr. Beth M. Lewkowski said in an interview with Reuters Health. As a result, "a lot of centres will advocate that obese women attempt to lose weight before considering fertility treatment."

Lewkowski's team reviewed the records of five obese women who underwent bariatric surgery followed by IVF. Currently, three of the women have delivered healthy full-term infants, Lewkowski said, and the other two women are still pregnant.

All five women had been infertile for two to 10 years before bariatric surgery. Three of the women became pregnant after one IVF cycle; their body mass index at the time of IVF ranged from 22,8 to 29,9. The other two women underwent three IVF cycles before they conceived. The body masss index during the first cycle was higher, at 36 and 39,2.

Body mass index(BMI) is the ratio of weight to height. A normal BMI ranges from 18,5 to 24,9.

Despite these outcomes, Lewkowski commented, adding infertility as a reason for bariatric surgery is something that requires more research before such a recommendation can be made.

In the second presentation, the Einstein team led by Dr. Alex J. Polosky discussed how morbid obesity affects follicle stimulating hormone, inhibin, and Mullerian inhibiting substance (MIS).

"Obesity leads to decreased fertility in women with irregular and regular menstrual periods alike," Polosky told Reuters Health. "However, weight loss only partially reverses reduced fertility; and we don't know why."

They studied seven morbidly obese women (with an average body mass index of 49) who underwent bariatric surgery, leading to an average BMI of 37 at six months after surgery, along with 36 normal-weight infertile women who had normal ovarian reserve.

At the start of the study, the obese women had levels of follicular stimulating hormone and inhibin B (an ovarian hormone) that were significantly lower than in normal-weight women.

The 25 percent average weight loss was associated with significant recovery of follicular stimulating hormone levels, but not of inhibin B. MIS, a measure of ovarian reserve, did not differ significantly between normal and obese subjects.

"Our data suggest that morbidly obese women do not produce enough follicular stimulatory hormone from their pituitary gland to make the ovary function properly," Polotsky noted. "Inhibition of follicular stimulatory hormone secretion via inhibin B was lower than expected. Yet, despite this inhibitory hormone being low, follicular stimulatory hormone did not rise."

Polotsky concluded: "This apparent deficit in follicular stimulatory hormone responsiveness in obese women is incongruous with their apparently normal ovarian reserve," as indicated by MIS levels. "These data imply that in a morbidly obese woman either the brain is not sensing the ovarian hormone signal (inhibin), or the ovarian hormone signal is not working properly."

Polotsky's group is now planning studies in which they will block the normal hormonal feedback from the ovary more completely and examine how the pituitary gland responds.


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Low dose of 'abortion pill' shrinks fibroids

As a treatment for uterine fibroids, a 5-milligram daily dose of the so-called abortion pill mifepristone is as effective as a 10-milligram daily dose at shrinking fibroids and alleviating symptoms, and may carry a lower risk of endometrial hyperplasia - an abnormal thickening of the lining of the uterus that can lead to cancer.

In a study, researchers found that treatment with the lower dose of mifepristone, also known as RU-486, reduced fibroid volume by 57 percent at three months, which is actually higher, although not significantly, than the 45 percent reduction seen with the higher dose.

Endometrial hyperplasia was noted in one woman treated with the higher dose, but in none given the lower dose.

Uterine fibroids can cause excessive menstrual bleeding, pelvic pain and frequent urination. The benign growths occur in about 25 percent of all women and are the leading cause of hysterectomy, or removal of the uterus, in the US.

The current investigation, conducted by Dr. Esteve and colleagues, involved 100 women who were randomised to receive 5mg or 10mg of mifepristone daily for 90 days.

Both doses of mifepristone provided significant and comparable reductions in fibroid size and improvements in fibroid-related symptoms, Dr. Josep Lluis Carbonell Esteve, from Clinica Mediterrania Medica in Valencia, Spain, and colleagues report in the medical journal Obstetrics and Gynecology.

Roughly 90 percent of women in each group no longer experienced menstrual bleeding following treatment, they say. Hot flashes and nausea were more common with the 10mg dose, but otherwise no differences in side effects were noted between the groups.


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Mini-incision no-scalpel vasectomy reversal

Men who want to have a vasectomy reversed may soon be able to opt for a "mini-incision, no-scalpel" operation, according to a group of surgeons who have performed a number of successful vasectomy reversals using this approach.

In vasectomy, the tube that carries sperm from the testes to the penis, the vas deferens, is severed. The operation can now be performed through a tiny incision in the scrotum, resulting in fewer complications than the more invasive approach requiring a larger incision.

Men who change their minds can choose to have the surgery reversed by reconnecting the severed ends of the vas deferens, or have sperm "retrieved" and used for in-vitro fertilisation.

Couples often chose sperm retrieval, note Dr. Keith Jarvi and colleagues from Mount Sinai Hospital at the University of Toronto, because the standard vasectomy reversal can require up to two weeks of recuperation. This operation involves making a two- to three-centimetre incision in the scrotum.

Jarvi and his team developed a new approach that allows them to reconnect the vas deferens through a much smaller (one-centimetre) incision. They have used the procedure with success in 10 cases.

"This is a simple, rapid technique that could easily be used by urologists familiar with the no-scalpel vasectomy techniques," Jarvi and colleagues report in the medical journal Urology.

However, they say it is still not known whether the new reversal technique will lead to fewer post-surgical problems than the more invasive approach.

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Infertile patients support embryonic research

Roughly three quarters of infertility patients favour using leftover embryos for stem cell research and a little more than half think that selling leftover embryos should be allowed, according to results of two surveys published in the current issue of the journal Fertility and Sterility.

Assisted reproductive technology has resulted in the creation and freezing of extra embryos at fertility centres across the country. It was estimated in 2002 that 396 526 embryos were in storage at US fertility clinics, according to previously published research.

"These embryos may be used for future pregnancy attempts, donated to other couples or agencies, given to researchers, or discarded," said Dr. Tarun Jain from University of Illinois Medical Centre, Chicago, who conducted the surveys with Stacey A. Missmer of the Harvard School of Public Health in Boston.

"Because infertility patients are the gatekeepers of these leftover embryos, it is important to understand their opinions," Jain said.

When asked if using leftover embryos for stem cell research should be allowed, most of those with definitive opinion, 73 percent (466 out of 636), answered yes. "Infertility patients, in general, are altruistic, and it makes sense that they would try to advance medicine and help others," Jain noted.

African Americans and Hispanics were less likely to approve of using leftover embryos for stem cell research, compared with Caucasians. Patients who were younger than age 30, Protestant, less wealthy and single were also less likely to support using leftover embryos for stem cell research.

In a related survey, Jain and Missmer asked their infertile patients if they would be willing to sell their extra embryos to other couples - a practice that is considered ethically unacceptable by the American Society for Reproductive Medicine and the American College of Obstetricians and Gynaecologists. "

"There is an emerging demand from infertility patients who cannot conceive using their own eggs to purchase left-over, pre-existing embryos because it is a more cost-effective option than using an egg donor," Jain explained.

When asked if selling leftover embryos to other couples should be allowed, 56 percent of the 588 respondents who stated a definitive opinion answered yes. "This finding may again reflect the altruistic nature of infertility patients along with perhaps a desire to recoup some of the expenses of treatment," Jain noted.

Hispanics were less likely to approve of selling extra embryos when compared with Caucasians, but all East Indian respondents approved of the practice. Women who had never been pregnant were also less likely to approve.

"Given the potential for a significant increase in the commoditizing of spare embryos, medical societies and policy makers may need to pay close attention to this controversial area," Jain said.


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Obesity not linked to poor semen quality

Dr. Anette S. Aggerholm and colleagues from Aarhus University Hospital in Denmark note in the medical journal Fertility and Sterility that the obesity epidemic has coincided with a decline in semen quality.

To investigate any connection, the researchers analysed associations between body mass index (BMI) - a measure of weight in relation to height - and male sex hormones and sperm quality among about 2 000 men.

The men, who were 18 to 66 years old and had no vasectomy or reproductive abnormalities, provided blood and semen samples, lifestyle information, and self-reports of body height and weight. Nearly half (47 percent) of the men were overweight.

Underweight men had the highest levels of sex hormones, the researchers found, and levels generally decreased as weight categories increased.

Aggerholm's team also noted that moderately overweight men showed a minor decrease in sperm density and total sperm count compared with men of normal weight. However, there was no drop in sperm count among the obese men.

These findings suggest a strong association between being overweight and hormonal changes, but not between obesity and semen quality, the investigators conclude.


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Dad's sperm linked to IQ

The results of a relatively small study suggest that children conceived using a fertility technique called intracytoplasmic sperm injection (ICSI) may have slightly lower IQ scores than children conceived naturally or with in vitro fertilisation (IVF).

ICSI is typically used for men who have low numbers of sperm in their semen or who have poor quality sperm. However, it can also be used in cases in which the mother's eggs are difficult for the sperm to penetrate.

With the procedure, a needle is placed into the testicle, under anaesthesia, to remove sperm. In a laboratory, a single sperm is isolated and then directly injected into an egg removed from the prospective mother. If fertilisation is successful, the embryo that develops a few days later is transferred into the mother and the steps are then the same as with IVF.

As reported in the journal Fertility and Sterility, Dr. Sylvia Veen and colleagues from Leiden University Medical Centre, the Netherlands, compared the IQ at age five to eight years of 83 children conceived by ICSI with that of 83 children conceived by IVF and 85 conceived naturally.

They report that the average IQ, based on the Revised Amsterdam Child Intelligence Test, was 103 in the ICSI group, 107 in the IVF group, and 110 in the naturally conceived group.

The four-point difference between ICSI children and IVF children was not considered significant from a statistical standpoint, meaning that it could have occurred by chance. However, the seven-point difference in favour of naturally conceived children versus ICSI children was statistically significant.

"The ICSI children performed worse on all subtests with differences in (average) scores ranging from 0.7 to 2.1," the investigators note.

Veen and colleagues point out that "the clinical significance of the differences in IQ between ICSI children and both IVF and natural conception controls is debatable."

"On the one hand, the (average) IQ of ICSI children was within the normal range," they explain. "On the other hand, a shift of the total ICSI population to lower IQs may result in children crossing borders at the lower edge of the normal range. Indeed, ICSI children more often scored less than 85 than natural conception children."



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Antidepressants may damage male fertility

A study of 35 healthy men given paroxetine - sold as Paxil or Seroxat by GlaxoSmithKline - found that, on average, the proportion of sperm cells with fragmented DNA rose from 13,8 percent before treatment to 30,3 percent after just four weeks.

Similar levels of sperm DNA damage have been linked to problems with embryo viability in couples trying to have children. The research by Peter Schlegel and Cigdem Tanrikut of the Cornell Medical Centre in New York was reported in New Scientist magazine and is due to be presented in November at a meeting of the American Society for Reproductive Medicine.

A copy of the study abstract was made available to Reuters.

"The fertility potential of a substantial proportion of men on paroxetine may be adversely affected by these changes in sperm DNA integrity," the experts concluded.

The study adds to concerns voiced by the same doctors in 2006, after finding that two men had developed low counts of healthy sperm following treatment with two different selective serotonin-reuptake inhibitors (SSRIs).

SSRIs like Paxil/Seroxat and Eli Lilly's Prozac, both of which are now available generically, are the most commonly prescribed class of antidepressant.

Glaxo said it was reviewing the investigators' findings, since the study was not conducted by the company.

"These medicines remain an important option, in addition to counselling and lifestyle changes, for treatment of depression and this study should not be used to cause unnecessary concern for patients," a spokesperson said.

"Patients should discuss their situation with their doctor before stopping use of their medicine."

Allan Pacey, Senior Lecturer in Andrology at the University of Sheffield, said the apparent increase in sperm DNA damage was "alarming", although he noted the level at which damage becomes clinically significant was open to debate.

"It is a shame that the authors appear not to have conducted a randomised controlled trial which would be the most scientific way to investigate the drugs effects, but I agree that the results are of concern and need to be investigated further," he said.

SSRIs have long been known to depress libido in some men and previous research has also found that women taking the medicines are more likely to have a low birth weight baby.


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Obesity may diminish a man's fertility

Researchers found that among 87 healthy men ages 19 to 48, those who were obese were less likely to have ever fathered a child. More importantly, they showed hormonal differences that point to a reduced reproductive capacity, the researchers report in the journal Fertility and Sterility.

Compared with their thinner counterparts, obese men had lower levels of testosterone in their blood, as well as lower levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) - both essential to reproduction.

According to the researchers, these relatively low levels of LH and FSH are suggestive of a "partial" hypogonadotropic hypogonadism. This is a condition in which the testes do not function properly due to signalling problems in the hypothalamus or pituitary gland, two brain structures involved in hormone secretion.

The findings suggest that obesity alone is an "infertility factor" in otherwise healthy men, write Dr. Eric M. Pauli and his colleagues at the Pennsylvania State University College of Medicine in Hershey.

Of the 87 men in the study, 68 percent had had a child. Pauli's team found that the average body mass index, or BMI, was lower among these men compared with those who'd never fathered a child; in the former group, the average BMI was 28, which falls into the range for "overweight," while the average BMI for childless men was nearly 32, which falls into the "obese" range.

When the researchers assessed the men for several reproductive hormones, they found that the more obese a man was, the lower was his LH and FSH levels. On the other hand, increasing obesity correlated with increasing oestrogen levels.

Excess body fat, Pauli's team explains, may increase the conversion of testosterone to oestrogen in a man's blood. Such hormone alterations could, in turn, signal the brain to suppress FSH and LH production.

Past studies have linked obesity with a dampened libido and increased risk of erectile dysfunction, the researchers note. Those effects, they say, along with the hormonal alterations seen in this study, could act together to decrease an obese man's fertility.


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Pros of injection outweigh bone risk

The potential bone loss that may occur with depot medroxyprogesterone acetate (DMPA), a long-acting, injectable contraceptive introduced in 1992, should not deter doctors from prescribing the agent when it seems appropriate, according to a Committee Opinion issued by the American College of Obstetrics and Gynaecology.

The recommendation is published in the journal Obstetrics & Gynaecology. Dr. Denise Jamieson, chair of ACOG's Committee on Gynaecologic Practice, and colleagues point out that "increased use of DMPA in the past 15 years has been parallelled by a decrease in the adolescent pregnancy rate. Although there are many factors contributing to the decrease in adolescent pregnancies, DMPA has likely played a role."

The Committee notes that while DMPA increases bone breakdown, with a resultant loss in bone thickness, this risk must be weighed against the benefits of the high pregnancy-prevention rate - especially in light of the fact that bone thickness returns after DMPA has been stopped.

Women should be counselled about the risks associated with DMPA, the panel advises, and for those who elect to use it, daily age-appropriate calcium and vitamin D supplementation should be recommended. Women should also be told about the importance of regular exercise in maintaining bone health.

However, concerns about DMPA's effect on bone thickness "should neither prevent practitioners from prescribing DMPA nor limit its use to two consecutive years," Jamieson and colleagues write.

Bone thickness monitoring is not needed "solely in response to DMPA use," they add, because any short-term bone loss is recoverable and probably won't increase the current or future risk of fracture, they note.



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Heated car seat may be too hot for men

Researchers found that 90 minutes on a heated car seat created a significant increase in men's scrotal temperature. Because heat stress on the testicles has been shown to impair sperm quality, the findings raise the possibility that over time, heated car seats could affect a man's fertility.

However, the study looked only at short-term changes in scrotal temperature, and not the effects on sperm, stressed lead researcher Dr. Andreas Jung, of Justus Liebig University Giessen in Germany.

"It is too early to (make) any conclusions concerning the influence of heating car seats on semen quality," Jung told Reuters Health.

Normal sperm production is temperature-dependent and requires a testicular temperature that is slightly below the body's core temperature, the researchers explain in the journal Fertility and Sterility.

In tests of 30 male volunteers, Jung's team found that, on average, 90 minutes on a heated car seat raised the men's scrotal temperature enough to nearly match their core body temperature.

Sitting for prolonged periods, on its own, raises a man's scrotal temperature, and the effect of a heated car seat is actually weaker by comparison, according to the researchers. However, they add, even a small additional effect on scrotal temperature might be enough to affect a man's sperm quality.

According to Jung, studies should now directly examine sperm quality to see if there is, in fact, a risk from heated car seats.


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Fertility treatments 'induce gene mutations'

The use of in vitro fertilisation (IVF) or another assisted fertility technique called intracytoplasmic sperm injection (ICSI) to conceive appears to increase the odds of Y-chromosome defects or "microdeletions" in male offspring, Chinese researchers report.

Such deletions could result in defective sperm production and possibly also hypospadias - a common birth defect of the penis that occurs when the urinary outlet develops on the underside of the penis rather than at the tip.

Although this study was small, it "at least sounds an alarm about the genetic safety of assisted reproductive technology," the investigators conclude.

Prior research has tied assisted reproductive technologies with low birth weight, preterm delivery, cerebral palsy, and major birth defects, leading some researchers to hypothesize that these therapies may induce gene mutations.

In the new study, Dr. He-Feng Huang, from Zhejiang University, and colleagues sought to answer this question by testing for genetic mutations in 19 male infants conceived through IVF, 18 conceived through ICSI, and 60 conceived naturally. The fathers of the infants were also tested. In an effort to isolate the impact of the fertility treatment, the researchers only studied infants whose parents had a normal genetic background.

Huang and colleagues found Y-chromosome microdeletions in one infant conceived with IVF (5,3 percent) and in three conceived with ICSI (16,7 percent). By contrast, no Y-chromosome deletions were seen in the control group.

One of the four infants with microdeletions had hypospadias, the report indicates.

This is not the first study to link ICSI with hypospadias, the investigators note, but the mechanism has been unclear. The current findings suggest that the association may be mediated through Y-chromosome microdeletions.

ICSI is the main method used to overcome male infertility. With ICSI, a single sperm is injected directly into a single egg. If successful fertilisation occurs, the embryo is then placed into the female to undergo development as usual.

Larger studies "should be conducted to confirm our preliminary results," the researchers conclude.



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Male infertility fix works for men over 40

A varicocele, an enlargement of veins in the scrotum, can impair a man's fertility. Fortunately, surgery can correct the problem, and now a new study shows the procedure is just as effective for older men as it is for younger men.

"Older men (in the age range of 35-45) with varicocele do benefit from varicocele repair," Dr. Armand Zini told Reuters Health, "particularly those men with secondary infertility" - i.e., infertility resulting from the varicocele.

Zini from McGill University in Montreal, Canada and his colleagues investigated the influence of age on pregnancy rates among partners of men who had undergone varicocele repair, comparing outcomes for men older and younger than 40 years.

There were no significant differences in the improvement in semen quality, the need for in vitro fertilisation, or pregnancy rates between older and younger men who underwent varicocelectomy, as the procedure is called, the team reports in the medical journal Urology.

In addition, the researchers looked at men older than 40 who opted for the procedure and those in the same age group who chose not to undergo surgery. The team found that the spontaneous pregnancy rate was significantly greater in the group that underwent varicocelectomy than in the group that didn't.

"This is the first study to examine the influence of paternal age on pregnancy rates after varicocelectomy," the authors point out. "The data support the practice of varicocelectomy in older men with infertility, particularly in men with secondary infertility."

"Men with very poor semen parameters or men with a genetic cause of infertility would least benefit from varicocelectomy," Zini commented. "A detailed evaluation may uncover other (less common) abnormalities that would be associated with a poor outcome after surgery."


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Shared sperm donor families seek genetic link

Results of a new survey suggest that most sperm-donor inseminated parents seeking contact with other families who share the same donor may be interested in creating a genetic family for their children.

"One's origins hold considerable significance to people - something that's very important when considering how much donor information should be accessible to donor-conceived people," Dr. Joanna E. Scheib told Reuters Health.

Parents seem to be moving away from being private about using a donor, said Scheib, of the University of California, Davis. Contact between shared-donor families and individuals can serve as a resource for learning more about one's donor.

Scheib and colleagues surveyed 14 families who participated in the family-matching service of The Sperm Bank of California. The service enables parents who had children via donor insemination to contact families of the same sperm donor.

Half the surveyed parents were single women, while 43 and seven percent, respectively, were lesbian and heterosexual couples, they report in the medical journal Fertility and Sterility. All had one child (57 percent female), ranging from six months to nine years of age at the time they entered the matched-family programme.

Of the 12 families who answered questions regarding their initial contact, five said they "clicked" with the other family, and four expressed excitement about the meeting. Just two families reported initial discomfort.

Another three families said they did not "connect" reportedly because the families were at different points on issues of openness or the amount of contact they wanted with each other.

During initial contact, which was most often by phone, most of the families compared their children's physical features and personality traits, and discussed donor disclosure issues. After about one year, most families have maintained ongoing contact, the researchers note.

Parents of the children old enough to understand their genetic parentage and aware of their matched family said the children were generally curious about and excited in knowing they have genetic siblings.

"Some of the older donor-conceived individuals from our programme seem more interested in their peers/half-siblings than in the donor himself," Scheib told Reuters Health.

Research that continues to assess relationships between donor siblings and their families and the long term impact of these relationships, Scheib's team concludes.


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Common fertility treatments have little use

This means doctors should rethink giving women the drug, known generically as clomiphene citrate, to stimulate the ovaries or administering a particular type of artificial insemination, said Siladitya Bhattacharya, who led the study.

"Traditionally over the last 30 or 40 years some treatments have crept into our repertoire without being robustly (tested)," said Bhattacharya, a gynaecologist at Aberdeen University.

"What we found - rather surprisingly - is these treatments did not produce a greater chance of pregnancy leading to live birth compared to no treatment."

One in six couples worldwide experience some form of infertility problem at least once and more couples are seeking assisted reproductive treatment.

The British study looked at the third of women for whom doctors cannot pinpoint a cause of infertility. These women often take Sanofi Aventis' Clomid or undergo a type of artificial insemination called unstimulated intrauterine insemination as first-line treatments.

Sanofi had no immediate comment.

The researchers recruited 580 volunteers, a third of whom were encouraged to try to conceive naturally and another two groups who were given the pill or had artificial insemination.

During the study, 101 women became pregnant and gave birth, including 17 percent in the group who tried naturally, 14 percent of those who took the pill and 23 percent of volunteers who were artificially inseminated.

The differences were not big enough to be statistically significant, Bhattacharya and colleagues wrote in the British Medical Journal.

"The message of this trial is people should think more carefully about going into these treatments as a fait accompli," he added.

The findings underscore the need to review widespread guidelines in many countries calling on doctors to use the two treatments, he said.


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Erectile dysfunction comes with age

Erectile dysfunction may be a feature of normal ageing in men, while urinary or bowel function doesn't necessarily decline with age, according to a Dutch study.

"I had expected that the association between urological function and age would be stronger," Dr. Ida J. Korfage from Erasmus University Medical Centre Rotterdam told Reuters Health.

Using data from more than 3 800 participants in the European Randomised Study on Screening for Prostate Cancer, Korfage and her colleagues assessed whether urinary, bowel, and sexual dysfunction "and the associated bother" were part of the "normal" ageing process.

As described in the medical journal Urology, the men - all of whom were cancer-free - were divided into five groups by age: 58-61, 62-64, 65-67, 68-70, and 71 years and older.

According to the investigators, the proportion of men with erectile dysfunction was significantly higher among older men, with more of them reporting either that they were sexually active but having problems with erections, or sexually inactive because of erectile problems.

Korfage added, "I like to stress that sexual inactivity is not necessarily the same as erectile dysfunction. Reasons for not being sexually active can also be not being interested (anymore) or not having a partner. Not everybody who is sexually inactive is in need of medication."

Although urinary function was poorer and more bothersome in older age groups, the differences between age groups were not very great.

Bowel problems were uncommon, with no significant differences among age groups, the report indicates.

So, when these problems are seen in older men who have been treated for prostate cancer, they are more likely due to the treatment rather than to age alone, the team points out.


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