Should obese, smoking and alcohol consuming women receive assisted reproduction treatment?

The European Society of Human Reproduction and Embryology (ESHRE) has published a position statement on the impact of the life style factors obesity, smoking and alcohol consumption on natural and medically assisted reproduction.

In a literature study the ESHRE Task Force on Ethics and Law summarised the negative effects of obesity, smoking and drinking on the natural reproductive potential of patients, on IVF results, pregnancy complications and outcomes and finally on the health of the future child. The paper was published online on 19 January 2010 in Europe’s leading reproductive medicine journal Human Reproduction. The group made five recommendations.

1) In view of the risks for the future child, fertility doctors should refuse treatment to women used to more than moderate drinking and who are not willing or able to minimize their alcohol consumption.

2) Treating women with severe or morbid obesity required special justification. The available data suggested that weight loss would incur in a positive reproductive effect, although more data was needed to establish whether assisted reproduction should be made conditional upon prior life-style changes for obese and smoking females.

3) Assisted reproduction should only be conditional upon life style changes, if there was strong evidence that without behavioural modifications there was a risk of serious harm to the child or that the treatment became disproportional in terms of cost-effectiveness or obstetric risks.

4) When making assisted reproduction conditional upon life style modifications, fertility doctors should help patients to achieve the necessary results.

5) More data on obesity, smoking and alcohol consumption as well as other life style factors were necessary to assess reproductive effects. Fertility doctors should continue research in this area.

ESHRE acknowledged that this was a complex issue due to personal, patient, professional and societal responsibilities and also in terms of what these responsibilities meant with regard to safety of mother and child and fair and equitable access to treatment. The respect for patient autonomy needed to be balanced with the moral weight of the interests of society and the future child.

Obesity

According to the group obesity negatively affected reproductive potential through interference with hormonal and metabolic mechanisms leading to lower ovulation frequency and reduced chances of conception. The risk of gestational diabetes increased from twofold in overweight women to eightfold for morbidly obese women. The infants of obese mothers were at risk of perinatal death, congenital abnormalities such as neural tube defects (80% increase) and cardiovascular anomalies (30% increase).

Smoking

The risk of infertility was thought to be twice as high in smokers compared to non-smokers. Female smokers needed more time to become pregnant, were less likely to do so spontaneously and had a higher risk of miscarriage. Having an accelerating effect on oocyte depletion, smoking was suggested to lead to an increase in 10 years with regards to IVF outcome. Lower birth weight, a higher risk of oral facial clefts and Sudden Infant Death Syndrome were associated with maternal smoking. Male smokers were at risk of producing sperm of reduced quality and concentration.

Alcohol Consumption

Reduced conception, lower pregnancy rates and higher miscarriage rates were suggested as adverse effects of alcohol consumption. The known effects of alcohol consumption were summarised under Foetal Alcohol Spectrum Disorders (FASD) such as physical anomalies and behavioural and cognitive deficits. Other risks associated with prenatal alcohol consumption were foetal death, preterm labour and compromised foetal growth.

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Fertility Preservation Decision Making in Cancer Patients

Atlanta, GA – New research presented at the American Society for Reproductive Medicine today highlighted the obstacles facing patients as they make decisions about preserving their reproductive options.

Investigators from Brown University used focus groups to explore the feelings of breast cancer patients about fertility preservation. They found that four main themes emerged for these patients:

1) costs, including time, money and emotional costs,

2) safety of the patient and any offspring,

3) prospects for successful treatment, and

4) having sufficient time to process information about fertility preservation.

Researchers at New York University used a more quantitative methodology to examine similar questions. They enrolled 16 patients in a registry, 11 of whom sought fertility preservation treatments. They found 10 of the 16 felt having a child was the most important thing in their lives. Eleven of them were concerned about the impact of their cancer treatment on their fertility. And 11 were unsure about the level of risks they would undertake to achieve their reproductive goals.

Physicians and nurses have important roles to play in counseling cancer patients about their reproductive options. A team from New York examined the current perceptions and practices of oncology nurses. Using an on-line survey, they found that nurses who were knowledgeable about fertility preservation were more than twice as likely to discus the impact of cancer treatments with their patients. More than 90% of the nurses reported that having guidelines would facilitate better discussion of reproductive issues with their patients.

Physicians’ attitudes about the potential for posthumous parenting were explored by a team from Tampa, Florida. They found a slim majority (50.5%) reported not having a view about posthumous parenting, and only 13% supported it. However, less than a quarter (22.8%) agreed with the statement “Patients with poor prognosis should not pursue fertility preservation.”

“As fertility preservation options for cancer patients continue to improve, the demands for quality information sharing between patients and their doctors and nurses must continue to improve, as well,” said R. Dale McClure, MD, President of the American Society for Reproductive Medicine.

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A quick and accurate way of diagnosing endometriosis

A quick and accurate test for endometriosis that does not require surgery has been developed by researchers from Australia, Jordan and Belgium, according to new research published online in Europe’s leading reproductive medicine journal Human Reproduction .

Until now there has been no way of accurately diagnosing endometriosis apart from laparoscopy – an invasive surgical procedure – and this often leads to women waiting for years in pain and discomfort before their condition is identified correctly and treated.

Now researchers at the University of Sydney and Mu’tah University in Karak, Jordan, have discovered that if they take a small sample of the endometrium (the lining of the uterus), which can be done by inserting the device for taking the biopsy via the vagina, and then test for the presence of nerve fibres in the sample, they can diagnose whether or not endometriosis is present with nearly 100% accuracy.

Endometriosis, which has been estimated to affect 10-15% of women of reproductive age, is a chronic gynaecological disease in which cells from the endometrium establish themselves outside the uterus, within a woman’s pelvic area. Symptoms associated with it include infertility, painful periods, pelvic pain and pain during sexual intercourse. Once laparoscopy has identified endometriosis as the cause of these symptoms, treatment involves surgical removal (usually via laparoscopy) of the abnormally sited endometrial cells. However, laparoscopy itself can be associated with complications and can adversely affect fertility in women who do not have endometriosis.

In a separate study also published online in Human Reproduction, another research group from Belgium and Hungary has found that the density of nerve fibres in the endometrium was about 14 times higher in women with endometriosis than in healthy women, and that using specific markers to identify the presence of nerve fibres could predict with nearly 100% accuracy the presence of minimal to mild endometriosis.

In the first study, led by Professor Ian S. Fraser, head of the Queen Elizabeth II Research Institute for Mothers and Infants at the University of Sydney and Dr Moamar Al-Jefout, assistant professor in reproductive medicine at Mu’tah University, researchers took endometrial biopsies from 99 women who had consulted doctors about pelvic pain, infertility or both and who were undergoing laparoscopy for the condition.

The results from the endometrial biopsies were compared with the results of the laparoscopies, and the researchers found that in 64 women who had endometriosis confirmed by laparoscopy, all but one tested positive for the presence of nerve fibres in the endometrial biopsy. In the 35 women who were found not to have endometriosis by laparoscopy, no nerve fibres were found in 29 of the endometrial biopsies. In the other six cases, the biopsy found there were nerve fibres present; three of these women had severely painful periods and painful sex, and also a history of infertility, and of the other three, one had adhesions that were considered too slight to be endometriosis, while the other had a previous history of endometriosis.

Women with endometriosis and painful symptoms had significantly higher nerve fibre density in comparison with women with infertility but no pain (2.3 nerve fibres per mm2 compared to 0.8 per mm2 respectively). The mean average of nerve fibre density in the women with a laparoscopic diagnosis of endometriosis was 2.7 per mm2.

The study showed that testing endometrial biopsies for the presence of nerve fibres was able to diagnose endometriosis with 83% specificity (the proportion of negative cases of endometriosis correctly identified) and 98% sensitivity (proportion of positive cases correctly identified). This double blind study confirmed the results of a pilot study published in 2007 by the same group.

Dr Al-Jefout said: “This study has shown that testing for nerve fibres in endometrial biopsies is a valid and highly accurate diagnostic test for endometriosis. This test is probably as accurate as assessment via laparoscopy, the current gold standard, especially as it is unclear how often endometriosis is overlooked, even by experienced gynaecologists. Endometrial biopsy is clearly less invasive than laparoscopy, and this test could help to reduce the current lengthy delay in diagnosis of the condition, as well as allowing more effective planning for formal surgical or long-term medical management. It may be particularly helpful in cases of infertility.”

Currently, diagnosing endometriosis via laparoscopy involves the woman being booked into hospital for the surgical procedure, an anaesthetic, and the presence of doctors, nurses and expensive equipment. In some countries there are long waiting lists for operations. In contrast, taking an endometrial biopsy is relatively quick and easy to organise and perform, and results are available within about three days. However, Dr Al-Jefout said: “It needs to be emphasised that this test requires a carefully collected endometrial biopsy and an experienced immunohistochemical pathology laboratory to confirm or exclude the presence of nerve fibres.”

He continued: “Our results indicate that a negative endometrial biopsy result would miss endometriosis in only one percent of women. Performing a planned laparoscopy only on a woman with a positive endometrial biopsy result would result in endometriosis being confirmed in eighty to ninety percent of these women. Thus, using this diagnostic test in an infertility workup would significantly reduce the number of laparoscopies performed without reducing the number of women whose endometriosis is diagnosed and surgically treated.”

In addition, he said it could be particularly useful in teenagers with spasmodic symptoms but a family history of endometriosis. “The usual diagnostic delay in this special group is greater than in older women. An endometrial biopsy to confirm or exclude the diagnosis of endometriosis will help initiating earlier treatment and possibly preventing the progress of endometriosis, thus improving life style and protecting their future fertility.”

The researchers plan to continue using the test in patients and to search for other markers to help refine the test further. “Ideally, we would like to develop a blood test as an even simpler means of providing early information on the presence or absence of endometriosis in order to assist doctors in early diagnosis. However, this endometrial biopsy test has proven so effective that it is currently the only test which appears to have equivalent efficacy to a diagnostic laparoscopy carried out by an experienced gynaecologist,” he concluded.

In the second study, led by Professor Thomas D’Hooghe, coordinator of the University of Leuven Fertility Centre (Belgium), researchers looked at 40 endometrial samples, half taken from women with minimal to mild endometriosis diagnosed by laparoscopy and histology (microscopic examination of tissue), and half from women without the condition. They analysed the tissues for several markers indicating the presence of four types of nerve fibres (sensory C, A?, adrenergic and cholinergic nerve fibres).

Dr Attila Bokor, a doctoral fellow at the University of Leuven, who did the study as part of his PhD project said: “We observed nerve fibres in the endometrial samples of ninety percent (18 out of 20) of the women with endometriosis. The density varied throughout the samples, with few specimens showing counts above 30 per mm2, and with most between 0 and 10 per mm2. None, or very few, nerve fibres, were detected in any of the samples from women without endometriosis. The density of the small nerve fibres was about 14 times higher in endometrium from patients with minimal to mild endometriosis when compared with women with a normal pelvis.”

Prof D’Hooghe said: “Our data show that the combination of three different neural markers increases the sensitivity, specificity and diagnostic accuracy of this method of testing for endometriosis. The test diagnosed endometriosis with 95% sensitivity and 100% specificity.”

Dr Bokor and the team of Prof D’Hooghe will do a blinded validation study in September 2009 to confirm the results of their research. “If this confirms our findings, we believe our research can be a solid base for a simple, reliable and relatively cheap method for non-invasive diagnosis of minimal and mild endometriosis, since trans-cervical endometrium sampling and immunohistochemical analysis are routine gynaecological and pathological procedures. Our research programme is also aimed at discovering new biomarkers that can enable a blood test for endometriosis to be developed,” said Prof D’Hooghe.

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Source: eshre.com

Céline Dion Pregnant with Embryo Frozen for Eight Years

 Céline Dion, known for belting out pop songs with window-rattling power, will be fine-tuning her repertoire of lullabies with the news today that she’s pregnant with her second child.

It’s an arrival Dion mused about almost nine years ago when she was expecting her first baby, Rene-Charles.

When Rene-Charles was conceived through in vitro fertilization at a world-renowned New York clinic, Dion told interviewers at the time that a sibling was already in the works.

The pop megastar and her husband, Rene Angelil, got the good news of the latest infant on Monday after undergoing another round of fertility treatments.

“Celine is very, very happy,” Murielle Blondeau, a spokeswoman for Dion, said today when she confirmed the pregnancy.

“Celine and Rene are full of joy. It’s been a big dream for Celine to have a second child.”

Although Rene-Charles and the new baby are siblings, fertility experts say they are not twins. Identical twins are created from a single embryo that splits in the womb while fraternal twins come from different embryos that are carried at the same time.

Dr. Seang Lin Tan, a world-renowned fertility expert at the McGill University Reproductive Centre in Montreal, said there are documented cases where frozen embryos have been successfully used after two decades.

“There have been babies born who are healthy after the embryos have been frozen for 20 years,” he said.

Dion’s first pregnancy was well-documented, unlike that of fellow music megastar Shania Twain, who virtually disappeared while waiting to give birth around the same time.

The revelation that Dion was pregnant with Rene-Charles followed a jaw-dropping announcement that she would retire from performing to have a family.

She gave interviews about her pregnancy in which she chatted about how the frozen eggs might one day become a “brother or sister” to Rene-Charles, and she appeared in a series of photos showcasing her protruding belly.

Dion has said that she and her husband turned to medical science to help conceive because Angelil had been diagnosed with cancer in 1999.

After a neck tumour was removed, he was treated with radiation and chemotherapy which are known to affect fertility. Angelil’s cancer went into remission.

Dr. Zev Rosenwaks, who counselled the couple on their fertility options, told The Canadian Press in a 2000 interview that Dion had an intracytoplasmic sperm injection, in which a single sperm is injected into the egg.

Rosenwaks, who works with the Weill Cornell fertility clinic, said in the interview that Angelil had previously frozen his sperm.

The second fertilized egg was frozen five days after conception and stored at the New York clinic, Dion said in the television interview.

Tan said there is no real concern about Dion giving birth at age 41 and he noted the embryos were also frozen when she was much younger.

He said he hopes Dion’s pregnancy will draw attention to in vitro fertilization.

“Apparently when she got pregnant the first time, the popularity of in vitro in Canada went up quite a bit,” he said.

Source: thestar.com

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Worldwide report shows an increase in Assisted Reproduction

An estimated 250,000 babies are born in one year

Assisted reproductive technology (ART) is responsible for an estimated 219,000 to 246,000 babies born each year worldwide according to an international study. The study also finds that the number of ART procedures is growing steadily: in just two years (from 2000 to 2002) ART activity increased by more than 25%.

The study, which is published online in Europe’s leading reproductive medicine journal Human Reproduction, gives figures and estimates for the year 2002, the most recent year for which world figures are available. A total of 1563 clinics in 53 countries provided data for the report, but data were missing from several other countries, mostly in Asia, Africa, Oceania and the West Indies. The authors estimated that these missing countries probably performed between 10-20% of ART procedures, and they took this into account when they calculated the total number of ART babies born worldwide.

Professor Jacques de Mouzon, a specialist in public health at INSERM (Paris, France), led the International Committee for Monitoring Assisted Reproductive Technology (ICMART) that compiled the report. He said: “This is the eighth world report on ART produced by ICMART since 1989, and is useful because, even if it is imperfect, it gives data that can inform debate and decision-making on issues such as availability and the benefits and risks of this important medical practice. It allows us to make comparisons between countries and regions, and to analyse trends by comparing with previous reports.

“There are several important points to highlight. There has been a constant increase in ART activity: it increased by more than 25% in the two years since the previous report for the year 2000. This is due not only to an increase in the number of countries participating in this report but also to an increase in ART activity in most individual countries.

“However, there are wide variations between countries in the availability and quality of ART. There are several reasons for this, such as fertility rates, women’s age, insurance cover, the national economy, but the most important is certainly inequality in access to healthcare and ART. In Western Europe it is easier for people to access good healthcare, and funding for ART tends to be more generous than in developing countries. This raises the question of developing so called ‘low cost’ ART in low-income countries; it would probably mean lower success rates (the problem would be to define what rates would be acceptable), but greater access to treatment. In addition, treatment is usually more aggressive in developing countries and in all countries where ART is expensive for patients, leading to the consequent problems of multiple births, ovarian hyperstimulation syndrome and the need for foetal reductions.”

Availability of ART varied from two cycles per million inhabitants (Ecuador) to 3688 per million in Israel.

Other key findings from the study include:

1. A large increase in the use of ICSI (intracytoplasmic sperm injection) as opposed to conventional IVF (in vitro fertilisation) worldwide. Since 2000 it increased from 54% to 61% in North America, 46% to 54% in Europe, and in 2002 it had reached 76% in Latin America and more than 92% in the Middle East.

2. Pregnancy and delivery rates have increased for both fresh and frozen embryo cycles despite a decrease in the number of embryos transferred. More than 601,250 ART cycles worldwide resulted in delivery rates after IVF, ICSI and frozen embryo transfer (FET) of 22%, 21% and 15% respectively per aspiration (attempt at egg retrieval). This compares with delivery rates after IVF, ICSI and FET in 2000 of nearly 19%, 20% and 12% respectively.

3. When cycles using fresh embryos were combined with frozen embryo cycles, the cumulative delivery rate per aspiration was 26%.

4. Cumulative delivery rates per aspiration varied among countries, ranging from 14% to 39%. While Tunisia and Libya reported the highest rates at 39%, this represented only a few fertility centres in each country. Therefore, the USA, where reports cover almost all fertility centres in the country, had the highest rate at 37.5%.

5. The transfer of multiple embryos has decreased, leading to a small decline in multiple births. The percentage of four or more embryo transfers decreased from 15.4% in 2000 to 13.7% in 2002. The proportion of twin and triplet pregnancies decreased from 26.5% to 25.7%, and from 2.9% to 2.5% respectively.

6. There has been a 47% increase in the proportion of FET cycles, which is due mainly to the decrease in the number of embryos transferred at one time, with any left over being frozen for future attempts.

Prof de Mouzon said: “It is difficult to explain the reasons behind the increase in ICSI as we have no reason to believe there has been a similar increase in the rise in male infertility, and ICSI has not been demonstrated to improve treatment results for infertility that is not caused by infertile men. It could be because more infertile men are agreeing to seek treatment, that the diagnosis of male infertility is improving, that male infertility per se is increasing (due to exposure to sperm-damaging compounds in the environment), that fertility teams turn to ICSI more rapidly when conventional IVF fails, or that ICSI is still viewed as more efficient, even in the absence of scientific proof, which may be the major factor in Latin America and the Middle East. I suspect the overall explanation is probably a mixture of several of these factors.”

The increased use of frozen embryo cycles was very good news because it improved cumulative pregnancy and delivery rates and helped reduce the number of multiple embryo transfers and multiple births, he said.

“Our report shows that delivery rates per aspiration increased in 2002 even though the average number of embryos transferred was reduced. For example, in Australia where a mean average of 1.8 embryos were transferred, the delivery rate per aspiration was 19.5% for fresh cycles and 29.4% for fresh and frozen cycles together. This should encourage countries to implement embryo transfer policies that reduce the risk of multiple births,” said Prof de Mouzon.

The authors warn that variation in data quality, in addition to differences in practices, legislation, guidelines, culture and religion, means that comparisons between countries “must be done with caution”.

SOURCE: www.eshre.com 

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