IVF News

Scientists in the United States claim that they have established a link between the use of frozen embryos during in vitro fertilisation (IVF) treatment and ectopic pregnancies. They say that ectopic pregnancies - where the embryo implants in the wall of the Fallopian tube, rather than the lining of the uterus - are 17 times more likely in women who conceive after IVF using embryos thawed after being in frozen storage. Ectopic implantations always result in the loss of the pregnancy, and can be potentially fatal for the woman, as well as affecting her future chances of conceiving.

It was already known that the IVF procedure itself - where eggs and sperm are combined in the laboratory and a fertilised egg (embryo) is later transferred to the woman's womb - results in a greater number of ectopic pregnancies than natural conception. But the latest research seems to add fuel to growing concerns about the safety of embryo freezing, for the health of both the women using IVF and their children.

The new study, undertaken at Brown University and the Women and Infants Hospital in Providence, Rhode Island, US, was led by David Keefe. It followed observations made by one of his staff that ectopic pregnancies appeared to occur more frequently when frozen/thawed embryos are used. The research team compared the results of the fertility treatments they performed with fresh and frozen embryos between January 1998 and March 2002. They found that only nine out of 490 (1.8 per cent) implantations achieved using fresh embryos resulted in ectopic pregnancy, compared with six out of 19 pregnancies (31.6 per cent) where the embryos used had been frozen.

Dr Keefe presented the results of the study at the annual conference of the American Society of Reproductive Medicine in San Antonio, Texas, this week. He said that the study showed that further research on his initial findings was necessary, especially 'given their importance for patient counselling'. 'We've made the observation, now the burden is to figure out why', he said. But, he noted that the sample of women studied who were using frozen embryos was very small. A larger research group may not lead to such startling results.

Asked why he thought embryo freezing might increase the risk of ectopic pregnancy, Dr Keefe posited several theories. 'One possibility is that freezing and thawing slows the development of the embryo, so the normal timing is disrupted', he said, adding that 'another theory is that freezing and thawing alters the zona pellucida. This could change its adherence: it shouldn't be sticking in the tube'. Last month, Professor Lord Robert Winston, a UK fertility specialist, claimed that the embryo freezing procedure might affect gene expression in embryos. Dr Keefe, when asked whether he believed Winston's theory might be linked to his own, replied 'possibly, yes'. Gillian Lockwood, another UK fertility specialist, said that 'if these findings are true it is worrying', but pointed out that about 250,000 babies have so far been born from frozen embryos and that more research was needed before any link could be proved.

Richard Kennedy, from the British Fertility Society, said there was no reason to believe that a greater risk of ectopic pregnancy was attached to the use of frozen embryos: 'We have been using frozen embryos for 15 years and have carried out thousands of frozen embryo cycles', he said. He continued: 'Nobody has previously reported an increased risk from this type of technique'. Alison Cook, speaking for the UK's Human Fertilisation and Embryology Authority (HFEA), said the American study showed abnormally high rates. She questioned whether freezing protocols differed between the UK and the US. 'It's surprising', she said. 'I've never seen anything like it before'.
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Having stumbled in its passage through parliament earlier this month, Canada's long awaited legislation on assisted reproductive technologies (ARTs) and related matters has finally been passed by the Canadian House of Commons. Bill C-13, entitled 'an Act respecting assisted human reproduction', was first introduced to the Canadian parliament in May 2002, but has been more than 10 years in the making. Now, federal MPs have voted 149-109 in favour of the comprehensive ART bill, a larger majority than was perhaps expected.

The Canadian legislation, which now has to pass through the Senate to become law, bans human cloning (for both reproductive and therapeutic purposes), the creation of human-animal hybrid embryos, sex selection of embryos for non-medical reasons, payments to women acting as surrogates, payment for donated gametes and the buying or selling of human embryos. It also regulates the collection, alteration, manipulation or treatment of any human reproductive material for the purpose of creating an embryo, storage of reproductive material and information about donors. Under the Act, donors must give fully informed written consent before their gametes or embryos are used, and children born following donation will be entitled to receive medical information about the donors. Donors will be identifiable only if they consent to be so. In addition, the bill allows embryonic stem (ES) cell research to take place on surplus IVF embryos, but prohibits the use of embryos created specifically for research purposes. The bill also establishes a regulatory body, the Assisted Human Reproduction Agency of Canada (AHRAC), which will license, monitor and enforce the new law, if passed by the Senate, in a similar way to the UK's Human Fertilisation and Embryology Authority (HFEA). The AHRAC will also collect and store data on ARTs.

Patricia Baird, the chair of a 1993 royal commission report on ARTs that recommended 'urgent action' to the government of the day, welcomed the news. She said 'I've been waiting for the legislation imminently for the last 10 years', adding 'it's taken far too long'. A previous bill died in the House of Commons six years ago. However, even though the House of Commons has passed the latest bill, it still has to move on to the Senate, where the whole debating, committee and voting process will begin again. In addition, it seems likely that the Canadian Parliament will adjourn, in early-mid November, for the winter, which could further delay the whole process. One potential benefit of this is that incoming Prime Minister, Paul Martin, who will begin the next session, has voiced support for the legislation. However, according to the Toronto Star newspaper, a spokesperson for Paul Martin refused to speculate on whether he would simply restart the process with an unchanged bill.

Those in opposition to the passage of the bill have vowed to continue their fight against it. Paul Szabo, one of 16 Liberal MPs who broke ranks from the party line in the Commons vote, and leader of those opposed to the bill who have been delaying its progress so far, believes the fight is not yet over: 'We're just starting', he said. He believes that poor drafting of the bill means that it does not properly ban human cloning or the creation of animal-human hybrids and says he will continue to make his voice heard in the Senate, adding 'This bill is so fatally flawed, there's no question about it'. Pro-life groups also oppose the measure, because it would allow limited ES cell research. They intend to seek amendments in the Senate that could prevent the proposal from getting final approval. According to one senator, about 20 members of the Senate are known to have some concerns about the legislation. But Health Minister Anne McLellan, sponsor of the bill, remains resolute. 'As far as I'm concerned, it will become law', she said, adding that she has spoken to Senator Michael Kirby, who will head a Senate committee that will examine the bill: 'I have every confidence that Senator Kirby will take this legislation and do a thorough job of reviewing it and move it forward', she said.
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Research published last week shows that women who take part in egg sharing programmes when they undergo fertility treatment do not compromise their own chance of having a baby. When a woman agrees to egg sharing, half of the eggs collected in one of her cycles are donated to another woman, while half are used in her own treatment. This is usually in return for a reduction in the usual price of IVF.

The new study, published in the journal Human Reproduction, evaluated egg sharing taking place at the private Lister Fertility Clinic in London, which has run an egg sharing programme since 1992. The researchers looked at 276 egg sharing cycles involving 192 women who had agreed to share their eggs, 274 IVF cycles in which women had received eggs and 1098 IVF or ICSI cycles (involving 718 women) where egg sharing had not been used. The different groups of women were studied to see if the doses and duration of drugs needed in ovarian stimulation, the numbers of eggs collected/donated, or rates of fertilisation, pregnancy or live birth were different.

Hossam Abdalla, director of the clinic and leader of the research team, said that no significant differences were found between the three groups of women. Women who shared eggs achieved a pregnancy rate of 42 per cent and a live birth rate of 33 per cent. This compared to a 40 per cent pregnancy rate and 30.9 per cent live birth rate for non egg sharers and 41 per cent and 28.6 per cent rates respectively for recipients. In addition, the number of eggs collected, the amount of drugs used and the average number of embryos transferred also differed only slightly between the groups.

Two previous studies have shown lower pregnancy rates in women who shared their eggs. But these studies used a small sample of patients. Mr Abdalla said that 'up to now, there has been no research in the UK carried out with large numbers of patients to ensure that the egg sharing programme is not detrimental to egg sharers and/or to the outcome of recipients' treatment compared with standard IVF or ICSI'. The premise that egg sharing lessens the chances of pregnancy for women who donate is based on the fact that their ovaries may be over stimulated to produce eggs. But Mr Abdalla said the egg sharers in the study were given the same standard drug regimen as other women receiving treatment and that the clinic's view was that 'the sharer should always be given priority and have the first call on her eggs'. The study has made sure that donors had the first four of their eggs collected. 'I believe that is the primary reason for the success of our programme', said Mr Abdalla.
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Viagra, the 'wonder-drug' promoted for its ability to relieve impotence in men, may have some unwanted side-effects. Research presented today in Cheltenham, UK, at the annual meeting of the British Fertility Society, suggests that men who are taking Viagra when trying to start a family may actually be decreasing their ability to father a child. However, Viagra manufacturers Pfizer deny that the drug causes fertility problems.

Viagra was designed to enable an increase of blood flow to the penis to overcome impotence problems. However, since its release it has increasingly been used 'recreationally', and is also used by fertility clinics in order to aid patients' semen production. Viagra is what is known as a 'phosphodiesterase inhibitor', a type of chemical known to affect sperm function, so the study looked at what effect the drug has on sperm. The researchers discovered that using Viagra speeds up chemical changes within sperm, rendering them infertile by the time they reach an egg. This chemical change, known as the acrosome reaction, normally only occurs when a sperm reaches an egg, and is when sperm release enzymes that break down the outer layer of the egg allowing the sperm head to penetrate it more easily. However, if the acrosome reaction occurs too early, the sperm become ineffective and unable to enter the egg, as they have no digestive enzymes left.

Scientists from the School of Medicine, Obstetrics and Gynaecology at Queen's University, Belfast, took 45 semen samples and split them into two groups. Half of the samples were treated with Viagra, while the other half was used as control. The research team found that while Viagra increased sperm motility, up to 79 per cent more sperm in the Viagra-treated samples had clearly undergone premature acrosome reactions. These findings lead the researchers to say they had 'significant concerns for Viagra use in assisted reproduction'. They added that the findings echo previous studies in mice that showed that the presence of Viagra meant that fewer eggs would be fertilised and fewer resulting embryos developed normally.

Dr Sheena Lewis, a member of the team, said that their 'message is that caution should be taken when using recreational drugs if you are hoping to start a family'. But a representative of the European Society for Sexual Medicine, Dr John Dean, said it was important that the study wasn't reported in an alarmist fashion, adding that sperm is highly sensitive in laboratory conditions. 'Childless couples - and the general population - should be aware that in the five years that Viagra has been around no overall detrimental effect on fertility has been observed', he said.

However, Pfizer says that there has been no evidence of Viagra affecting fertility following its use by 23 million men over six years. 'It's one study and it was in a test tube basically, not in real people', said spokesman David Watts.
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The issue of parenthood following fertility treatments has also been raised in New Zealand recently, where the Law Commission has published a discussion paper on the subject. In the paper, called 'New Issues in Legal Parenthood', the Commission has called for feedback on whether laws governing parenthood and related matters should be changed to bring them in line with 'the fast pace of social change'.

Part of the 'social change' referred to includes the increased use of assisted reproductive technologies, including surrogacy and the increased incidence of single women and lesbians having children. The Law Commission also says that current laws in New Zealand 'fail to recognise the Maori practice of children sometimes being raised by adults who are not their genetic parents'. According to the Law Commission, 'one in three children in New Zealand lives outside the traditional nuclear family of a genetic mother and father living in the same household'.

The discussion paper reviews and asks for submissions on the laws relating to parental status and parental rights and responsibilities in light of social changes and new developments in assisted human reproduction. It considers, in particular, the laws that govern parenthood in cases of donor gamete conception and surrogacy, and asks whether the 'traditional' idea of a child having only two legal parents needs to be changed, while presenting a number of options for reallocating parenthood in these situations.

Submissions on this paper should be made before 24 May 2004.

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US doctors report that they have helped five couples to have IVF babies which are able to provide tissue-matched cord blood for ill siblings. Four of the so-called 'saviour siblings' were conceived to help children with leukaemia, while another was born to help Charlie Whitaker, a British boy affected by Diamond-Blackfan anaemia. Scientists and clinicians at the Reproductive Genetics Institute in Chicago have now published details of the procedure, which involves genetic testing of embryos to establish their tissue type. The authors, who published their findings in the Journal of the American Medical Association, claim the technique has 'wide implications in medical practice'.

The Chicago doctors helped the Nash family conceive the world's first saviour sibling, a baby boy born in October 2000. Adam Nash provided umbilical cord blood stem cells used to treat his sister Molly, who was affected by a rare genetic condition called Fanconi's anaemia. The procedure involved testing IVF embryos to identify those which were both free from the disease, and also a tissue match for Molly. The five latest cases have sparked debate in the US, since all the embryos were tested solely for tissue type, and not for any genetic condition. Gilbert Meilander, a member of the President's Council on Bioethics, called the technique 'morally troubling'.

The doctors treated nine couples, who had existing children affected by acute lymphoid leukaemia, acute myeloid leukaemia, or Diamond Blackfan anaemia. After testing a total of 199 embryos, they identified 45 tissue-matched embryos for implantation. The team used 28 of these in 12 IVF cycles, which resulted in five singleton pregnancies. 'Screening embryos is still highly controversial and even not allowed in some countries, but it appears to be a reasonable option for couples', said the Institute's director Yury Verlinsky. The Whitaker family travelled to Chicago for treatment, after being refused permission to have the procedure carried out in the UK.

A new poll suggests that the majority of Americans support the use of preimplantation genetic diagnosis (PGD) for establishing tissue type only. A survey of 4005 people by the Genetics and Public Policy Center revealed that 61 per cent approve of using PGD to help an ailing sibling, while 33 per cent disapprove. By contrast, 57 per cent of respondents disapprove of using PGD to select embryos on the basis of sex. However, 80 per cent expressed concern that if not regulated, genetic technologies such as PGD could 'get out of control'. 'There is strong support for using these technologies when there is a health benefit, even when that benefit is for another person, but this support coexists with deep-seated worries about where all these new technologies may be taking us', said Center director Kathy Hudson.
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A review of IVF procedures undertaken in the last ten years at the Mayo Clinic in Minnesota, US, has shown that it makes no difference to success rates whether frozen or fresh sperm is used. The results of the study were presented last week at the Annual Scientific Meeting of the American Urological Association in San Francisco.

The researchers reviewed 2,039 IVF cycles that took place at the clinic between 1993 and 2003. Fresh sperm was used in 1580 cycles and frozen sperm in 309 cycles. The overall outcomes of IVF using frozen and fresh sperm were compared, as well as comparative outcomes for various methods of sperm retrieval, including MESA (microsurgical epididymal sperm aspiration), TESE (testicular sperm extraction) and electrically stimulated ejaculation. The outcomes measured included the average fertilisation and pregnancy rates, embryo quality and the likelihood of having at least one live birth from a single IVF cycle. When comparing the use of fresh or frozen sperm, no difference was found in the pregnancy rate or the number of live births.

The study's lead author, Dr Alan Thornhill, said that the researchers were concerned that frozen sperm might reduce the birth rate, but now, he said 'we believe that concern is unwarranted'. Dr Shane Russell, leader of the research team, told the conference that the 'data supports the continued and expanded use of frozen sperm for IVF'. Dr Thornhill added: 'IVF can be a physically, financially and emotionally draining process for couples, and use of frozen sperm eliminates the pressure of obtaining sperm on a specific day and unnecessary risk to the woman due to ovarian hyperstimulation'.
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Gay and lesbian couples in the UK will get easier access to fertility treatments following a review of the existing law governing the area, it is reported. The 1990 Human Fertilisation and Embryology Act is currently under review by the House of Commons Science and Technology Committee, whose comments will feed into a second review and consultation, due to be undertaken next year by the Department of Health (DH).

According to an article in the UK's Observer newspaper, the DH is apparently planning to make the changes to the law in light of the Civil Partnerships bill, which is currently passing through parliament, and 'changes in societal attitudes' since the 1990 Act was passed. Currently, the law states that fertility doctors should make treatment decisions taking into account the welfare of the child to be born, including the 'need of a child for a father'. Many clinics have refused to provide fertility treatments to lesbian couples on this basis.

However, the passage of the Civil Partnerships bill would mean for the first time that lesbian and gay couples wishing to have their relationship legally recognised could apply to do so. Entering a formal 'civil partnership' will give same-sex couples similar rights and responsibilities to those currently enjoyed by married couples. What this means, suggests the DH, is that other legislation drawn up with heterosexual couples in mind may also need updating.

The Observer reported that a DH submission to the Commons Committee review panel claims that changes in the way the law is framed could lead to legislation that can 'better recognise the wider range of people who seek and receive assisted reproduction treatment in the 21st century'. Professor Alison Murdoch, chair of the British Fertility Society, said that she favoured extending the provision of fertility services to same-sex couples. 'We have to stand back from it and say, what is the evidence that there is any harm to anybody from them having a child', she said. She added: 'Children need to be brought up in a loving, caring environment - it's the loving care that's important, not the sexuality of the parent'.

Single women and lesbian couples in Victoria, Australia, will now be able to inseminate themselves thanks to a loophole in the law found by Victoria's Infertility Treatment Authority (ITA) and Melbourne IVF. While clinical reproductive services in Victoria are legally limited to women who are 'medically infertile' (rather than 'socially infertile'), allowing women to take screened sperm samples home from clinics for self-insemination does not breach the prohibition. Dr John McBain, chairman of Melbourne IVF, said 'It is not a reproductive service if we're not performing it'. If self-insemination has failed four times, then the woman can be classed as medically infertile and can receive full access to IVF procedures.
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Stephanie had undergone premature menopause at the age of 13 - her ovaries stopped functioning and she became infertile. She and her husband tried a number of times to have a child both naturally and using IVF, including two cycles using eggs donated by her twin sister Melanie, but without success. Melanie was not affected by premature menopause and has three children conceived naturally.

Doctors have been working on ovarian transplantation techniques for a long time. As with other forms of organ or tissue transplant, one of the main problems is rejection by the body's immune system. So transplanting ovarian tissue from an unrelated woman would require the use of immunosuppressant drugs, which may themselves affect ovulation and fertility. For this reason, it is unlikely that there will be many ovarian transplants from woman to woman. But an identical twin, sharing the same genetic information, seemed like the ideal candidate to donate functioning ovarian tissue.

The medical team, led by Dr Sherman Silber at St. Luke's Hospital in St. Louis, Missouri, said at the time that the surgery had gone well and that they expected Stephanie to start ovulating within three months. They also said that, after that time, they expected that she would be able to conceive naturally. Stephanie found out early last week that she was pregnant, after using a home testing kit and confirming the result with her doctor. Her reaction was to immediately telephone her sister, who said that she announced 'I'm pregnant! Praise the Lord!'
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A panel of fertility experts has analysed medical data on children conceived by in vitro fertilisation (IVF), and found that overall, they are no more likely to have major health problems than naturally conceived children. They found no evidence to suggest that IVF increases the incidence of major birth defects, cancers or problems in psychological or emotional development. However, it was found that IVF might have a 'negative impact' on some children during birth. The study also confirmed earlier work linking IVF to a slightly increased risk of some rare genetic conditions. The panel, which reviewed 169 published studies, reported its findings at the annual meeting of the American Society for Reproductive Medicine in Philadelphia on Tuesday.

The panel found that twins born after IVF were at no more risk of health problems than twins conceived naturally. But, they said, with singleton IVF babies, there was more likelihood of a premature birth or a clinically low birth weight. It is known that this can sometimes cause health and developmental problems as a child grows up. The panel also found that IVF babies are also twice as likely to die during birth, or soon after. The evidence also suggested that IVF babies are at greater risk of being born with some rare disorders caused by a failure of 'genetic imprinting', such as Beckwith-Wiedemann syndrome. Some scientists think this may be due to the conditions in which embryos are kept in the laboratory, before being transferred to the womb.

The panel estimated that about one per cent of babies born in the US are conceived using IVF, and while there has always been some concern that IVF might affect aspects of children's health, previous studies examining IVF children have not borne this out. The panel members said they did not know exactly what caused birth problems to occur in some IVF children - it may be the IVF process itself, they said, as it cannot exactly mirror 'normal' fertilisation. But, they said, it is also possible that infertile parents may pass on problems to their children, or infertile mothers may be more likely to have problems during pregnancy. Panel member Marcelle Cedars, from the University of California, San Francisco, said 'I think these women are different'.

The panel's next task is to make recommendations for those working in IVF as to how to find out what causes health problems in IVF children at birth, as well as how to avoid the problems in the future. They advocate larger, longer and more detailed studies of children born from IVF, which might reveal, 'particular groups of parents who are at greater risk of health problems, and who could be given additional testing or support'. In addition, they want research to be conducted on how growth solutions used to nurture embryos in labs might affect children's well-being.
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