IVF News

WiCell Research Institute, Madison, Wisconsin, announces an additional sessions of its "Introduction to Human Embryonic Stem Cell Culture Methods" course. This hands-on, basic techniques training is offered over two full days, with an additional half-day option available at no additional cost.

The optional half day will include freezing mouse embryonic feeder cells and human embryonic stem cells. In addition, students may use this day to consult with the instructors on any protocols covered during the first two days of class. PLEASE NOTE: This class does NOT cover directed differentiation of HES cells or the derivation of HES cell lines. The new session dates are July 11-13, 2005. Additional information and on-line registration are available at www.wicell.org.

A British woman is expecting the country's first 'frozen egg' twins, it was revealed last week. The 36-year-old woman is said to be five months pregnant, following the use of fertility treatments that included the freezing of one of her eggs. Doctors at the West Midlands-based Midland Fertility Services (MFS), where the treatment took place, say hers is a 'normal and healthy pregnancy'.



Her eggs were stored in liquid nitrogen for 18 months before being thawed, fertilised in the laboratory with her husband's sperm, then implanted into her womb. The woman, who had previously undergone fertility treatment in 2003 chose to use egg freezing because she ethically objects to traditional IVF methods that involve the creation of multiple embryos and the destruction of surplus embryos. When she had IVF the first time, she had other eggs removed, dried and frozen before being stored.



The first baby to be born following the use of a frozen egg in the UK was Emily Perry, in June 2002, also after treatment at MFS. It is believed that Emily's mother, Helen, is the only woman in the UK to have successfully given birth after a frozen-thawed egg was used. Only about 200 women worldwide are thought to have become mothers this way. Egg freezing is more difficult than freezing sperm, as eggs contain more water and therefore ice crystals can form inside the egg and damage it. Because the process is so sensitive, British clinics have only been allowed to perform the procedure since 2000.



Dr Gillian Lockwood, medical director of MFS, said that egg freezing was an invaluable treatment for women whose reproductive capacity may be harmed by treatment for cancer or other conditions. 'It is wonderful to have further proof that this new development in assisted conception can offer real hope of genetic motherhood to many women who require fertility treatment', she said. But a spokesman for pro-life group Life said they had concerns about such techniques. 'There has been a lack of follow-up studies on the children that are born using them', he said, adding 'the effect of liquid nitrogen upon eggs has not been fully investigated at this stage'.

Canadian researchers have discovered that a woman's fertility can be affected almost as much by passive smoking as by actual smoking. Published this week in the journal Human Reproduction, the study shows that exposure to 'side-stream smoking' - defined as smoke given off by a smouldering cigarette - is equally damaging to women undergoing fertility treatment.



The researchers, from McMaster University and Hamilton Health Sciences in Ontario, studied the quality of embryos produced by 225 women undergoing IVF or ICSI. The women were grouped according to whether they smoked, did not smoke, or lived with a partner who regularly smoked. While they found no difference in the quality of the women's embryos, they noticed a striking difference in embryo implantation and pregnancy rates between the three groups. The implantation rate among non-smokers was 25 per cent, whereas among the other two groups it was only around 12 per cent. Among the non-smokers, the pregnancy rate per embryo transfer was around 48 per cent. Among the smokers, it decreased to 19 per cent, and the 'side-stream smokers' had a pregnancy rate of 20 per cent.



The researchers pointed out that this was a retrospective study that relied on women self-reporting their smoking habits and that more work would have to be done to produce conclusive evidence. However, they concluded that the evidence from the study is clear enough to show the damaging effects of passive smoking on fertility and suggest that all patients be warned of the potential hazards. Professor Warren Foster, director of IVF and reproductive biology at McMaster University's department of obstetrics and gynaecology, said that 'the findings from our study already warrant a warning to women to reduce or, if possible, prevent exposure to cigarette smoking, especially if they are trying to conceive'.



The researchers now hope to undertake a prospective study to try and confirm their results. Meanwhile, they are trying to work out why the embryos from the three different groups of women all seemed to be of similar quality, yet showed distinctive differences in their ability to implant and go on to establish a pregnancy. They believe this might possibly be because cigarette smoke compromised the egg in some way, but that the 'lethal' results did not become apparent until later in embryonic development.



Dr Richard Kennedy, spokesman for the British Fertility Society, said that from such a small study it would be 'premature' to say that passive smoking was as damaging to fertility as smoking. But, he added, 'it is already established that smoking adversely affects IVF outcome and fertility so I am not surprised by the findings'.

UK scientists have used preimplantation genetic diagnosis (PGD) to help a couple conceive a baby unaffected by haemophilia, a serious inherited blood clotting disorder. A team at the Clinical Sciences Centre in Hammersmith, London and colleagues at Queen Charlotte's Hospital used a new test that directly detects the gene mutation responsible, allowing unaffected male and female embryos to be identified. Previously, PGD for haemophilia involved discarding all male embryos, since only boys are affected by the condition.



PGD can be carried out on IVF embryos, to ensure that only those unaffected by a particular genetic condition are returned to the woman's womb. It has been used since 1989 to test for diseases where the single gene involved has been identified (for example cystic fibrosis), and for disorders caused by mutations in X-chromosome genes. In the case of haemophilia and many other X-linked conditions, only boys are usually affected - the harmful effects of the mutated gene are masked by a working copy in girls, who have two X-chromosomes. Until now, PGD to avoid an X-linked condition involved testing embryos for the presence of a Y-chromosome, to identify male embryos. However, 50 per cent of these male embryos would be unaffected by the disorder.



In the latest case, reported by the Daily Telegraph, doctors used the new haemophilia test to help Debbie and Steve Hunter conceive an unaffected baby. Mrs Hunter is a carrier of haemophilia A, the most serious form of the disease, and her ten-year-old son Ben is affected by the condition. It is caused by a mutation in the Factor VIII gene, which makes a protein involved in blood clotting. All boys born to carrier women have a 50 per cent chance of being affected, while all girls will be unaffected. However, any girl born to a carrier mother has a 50 per cent chance of being a healthy carrier herself.



The Hunters underwent two cycles of IVF treatment, and the resulting embryos were tested for the presence of the mutation. 'We had two embryos suitable for return, one normal (either boy or girl) and one female who carried the disease', said team leader Professor Tuddenham. Both were implanted, one of which resulted in the birth of a healthy baby girl, Grace, who is now 12 weeks old. It is not yet known whether Grace is a carrier of the disease herself, but Professor Tuddenham says that 'we now have the means to end haemophilia in an affected blood line'. Mrs Hunter describes Grace as 'like any other normal baby. She is lovely, really lovely'.



The new test should lead to greater success rates when carrying out PGD for haemophilia, says team member Stuart Lavery. He explained that this is because there is a greater chance of having better quality embryos to transfer, since doctors can choose from a pool of 75 per cent of the embryos produced by the couple instead of 50 per cent. It also means that patients will potentially have the opportunity to have an unaffected son, as well as unaffected daughters. 'As the technology of single cell analysis becomes increasingly sophisticated, I expect that specific mutation analysis will replace embryo sexing for all X-linked conditions', Dr Lavery told BioNews.

A UK woman left brain-damaged after a stroke caused by a rare side effect of IVF treatment is set to receive 'very substantial' agreed damages. The 34-year-old patient, who cannot be identified for legal reasons, became pregnant but then developed ovarian hyperstimulation syndrome (OHSS). Fertility doctor Paul Rainsbury, of the Bupa Roding Hospital in Ilford, Essex, agreed last week in the High Court to pay her an undisclosed amount of compensation.



OHSS is caused by the drugs used in IVF to make the ovaries produce more eggs than usual. Mild symptoms of the syndrome, such as swelling and breathlessness, apparently affect up to 20 per cent of women undergoing treatment. However, very rarely, the symptoms are more severe and potentially fatal. Only one death from OHSS has been reported by the UK media to date, that of 33-year-old Temilola Akinbolagbe earlier this year. The total number of fatalities in the 30 years that IVF has been available in the UK is unknown, but it is believed to be less than five.



In the latest case, the woman became pregnant after receiving IVF treatment in 2000. She then developed symptoms of OHSS, which Mr Rainsbury identified on 7 August 2000, but diagnosed as 'mild'. Crucially, on 11 August, she telephoned Mr Rainsbury to say she felt very unwell. She claimed he told her not to worry, but she then later miscarried, the court heard. The next day, she suffered a stroke, and now has great difficulty with her speech, mobility, reasoning and decision-making. But Rainsbury's QC, John Grace, told the judge that if the case had gone to trial, the woman's evidence would have been contradicted by her medical notes - which show that many of her symptoms were still mild when she was admitted to hospital on 12 August.



Mr Rainsbury did not admit liability, but the woman is now set to receive a 'seven-figure' sum, according to the Daily Mail. Her barrister, James Badenoch, said the award meant that she could retain care of her only son and have some freedom from the constraints upon her. The judge, Mr Justice Nelson, approved the settlement.

The risk of having a child born with certain congenital problems may increase with the father's age, US and Danish researchers say. In a study of over 70,000 births, published online in the journal Human Reproduction, they report that the risk of Down syndrome and other conditions begins to increase in children fathered by men aged over 35. The results could be due to genetic mutations in sperm caused by biological or environmental factors, the researchers say.



It is known that the rate of genetic errors in a man's sperm-producing cells increases with age, and previous research has suggested a link between increased paternal age and certain genetic conditions. However, the strong association between older mothers and a raised risk of conditions such as Down syndrome has hampered efforts to investigate the impact of paternal age. In the latest study, the team looked at data from 71,937 firstborn babies born in Denmark between 1980 and 1996. All had mothers aged between 20-29 years, to reduce the potentially confounding effects of increased maternal age.



The researchers found that there was no overall increased risk of birth defects related to increasing paternal age. However, they did find a link between older fathers and a raised risk of certain conditions - including Down syndrome and some syndromes involving multiple body systems or limb malformations. Compared to younger men aged between 20-29 years, the incidence of Down syndrome increased by 15 per cent in men aged over 35, rising to 30-40 per cent in fathers over 40. In men over 50, the risk was around three times higher that of younger men.



Previous research has shown that 5-9 per cent of Down syndrome cases are caused by a chromosome abnormality (an extra copy of chromosome 21) inherited from the father. The scientists say their results suggest that a high paternal age - as well as a high maternal age - could be 'an indication for screening'. They conclude that 'advanced paternal age may be associated with an increased occurrence of some specific malformations, including Down syndrome'.

The eighth child of Charlie Chaplin was born when he was 73 and as far as we know has lived a healthy life. However, whilst most men remain fertile into their old age, it has long been recognised that to father children later in life increases the risk of their being born with a variety of conditions such as Down syndrome, achondroplasia and even schizophrenia. Therefore, the recent report published by Danish scientists showing that increased paternal age is linked to a greater risk of some congenital malformations (as well as Down Syndrome) is perhaps not surprising.



What makes the study interesting is that the conclusions are derived from an analysis of nearly 72,000 singleton birth records taken from the Danish Fertility Database. With such large numbers it is possible to adequately control for the known risks of female age and therefore look at the children fathered by older men whose partners were between the ages of 20 and 29. The conclusions were striking: the risk of some conditions rose significantly in fathers as young as 35 and by the time a father is over 50, the risk of Down syndrome had increased fivefold above that seen in fathers aged 20-29.



So why should this be of interest to anyone other than male celebrities who find that they have managed to snap up a younger bride? Well, we at fertility clinics are now being encouraged to preferentially recruit as sperm donors, men who have completed their own families and who apparently better appreciate the joys of children and the responsibilities of being a father. However, data from the Office for National Statistics suggests that the age at which men are choosing to be fathers is increasing and in 2003 a third of all UK births were in men older than 35. This, in combination with the fact that current guidelines for the recruitment and screening of sperm donors recommend that they be no older than 39 (because of the risk of age related new mutations in the male germ line that this Danish study confirms), means that our pool of candidate sperm donors may be much smaller than we have previously realised.



We have no choice about what age our parents choose to reproduce and what legacy that decision may have for our own genetic health. But in a medical setting, when donor gametes are being used, we have a duty to minimise risk both to the patient (of acquiring infection or disease from the donor) and any donor-conceived person (of inheriting a serious genetic disease). Political and social pressure to increase the upper age limit for sperm donation - as an easy way of increasing the supply of suitable donors - should be resisted at all costs because it does not logically follow that the removal of donor anonymity allows us to increase the level of risk to patients and donor conceived people. However, studies like this are extremely helpful in reviewing the current recruitment guidelines to see if they are still appropriate and adequately supported by evidence.

A survey that asked 2432 members of the UK public about its attitudes to current ethical and moral issues in medicine shows that most are in favour of some embryo and stem cell research, but draw the line at human reproductive cloning. It also shows that people think the time limit for legal abortions should be reduced and that assisted suicide for the terminally ill should be allowed.



Sixty per cent of the people surveyed in the YouGov poll for the Daily Telegraph newspaper said that they did not feel well enough informed about the issues raised by cloning and stem cell research to be able to make judgements. However, 79 per cent said that the use of cloned embryo stem cells to treat serious or life-threatening disease or conditions - such as cancer, heart disease, Parkinson's disease and arthritis - is acceptable. But six per cent wanted this research on embryos to be restricted to diseases that threaten children's lives only. Thirty per cent of respondents said they would allow infertile couples to use reproductive cloning in order to have children, but 60 per cent were totally opposed to any reproductive cloning, either 'in the foreseeable future' or 'ever'.



Sixty-eight per cent said that the use of embryos left over from fertility treatments for medical research purposes was acceptable and 41 per cent would allow the creation of embryos solely for research purposes. The pollsters had explained to participants that UK scientists are already permitted to carry out experiments on embryos for a range of purposes up to 14 days development. Only 16 per cent held the view that an embryo was a person from the moment of conception, and should therefore receive the same protection as new-born babies.



On the issue of germline gene therapy, 43 per cent said that doctors should be allowed to alter the genetic make-up of a child before birth, but only to prevent a serious genetic disorder. Seventy-seven per cent said that couples should not be able to select the sex of their baby, while only 14 per cent said this should be allowed. Fifty-eight per cent approved of the use of IVF technology to create 'saviour siblings'.



Anthony King, professor of government at Essex University, who analysed the results for the Daily Telegraph, said that the UK public seem to be mainly against 'casual and cosmetic' uses of new technologies. However, the campaign in America against research on embryos and in particular embryonic stem (ES) cell research 'finds almost no echo in this country', he said.

A study for Norwich Union Healthcare has shown that more than 2.5 million men in the UK could have fertility problems. The researchers asked doctors in general practice (GPs) about male infertility, finding that a nearly a third of them worried that declining male fertility will impact on an already ageing population, unless men take action to reverse the trend. Many of the doctors surveyed blamed the decline in male fertility on the modern lifestyle.

The Norwich Union research showed that the quality and quantity of sperm produced by men in the UK has declined over the past 30 years. It also showed that while infertility is commonly thought to be a female problem, including by the majority of men surveyed for the research, that in about one third of all couples who have trouble conceiving, it is male infertility that is the root of the trouble.

The study results show that about nine per cent of men in the UK could be suffering from reduced or poor fertility. Many of the GPs surveyed said that this might be caused by lifestyle choices such as drinking large quantities of alcohol, smoking, or not taking enough exercise. Of these factors, smoking was believed to be the most likely, with 44 per cent of doctors surveyed saying that this was likely to be the main contributing factor. In comparison, only 11 per cent blamed alcohol and only seven per cent blamed stress. However, a number of GPs also said that other factors, such as delaying having children until slightly older, might also contribute, as fertility in both men and women decreases with age.

Dr Ann Robinson, a GP, said that 'the results of this survey are shocking and should be a wake-up call to men and women that drinking and smoking too much not only gives you a bad headache in the morning but can affect your ability to start a family'. However, 94 per cent of the doctors said they do not have enough time to offer fertility 'MOTs' to men wishing to start a family.

Men were also asked about their attitudes to and awareness of infertility. The results showed that 51 per cent (of the 797 men surveyed) were more concerned with the financial implications of raising a child than their ability to become a father. Nevertheless, more than two thirds felt it would be beneficial for doctors to offer fertility check-ups to men wanting to start their families. Dr Doug Wright, clinical spokesman for Norwich Union Healthcare, said that men were evidently wrong to assume that women were the only ones likely to be infertile. He added: 'With the next generation facing increasing pressure as a result of declining fertility and mortality rates, it's only fair that men accept their responsibility in the equation'.

Montreal, Quebec- Even embryos formed from the eggs of healthy young donors exhibit a startlingly high number of abnormalities. Researchers presented work today at the conjoint meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society focusing on the use of Preimplantation Genetic Diagnosis (PGD) for embryos created with donor eggs .

PGD is used to increase the chances of pregnancy resulting from an IVF cycle and to prevent the transfer of embryos with identifiable genetic defects. It is recommended for women who have experienced recurrent pregnancy loss, women of advanced maternal age, those who have had previous failed IVF attempts with embryos of good appearance and couples seeking to avoid passing on a heritable disease. Up until now, all information on rates of chromosomal abnormality in embryos has come from infertility patients and those who know they carry a genetic disorder

Hypothesizing that routinely using preimplantation genetic diagnosis for chromosomal abnormalities would improve conception rates in donor egg IVF cases, researchers from the Huntington Reproductive Center in Pasadena, California evaluated 289 embryos from 22 egg donors in 26 fresh and two frozen embryo transfer cycles. They found that 46% of the embryos were chromosomally normal and 42% were abnormal. Only normal embryos were transferred to gestational surrogates on the fifth day after fertilization with an average of 2.4 embryos transferred per cycle. Sixty-four percent of the transfers resulted in an on-going pregnancy. The average age of the donors providing the eggs was 25.8 (all the donors were under 30) but interestingly, the donors? abnormal embryo percentages varied widely from 29% to 83% and it was impossible to tell from the appearance of the embryos which would test normal and which abnormal.

Dr William Kearns and his colleagues at the Shady Grove Fertility Reproductive Science Center in Rockville, MD, sought to determine the incidence of embryonic aneuploidy among the general population. They therefore examined a series of donor egg IVF cases, thus eliminating from consideration the major groups for which PGD is recommended- couples with a history of failed IVF cycles and women of advanced maternal age. They looked at 13 couples who had decided to engage an egg donor due to poor outcomes of their prior therapies. The 13 couples had 14 cycles with a total of 159 embryos examined. The donors? average age was 26.6 (21-31 range). Fifty-two percent of the embryos were found abnormal; 6% could not be diagnosed. All 13 patients had an embryo transfer with clinical pregnancy resulting for eight of the 13 patients. Pregnancy rates among the patients in this group were similar to those in patients using donor eggs who do not use PGD.

At Reproductive Biology Associates in Atlanta, GA, researchers investigated the differing incidence of aneuploidy in young infertility patients as compared with older patients and found that the frequency of chromosomally abnormal embryos is unexpectedly high in those of young reproductive age. In a prospective on-going study, 36 infertile patients (average age 32.5, all under 35), with no prior treatment and representing all diagnoses of infertility proportionally, had IVF with PGD. Their PGD results were compared with a control population of women over 38 (average age 40.7) who were undergoing IVF at the same time. Young patients in the study population had an average of 17.6 eggs retrieved, of which 70% fertilized; the older control patients had 13.5 eggs on average, of which 69% fertilized. The younger women in total had 103 embryos identified as normal and 198 abnormal embryos. The older women had, as expected, a higher proportion of abnormal embryos: 323 abnormal to 116 normal. Of the younger patients, 56% became pregnant, while 33% of the older patients became pregnant.

Eric Surrey, MD, President of SART, remarked, ?PGD may become a very useful technique for maximizing the chances of success of a particular cycle of IVF. And these results do shed light on some of the reasons why a particular young donor or patient might produce many eggs, which fertilize and develop as embryos of normal appearance, but do not result in pregnancy. However, PGD, especially using a single cell, is not fail-safe. Mosaicism, the presence of normal and abnormal cells in the same embryo can confound the results of single-cell PGD.?