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Girl or boy? It's in dad's genes

Alison Cranage

Progress Educational Trust

16 December 2008

[BioNews, London]

New research hints that whether a man has sons or daughters is influenced by his genes. The study, by Mr Correy Gellatly from Newcastle University, was published in the journal Evolutionary Biology last week.

Mr Gellatly looked at 927 family trees from Europe and North America, detailing over 556,387 people, dating back to 1600. He observed that a man with many brothers is more likely to have sons, while a man with many sisters is likely to have more daughters. This effect was not seen in women.

The sex of a baby is determined by its father's sperm, an 'X' sperm (after the version of the sex chromosome it carries) makes a girl and a 'Y' sperm a boy. Mr Gellatly hypothesises that there is a gene, only active in males but a version of which is inherited from both parents, which determines the ratio of X and Y sperm a man produces.

He also suggests such a gene could explain the increase in baby boys being born after World War I. Mr Gellatly explains that the odds were in favour of men with more sons seeing a son return from the war. This would mean such men were likely to have sons, a trait inherited from their father. In contrast men with more daughters may have lost their only sons in the war, and those sons would have been more likely to father girls.

Other explanations have been proposed as to why the birth rate is not 50:50 in certain couples. It has been suggested that the sex of a baby could be influenced by differences in the time in a woman's monthly cycle sex happens, or the amount of time sperm spends in the testicles. Mr Galletly's study indicates there is a genetic component.

He says the net effect of such a gene is to balance out the population: 'If there are too many males in the population, for example, females will more easily find a mate, so men who have more daughters will pass on more of their genes, causing more females to be born in subsequent generations.'

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Research links intelligence to sperm quality

Katy Sinclair

Progress Educational Trust

16 December 2008

[BioNews, London]

Researchers at London's Institute of Psychiatry have found that more intelligent men have better quality sperm, suggesting a correlation between intelligence and evolutionary fitness, in a study published in the journal Intelligence.

The research team embarked on the study to test the hypothesis that more intelligent people were healthier, not only due to lifestyle factors, for example that brighter people are less likely to smoke, but in an underlying genetic sense. Some research has rather controversially suggested that intelligence and sperm quality are linked, which historically has served the purpose of putting clever men at an advantage in reproductive terms.

The study analysed 425 former US soldiers, who had served in the Vietnam War, and who had provided semen samples and undertaken intelligence tests. After adjusting for lifestyle factors, it was found that the more intelligent men both had more sperm and sperm that could swim better. Researcher Rosalind Arden stated, 'we found a small positive relationship: brighter men had better sperm. This association wasn't caused by habits like avoiding smoking or drinking - the big hitters of health'.

However, researchers have emphasised that the relationship between intelligence and sperm quality is small, and that it does not mean that bright men are more likely to have more children, nor that undertaking brain-training games was likely to improve sperm quality. Arden commented, 'this does not mean that men who prefer Play-Doh to Plato always have poor sperm: the relationship we found was marginal'.

Meanwhile, the team are now interested in the relationship between overall physical health and intelligence, the 'fitness factor' idea, which suggests that there might be an underlying relationship between many genetic factors in order to improve chances of longevity and reproduction. 'We were interested in testing the idea that if most of our genes act on many characteristics there might be a weak but discoverable relationship right across all of our characteristics - from nose to toes', explained Arden.

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Study shows passive smoking causes fertility problems

Katy Sinclair

Progress Educational Trust

11 December 2008

[BioNews, London]

Research published by scientists at the US University of Rochester Medical Centre in the Journal of Tobacco Control reveals that women exposed to second-hand smoke as children or young adults have an increased likelihood of experiencing miscarriages or trouble conceiving.

The research team studied 4,800 women treated at the Roswell Park Cancer Institute in New York, who were asked to give details of their pregnancies, miscarriages, smoking history and whether they were exposed to second-hand smoke at any points in their lives. The team found that those exposed to send-hand smoke for six or more hours per day in the past had a 68 per cent increased chance of miscarriage or experiencing problems getting pregnant, as compared to women who had never been exposed to second-hand smoke.

Luke J Peppone, a research assistant at the James P Wilmot Cancer Centre at Rochester, commented: 'we all know that cigarettes and second-hand smoke are dangerous, breathing the smoke has lasting effects, especially for women when they're ready for children'.

Four out of five women taking part in the study had been exposed to second-hand smoke at some point in their lives, and half grew up in a home with smoking parents. Of those women whose parents were smokers, the study found they were 26 per cent more likely to have difficulty conceiving and 39 per cent more likely to have miscarried. Peppone called the results 'breathtaking', and stated that the study, 'certainly points to yet anther danger of second-hand smoke exposure'.

Scientists believe that second-hand smoke causes changes in hormonal action relating to fertility and pregnancy and that it can affect the cervix. In the past links have been found between smoking and sudden infant death syndrome, miscarriage and birth defects. Despite the warnings, an estimated 15 per cent of mothers continue to smoke during pregnancy, and approximately 43 million US women are exposed to others' smoke.

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Fertility patients' indecision about fate of stored embryos

Sarah Guy

Progress Educational Trust

11 December 2008

[BioNews, London]

A study undertaken in the US has revealed that fertility patients with frozen embryos in storage are unhappy with the options available in relation to embryo disposal. Anne Drapkin Lyerly MD, an obstetrician/gynaecologist and bioethicist at Duke University was lead investigator of the study published online in Fertility and Sterility. She said of patients in this situation that, they 'have had hard times thinking about destroying their embryos when they are emotionally and financially invested in trying to make a baby'.

1,020 fertility patients at nine clinics were canvassed for their thoughts about what should happen to embryos created during IVF processes and stored when they were not used. Only about two-thirds said that they were likely to use their embryos. Twenty per cent declared that they were likely to leave leftover embryos frozen 'forever'.

Researchers presented four 'disposition options'; thawing and discarding, reproductive donation, indefinite freezing and donation for research. The majority found each option unacceptable except donation for research; about 66 per cent of respondents said that they would be likely to donate the embryos for research, but that donation for that purpose was not available in all clinics. A ban on federal funding for research involving human embryos prevents many patients choosing this option.

More than half of patients said that they were 'very unlikely' to donate 'spare' embryos to another couple, citing reasons such as not wanting someone else bringing up their children. Lyerly believes this contradicts the conventional wisdom that 'if you respect or care about an embryo, you would want it to become a child' noting also that 'patients feel responsible for the care of the children resulting from their embryos'.

Elizabeth Ginsburg, medical director of the IVF clinic at Boston's Brigham and Women's Hospital remarked that patients have asked for their embryos once they themselves have decided not to use them. Small numbers of respondents in Lyerly's study suggested solutions which were not widely offered, such as holding a small ceremony whilst the embryos were thawed and disposed of, or placing them in the woman's body at a point in her cycle when she would be unlikely to conceive, thus letting them die naturally.

Anne Lyerly co-authored an earlier study in 2007 which questioned how many fertility patients would support donating their 'spare' embryos to embryonic stem (ES) cell research, rather than to general medical research; a 60 per cent majority were in support of this option compared to a 22 per cent group who would prefer to discard them or donate them to other couples for adoption. Despite this support, a removal of the ban to use federal funding for human cell research was vetoed on the same day as Lyerly's results were published.

Assisted reproduction associated with elevated risk of birth defects

Lorna Stewart

Progress Educational Trust

24 November 2008

[BioNews, London]

A study published last week in the journal Human Reproduction found an elevated risk of birth defects amongst babies conceived through assisted reproductive techniques, including IVF. The research, headed by Dr Jennita Reefhuis of the US Centre for Disease Control and Prevention, used data from the National Birth Defects Prevention Study to compare the health of babies born to women who had used the techniques with infants born to women who had conceived naturally.

Dr Reefhuis and colleagues found that babies conceived using assisted reproductive techniques are between two and four times more likely to have certain birth defects than those who were conceived naturally. They are twice as likely to be born with a cleft lip, four times as likely to have abnormalities of the oesophagus or rectum, and two to three times as likely to have cardiac defects. The researchers point out, however, that even with the increased risks birth defects are still uncommon in these babies.

All the births included in the study were single births, though multiple births are relatively common in assisted reproductive techniques. Multiple births in general are known to be at higher risk of birth defects, and this is one of the reasons that techniques such as IVF have previously been thought to be associated with a higher incidence of birth defects. This study also corrected for other factors such as the age of the mother, folic acid use and alcohol intake.

The researchers are explicit in their report that they do not know the cause of the elevated risks. 'Our findings could have been because of underlying infertility, small (sample) numbers or chance,' they said. Dr James Grifo, director of the fertility clinic at New York University Medical Center, US, agrees. He feels that due to the small sample size (281 assisted reproduction babies, 14,095 babies conceived naturally) more research is needed to confirm the findings. He also said that if the association with birth defects was real, the underlying cause was more likely related to the patients' infertility than to the treatments they had undergone.

'Any couple who is considering these treatments wants to be aware of all the pros and cons of the treatment,' Dr Reefhuis said, adding 'I think it's important for couples to be aware that there may be some increased risk for birth defects as well.' Professor Michael Chapman, a senior fertility specialist with IVF Australia, said 'There's no question that the evidence shows a slight increase, and responsible IVF doctors are saying that to their patients. But if your only way forward is IVF, then an increase in risk from one in 100 to two in 100 for most people is an acceptable risk.'

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Overweight women more likely to miscarry healthy babies

Rebecca Robey

Progress Educational Trust

17 November 2008

[BioNews, London]

Overweight women are at greater risk of miscarrying a genetically normal baby in the early stages of pregnancy than women who maintain a healthy weight, according to a new study by scientists at the Stanford University School of Medicine in California, US. The researchers, presenting at the annual American Society for Reproductive Medicine (ASRM) conference, suggested that this indicates that a mother's weight can affect the outcome of an otherwise healthy pregnancy.

The UK's National Health Service (NHS) estimates that around a quarter of all pregnancies in the UK end in miscarriage. The majority of these occur in the first 12 weeks of pregnancy, but can occur up to 24 weeks. The cause of miscarriage is not always known, but it is thought that between 50 and 70 per cent occur as a result of chromosomal abnormalities (genetic defects) in the fetus. The California researchers tested DNA from 204 fetuses miscarried in the first eight weeks of pregnancy. They compared the rate of chromosomal abnormalities in the fetuses from women with a normal body mass index (BMI) with the rate of abnormalities in fetuses from women with a BMI that classified them as overweight or obese. They found that 53 per cent of babies lost by overweight women had no chromosomal abnormalities compared to just 37 per cent of babies lost by women of a more healthy BMI.

Dr Inna Landres, who led the research team, said that these findings indicate that 'obesity predisposes women to miscarry normal babies.' The reason for this is not yet understood, but Dr Landres suggested that one explanation could be altered levels of hormones such as oestrogen and androgens seen in overweight women. She emphasised: 'It's important to identify elevated BMI as a risk factor for miscarriage and counsel those women who are affected on the importance of lifestyle modification.'

An individual's BMI is calculated by dividing their weight in kilograms by their height in metres squared. A BMI of 18 to 25 is considered normal, whilst over 25 is classed as overweight and over 30 as obese. All the women in the current study were attending an academic centre for fertility counselling and had their BMI calculated before conception.

Dr Mark Hamilton, chairman of the British Fertility Society (BFS), said: 'It is recognised that women who are overweight are at a greater risk of miscarriage. It has not been defined if that risk is related to genetic problems for the embryos or the obesity itself is linked to implantation mechanisms. This study will aid our understanding of the known association with being overweight and reproductive loss.'

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Slow-frozen embryos seem to produce healthier babies in IVF [Correction]

Alison Cranage

Progress Educational Trust

17 November 2008

[BioNews, London]

Three new independent studies have provided further evidence that embryos stored using slow-freezing techniques may be better than fresh for IVF. The studies were presented at the American Society for Reproductive Medicine conference in San Francisco, US, last week. The studies indicate that using frozen embryos rather than fresh embryos reduces the risk of stillbirth and premature delivery.

It is unclear why this is the case; there are several theories. Some experts have suggested that when fresh embryos are used women may still be suffering from the effects of the powerful drugs that are used to stimulate the ovaries, temporarily disrupting any IVF attempt shortly afterwards. Dr Allan Pacey, from the University of Sheffield and secretary of the British Fertility Society (BFS), said: 'These findings are really quite interesting. It kind of defies logic to a certain extent, because the stimulation drugs and anaesthetics that are used in egg collection have worn off by the time fresh embryo transfers are done. It seems to be an issue with the formation of the placenta, but how it has an effect isn't known.' Another theory is that only the 'best' embryos surviving the freezing and thawing processes, which can damage the embryo either as the result of ice crystals forming or of an increase in the concentration of solutes as progressively more ice is formed.

The three large, independent studies took place in Finland, Australia and the US. The Finnish study, found that babies born from fresh embryos were 35 per cent more likely to be premature and 64 per cent more likely to have a low birth weight when compared to those born from frozen embryos. The research that took place in Melbourne, Australia, showed that 11 per cent of babies born from fresh embryos had a low birth weight, compared to 6.5 per cent of those born from frozen embryos. They also found that 12.3 per cent of babies born from fresh embryos were premature, compared with 9.4 per cent of those born from frozen embryos. Also, 1.9 per cent of babies from fresh embryos died a few days after birth, compared to 1.2 per cent from frozen embryos. Similar findings were reported in June this year from a Danish study.

Typical IVF treatment involves stimulating a woman's ovaries with hormones to produce eggs which are then collected and fertilised in the laboratory, with one or two embryos being transplanted into the womb two days later. The remaining embryos can be slow-frozen and then stored, to be used later if the initial cycle fails.

The new data may provide a dilemma for IVF clinics, as although frozen embryos seem to result in a healthier pregnancy, the pregnancy rate is less successful. Commenting on this, Dr Pacey said: 'Frozen embryo transfers are not as successful as fresh ones in terms of getting a pregnancy. So it may be that we have to balance the health of children against chance of success.'

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Woman gives birth to twins conceived with 13 year-old sperm

Sarah Guy

Progress Educational Trust

17 November 2008

[BioNews, London]

A woman in Taiwan has used the frozen sperm of her cancer-survivor husband to conceive and give birth to healthy twins. The woman's husband, surnamed Chen, was diagnosed with testicular cancer whilst studying at university aged 23. He cryogenically preserved samples of his sperm at Taipei's Medical University Hospital sperm bank, before undergoing chemotherapy which would potentially leave him infertile. Chen overcame the cancer but ceased to produce sperm. After getting married earlier this year, 36 year-old Chen and his wife decided they wanted their own child and so asked doctors to assist them using Chen's preserved sperm.

'The birth is a record in Taiwan' said Tseng Chi-jui, head of the Centre for Reproductive Medicine and Sciences at Taipei Medical University's College of Medicine. 'Never before has a case involving such a long period of time between the freezing of male sperm and procreation been reported in Taiwan'.

Tseng used IVF to extract four eggs to be fertilised with Chen's unfrozen sperm and only two of the four re-implanted successfully into his wife's womb. As sperm tend to lose motility (the number of sperm active or moving) after defrosting, the fertility expert used intracytoplasmic sperm injection (ICSI) technology to ensure precise fertilisation with Mrs Chen's eggs.

Improvements in cryogenics and assisted reproductive technologies have the potential to assist those with serious illnesses facing treatment which may render them infertile, Tseng said. Sperm cryopreservation enables such patients to 'save' their sperm for future procreation.

Mrs Chen gave birth to healthy twin boys at 37 weeks, one weighing four pounds six ounces, and the other weighing six pounds.

Earlier this year, a UK couple conceived a second baby using sperm frozen 19 years ago at St Mary's Hospital in Manchester. Emmanuel and Zoe Iyoha received IVF treatment using sperm preserved on Mr Iyoha's behalf in 1989, before he underwent successful treatment for cancer. In 2004, doctors at St Mary's hospital reported the birth of baby conceived using sperm that had been frozen for 21 years, believed to be the longest reported storage period for sperm successfully used for treatment.

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Screening embryos before IVF improves success rate

Lorna Stewart

Progress Educational Trust

17 November 2008

[BioNews, London]

The first trial of a procedure which selects IVF embryos with the best chance of developing into healthy babies was presented last week at the American Society for Reproductive Medicine conference in San Francisco. Dr Dagan Wells and colleagues at Oxford University, UK screened embryos for 23 women before implantation and showed a much improved success rate of IVF; 18 out of the 23 women have either already given birth or have passed the point in pregnancy at which miscarriages typically occur.

The embryo quality test, which uses a technique called comparative genomic hybridisation (CGH), means embryos' chromosomes can be more comprehensively screened for abnormalities. This is not the first pre-implantation genetic test to be developed but Dr Wells' test screens embryos at a later stage of pregnancy (when the embryo is five days old and has more than 100 cells). This means that every chromosome pair in the embryo can be examined and, since more cells can be removed for analysis, it yields more accurate results.

The 78 per cent success rate reported by Dr Wells and colleagues is significantly better than the rate usually achieved (60 per cent) in a patient group like this who have all had unsuccessful IVF treatment previously and have an average age of 37. Following CGH screening, the implantation rate for each individual embryo is 62 per cent - the normal rate is 28 per cent. Dr Wells said, 'The pregnancy rates we've got so far are absolutely phenomenal. The probability that one embryo leads to a pregnancy is doubled. That means that you've got a much better chance of a pregnancy if you do a single embryo transfer.'

Dr Wells and colleagues are now ready to begin a larger scale trial in the UK and have applied for permission from the Human Fertilisation and Embryology Authority (HFEA, the fertility watchdog) to offer the test to patients at the Oxford Fertility Unit. It is anticipated that the test would add around £2000 to the present £4000 cost of IVF treatment.

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