91av

WHILE fertility researchers continue to push the boundaries of what’s possible, doubts have been raised about the safety of one widely used treatment.

The largest and longest-running study of children born after in vitro fertilisation has found that 6.2 per cent of those conceived by intracytoplasmic sperm injection have malformations, compared with just 2.4 per cent of children conceived normally. In ICSI, a single sperm is injected directly into the egg. The treatment is offered to couples when a man has a low sperm count or a high level of abnormal sperm.

The study, in Belgium, Denmark, Greece, Sweden and the UK, compared 541 ICSI children, 440 children conceived by normal IVF and 542 children conceived in the traditional way. ICSI children were more likely to have malformations in their urogenital system, gut, muscles, bones and skin, Christina Bergh of Sahlgrenska University Hospital in Gothenburg, Sweden, told the meeting. But there were no differences between the groups in intelligence – the main concern of the study – or in birthweight or height.

Her team thinks the apparently higher rate of abnormalities in the ICSI group might simply be a result of the way the children were selected for the study. In some countries, the children conceived normally had to be chosen from school records, which could have led to disabilities being under-represented. “Severely ill children tend not to go to ordinary schools,” Bergh says.

But the findings add to a growing list of studies suggesting that assisted reproduction is not as safe as normal reproduction. Last year, one Australian study found that 9 per cent of all IVF children had abnormalities compared with 4 per cent of controls (91av, 16 March 2002, p 17), while others have linked ICSI to lower intelligence and rare disorders such as Beckwith-Wiedemann syndrome.

While these studies remain controversial, one thing is certain: ICSI can allow the genetic mutations responsible for male infertility to be passed on to male children, meaning they may also need ICSI to have children. “It is paramount that couples are aware of the potential to pass on genetic defects to their children,” Gianpiero Palermo of the Cornell Institute for Reproductive Medicine in New York told the conference.

There is no way to avoid passing on defects, short of genetic engineering, but there may be ways to improve ICSI. One theory is that damage done to the egg’s internal structure by the injection causes problems. “It’s an invasive technique; you are injecting the sperm with a needle into the oocyte quite near the nucleus,” said Bergh. Peter Nagy’s team at Reproductive Biology Associates in Atlanta presented results which show that laser-assisted ICSI, in which a laser is used to drill a tiny hole through which the sperm is introduced – which should reduce internal damage – increases the chances of fertilisation and successful development into an embryo.

A simpler way to improve the safety of IVF generally is to transfer single embryos, as this eliminates the chance of multiple births, with all the risks they entail. Jim Catt of the Sydney IVF, a clinic in Australia, argued that the success rate per IVF cycle can be just as high as when two embryos are transferred. His study of 382 women showed that 50 per cent of those who had two embryos implanted during the first treatment had a live birth, compared with just 36 per cent of women given a single embryo. But when subsequent successful transfers of embryos stored from the first round of IVF were also taken into account, the cumulative success rate for both groups was 60 per cent.

Meanwhile, other groups are trying to establish the safety of experimental techniques. Last August, a team led by Mats Brännström of Gothenburg University announced that mice had been born from mothers with transplanted wombs. The offspring are healthy and fertile, Brännström told the conference. The first human birth from a transplanted womb could take place within three years, he claims.

Womb transplants could help the 4 per cent of infertile women who have uterine problems, offering them an alternative to finding a surrogate mother. The first human womb transplant was performed in Saudi Arabia in 2000, but doctors had to remove the womb after 99 days because its blood supply failed. It took the Swedish team two years to develop the complex surgical methods needed to transplant a uterus, which involves reconnecting nerve and lymph vessels as well as blood vessels. Brännström says potential donors include women’s mothers, meaning their child would grow in the same womb they did.

Immune rejection in the mice was avoided by using genetically identical animals. But Brännström does not envisage major problems in humans. “[The womb] is mainly a big muscle,” he said. And many women who take immunosuppressants while pregnant give birth successfully, he points out. Not all experts share his optimism.

Another group claims it is a step closer to creating “artificial eggs” using a technique called haploidisation, which replaces the DNA from a donor egg with that from a normal cell taken from a would-be parent (91av, 7 July 2001, p 5). Nagy told the conference that his team had managed to reduce the number of resulting chromosomal abnormalities by using an egg at an earlier stage in its development and a body cell at a later stage than in previous attempts. “I am confident that haploidisation will work and that we will be able to obtain gametes in one or two years,” he said.

Artificial eggs would allow women who cannot produce their own eggs, and perhaps even two men, to have children. But ensuring that an artificial egg has the same genetic imprint – the same genes switched on or off – as a normal egg remains a huge obstacle, which means there will be serious concerns about the health of any children born this way.

There was some good news for men with fertility problems – they don’t need to abstain from sex for a week or more before providing sperm for testing or fertility treatments. A team at Soroka University in Israel found that in men with low sperm counts, the proportion of motile sperm falls significantly two days after last having sex, and continues to decline the longer the period of abstinence.