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• Concern over hormonal medication for over-35s • Study suggests increased risk of Down’s syndrome High doses of drugs used to stimulate the ovaries of older women undergoing fertility treatment may be causing chromosomal abnormalities in their eggs, leading to failed pregnancies and even, potentially, babies with conditions such as Down’s syndrome. Hormonal drugs are used in IVF to encourage the ovaries to produce extra eggs, increasing the chances that some will be successfully fertilised and implanted in the womb. One of the biggest hazards of IVF is overstimulation, which can make a woman very ill. Under the age of 35, mild stimulation is used. But over 35, when the ovaries are naturally producing fewer eggs, larger doses of hormones have conventionally been used. Research led by a UK team, presented at the annual European Society of Human Reproduction and Embryology (ESHRE) conference in Stockholm, has now shown that the resultant eggs have a higher proportion of chromosomal abnormalities than would be expected in untreated women of the same age group. Embryos created from eggs with chromosomal abnormalities do not usually proceed to a successful pregnancy and live birth. They may not implant in the womb or the woman may miscarry very early on. But it has usually been thought in the past that the lack of success in IVF among older women was the result of their less viable eggs, which were assumed more likely to have chromosomal abnormalities than those of younger women. “What this paper shows is that a lot of the chromosomal abnormalities are not those that are conventionally age-related,” said Stuart Lavery, consultant gynaecologist and director of the IVF clinic at Hammersmith hospital in London. It raised concerns, he said, that the treatment might be responsible for the abnormalities – possibly by allowing eggs to develop “that nature would have excluded”. These could include – if a pregnancy went to term – the birth of a baby with Down’s syndrome, which is the result of a chromosomal abnormality. The research, carried out by Professor Alan Handyside, director of the London Bridge Fertility, Gynaecology and Genetics Centre, and colleagues from eight countries, establishes that the excessive abnormalities exist but other work will be needed to find out the causes. The discovery came out of research they were conducting on a novel way of screening small cells that are the by-product of egg development, called polar bodies, to see whether it was a reliable method of screening for chromosomal abnormalities. Tony Rutherford, chair of the British Fertility Society and honorary senior lecturer at the University of Leeds, said the discovery “put meat on the bones” of what they had known for some time – that driving the ovaries hard with high drug doses produced more eggs but not more embryos. “The bottom line is that the number of normal embryos is the same whether you stimulate in the conventional manner as we have for 25 years [with higher doses of hormones] or whether you do it in a much milder manner.” Lavery said that, where stimulation was not producing many eggs, “the common answer is to give more [hormonal medication]. But the work coming out suggests that isn’t necessarily a good thing.” Handyside said scientists needed to look further at the pattern of abnormalities in different stimulation regimes including mild stimulation and natural cycle IVF, where one egg per cycle is removed, fertilised and returned to the woman. “The results of such research should enable us to identify better clinical strategies to reduce the incidence of chromosome errors in older women undergoing IVF,” he said. “We also believe that our research will help identify women who want to have their own offspring but have practically no chance of doing so that we can advise them to use donor [eggs],” said Professor Joep Geraedts, co-ordinator of the ESHRE task force on preimplantation genetic screening. “This in itself is already a big step forward that will aid couples hoping for a healthy pregnancy and birth to be able to achieve one.” Medical research Fertility problems Down’s syndrome Health & wellbeing Drugs Sarah Boseley guardian.co.uk