High doses of IVF drugs given to women over 35 may be causing abnormalities in their eggs that reduce the chances of pregnancy, new research has suggested.
British scientists have discovered a distinctive pattern of genetic defects in eggs from IVF patients aged over 35, which they believe may be caused by the drugs used to stimulate their ovaries prior to fertility therapy.
As these genetic errors make eggs unviable when they are fertilised, the findings raise the possibility that IVF techniques commonly used to treat women in their late 30s and 40s may be counterproductive, actively harming their chances of conception.
If the results are confirmed, they could lead to significant changes in procedures used by many clinics, so that they are given milder drug therapy that reduces genetic damage to eggs.
The research, led by Professor Alan Handyside, of the Bridge fertility clinic in London, examined a type of problem called aneuploidy, in which eggs have too many or too few chromosomes.
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When an aneuploid egg is fertilised, it creates an embryo with an abnormal number of chromosomes, and most of these fail to implant in the womb or miscarry. The few that survive have chromosomal disorders such as Down’s syndrome, in which babies inherit an extra copy of chromosome 21.
In the study, which Professor Handyside will present today at the European Society of Human Reproduction and Embryology conference in Stockholm, he used a screening technique to examine patterns of aneuploidy in eggs from IVF patients aged over 35. This identified a pattern of aneuploidy that is not seen in eggs that are ovulated naturally as part of the normal menstrual cycle.
“When we look at eggs from older women, who have heavy ovarian stimulation, we see a pattern of errors that is opposite from what we see in pregnancies following natural conceptions,” Professor Handyside told The Times. “It raises the question of whether the stimulation is causing those errors.”
In an IVF cycle, women are given follicle-stimulating hormone (FSH) to coax their ovaries into producing plenty of mature eggs at once, so that doctors have enough to use in fertility treatment.
Women in their 20s are usually given low doses of FSH, typically up to 150 international units. Older patients are given higher doses because their ovaries need more stimulation: a woman of 40 may receive three times the dose given to a patient of 30.
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Professor Handyside believes that these high doses may be damaging the eggs of older IVF patients. “Other papers show that if you grow eggs in very high levels of FSH, the drug used in ovarian stimulation, it increases rates of aneuploidy,” he said. “In older women, we use much higher levels of FSH to get any eggs at all. This is something that hasn’t been investigated before in patients.”
Asked whether this may be harming patients’ chances of conception, he said: “It’s possible, but we don’t have firm evidence yet. Other IVF doctors are reluctant to consider this, but if you ask geneticists they all say it’s likely that follicle stimulation has this effect.”
Professor Handyside now intends to follow up the results in patients, to determine whether mild ovarian stimulation or no stimulation at all produces lower error rates. “I think we have to analyse the origins of miscarriage in IVF pregnancies and compare that with miscarriage and the instances of abnormalities with eggs from natural cycle IVF,” he said.
The findings have emerged from an international study investigating whether an egg-screening technique can detect aneuploidy and improve pregnancy rates.
Tony Rutherford, Chairman of the British Fertility Society, said the findings concord with evidence that while stronger stimulation produces more eggs and embryos, it does not increase pregnancy rates. “Driving the ovaries hard to produce as many eggs as you can isn’t necessarily in the best interests of patients,” he said.
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Stuart Lavery, director of IVF Hammersmith, said: “Previously, it was always thought that chromsomal abnormalities were related to the age of the egg. This raises concern that some of those chromosomal abnormalities might be treatment related.”