Worrying evidence of IVF, Down’s syndrome link

A test designed to spot chromosome abnormalities in eggs could be a "revolution" in fertility, helping older women determine their chances of having an IVF baby, doctors said on Monday. But in developing the test, they added, worrying evidence emerged that in-vitro fertilisation (IVF) may boost the risk of a baby with Down's syndrome. "It is a fair question to ask," said Alan Handyside, director of The London Bridge Fertility, Gynaecology and Genetics Centre, who led a team of doctors from eight countries. "But we have no direct evidence yet, and I don't want to worry women." The test was presented Monday at the annual conference of the European Society of Human Reproduction and Embryology (ESHRE) in Stockholm. The method entails counting the sets of chromosomes in oocytes, as human eggs are called, at stages in a maturation process known as meiosis. The idea was to vet imbalances in chromosome numbers that cause embryo abnormalities and thus miscarriage -- or, in the case of an additional chromosome 21, the mental handicap known as Down's syndrome. The technique looks at something called a polar body, a tiny by-product cell jettisoned by the egg during the meiosis phases. The investigators scrutinised eggs provided by 34 women, average age 40, who were undergoing IVF. It compared polar bodies left from two meiosis stages with the egg after it was fertilised by her partner's sperm. The new test helps pinpoint healthy eggs and damaged eggs, enabling doctors to advise a woman whether it is worth the emotional and financial investment to try for a pregnancy, said Handyside. At present, IVF clinics tend to go for a wholesale approach. They administer powerful hormones to prod follicles in the ovaries into producing eggs. The eggs are harvested, fertilised in a lab dish and two or more early-stage embryos are then transfer to the uterus in the broad hope that one will develop into a pregnancy and eventually a life birth. Handyside predicted the new technique would be a boon for women aged 35-plus, an age where the remaining stock of oocytes dwindles as menopause looms. Oocytes among these older women also tend to have a higher rate of abnormalities, although the risk varies enormously from individual to individual. "I think it will cause a revolution because we will be able to say to some women, 'we recovered eggs but unfortunately all of them are abnormal so your only option is oocyte donation,'" Handyside said by phone. "But for another group we will be able to say, 'actually it's good news, only about half of your eggs were abnormal, so you have a good likelihood of getting pregnant.' And at the same time we can screen and reduce the possibility of having a Down's child." The "proof-of-concept" study entailed unravelling the DNA of the polar bodies through so-called array comparative genomic hybridisation. But, in so doing, the team also found troubling, but unconfirmed, evidence that IVF may lead to more Down's babies. After IVF hormone stimulation, fertilised eggs bore patterns of chromosome abnormalities that were quite distinct from abnormalities in eggs that had been harvested naturally, said Handyside. "We raise the possibility that ovarian stimulation in some of these women has something to do with it, because we find so many of these errors," Handyside said. One theory is that fertility drugs break the "glue" that holds the multiple sets of 23 chromosomes together during a key stage of meiosis. As a result, chromosome numbers get mixed up in the oocyte before fertilisation, when a single set of chromosomes from the egg teams up with a single set from the sperm. "It could be stimulation, particularly as there is evidence (for this) in vitro," he said referring to earlier research on oocytes in the lab dish. "But we don't have any direct evidence as yet."