In The Field

ESHRE: The risks of IVF

A big question researchers here are asking is whether babies born after IVF are as healthy as those conceived naturally.

The bottom line seems to be that most of them look fine, though it’ll be important to keep monitoring them into later life. But when it comes to understanding the biology of how culturing an embryo might affect the resulting child, there’s a lot of work to do.

One of the more controversial techniques in terms of safety is ICSI (intra-cytoplasmic sperm injection), where a single sperm is injected directly into the egg. The worry is that fertilising the egg with a sperm that probably wouldn’t have been able to do so naturally might affect the health of the resulting baby. The first baby born from the technique was in 1992, so there isn’t a great amount of detail on how the kids turn out. Studies tracking them up the age of 5 didn’t throw up major problems. Florence Belva of the Dutch-speaking Free University of Brussels has just presented to the Prague meeting the first results on ICSI kids at the age of 8. It’s a small study, just 150 children, but the data are reassuring. There was no particular difference in how the pregnancies and births went, or in the results of psychological and neurological studies. The rate of “major congenital malformations” (defined as those causing functional impairment and/or needing surgical correction) went up from 3.3% in the normal children to 10% in the ICSI group. That sounds worrying, but because of the small numbers involved, the difference mostly came down to two ICSI children with a type of hernia, and five with port wine stain birthmarks. The important thing, says Belva, will be tracking the children as they go through puberty and starting wanting to have kids of their own.

Recently there’s also been a number of studies suggesting that normal IVF techniques (including ICSI) could be affecting embryos by causing problems with “imprinting”, a mechanism by which DNA is chemically modified in a way that affects the expression of genes. IVF children seem to have an increased risk of birth defects, and particularly of imprinting disorders, such as Angelman or Beckwith-Wiedemann syndrome, which can be caused when genes are improperly modified. Researchers are now starting to look at which genes are affected when embryos are grown outside the womb, and how the culture conditions might affect imprinting. Paolo Rinaudo of the University of California, San Francisco, speaking on behalf of his colleague Gnanaratnam Giritharan, described how the researchers cultured mouse embryos in different conditions, then used DNA chips to look at the levels of gene expression in those embryos. Thousands of genes were expressed differently in the IVF embryos, and importantly, 5 of 38 genes known to be imprinted were significantly affected, including H19, which is associated with Beckwith-Wiedemann syndrome. The nearer the culture conditions were to the conditions in the womb, the fewer genes were affected, although all the experiments showed some abnormalities. Rinaudo cautioned that mouse results don’t necessarily translate into humans, but said he hopes the results will help the development of better culture conditions for clinical IVF.

At the end of the talk, one member of the audience asked whether IVF children should be given a copy of the specific conditions in which they were cultured as an embryo, presumably in case of problems in later life. Rinaudo said he wouldn’t advocate that, although everyone agreed that the risks should be properly discussed with couples thinking of having IVF.


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