Excess folate linked to increased birth of twins after in-vitro fertilisation

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With the UK government currently considering whether to fortify flour with folic acid, results of a study in this week's issue of THE LANCET highlight how such fortification may increase the rate of twin births after in-vitro fertilisation (IVF) where more than one embryo is transferred.

IVF is a popular treatment for infertility, but despite recent advances, only one in five treatment cycles results in pregnancy and livebirth. Most IVF practitioners try to increase pregnancy rates by implanting multiple embryos each cycle. In the UK, where double embryo transfer is the norm, a quarter of successful IVF procedures result in the birth of twins. All women trying to conceive are advised to take folic-acid supplements up to week 12 of pregnancy to avoid neural-tube abnormalities such as spina bifida. But around half of pregnancies in the UK are thought to be unplanned, therefore many women will not be able to increase their intake early enough. Hence the proposal to fortify the diet in the UK with folic acid.

Paul Haggarty and colleagues from the Rowett Research Institute and Department of Obstetrics and Gynaecology at Aberdeen University, UK, enrolled 602 women undergoing IVF treatment to a prospective cohort study and related their intake of dietary and supplementary folate, their blood concentrations of folate, and variations in 6 genes involved in folate metabolism, to the outcome of their IVF treatment.

Results showed that twin births after transfer of two embryos were associated with high plasma folate and low age, but that high folate status did not increase the chance of successful pregnancy after IVF. This finding is consistent with the actual experience in the US, where flour fortification with folic acid in 1998 was associated with an 11-13% increase in the incidence of multiple births after fertility treatment.

The current study also identified a link between one of the genes involved in folate metabolism and the success of IVF treatment. The authors discuss the implications of this finding for future research and fertility treatment.

Dr Haggarty comments: "Our results suggest that the high incidence of twin births associated with treatment for infertility could be reduced, while maintaining livebirth rates, by encouraging women not to exceed recommended doses of folic acid." In an accompanying Comment, also in this week's issue of THE LANCET, Gary Steinman discusses the effects of diet on twinning rates around the world.

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