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Genes predict IVF success

October 24, 2006 By Helen Pearson This article courtesy of Nature News.

Unpicking the problems of infertility may help guide treatment.

A battery of genetic tests might soon foretell which women are more likely to become pregnant by in vitro fertilization (IVF) and which are more likely to face problems and disappointment.

IVF, in which egg and sperm are united in a dish and the resulting embryos are transplanted into the womb, has a notoriously low success rate. Less than 37 of women give birth after a given attempt. A woman's age and her supply of eggs all contribute to the success rate but additional genetic factors are also thought important.

Now researchers at Cornell University in New York have identified specific genetic variations that lower a woman's chances of becoming pregnant through IVF.

They suggest that women who choose IVF could one day undergo genetic tests that would help predict the procedure's chances of success, and help direct treatment.

Hormonal support

Steven Spandorfer and his colleagues focused on a protein receptor, found throughout the body, that binds the reproductive hormone progesterone. This hormone is essential for the embryo to implant in the uterus.

Some people carry an altered version of the receptor gene that differs from the normal version by a single chemical letter. In a group of 240 women undergoing IVF, about one in six had one or two copies of the altered gene, the team found.

Nearly 50 of those with the normal version became pregnant, but less than 30 of the women carrying the variant became pregnant.

The progesterone receptor gene normally makes two slightly different proteins, called PR-A and PR-B. The balance between these controls the activity of many other genes. The variant gene makes more PR-B, upsetting this balance.

The end result is probably an alteration to the lining of the uterus, Spandorfer says.

The variant gene seems to specifically affect the chances of an embryo implanting and surviving, rather than other aspects of fertility. The researchers found no correlation between the type of gene women carried and their type of infertility, the numbers of eggs they produced or the number of embryos created after IVF.

Genetic success

Spandorfer's team also looked at three genes previously associated with the success of implantation and embryo development in animal studies. These also affected the chances of successful IVF: 92 of women with 'normal' versions of all three genes became pregnant, compared with 41 who had altered versions of one or more of these genes.

The results, presented at the American Society for Reproductive Medicine meeting in New Orleans, are among the first to show how specific genes affect IVF success.

Genetic tests to identify women who have problems with implantation might help decide how many embryos should be transferred back into a woman's womb after IVF. Commonly, two to three embryos are put back, but this increases the chance of multiple births, which carry health risks for both mother and children.

Women whose genes suggest they are likely to have success with IVF could have only one embryo transferred; women more likely to have problems might improve their chances if several embryos are transferred.

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