Genetic screening could reduce recurrent miscarriages

2 July 2014

A new genetic variant that may be present in either parent has been linked with repeated pregnancy loss (miscarriage).

As many as one in four pregnancies is estimated to result in miscarriage, though a significant proportion of these may occur very early before a woman realises she is pregnant, often due to major chromosomal abnormalities. Overall, perhaps  one in seven known pregnancies end in miscarriage.

Recurrent pregnancy loss (RPL) or recurrent miscarriage, defined as three or more consecutive pregnancy losses in a row, is much rarer, occurring in around one woman in every hundred. However, it may affect larger numbers of couples than infertility alone, although many infertile couples may also suffer from the repeated loss of pregnancies established via in vitro fertilisation (IVF).

The presence of a specific genetic variant in the annexin A5 (ANXA5) gene known as the C4/m2 variant or M2 haplotype in either parent has already been implicated in both obstetric complications such as pre-eclampsia, intrauterine fetal growth restriction and death, and in recurrent pregnancy loss (RPL). It is involved in fetal-induced disruption of normal blood clotting in the placenta, thought to interfere with normal implantation of the embryo. If either parent has the genetic variant, the risk of miscarriage is significantly increased.

Now new data from researchers at the private IVF treatment provider Care Fertility have published data suggest that screening for M2 halotype carrier status among couples seeking fertility treatment could be important.

The study published in the journal Reproductive Biomedicine Online reports that of 157 infertile couples with at least one unsuccessful attempt at IVF, 44% were M2 haplotype carriers, with one or both partners having one or two copies of the gene variant. This compared with 15% of individuals from a healthy German population biobank used as healthy controls.

Critically, the defective blood clotting can be treated with anti-coagulant drugs such as aspirin and heparin. None of the couples receiving IVF without treatment established healthy pregnancies leading to the birth of a live child, but 38% of those who received treatment alongside IVF did – a similar proportion to unselected couples of the same age receiving IVF.

Lead author and managing director of Care Fertility Professor Simon Fishel said that in future they would be screening selected couples for the variant and treating those found to be affected, adding: “We hope to increase the chance of pregnancy and live birth, decrease the risk of miscarriage and reduce the incidence of obstetric complications arising from this genetic mutation”.

It is possible that a similar approach could benefit couples who do not suffer from infertility, being able to conceive, but who experience RPL. The potential involvement of male genetic factors is a new issue for consideration in such cases.

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