The first prospective study into the outcome of untreated pregnancies in a group of women carrying a mutation in the Factor V Leiden gene** and with a history of recurrent miscarriages at around 12 weeks, showed that under 40% had live births compared with nearly 70% in a control group of women with a similar history but with a normal copy of the gene.
For women with the rogue gene who had a history of late miscarriage only one out of nine had a live birth compared with 22 out of 45 of the women with the normal gene.
The research was carried out by teams from the Department of Reproductive Sciences, Imperial College of Science, Technology and Medicine, London, and the Department of Haematology, St. Mary’s Hospital NHS Trust, London.
Pregnancy complications associated with the mutated gene and other genetic mutations affecting the blood clotting mechanism are thought to be due to thrombosis in the blood vessels of the placenta.
Now the researchers have called for doctors to screen women for Factor V Leiden (FVL) mutations if they have a history of recurrent miscarriages associated with placental thrombosis. They also want targeted anti-blood clotting treatment for these women to be tested in a randomised clinical trial.
Dr Raj Rai, Clinical Lecturer in Reproductive Medicine at Imperial College and co-author of the study, said that it was important to stress that many women with the mutation had perfectly normal pregnancies: it was likely to be the women who had multiple risk factors for thrombosis that were most at risk of miscarrying.
"However, the low live birth rate in our study suggests that Factor V Leiden is an important and potentially treatable cause of recurrent miscarriages. Our findings support a hypothesis that recurrent miscarriage is due in some cases to an exaggeration in the pro-thrombotic changes that occur during normal pregnancy. There are also indications from other research we have done that a proportion of women with recurrent miscarriage are in a pro-thrombotic state even when they are not pregnant. Clearly, this may have implications for their future health beyond their reproductive years."
But, he said that there was no justification for screening women routinely prior to pregnancy, nor was it appropriate to undertake routine anti-clotting treatment outside of a clinical trial. "Long term use of heparin (the anti-clotting drug) has risks. It is associated with thinning of the bones, allergies to some preparations and, paradoxically, a theoretical risk of inducing thrombosis. Also, it has to be given by daily injection."
One of the major challenges facing doctors as a result of the findings is how to distinguish between those women with FVL who are likely to miscarry and those who are not.
Said Dr Rai: "The major disadvantage of just checking for FVL or other mutations is that this ignores the fact that blood clotting is a dynamic process involving interaction of clotting and anti-clotting factors. However, we are investigating the use of a global test called Thromboelastography, which is able to take account of the dynamic nature of blood clotting in the body."
The 25 women with FVL who took part in the study had either a history of three or more consecutive miscarriages before or around 12 weeks of pregnancy or at least one late miscarriage (over 12 weeks). The control group of 198 had a similar pregnancy history but carried a normal Factor V gene. None had a personal history of previous thrombosis.
The livebirth rate for the FVL group with early miscarriages was 37.5% (controls 69.3%). For those with a late miscarriage the livebirth rate was 11.1% (controls 48.9%).
* Factor V Leiden and recurrent miscarriage - prospective outcome of untreated pregnancies. Human Reproduction. Vol 17. pp 442-445.
** FVL is carried by five per cent of Caucasians, but is rarely found among black people. It carries a four-fold risk of venous thrombosis and a 10-fold risk if the carrier is taking the oral contraceptive pill.
Notes:
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2 Human Reproduction is a monthly journal of the European Society of Human Reproduction and Embryology (ESHRE). Please acknowledge Human Reproduction as a source. ESHRE’s website is: http://www.eshre.com
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