Recurrent pregnancy loss (RPL) affects up to 2% of couples trying to become parents, and the cause of this frustrating condition is unknown in 50% of cases. One prevailing theory is that blood clots that block the flow of nutrients to the fetus may play a role. While factor V Leiden (FVL) is the most commonly studied mutation when it comes to inherited thrombophilias, or genetic predispositions toward blood clots, MTHFR C677T and A1298C polymorphisms are also highly suspect.
That’s largely because we know that when the MTHFR gene isn’t doing its job well due to mutations that limit its functioning, homocysteine levels rise. High homocysteine levels are a known risk factor for RPL. Researchers suspect that the reason is because high levels of homocysteine create vascular problems like blood clots. Sometimes these clots lead to strokes, and MTHFR polymorphisms are well-known for their association with these events.
However, in pregnant women, some researchers think these genetic mutations may cause clots near the placenta that block the flow of nutrients to the fetus early in its development. While blood is supposed to coagulate during pregnancy in order to avoid hemorrhage, inherited thrombophilias may send this process into overdrive, in a sense. However, the results of studies on the subject have been mixed, and not all medical researchers accept these small clots as a cause of recurrent pregnancy loss.
A 2015 study of Iranian women delved into this issue further. The study looked at 330 women with three or more consecutive RPLs and no children, and compared them to 350 healthy women with at least one child and no history of pregnancy loss. The women were tested for MTHFR C677T and A1298C variants, as well as Factor V Leiden (FVL) and Prothrombin G20210A mutations.
The results showed that more Northern European women have the Factor V Leiden gene mutation and even being heterozygous for this mutation can increase the risk of venous thrombosis by 3-7%. But if you are homozygous that risk increases to 50-100 x increased risk.
Factor V Leiden was associated with second trimester losses. When looking at the MTHFR gene they found that pregnancy losses were more likely to happen in the first trimester because implantation and invasion of the embryo in first trimester of pregnancy is regulated by DNA methylation. The results showed that when you combine FVL (even heterozygous) with MTHFR genes (heterozygous or homozygous) you get a significantly higher frequency of recurrent miscarriage.
What was interesting was that there were more losses with the A1298C. There were more women who had the A1298C mutation with recurrent miscarriages that any other group. We are seeing more and more research now that supports the fact that we should be looking at both mutations of the MTHFR gene and not just the A1298C.
So the take out should be, women who have a family history of, or are currently suffering from recurrent pregnancy loss should be tested for the MTHFR, Factor V Leiden and Prothrombin genes. Evidence clearly demonstrates the risk is there, and by addressing these gene issues we may be able to prevent many of these miscarriages. Information is half the battle; knowing the risks can help you take the best steps to prepare for a healthy pregnancy.