Do clots caused by MTHFR mutations lead to recurrent pregnancy loss? by Carolyn Ledowsky
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 recent 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 study compared the frequency of each thrombophilic gene mutation in isolation, as well as combinations of multiple variants between the RPL and healthy groups.
The frequency of mutations was much higher among the RPL patients than the healthy women, particularly when it came to MTHFR mutations. The results were most striking for the MTHFR 1298AC genotype, which was present in 152 RPL patients (46.07%) and only 20 healthy controls (5.71%). The difference for the homozygote genotype 1298CC was also remarkable – it was present in 44 RPL patients and only 1 healthy woman (13.33% versus 0.29%). FVL (8.48% vs. 2.86% healthy) and Prothrombin G20210A (4.24% vs. 2.86% healthy) mutations were also more frequent among RPL patients than the healthy controls, though the difference was less pronounced. In addition, combinations of these mutations significantly increased the risk of RPL. This was particularly true in cases where both FVL and MTHFR mutations were present.
This is why it’s so important to be tested for all of the above thrombophilic gene mutations, including MTHFR. Information is half the battle; knowing the risks can help you take the best steps to prepare for a healthy pregnancy.
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