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.
I have factor five and mthfr no miscarriage 😲2 births no complications at all now At 57 2 strokes and put on warfarin any information on how to go forward?
Hi Kim, sorry to hear. MTHFR is linked to homocysteine levels which can negatively impact cardiovascular health. If you haven’t already, I would recommend having your folate levels checked and taking an activated folate supplement to help boost your levels and reduce homocysteine. B6 and B12 would also be important to consider
I am from Poland , I do not have baby yet. I have 3 miscarriage. What i should do to have baby ? What I can do better?
paulinamaciejewska7@interia.pl
Hi Paulina, so sorry to hear. There are many causes of miscarriage. MTHFR issues as mentioned in this article can be one. If you haven’t had an MTFHR test, this may be useful. You should be able to request this from your Doctor or Naturopath. This webinar provides some excellent advice on proactive prevention. I would also recommend joining our Facebook Group and our Newsletter. And for individual support I work with women and couples personally at TashaJennings.com.au
I have both factor V and MTHFR heterzygous genotype mutant
and in week 3 of pregnancy and i take only baby aspirin is it safe or should take clexane 40 mg
Clexane and aspirin have similar but different mechanisms so this should be decided by your Doctor. Aspirin predominantly works to prevent platelet aggregation and clexane predominantly works to prevent thrombus formation. Clexane is indicated in your condition but is a stronger drug with more risk factors so this should be assessed by your specialist
Such a great article. I was recently diagnosed with FVL (hetero) and MTHFR A1298C after our 17wk loss. Besides that, I have two healthy term pregnancies and one 9wk miscarriage. Have you heard of a drug called EnLyte? OB prescribed to me even before these diagnoses when both my kids were around 10mo. I asked to take it again after our recent loss. I’m wondering if it works so well for me because of the MTHFR. Do you have any knowledge of this drug?
Hi Amber, EnLyte is a vitamin supplement with 3 forms of folate, methyl folate, folinic acid and folic acid as well as other B vitamins. Sorry to hear about your miscarriage. Yes, it would likely be helpful for your MTHFR diagnosis. I do caution the use of methyl folate because it can cause side effects depending on your other methyl pathways but it works well if this was prescribed by a practitioner who understands your pathways. We also have a prenatal supplement which can be useful for those with MTHFR issues https://conceivebaby.com.au/product/zycia-natal-nutrients-90-tabs/.
Hello. I was recently diagnosed with FVLeiden (hetero) and MTHFR A1298C (hetero)
after a 15wk loss – Feb.2018 , after trying for about 3 years..
I have one healthy to term pregnancy in 2013 hardly obtained .
Is the mutations part of my issue not getting pregnant easily?
I’m 38 – what should help me now improve my ovocite quality and try again?
Thank you!
Hi Andy, sorry to hear about your struggles. I usually find there are a number of factors involved in fertility issues but yes FVL and MTHFR can definitely play a role. Getting plenty of natural folate is a good first step. Omega 3 and herbs like turmeric and ginger can help support healthy circulation and reduce inflammation associated with these conditions. Also avoid toxins where possible by avoiding plastics, using natural body products and cleaning products, avoiding chemical ‘air fresheners’ and fly sprays and eating organic where possible. Address any gut health issues to support healthy metabolism and absorption and lighten the load on the liver to support healthy hormone production. Are you seeing a natural fertility specialist who can provide personalised support? If you would like to chat further about your best steps forward, feel free to contact me at tasha.jennings@conceivebaby.com.au.
Hello,
I was recently diagnosed with FVLeiden (hetero) and MTHFR (hetero)
after a 7 week loss. I’m 27 years and it’s was my first time trying.
I was prescribed Jusprin 81 mg and Folic Acid 5 mg before pregnancy, and Clexane 40 mg and Optimized Folate as soon as my pregnancy starts..
Should I continue Jusprin after positive pregnancy as well?
Thank you!
Sorry for your loss. Medications are usually continued but this would be a question best asked of your prescribing Doctor. Wishing you all the best