MTHFR Mutations and Recurrent Miscarriages

Why Some Scientists Doubt an Association Exists

MTHFR mutation and miscarriage
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Increasing focus has been placed on something called the MTHFR genetic mutation and its associations with a host of abnormal health conditions, some of which are strongly supported and others of which are speculative at best.

In recent years, a handful of scientists have suggested that the mutation could very well explain why certain women have recurrent miscarriages. While the theory is far from conclusive, it does bring into the spotlight the role that genetics may play in unexplained miscarriages, if only in part.

Explaining the MTHFR Mutation

The MTHFR mutation is an anomaly in a person's genetic coding which interferes with the body's ability to produce MTHFR enzyme. The MTHFR enzyme, in turn, is the chemical produced by the body to properly metabolize folic acid (vitamin B9).

The resulting lack of enzyme can potentially cause a host of problems. The most severe tends to occur in persons who have inherited the MTHFR mutation from both parents (a characteristic referred to as homozygosity), while those who inherit one gene (heterozygosity) may have few if any, notable problems. Having the MTHFR mutation doesn't mean that you'll get a certain illness; it simply increases your general risk.

Some of the health problems commonly linked to the MTHFR mutations include:

  • Homocystinuria, a disorder in which the body is less able to process homocysteine, often leading to eye problems, abnormal blood clotting, skeletal abnormalities, and cognitive problems
  • Anencephaly, a birth defect characterized by missing or incompletely formed parts of the brain or skull
  • Spina bifida, the incomplete formation of bone around the spinal cord
  • Aging-related hearing loss

Other studies have linked the MTHFR mutation to heart disease, stroke, hypertension, preeclampsia (high blood pressure during pregnancy), glaucoma, psychiatric disorders, and certain types of cancer. Most of these studies have been largely mixed. with associations found in some but not in others.

All told, MTHFR genetic mutations are fairly common, with nearly half the U.S. population likely to be at least heterozygous for the mutation.

MTHFR and Miscarriage Risk

Because the current evidence so loosely supported, there are many scientists who challenge the notion that miscarriages and the MTHFR mutation are somehow linked. Those who support the hypothesis do so based on the increased incidence of miscarriage among women with a specific variant known as the MTHFR C677T mutation.

Key to the argument is the role that homocysteine is believed to play. Homocysteine is amino acid naturally produced by the body that aids in the metabolism of B vitamins. In the presence of the C677T mutation, homocysteine cannot be effectively recycled and begins to accumulate in the blood. When this happens, it can lead to an inflammatory condition called homocysteinemia which is a known risk factor for coronary artery disease.

Those who support the theory have suggested that homocysteinemia may cause the formation of tiny blood clots which block the flow of nutrition to the placenta, essentially starving the fetus and triggering a spontaneous abortion. It's a highly contentious theory and one for which there really isn't any hard evidence.

With that being said, many women with recurrent miscarriage will test positive for the MTHFR mutation. As such, some doctors have endorsed the use of anti-clotting drugs such as heparin and low-dose aspirin to reduce the risk of blood clots. Others recommend high doses of folic acid and other B vitamins, believing that may provide homocysteine a target and route by which to be eliminated from the body.

While there is no proof that any of these measures will reduce the risk of miscarriage, there is also little evidence to suggest that will do any harm.

A Word From Verywell

A debate continues to rage as to the impact of the MTHFR mutation on pregnancy, a 2013 advisement from the American College of Obstetricians and Gynecologist stated that current evidence regarding the issue is either "limited" or "inconsistent" and advised against using an MTHFR genetic analysis or fasting homocysteine test as part of a routine prenatal exam.

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  • American College of Obstetricians and Gynecologists. "ACOG Practice Bulletin No. 138: Inherited thrombophilias in pregnancy." Obstet Gynecol. 2013; 122(3):706-17. DOI: 10.1097/01.AOG.0000433981.36184.4e.
  • Chen, M.; Yang, X; and Lu, M. "Methylenetetrahydrofolate reductase gene polymorphisms and recurrent pregnancy loss in China: a systematic review and meta-analysis." Arch Gynecol Obstet. 2016 Feb;293(2):283-90. DOI: 10.1007/s00404-015-3894-8.