Methylenetetrahydrofolate Reductase (MTFHR)

Last Updated: December 6, 2016

Definition - What does Methylenetetrahydrofolate Reductase (MTFHR) mean?

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that affects a variety of crucial functions in the body. Its job is to help convert the amino acid homocysteine into methionine. If MTHFR doesn't do its job correctly, homocysteine levels may rise (which can lead to a tendency to excessive blood clot formation) and methionine levels may be too low (which can lead to errors in chromosome number during cell division). Finally, MTHFR is involved in the metabolism of folate, a B vitamin necessary for the formation of the brain and spinal cord during development. This results in three different avenues through which MTHFR can affect fertility. The formation of blood clots could potentially affect the functioning of the placenta, and aneuploidy (missing chromosomes) or severe neural tube defects can cause miscarriage.

Surprisingly for an enzyme of such importance, nearly 70 different mutations have been identified. A high proportion of the population carries a mutated form of the MTHFR gene, producing an altered enzyme. While many studies have shown associations between MTHFR gene variations and implantation difficulties or pregnancy loss, others have failed to confirm these effects. Research is ongoing into which MTHFR gene variations affect fertility, and how.

FertilitySmarts explains Methylenetetrahydrofolate Reductase (MTFHR)

Most genetic variations of the MTHFR enzyme are very rare and have not been adequately studied, or have been found to have no effect on fertility. We will focus here on two of the variants (677T and 1298C) that studies have shown are most likely to affect fertility.

The first, MTHFR 677T, reduces the functioning of MTHFR to about 45% of normal levels. This variant can lead to an increased level of homocysteine (homocystinuria), which in other medical conditions is associated with thrombophilia (overactive blood clotting). The link between thrombophilia and MTHFR 677T is not proven, but there does appear to be a loose association between MTHFR 677T and infertility and miscarriage, seen in some studies but not in others. MTHFR 677T is heat sensitive, so controlling fevers and avoiding hot tubs may be helpful to avoid inactivating the enzyme. Supplementing with folic acid before and during the first weeks of pregnancy (when early development of the nervous system takes place) may allow women with this mutation to increase their chances of having a healthy baby.

The second variant, MTHFR 1298C, may be associated with missing chromosomes (aneuploidy) leading to miscarriage, but usually doesn't result in elevated homocysteine levels unless the person also has one copy of MTHFR 677T.

For every study that shows MTHFR affects fertility, there is another that doesn't. Although some studies are inconclusive, research is active in this area and our knowledge is growing steadily.

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