MTHFR Gene and Risk of Male Infertility

Infertility affects up to 15 percent of couples. In up to a third of these couples, male infertility plays a role. Male infertility is due to low sperm production, abnormal sperm function or blockages that prevent the delivery of sperm. Illnesses, injuries, chronic health problems, lifestyle choices, and other factors can play a role in causing male infertility.

Medical causes of infertility are numerous. They include Hormone imbalances, Antibodies that attack sperm, Celiac disease, Infection, Certain medications, Heavy metal exposure, Industrial chemicals, Radiation or X-rays, and Overheating of the testicles. Genetic causes include Chromosome defects like Klinefelter's syndrome, Cystic fibrosis and Kallmann's syndrome. Recently studies have associated some variants of the MTHFR gene with male infertility.

The MTHFR gene provides instructions for making a key enzyme in the folate metabolism pathway which regulates DNA methylation, synthesis, and repair. The MTHFR enzyme catalyzes the conversion of folate found naturally in foods, to its active form. Impairment of this process leads to the build-up of Homocysteine which is a potentially toxic amino acid and cardiovascular risk factor. MTHFR 1793G>A and MTHFR 677C>T both increase infertility risk, but no association was found for MTHFR 1298A>C.

Studies have shown a positive correlation between folate concentrations and sperm density, the percentage of sperm with progressive motility, as well as the percentage of sperm with normal morphology. Folic acid supplementation is known to reduce Homocysteine levels and the incidence of birth defects in women and a significant increase in sperm count and motility in men.