5-Methyltetrahydrofolate reduces blood homocysteine level significantly in C677T methyltetrahydrofolate reductase single-nucleotide polymorphism carriers consulting for infertility

J Gynecol Obstet Hum Reprod. 2020 Jan;49(1):101622. doi: 10.1016/j.jogoh.2019.08.005. Epub 2019 Aug 22.


Purpose: Methyltetrahydrofolate reductase (MTHFR) C677T (ala222Val) is a single-nucleotide polymorphism (SNP) that affects the formation of 5-methyltetrahydrofolate (5-MTHF), the active folate that allows the recycling of homocysteine (Hcy) to Methionine. Hcy is at the epicentre of oxidative stress and DNA methylation errors. This SNP often increases the circulating Hcy levels and consequently reduces the methylation process, which is involved in the epigenesis and imprinting of markings in gametes. This study aimed to investigate decreases in Hcy levels in MTHFR SNP carriers.

Procedure: Eighty-nine couples with fertility problems for at least 3 years were included in this program. The women were systematically tested for the MTHFR C 677T isoform. If the woman tested positive, testing of the male partner was proposed. All the carriers had well-controlled blood Hcy levels before and after treatment (600μg of 5-MTHF/day, with a backup of one carbon cycle during at least 3 months).

Findings: As expected, the circulating Hcy level was higher in the homozygous patients than in the heterozygous and wild-type patients. The treatments caused a significant decrease of the circulating Hcy in the SNP carriers group.

Conclusions: Couples with a long history of infertility should be analysed for MTHFR SNP and homocysteine and should be treated with physiological doses of 5-MTHF instead of high doses of folic acid.

Keywords: 5-MTHF; C677T MTHFR SNP; Folic acid; Gametes; Homocysteine; Infertility; Methylation.

MeSH terms

  • Female
  • Genetic Testing / methods
  • Heterozygote
  • Homocysteine / blood*
  • Homozygote
  • Humans
  • Infertility / drug therapy
  • Infertility / genetics*
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / blood
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Polymorphism, Single Nucleotide*
  • Tetrahydrofolates / therapeutic use*


  • Tetrahydrofolates
  • Homocysteine
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • 5-methyltetrahydrofolate