Journal of Assisted Reproduction and Genetics

, Volume 36, Issue 1, pp 65–67 | Cite as

A successful treatment with 5 methyltetrahydrofolate of a 677 TT MTHFR woman suffering premature ovarian insufficiency post a NHL (non-Hodgkin’s lymphoma) and RPL (repeat pregnancy losses)

  • Luz E. Goyco Ortiz
  • Edouard J. Servy
  • Yves J. R. MenezoEmail author


Methylation is an ubiquitous regulatory biochemical process in cellular physiology. It is involved in immune response, neurotransmitter function, trans-membrane transport and DNA repair. But it also plays a mandatory role in gene expression regulation and silencing via imprinting and epigenesis, two processes totally dependent upon methylation of DNA and histones. These two last biochemical regulations are of major importance in gametogenesis and early embryo development. The folate cycle is a major partner in methylation: it allows the regeneration of methionine from homocysteine post methylation via SAM (S Adenosyl Methionine) the ubiquitous co factor of Methylation (see fig. 1). MTHFR is a strong effector of the folate cycle, but its genetic variants, 677CT and 1298AC, exert a reduced enzymatic activity. Besides being implicated in circulatory and cardiac problems and cancer, these variants exert a strong correlation with the impairment of reproductive functions...


  1. 1.
    Gong M, Deng W, He T, Shi Z, Huang G, et al. MTHFR 677C>T polymorphism increases the male infertility risk: a meta-analysis involving 26 studies. PLoS One. 2015;10(3):e0121147.CrossRefGoogle Scholar
  2. 2.
    Enciso M, Sarasa J, Xanthopoulou L, Bristow S, Bowles M, Fragouli E, et al. Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy. Hum Genet. 2016;135:555–68.CrossRefGoogle Scholar
  3. 3.
    van der Put NMJ, Blom HJ. Neural tube defects and a disturbed folate dependent homocysteine metabolism. Eur J Obstet Gynecol Reprod Biol. 2000;92:57–61.CrossRefGoogle Scholar
  4. 4.
    Serman L, Dodig D. Impact of DNA methylation on trophoblast function. Clin Epigenetics. 2011;3:7.CrossRefGoogle Scholar
  5. 5.
    Branco MR, King M, Perez-Garda V, Bogutz AB, Caley M, et al. Maternal DNA methylation regulates early trophoblast development. Dev Cell. 2016;36:152–63.CrossRefGoogle Scholar
  6. 6.
    Unfried G, Griesmacher A, Weismüller W, Nagele F, Huber JC, Tempfer CB. The C677T polymorphism of the methylenetetrahydrofolate reductase gene and idiopathic recurrent miscarriage. Obstet Gynecol. 2002;99:614–9.Google Scholar
  7. 7.
    Yang Y, Luo Y, Yuan J, Tang Y, Xiong L, Xu MM, et al. Association between maternal, fetal and paternal MTHFR gene C677T and A1298C polymorphisms and risk of recurrent pregnancy loss: a comprehensive evaluation. Arch Gynecol Obstet. 2016;293:1197–211.CrossRefGoogle Scholar
  8. 8.
    He J, Liao XY, Zhu JH, Xue WO, Shen GP, et al. Association of MTHFR C577T and A1298C polymorphisms with non-Hodgkin lymphoma susceptibility: evidence from a meta-analysis. Sci Rep. 2014;4:6159.CrossRefGoogle Scholar
  9. 9.
    Bailey SW, Ayling JE. The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake. Proc Natl Acad Sci U S A. 2009;106:15424–9.CrossRefGoogle Scholar
  10. 10.
    Dattilo M, D Amato G, Caroppo E, Ménézo Y. Improvement of gamete quality by stimulating and feeding the endogenous antioxidant system: mechanisms, clinical results, insights on gene-environment interactions and the role of diet. J Assist Reprod Genet. 2016;33:1633–48.CrossRefGoogle Scholar
  11. 11.
    Servy EJ, Jacquesson-Fournols L, Cohen M, Menezo YJR. MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series. J Assist Reprod Genet. 2018.Google Scholar
  12. 12.
    Jacquesson-Fournols L, Servy EJ, Dale B, Clement A, Menezo Y. MTHFR testing in ART should be compulsory in both male and female patients including oocyte donation programs. J Gynecol Women’s Health. 2017 MS Id 555706.Google Scholar
  13. 13.
    Silvestris E, Cohen M, Cornet D, Jacquesson-Fournols L, Clement P, Chouteau J, et al. Supporting the one-carbon cycle restores ovarian Reserve in Subfertile Women: absence of correlation with urinary bisphenol a concentration. Biores Open Access. 2017;6:104–9.CrossRefGoogle Scholar
  14. 14.
    Cornet D, Clement A, Clement P, Menezo Y. High doses of folic acid induce a pseudo MTHFR syndrome in a wild type patient: a case report. Sage Open Med Case Rep. 2018.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Servy Institute of Reproductive EndocrinologyAugustaUSA
  2. 2.Laboratoire ClementParisFrance

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