Methylenetetrahydrofolate reductase (MTHFR) C677T andA1298C variants do not affect ongoing pregnancy rates following in vitro fertilization.

Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA 94143, USA.
Human Reproduction (Impact Factor: 4.57). 03/2007; 22(2):450-6. DOI: 10.1093/humrep/del396
Source: PubMed


There is concern that IVF could compromise normal imprinting and methylation of DNA. Methylenetetrahydrofolate reductase (MTHFR) regulates the flow of folic acid-derived, one-carbon moieties for methylation and is critical to early embryonic development. Therefore, we hypothesized that common polymorphisms in MTHFR could associate with IVF outcome.
MTHFR C677T and A1298C polymorphism genotyping was performed on 374 subjects for this study, representing 197 couples undergoing IVF in a university setting from July 2005 to January 2006. Analysis of variance (ANOVA), chi-square and/or multivariate analyses were used to assess whether these polymorphisms are associated with embryo quality or with ongoing pregnancy or spontaneous abortion rates.
Allele frequencies for C677T ( p=0.67, q=0.33) and A1298C ( p=0.71, q=0.29) were in Hardy-Weinberg equilibrium. The C677T and A1298C variants, either alone or in combination, did not associate with embryo quality or short-term pregnancy outcome.
The common polymorphisms in MTHFR are not associated with embryo quality, as defined by cell number or fragmentation score, or with short-term pregnancy outcomes. Therefore, in our population in which women receive adequate folic acid, MTHFR genotypes are not informative in explaining IVF failure. Further studies, however, examining birth outcomes and the other enzymes in the folic acid pathway are warranted.

Download full-text


Available from: Paolo Rinaudo, Feb 24, 2015
  • Source
    • "A previous study published by Dobson et al. in 2007 evaluated 197 couples undergoing assisted reproduction cycles and investigated the association between MTHFR polymorphisms C677T and A1298C in men and women in relation to laboratory results and pregnancy outcomes. The study found no association in any of the evaluations between the presence of polymorphism and laboratory results such as number and quality of embryos transferred and pregnancy rate in the assisted fertilization cycles performed (Dobson et al., 2007). Another study also associated the presence of the MTHFR polymorphism C677T with embryo quality by evaluating the genetic variants of folate metabolism and IVF outcomes in 439 women undergoing assisted fertilization cycles. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to investigate the association between MTHFR gene polymorphisms and IVF outcomes in Brazilian women undergoing assisted reproduction treatment. A prospective study was conducted in the Human Reproduction Department at the ABC University School of Medicine and the Ideia Fertility Institute between December 2010 and April 2012. The patient population was 82 women undergoing assisted reproduction cycles. The MTHFR polymorphisms C677T and A1298C were evaluated and compared with laboratory results and pregnancy rates. The C677T variant was associated with proportions of mature (P = 0.006) and immature (P = 0.003) oocytes whereas the A1298C variant was associated with number of oocytes retrieved (P = 0.044). The polymorphisms, whether alone or in combination, were not associated with normal fertilization, good-quality embryo or clinical pregnancy rates. This study suggests that the number and maturity of oocytes retrieved may be related to the MTHFR polymorphisms C677T and A1298C.
    Full-text · Article · Mar 2014 · Reproductive biomedicine online
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Folates belong to the vitamin B group and are involved in a large number of biochemical processes, particularly in the metabolism of homocysteine. Dietary or genetically determined folate deficiency leads to mild hyperhomocysteinemia, which has been associated with various pathologies. Molecular mechanisms of homocysteine-induced cellular dysfunction include increased inflammatory cytokine expression, altered nitric oxide bioavailability, induction of oxidative stress, activation of apoptosis and defective methylation. Whereas the involvement of folate metabolism and homocysteine in ageing-related diseases, in several developmental abnormalities and in pregnancy complications has given rise to a large amount of scientific work, the role of these biochemical factors in the earlier stages of mammalian reproduction and the possible preventive effects of folate supplementation on fertility have, until recently, been much less investigated. In the present article, the possible roles of folates and homocysteine in male and female subfertility and related diseases are systematically reviewed, with regard to the epidemiological, pathological, pharmacological and experimental data of the literature from the last 25 years.
    Full-text · Article · Jan 2007 · Human Reproduction Update
  • [Show abstract] [Hide abstract]
    ABSTRACT: Polymorphisms in the MTHFR gene have been associated with decreased cell division and apoptosis. This finding led us to evaluate whether MTHFR polymorphisms were associated with follicular growth within the ovary. More specifically, we investigated the effect of the two common polymorphisms C677T and A1298C in our population of women undergoing ovarian stimulation. Prospective cohort study. Academic medical center. Two hundred twenty-three women undergoing ovarian stimulation. The DNA from patients was genotyped at the MTHFR C677T and A1298C polymorphisms. Day 3 FSH, E(2), antral follicle count, amount of gonadotropin used, the number of follicles >13 mm, E(2) on the day of hCG administration, and oocyte number. Women with the variant MTHFR 1298 C allele had significantly higher basal FSH levels, and after ovarian stimulation, produced fewer follicles >13 mm, had lower E(2) levels on the day of hCG administration, and required more ampules of gonadotropin hormone during treatment. Women with the variant MTHFR 677 T allele demonstrated no significant differences. The MTHFR A1298C polymorphism, but not the C677T polymorphism, is associated with higher basal FSH levels and may be a determinant of response to ovarian stimulation. These findings make a compelling case for the MTHFR A1298C polymorphism to modulate folliculogenesis.
    No preview · Article · Oct 2007 · Fertility and sterility
Show more