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: 4.59). 03/2007; 22(2):450-6. DOI: 10.1093/humrep/del396
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND Most reproductive failures originate during the periconceptional period and are influenced by the age and the lifestyle of parents-to-be. We advance the hypothesis that these failures can arise as a partial consequence of derangements to one-carbon (1-C) metabolism (i.e. metabolic pathways that utilize substrates/cofactors such as methionine, vitamin B12, folate). 1-C metabolic pathways drive the synthesis of proteins, biogenic amines and lipids required for early growth, together with the synthesis and methylation of DNA and histones essential for the regulation of gene expression. We review how deficiencies in periconceptional 1-C metabolism affect fertility and development together with underlying mechanisms derived from animal studies.METHODSA literature search was performed using PubMed and bibliographies of all relevant original research articles and reviews.RESULTSWe define 'periconception' as a 5-6-month period in women embracing oocyte growth, fertilization, conceptus formation and development to Week 10 of gestation (coinciding with the closure of the secondary palate in the embryo). During this period significant epigenetic modifications to chromatin occur that correspond with normal development. Subtle variations in 1-C metabolism genes and deficiencies in 1-C substrates/cofactors together with poor lifestyle, such as smoking and alcohol consumption, disturb 1-C metabolism and contribute to subfertility and early miscarriage and compromise offspring health. Procedures used in assisted reproduction can also disturb these metabolic pathways and contribute to poor pregnancy outcomes.CONCLUSIONS Evidence presented indicates that parental nutrition and other lifestyle factors during the periconceptional period can affect reproductive performance via 1-C metabolic pathways. This knowledge provides opportunities for treatment and prevention of reproductive failures and future non-communicable diseases.
    Human Reproduction Update 08/2013; DOI:10.1093/humupd/dmt041 · 8.66 Impact Factor
  • 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.
    Human Reproduction Update 01/2007; 13(3):225-38. DOI:10.1093/humupd/dml063 · 8.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: During the last couple of years, ground-based gamma-ray astronomy has witnessed a major breakthrough with the physics results obtained by the current generation of imaging atmospheric Cherenkov telescopes. In order to exploit the full physics potential of this field, the next generation instrument - the Cherenkov Telescope Array CTA - aims for an improvement in sensitivity by an order of magnitude with respect to current experiments, an extension of the accessible energy regime from some tens of GeV into the 100 TeV range, and for an improved angular and energy resolution []. CTA will be operated as an observatory, open to a wide scientific community, not only to attack astrophysical questions, like the origin of Galactic cosmic rays, but also to find answers to fundamental questions like the constitution of Dark Matter. A world-wide collaboration of more than 100 groups has formed to face the challenge of developing a cost-effective design of CTA. After about four years of intense work on the design of CTA, the project has entered its FP7-funded Preparatory Phase, with the goal to be ready to start implementation by the end of 2013.
    Nuclear Physics B - Proceedings Supplements 03/2011; 212:170-177. DOI:10.1016/j.nuclphysbps.2011.03.024 · 0.88 Impact Factor