T677T Methylenetetrahydrofolate Reductase Single Nucleotide Polymorphisms Increased Prevalence in a Subgroup of Infertile Patients with Endometriosis.

<b><i>Background:</i></b> Approximately 10% (190 million) of women worldwide are affected by endometriosis, ectopic deposits of endometrial tissue that create a major source of pain that affects lifestyle and reproductive function. The pathogenesis of endometriosis is an estrogen-dependent inflammatory process, influenced/catalyzed by oxidative stress and consequently defective methylation, with biochemical features centered around the folate and one-carbon cycles. We aimed to determine whether a link could be found between the two major methylenetetrahydrofolate reductase single nucleotide polymorphisms (MTHFR SNPs), c.677C&gt;T and c.1298A&gt;C, involved in methylation process/epigenetic marking failures, and endometriosis. <b><i>Material and Methods:</i></b> We studied a population of 158 patients in a group of &gt;1500 referred for treatment of infertility. All the patients had experienced &gt;2 failed assisted reproductive technology cycles and/or &gt;2 miscarriages, a classical cohort for investigation in our group. Patients with endometriosis had at least stage 2+ disease confirmed by laparoscopy. <b><i>Results:</i></b> The prevalence of the homozygous c.677C&gt;T isoform is doubled in the endometriosis group, 21.5% versus 10.2% in the non-endometriosis group (<i>p</i> &gt; 0.01). Symmetrically, the percentage of patients in the endometriosis group with the wild type MTHFR significantly decreased by one-half (8.2%-17.2%) in the non-endometriosis group (<i>p</i> &lt; 0.001). <b><i>Conclusion:</i></b> Determination of MTHFR c.677C&gt;T should not be overlooked in patients with harmful endometriosis affecting their fertility. As folates metabolism is impaired in these MTHFR SNPs carrier patients, co-treatment with 5-methyl folate may constitute a successful (co)-treatment modality.