Divergent effects of the 677C>T mutation of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene on ovarian responsiveness and anti-Müllerian hormone concentrations

ObjectiveTo investigate the influence of the 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T mutation on serum anti-Müllerian hormone (AMH) concentrations and on the numbers of oocytes retrieved (NOR) following controlled ovarian hyperstimulation (COH).DesignProspective cohort study.SettingUniversity-based infertility clinic.Patient(s)Two hundred and seventy women undergoing COH for IVF with or without intracytoplasmic sperm injection.Intervention(s)None.Main Outcome Measure(s)AMH levels were determined from blood samples collected after 10 days of GnRH superagonist treatment and before COH. The MTHFR 677C>T genotype was characterized by a TaqMan 5′ nuclease assay.Result(s)AMH serum concentrations correlated significantly with the NOR in all individuals studied. Average (±SD) AMH levels of TT carriers (2.85 ± 2.23 ng/mL) were significantly higher than those of homozygous CC (1.91 ± 1.59 ng/mL) or heterozygous CT individuals (2.23 ± 1.74 ng/mL). When evaluated by multiple regression analysis, AMH had a significant positive effect on NOR, whereas age and MTHFR 677TT genotype had significant negative effects.Conclusion(s)The MTHFR 677TT genotype is associated with higher serum AMH concentrations and has a negative effect on NOR. This apparent paradox might be resolved in light of recent findings describing a negative feedback function of AMH in the coordination of follicle development.