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

Objective: To investigate the influence of the 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T mutation on serum anti-Mullerian hormone (AMH) concentrations and on the numbers of oocytes retrieved (NOR) following controlled ovarian hyperstimulation (COH). Design: Prospective cohort study. Setting: University-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. (Fertil Steril (R) 2011;95:2257-62. (C)2011 by American Society for Reproductive Medicine.)