Effects of the common 677C>T mutation of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene on ovarian responsiveness to recombinant follicle-stimulating hormone.

The common 677C>T mutation of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene is less prevalent in mothers of spontaneously conceived dichorionic twins than in those with singleton pregnancies. (Hasbargen U, Lohse P, Thaler CJ: Hum Reprod 2000; 15:2659-2662). As polyovulation is a pre-requisite for dichorionic pregnancies, we investigated whether the T allele is associated with reduced ovarian responsiveness to follicle-stimulating hormone (FSH). We studied 105 infertility patients undergoing a total of 269 A.R.T cycles stimulated with recombinant (r)-FSH. The MTHFR 677C>T genotype was analyzed by digestion of polymerase chain reaction-amplified DNA fragments. Homozygous 677C patients older than 35, required significantly (P <0.02) less r-FSH and produced significantly more oocytes (P < 0.04) and higher maximal serum estradiol concentrations (P < 0.002) than heterozygous or homozygous carriers of the 677T allele. Our results suggest that, in patients of advanced reproductive age, the MTHFR 677C>T mutation affects ovarian responsiveness.