Ovarian response to follicle-stimulating hormone (FSH) stimulation dependson the FSH receptor genotype

Because the ovarian response to FSH stimulation in assisted reproduction is variable, ranging from hyporesponse to hyperresponse, with the possible co mplication of ovarian hyperstimulation, it would be of great benefit to pre dict the response of the patients to FSH. To date, no clear-cut predictors of ovarian responsiveness to FSH have been identified. In this study, we in vestigated the role of two distinct FSH receptor (FSHR) variants, Thr307/As n680 and Ala307/Ser680, in the response to FSH in women undergoing controll ed ovarian stimulation. The FSHR polymorphism at position 680 was analyzed by restriction-fragment- length polymorphism in 161 ovulatory women below the age of 40 yr. With ref erence to the couple, infertility has been diagnosed as being attributable to male causes (76%), tubal factor (11%), or both (13%). The distribution w as 29% for the Asn/Asn, 45% for the Asn/Ser, and 26% for the Ser/Ser FSHR v ariant. Peak estradiol levels, number of preovulatory follicles, and number of retrieved oocytes were similar in the 3 groups. However, basal FSH leve ls were significantly different among the 3 groups (6.4 +/- 0.4 IU/L, 7.9 /- 0.3 IU/L, and 8.3 +/- 0.6 IU/L for the Asn/Asn, Asn/Ser, and Ser/Ser gro ups, respectively, P < 0.01). The number of FSH ampoules required for succe ssful stimulation was significantly different among the 3 groups (31.8 +/- 2.4, 40.7 +/- 2.3, and 46.8 +/- 5.0 for the Asn/Asn, Asn/Ser, and Ser/Ser g roups, respectively, P < 0.05). According to multiple linear regression ana lysis, the number of ampoules needed could be predicted from a linear combi nation of both the type of polymorphism and basal FSH levels (P < 0.001). These clinical findings demonstrate that the ovarian response to FSH stimul ation depends on the FSHR genotype.