Context: FSH is essential for follicular maturation. Data from ovarian hyperstimulation cycles suggest that FSH action is attenuated by a frequent single nucleotide polymorphism of the FSH receptor gene exchanging Asn for Ser at codon 680.
Objective: We hypothesized that the FSH receptor genotype influences menstrual cycle dynamics.
Design: Menstrual cycle was monitored from the midluteal phase through ovulation until the consecutive menstruation.
Setting: The study was conducted at the University research center.
Subjects: Women homozygous for the Asn680 (n = 12) and Ser680 (n = 9) variants with normal menstrual cycles volunteered for the study.
Interventions: There were no interventions.
Main outcome measurements: Follicular growth, serum LH, FSH, estradiol, progesterone, inhibin A, inhibin B and antimullerian hormone were measured.
Results: During the luteo-follicular transition, serum levels of estradiol, progesterone, and inhibin A were significantly lower, and FSH started to rise earlier in the Ser680/Ser680 group. FSH levels were steadily and significantly higher, and the mean area under the FSH curve was 31% greater in this group (P < 0.002). No differences were observed in estradiol, inhibin B, and growth velocities of dominant follicles. The time from luteolysis to ovulation was significantly longer in women with the Ser680/Ser680 (13.6 +/- 1.01 d) compared with Asn680/Asn680 (11.3 +/- 0.61 d, P < 0.05) genotype with a significant difference in total menstrual cycle length (29.3 vs. 27.0 d, respectively; P < 0.05).
Conclusions: The FSH receptor Ser680/Ser680 genotype is associated with higher ovarian threshold to FSH, decreased negative feedback of luteal secretion to the pituitary during the intercycle transition, and longer menstrual cycles.