Corpus luteum insufficiency induced by a rapid gonadotropin-releasing hormone-induced gonadotropin secretion pattern in the follicular phase

Abstract

The pulse frequency of LH and FSH (and by inference, GnRH) is a major determinant of the relative baseline plasma levels of LH and FSH. Luteal phase deficiency has been reported to be associated with increased gonadotropin pulse frequency and inadequate preovulatory follicular development. In this study we induced in normal women a supraphysiological gonadotropin pulse frequency in the follicular phase to determine its effect on follicular development and corpus luteum function. Specifically, we tested the hypothesis that a supraphysiological GnRH pulse frequency would result in deficient luteal phase production of progesterone. The subjects were six normal ovulatory women (age range, 23-35 yr). They were initially studied during a control cycle (cycle 1). Then, 25 ng/kg GnRH was administered iv every 30 min from the early follicular phase of the next cycle (cycle 2) until ovulation occurred. GnRH administration resulted in increased follicular phase plasma LH and FSH levels and LH to FSH ratios, multiple preovulatory follicles (mean, 2.8) with increased mean integrated estradiol [1302 (pg/mL)day (cycle 1) vs. 2550 (pg/mL)day (cycle 2); P less than 0.05; 4780 vs. 9360 (pmol/L)day, Systeme International units], spontaneous ovulation, decreased luteal phase plasma immunoreactive and bioactive LH levels, decreased luteal phase length [13.5 days (cycle 1) vs. 8.8 days (cycle 2); P less than 0.05], and decreased mean integrated progesterone secretion [152 (ng/mL)day (cycle 1) vs. 66 (ng/mL)day (cycle 2); P less than 0.01; 482 vs. 209 (nmol/L)day, Systeme International units]. We conclude that high frequency LH and FSH secretion during the follicular phase can induce inadequate progesterone secretion during the subsequent luteal phase, and we infer that the pathophysiological basis for this induced luteal phase deficiency is decreased LH support of corpus luteum function.