Induction of multiple ovulation by pulsatile administration of gonadotropin-releasing hormone

Pharmacologic doses of gonadotropin-releasing hormone (GnRH) pulses (10 micrograms) were used for the induction of multiple follicular development in six normal cycling women. GnRH administration via an autoinfusion pump (intravenously at 60- to 120-minute intervals) was begun on day 5 after the onset of menses. During these stimulated cycles, two to five follicles of preovulatory size were detected by sonography in all subjects. In two subjects, follicle aspiration was performed with successful oocyte recovery. Assessment of the follicular fluid steroid concentrations from these follicles suggests that two of three (subject 5) and four of five (subject 6) follicles were mature. Gonadotropin levels of treated cycles were significantly higher than in normal cycles. Both follicular and luteal phases were of normal duration but were associated with significantly elevated estradiol and progesterone levels, respectively. Timely midcycle gonadotropin surges occurred by days 12 to 14 in all cases. Thus, ovarian steroid feedback control of gonadotropin secretion can be overridden by larger pulses of GnRH, resulting in the development of multiple follicles. This technique may prove useful for in vitro fertilization.