Ovulation induction with gonadotropin-releasing hormone

The pulsatile administration of gonadotropin-releasing hormone (GnRH) is emerging as an attractive approach for ovulation induction in certain women. Ideal candidates for therapy are women with abnormalities of the GnRH pulse generator. These women have the diagnosis of primary hypothalamic amenorrhea or clomiphene-unresponsive secondary hypothalamic amenorrhea. GnRH can be administered intravenously or subcutaneously. The routes are equivalent in terms of inducing ovulation and pregnancy. The advantages and disadvantages of each route can dictate which will be most suitable for a given patient. Current recommendations suggest that GnRH be initiated at 5 μg/pulse given at 90-minute intervals by an automated mini-pump. The dose should be increased at specified intervals if ovulation does not occur. Patients require minimal monitoring, but surveillance of follicular development with ovarian ultrasound is useful during the initial cycle. The corpus luteum can be supported with continued pulsatile GnRH therapy or with human chorionic gonadotropin. The rate of ovulation approaches 80–100%. Pregnancy occurs in 25–62% of treatment cycles. Although minor adverse side effects occur, ovarian hyperstimulation is rare. Multiple pregnancy (usually twins) occurs in 7–12% of pregnancies. Given the physiologic rationale, safety, and associated ovulation/pregnancy rates, ovulation induction using GnRH is the preferred therapy for many patients.