Pulsatile GnRH therapy for the induction of ovulation in hypogonadotropic hypogonadism.

Twenty-eight patients with hypogonadotropic hypogonadism resistant to clomiphene therapy were treated with pulsatile GnRH. All the patients ovulated and there were 20 pregnancies in 16 women. Administration of the GnRH sc was successful at inducing ovulation in 19 of 22 patients whereas the treatment was successful in all of the 17 patients treated iv. There was no difference between iv and sc therapy in the rate of ovulation. Treatment was stopped after ovulation and hCG given for luteal support. The follicular phase pulse frequency was usually 90 min. In one patient ovulation only occurred with frequencies of 60 min. Higher pulse doses were usually required with sc therapy for primary amenorrhoeic patients and for those with pituitary lesions. The additional use of clomiphene increased pituitary sensitivity to GnRH resulting in ovulatory cycles in patients refractory to treatment and in ovarian hyperstimulation in a normally responsive patient. Two of the 20 pregnancies were twin--the rest were singletons. None aborted. The median time to conception was 3 ovulatory cycles. Although there were no serious complications with iv or sc therapy, the iv route is now reserved for those patients unresponsive to sc treatment as the sc route is potentially safer and more acceptable to the patient. In correctly selected patients pulsatile GnRH is a highly effective and safe new treatment for the induction of ovulation.