Pulsatile administration of GnRH for the treatment of hypogonadotrophic hypogonadism

Fourteen patients, aged 22-35 years, complaining of infertility and failing to ovulate on clomiphene, were treated with GnRH administered in pulses at 90 min intervals. Four patients received a total of eight courses of GnRH given subcutaneously and 13 were given a total of 20 months of treatment with GnRH given intravenously. Serum concentrations of immunoreactive GnRH were measured in six patients before administration of the drug and at regular intervals for 60 min after subcutaneous and intravenous injections of 5, 10 and 20 micrograms GnRH. Maximum concentrations of GnRH were reached by 5-10 min after subcutaneous injections and within 2 min after intravenous injections. The peak concentrations were 3.6-6.3 times and the sums of increments were 2.0-3.9 times greater following intravenous injections than after subcutaneous injections. Subcutaneous treatments extended for 15-29 days with doses of 5-20 micrograms per pulse. Only one patient ovulated as judged by the luteal phase progesterone and ultrasonic scanning of the follicle. Intravenous treatments were from 12-22 days with doses of 10 micrograms per pulse and 16 treatments out of 20 were ovulatory with four pregnancies. HCG (5000 i.u.) was given when ultrasonic scanning indicated adequate follicular growth, but in eight of the cycles, including three of the pregnancies, the follicle had ruptured before HCG was given. Pulsatile administration of GnRH proved to be an effective treatment for infertility in hypogonadotrophic hypogonadism. Possible reasons for the better results by intravenous rather than subcutaneous injections are discussed.