Ovarian Hyperstimulation during Chronic Pulsatile GnRH Therapy

M.O. Schweditsch, Department of Gynecology and Obstetrics, University of Zürich, CH-8006 Zürich (Switzerland) Chronic pulsatile administration of go-nadotropin-releasing hormone (GnRH) is now being used successfully for ovulation induction in infertile women with hypotha-lamic amenorrhea [1, 2]. The physiological approach and the minimal risk of ovarian hyperstimulation have been claimed as the obvious advantages of this therapy. As illustrated by the following case, however, proper clinical monitoring remains a prerequisite. The present article reports a 32-year-old woman suffering from primary oligomenor-rhea with intervals of up to 4 months and primary infertility for 15 years. The physical and endocrine examinations revealed no abnormalities, follicle-stimulating hormone was 4.3 IU/1, luteinizing hormone 9.8 IU/1 and prolactin 10.7 μg/l; laparoscopy showed ovaries of normal appearance and patent tubes. Since clomiphene in various doses between 50 and 150 mg daily for 5 days failed to induce adequate follicular maturation, treatment with human menopausal gonado-tropins and human chorionic gonadotropin was performed, resulting in ovulatory cycles, but not in pregnancy. Despite close monitoring repeated ovarian hyperstimulation was noted. It was therefore decided to use GnRH as an alternative, but presumably less risky therapy. The pulsatile administration was started on the 5 th day of a spontaneous menstruation by means of a preprogrammed portable pump (Zyklomat). Every 90 min the patient received a pulse of 20 ng GnRH via a catheter placed into the left antecubital vein. Follicular development was monitored by daily ultrasonography and hormone analyses. In the first 3 days after initiation of therapy a very high release of luteinizing hormone was observed. The serum levels ranged between 30.8 and 78.0 IU/1, while the increase in follicle-stimulating hormone was rather moderate. This exaggerated response was most likely due to an unusual pituitary sensitivity and reserve and might explain the subsequent ovarian enlargement. Further follow-up revealed fairly normal gonadotropin patterns and apparently adequate stimulatory effects until the 14th day of the cycle, when there was a dominant follicle of 24 mm in the right ovary and a serum estradiol level of 1,250 pmol/l. Presumably shortly afterwards ovulation occurred as indicated by a rise in Ovarian Hyperstimulation during Chronic Pulsatile GnRH Therapy 277