Ovarian hyperstimulation for in-vitro fertilization controlled by GnRH agonist administered in combination with human menopausal gonadotrophins

Abstract

Surges of luteinizing hormone (LH) in serum that result in luteinization, but occur prematurely with respect to the diameter of the leading follicle, frustrate attempts to induce multiple follicular maturation for in-vitro fertilization (IVF) in a number of women. We examined the possibility of blocking premature LH surges by the administration of D-TRP6-LH-RH, a potent agonistic analogue of gonadotrophin-releas-ing hormone (GnRH). Six patients who had repeatedly shown premature LH surges were treated for 10 days, beginning between days 1 and 3 of the cycle with daily s.c. injections of 500 μg D-Trp6-LH-RH followed by a daily injection of 100 μg of the analogue until the day of administration of human chorionic gonadotrophin (HCG). When pituitary and ovarian suppression had occurred, ovarian stimulation with human menopausal gonadotrophin was started and adjusted in dose according to the ovarian response. HCG was injected when the dominant follicle had reached a diameter of at least 18 mm and oestradiol levels were above 300 pg for each follicle > 15 mm. Oocyte collection was performed 36 h later via laparoscopy, followed by IVF and embryo transfer. The six patients studied to date responded to therapy and treatment could be completed up to embryo transfer. Two patients became pregnant; one of the pregnancies, however, resulted in abortion. Combined treatment with GnRH analogue for suppression of pituitary gonadotrophin secretion followed by the administration of gonadotrophins thus seems to be a promising method for ovarian stimulation in patients who frequently exhibit premature LH discharges and therefore fail to complete treatment.