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-releasing 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 micrograms D-Trp6-LH-RH followed by a daily injection of 100 micrograms 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 greater than 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.

Induction of Pharmacological Hypogonadotropism Using Gonadotropin-Releasing Hormone Agonists in Patients Undergoing Controlled Ovarian Stimulation

“…8 and 9], However, although com bined GnRH-A/HMG therapy is increasingly being used in the management of infertility, precise data on the duration of GnRH-A treatment necessary to cause com plete pituitary desensitization have only rarely been ob tained. The occasional occurrence of endogenous LH surges during HMG stimulation, indicating incomplete pituitary desensitization, has been a feature of earlier studies in which various GnRH-A/HMG treatment regi mens have been used [10][11][12]. The data shown in the present work demonstrate that the pituitary desensitiza tion time depends upon the treatment regimen.…”

The state of “freeze-for-all” in human ARTs

“…The use of oral contraceptive pills prior to ovarian stimulation was an early step toward programming IVF cycles [19,20], but later, the introduction of gonadotropin-releasing hormone agonists (GnRH agonists) led to a major change in terms of IVF logistics. GnRH agonists are widely used to downregulate endogenous FSH and LH secretion, to prevent premature endogenous luteinizing hormone (LH) surge and to reduce cancelations due to luteinization [21,22]. For many years, GnRH agonists have been considered the Bgold standardp rotocol, especially in young normo-responders.…”

The Evolution of in Vitro Fertilization: Integration of Pharmacology, Technology, and Clinical Care

“…Porter et al (1984) first used GnRH-a for ovulation suppression in in vitro fertilization cycles. Wildt et al (1986) similarly used GnRH-a in patients who had previously failed IVF due to premature LH surges, resulting in the successful completion of all IVF cycles. Gonadotropin-releasing hormone agonists greatly improved success rates as well as convenience in scheduling IVF cycles.…”