Ganirelix

Purpose of review Gonadotropin-releasing hormone (GnRH) receptors are not only detected in the central nervous system but also in tissues such as ovary, endometrium, breast, gastrointestinal system, placenta and malignant tumors of ovary and breast. The direct role of GnRH-antagonists in ovarian function, implantation, cancer pathogenesis and treatment is under extensive investigation. This study reviews the biochemistry and molecular and cellular biology of GnRH-antagonists as well as GnRH types and their receptors. Recent findings The best clinical evidence with GnRH-antagonists has accumulated in controlled ovarian hyperstimulation protocols for prevention of premature luteinizing hormone surge (cetrorelix, ganirelix) and in the treatment of advanced-stage prostate cancer (abarelix and degarelix). GnRH-GnRH receptor pathways may have a role in the embryo implantation. The controversy still exists whether GnRH antagonist protocols result in slightly decreased clinical pregnancy rates compared with the GnRH agonist protocols. GnRH-antagonists could be used in the near future to treat some cancer types that express GnRH receptors. Summary GnRH-antagonists have various clinical applications in gynecology, reproductive medicine, urology and oncology. The emergence of well tolerated, orally active GnRH-antagonists may provide an alternative to long-term injections and is likely to have a major impact on the utility of GnRH analogues in the treatment of human diseases.

Objective: To compare the clinical outcome of controlled ovarian hyperstimulation (COH) in unselected patients undergoing IVF using multidose ganirefix acetate versus 4 days of administration of leuprolide acetate. Design: Retrospective cohort study. Setting: A fertility and IVF center. Patient(s): Two hundred forty-seven women who underwent COH-IVF between April 1, 1999, and January 30, 2001. Intervention(s): Pituitary suppression according to a 4-day follicular phase leuprolide acetate protocol (236 women) or a multidose ganirefix acetate regimen (133 women). Main Outcome Measure(s): Amount of gonadotropin used, days of stimulation, cancellation rate, number of oocytes retrieved, implantation rate, and clinical pregnancy rate. Result(s): Compared with leuprolide acetate recipients, ganirefix recipients required significantly less gonadotropin and the mean day of hCG administration was 4 days earlier. Among women younger than 35 years of age, the implantation rate (15% vs. 6%) and the clinical pregnancy rate per initiated and transferred cycle (27% vs. 12% and 32% vs. 15%, respectively) were significantly higher in the ganirelix group than the leuprolide acetate group. Conclusion(s): Compared with a 4-day leuprolide acetate protocol, COH-IVF using a multidose ganirelix acetate protocol reduces treatment duration and amount of gonadotropin used. In younger women, the latter protocol is associated with significantly better pregnancy and implantation rates. (C) 2003 by American Society for Reproductive Medicine.