CLINICAL AND ENDOCRINE EFFECTS OF A MICRODOSE GNRH AGONIST FLARE REGIMEN ADMINISTERED TO POOR RESPONDERS WHO ARE UNDERGOING IN-VITRO FERTILIZATION

Objective: To assess the endocrine and clinical responses to microdose GnRH agonist (GnRH-a) that was administered in the early follicular p hase before controlled ovarian hyperstimulation to poor responders who were candidates for IVF-ET. Design: Prospective nonrandomized trial w ith historical controls. Setting: Tertiary care university-affiliate i nfertility practice. Patient(s): Thirty-four IVF-ET candidates with a prior poor response to a standard long-protocol GnRH-a controlled ovar ian hyperstimulation regimen (cycle A). Patients were divided into two groups based on their age at the initiation of cycle A (Group 1: less than or equal to 39 years, n = 15; Group 2: greater than or equal to 40 years, n = 19). Intervention(s): Low-dose oral contraceptive (x 21 d) followed by GnRH-a (leuprolide acetate; 40 mu g SC b.i.d.) flare an d urofollitropin initiated on day 3 of GnRH-a administration (cycle B) . Main Outcome Measure(s): Comparative analysis of clinical responses (total urofollitropin dose used and number of oocytes retrieved as wel l as fertilization and clinical and ongoing pregnancy rates) and endoc rine responses (serum E-2, FSH, LH, T, and P levels) between cycles A and B in the two groups. Early follicular phase serum E, and FSH chang es in groups 1 and 2 were compared with changes in nine normal respond er controls who were receiving a standard long-protocol GnRH-a/urofoll itropin regimen (group 3). Result(s): Maximal E-2 levels as well as cl inical and ongoing pregnancy rates were higher in cycle B patients rec eiving microdose GnRH-a. Cancellation rates in cycle B were lower than in cycle A. Statistically significant increases in treatment day 6 se rum FSH levels were noted during cycle B in both groups 1 and 2 but no t in group 3 controls. No abnormal rises in LH, P, or T were noted in any of the groups. Conclusion(s): Microdose GnRH-a enhances urofollitr opin response and clinical outcome in poor responders undergoing IVF-E T. This may be due to enhanced release of early follicular phase endog enous FSH without concomitant deleterious rises in androgen levels or corpus luteum rescue. (C) 1998 by American Society for Reproductive Me dicine.