Clinical and endocrine effects of a microdose GnRH agonist flare regimen administered to poor responders who are undergoing in vitro fertilization.

ABSTRACT

OBJECTIVE: To assess the endocrine and clinical responses to microdose GnRH agonist (GnRH-a) that was administered in the early follicular phase before controlled ovarian hyperstimulation to poor responders who were candidates for IVF-ET. DESIGN: Prospective nonrandomized trial with historical controls. SETTING: Tertiary care university-affiliated infertility practice. PATIENT(S) Thirty-four IVF-ET candidates with a prior poor response to a standard long-protocol GnRH-a controlled ovarian hyperstimulation regimen (cycle A). Patients were divided into two groups based on their age at the initiation of cycle A (Group 1 < or = 39 years, n = 15; Group 2 > or = 40 years, n = 19). INTERVENTION(S) Low-dose oral contraceptive (x 21 d) followed by GnRH-a (leuprolide acetate; 40 micrograms s.c. b.i.d.) flare and 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 well as fertilization and clinical and ongoing pregnancy rates) and endocrine responses (serum E2, FSH, LH, T, and P levels) between cycles A and B in the two groups. Early follicular phase serum E2 and FSH changes in groups 1 and 2 were compared with changes in nine normal responder controls who were receiving a standard long-protocol GnRH-a/urofollitropin regimen (group 3). RESULT(S) Maximal E2 levels as well as clinical and ongoing pregnancy rates were higher in cycle B patients receiving microdose GnRH-a. Cancellation rates in cycle B were lower than in cycle A. Statistically significant increases in treatment day 6 serum FSH levels were noted during cycle B in both groups 1 and 2 but not 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 urofollitropin response and clinical outcome in poor responders undergoing IVF-ET. This may be due to enhanced release of early follicular phase endogenous FSH without concomitant deleterious rises in androgen levels or corpus luteum rescue.