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: ≤39 years, n = 15; Group 2: ≥40 years, n = 19). Intervention(s): Low-dose oral contraceptive (× 21 d) followed by GnRH-a (leuprolide acetate; 40 μg SC 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 E 2, FSH, LH, T, and P levels) between cycles A and B in the two groups. Early follicular phase serum E 2 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 E 2 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.