INITIAL ESTRADIOL RESPONSE PREDICTS OUTCOME OF EXOGENOUS GONADOTROPINS USING A STEP-DOWN DOSE REGIMEN FOR INDUCTION OF OVULATION IN POLYCYSTIC-OVARY-SYNDROME

Objective: To study ovarian stimulation and response patterns during a gonadotropin step-down dose regimen for induction of ovulation by app lying st decremental dose regimen in polycystic ovary syndrome (PCOS) patients. Design: The present prospective study involves 28 infertile clomiphene citrate-resistant PCOS patients during gonadotropin-induced cycles using a modified step-down dose regimen (and adjuvant GnRH ago nist medication). Applied gonadotropin doses included initial daily do ses of 150 IU IM followed by two reducing steps (37.5 IU each) based o n sonographic criteria to a final daily dose of 75 IU IM. Setting: Ano vulatory infertile women in an academic referral center. Intervention: Daily blood withdrawal and transvaginal pelvic ultrasound. Main Outco me Measures: Serum FSH and Ea concentration and follicle growth were i nvestigated daily during gonadotropin administration. Results: An init ial 2.1-fold increase in serum FSH levels was observed followed by a s ubsequent decrease of 10% (median) per day for 4 days. Growth of ovari an follicles was sustained and ovulation achieved (midluteal P, 11.7 /- 1.3 ng/mL; conversion factor to SI unit, 3.180; mean +/- SD) in 22 patients. Major variability in day 3 E(2) increase (range, 67 to 866 p g/mL; conversion factor to SI unit, 3.671)-not related to differences in FSH serum concentrations and without changes in follicle number and size-suggests differences in ovarian sensitivity for FSH stimulation. A strong correlation (r = 0.82) was found between day 3 E(2) increase and the chance of ovulation. Moreover, E(2) levels on the day of gona dotropin dose reduction predict (r = 0.68) chances of late follicular phase E(2) levels exceeding 871 pg/mL (conversion factor to SI value, 3.671). Conclusions: These findings provide the endocrine basis for th e concept of gonadotropin induction of ovulation using a step-down dos e regimen. Initial E(2) increase (before initiation of follicle growth ) represent differences in ovarian sensitivity to gonadotropins and pr edict treatment outcome.