A novel protocol of ovulation induction with delayed gonadotropin-releasing hormone antagonist administration combined with high-dose recombinant follicle-stimulating hormone and clorniphene citrate for poor responders and women over 35 years

Objective: To evaluate the efficacy of a novel protocol of ovulation induction for poor responders. Design: Prospective, controlled, clinical study. Setting: Research institute's reproductive unit. Patient(s): One hundred forty-five infertile women, aged 27-39 years, candidates for assisted reproductive techniques (ART). Intervention(s): Before undergoing ART, 85 patients received clomiphene citrate, high-dose recombinant human FSH, and a delayed, multidose GnRH antagonist, whereas 60 patients underwent a standard long protocol. Main Outcome Measure(s): Estradiol levels (pg/mL), cancellation rate, oocyte retrieval, embryo score, and fertilization and pregnancy rates. Result(s): Patients undergoing the study protocol obtained lower cancellation rates (4.7% vs. 34%) and higher E-2 levels (945.88 +/- 173.2 pg/mL vs. 169.55 +/- 45.07 pg/mL), oocyte retrieval (5.56 +/- 1.13 vs. 3.36 +/- 1.3), and pregnancy (22.2% vs. 15.3%) and implantation rates (13.5% vs. 7.6%) compared with those receiving the long protocol. Age negatively correlated with ovarian response in the latter, whereas the ovarian outcome results were comparable in younger (<35 yrs) and older (>35 yrs) women treated with the study protocol. Conclusion(s): The proposed protocol of ovulation induction can be usefully administered in poor responders as well as in aged woman, probably because the delayed administration of GnRH antagonist prevents its adverse effects on ovarian paracrine activity and on oocyte maturation.