Background:Gonadotropin-releasing hormone (GnRH) antagonist protocol has been proposed as a potentially proper option for the patients with limited ovarian reserve. Nevertheless, there is no significant difference in terms of clinical pregnancy between the GnRH antagonist and agonist cycles. The use of aromatase inhibitors such as letrozole was suggested by some studies. Objective:The object of this study was to evaluate the efficacy of letrozole co-treatment with GnRH-antagonist protocol in ovarian stimulation of poor responder patients undergoing intracytoplasmic sperm injection.Materials and Methods:A double-blinded randomized control trial was conducted on 70 infertile women with poor ovarian response based on Bologna criteria in two groups: letrozole+GnRH-antagonist (LA) group and placebo+GnRH-antagonist (PA) group (n=35/each). The LA group involved at letrozole 2.5 mg daily over 5 days and recombinant human follicle stimulating hormone 225 IU/daily. The PA group received placebo over 5 days and recombinant human follicle stimulating hormone at the same starting day and dose, similar to LA group. GnRH-antagonist was introduced once one or more follicle reached ≥14 mm. The main outcome measures were the number of oocytes retrieved, fertilization rate, implantation rate, cycle cancellation rate, and clinical pregnancy rate.Results:There were no significant differences in demographic characteristics between groups. There were no significant differences between groups regarding the number of oocytes retrieved (p=0.81), number of embryos transferred (p=0.82), fertilization rate (p=0.225), implantation rate (p=0.72), total cycle cancelation rate (p=0.08), and clinical pregnancy rate (p=0.12). Conclusion:The use of letrozole in GnRH-antagonist cycles does not improve clinical outcomes in poor responder patients undergoing intracytoplasmic sperm injection.