Objective

Is combination therapy with clomiphene citrate (CC) plus letrozole (L) associated with a higher efficacy than L and CC alone in patients undergoing ovarian induction (OI) plus intrauterine insemination (IUI)?.

Methods

The present multicenter randomized controlled clinical trial was performed between 2018 and 2020. Participants were randomized into three groups: L (n=167) (5 mg/day), CC (n=167) (100 mg/day) and L + CC (n=167) (2.5 mg/day+50 mg/day) from day three. Ovarian stimulation was continued with the appropriate dose of gonadotropins daily starting from day eight and continued until follicular size (FS) ≥ 20mm followed by human chorionic gonadotropin (10000 IU) administration. Semen samples were prepared by direct swim up technique.

Results

In CC, gonadotropin dose was significantly higher but endometrial thickness was significantly lower compared with other groups. Number of follicles ≥18 mm were significantly lower in L compared with other two groups. Number of follicles < 15mm was meaningfully higher in CC comparing with other groups. In L + CC, total and largest FS, the rate of chemical, clinical, and ongoing pregnancy, and live birth was significantly higher compared with other groups.

Conclusion

Combination therapy with L + CC was superior to either L or CC for achieving pregnancy in women undergoing OI+ IUI.