Objective

To investigate if combination therapy with clomiphene citrate (CC) plus letrozole (L) was associated with a higher efficacy than L and CC alone in patients undergoing ovarian induction plus intrauterine insemination.

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 3. Ovarian stimulation was continued with the appropriate dose of gonadotropins daily starting from day 8 and continued until follicular size was 20 mm or more followed by administration of human chorionic gonadotropin (10 000 IU). Semen samples were prepared by direct swim-up technique.

Results

In the CC group, gonadotropin dose was significantly higher but endometrial thickness was significantly lower compared with other groups. Number of follicles of 18 mm or more was significantly lower in the L group compared with the other two groups. Number of follicles less than 15 mm was meaningfully higher in the CC group compared with the other groups. In the L + CC group, total and largest follicular size, and the rates of chemical, clinical, and ongoing pregnancy, and live birth were 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 ovarian induction plus intrauterine insemination.