Comparison of Letrozole Versus Combination Letrozole and Clomiphene Citrate (CC) for Ovulation Induction in Sub Fertile Women with Polycystic Ovarian Syndrome (PCOS)-An Open Label Randomized Control Trial

To evaluate the effectiveness of Letrozole and Clomiphene (CC) combination versus Letrozole alone for ovulation induction in infertile women with PCOS. This was an open label randomized controlled trial conducted between September 2020 and March 2023 at a tertiary level hospital. Women with a diagnosis of infertility and PCOS were included. Participants were randomized in a 1:1 ratio, to either the combination of 2.5 mg letrozole and 50 mg Clomiphene Citrate (CC) daily or 2.5 mg letrozole alone from 2nd to 6^thday of menstrual cycle for up to three treatment cycles. The primary outcome was ovulation rate per cycle. The secondary outcomes included ovulation rate per woman randomised, cumulative pregnancy and live birth rates. A total of the 120 participants, 59 women in Letrozole and CC arm (intervention) and 61 women in the Letrozole alone arm (control) were recruited. The woman per cycle ovulation rate following Letrozole and CC combination versus Letrozole alone (71/92 (77.2%) vs. 52/83 (62.6%), RR 1.43, 95%CI 0.99 to 2.06) but was not statistically significant. A per ITT analysis, the clinical pregnancy rate per woman randomized (16/61(26.2%) vs. 13/59(22%), RR 1.12, 95%CI 0.76 to 1.64) and live birth rate per woman randomized (10/61(16.4%) vs 11/59(18.6%), RR 0.92, 095%CI 0.57 to 1.50) did not differ significantly between Letrozole and CC versus Letrozole group. There was no significant improvement in ovulation, clinical pregnancy, or live birth rates with a combination of letrozole and CC versus letrozole alone in per woman randomized with PCOS. Trial RegistrationThe trial was prospectively registered in the clinical trial registry of India (CTRI registration number CTRI/2020/07/026263), Registration dated: February 26, 2020.