P-688 Combination of letrozole and clomiphene citrate versus letrozole alone for ovulation induction in women with polycystic ovary syndrome - a randomized controlled trial

Abstract Study question Does clinical pregnancy rate improve using combination of letrozole and clomiphene versus letrozole alone for ovulation induction in infertile women with PCOS Summary answer The present study showed that combination drugs had no added advantage over Letrozole alone in terms of ovulation induction. What is known already Letrozole can offer a benefit over CC for ovulation induction because it doesn’t block estrogen receptors in both central and peripheral target tissues, therefore normal central feedback mechanisms remain intact. As letrozole and CC have different mechanisms of action, the combination of these medications can achieve an improved ovulatory rate over letrozole alone. We aimed to test the hypothesis of whether combined therapy of letrozole and CC is effective and superior to the use of letrozole alone to achieve pregnancy in women with PCOS. Study design, size, duration Prospective Randomized Controlled Trial conducted from July 2019 to December 2020 at tertiary care centre in Uttarakhand According to studies done earlier (49), it was observed that proportion of positive outcome in letrozole and clomiphene citrate combined therapy was assumed to be 0.7700 and for letrozole therapy alone was 0.4400. With significance level of 0.05 and power 90% a sample size of 42 in each group to detect assumed 0.33 difference between the two groups. Participants/materials, setting, methods 68 patients randomised in two group. Group I received combination of Letrozole (2.5mg) and clomiphene citrate (50 mg) once daily for 5 days (day 3-7 of cycle). Group II received Letrozole 2.5mg once daily for 5 days (day 3-7 of cycle) for 4 cycles. After induction follicular monitoring done and HCG given when dominant follicle size > =18mm with ET > =8mm followed by timed intercourse. Main results and the role of chance No statistically significant difference seen between the two groups in baseline characterstics. Comparing the pregnancy rate, 9.3% in Group 1 (n = 3) & 6.3% in Group 2 (n = 2) became pregnant after first cycle of ovulation induction (OVI), after 2nd cycle, 7.1% in Group 1 (n = 2) & 13.8% in Group 2 (n = 4) became pregnant. 11.5 % in Group 1 (n = 3) & 8.0 % in Group 2 (n = 2) became pregnant after cycle 3 and 21.7% in Group 1 (n = 5) & 8.7% in Group 2 (n = 2) became pregnant after 4th cycle of OVI. Though the pregnancy rate was statistically not significant in all the cycle (p < 0.615,0.413,0.671,0.218 respectively). The median number of cycles required for conception in Group 1 was 3 and that of group 2 was 2. Limitations, reasons for caution Small sample size Larger multicentric randomised controlled trials required Wider implications of the findings Pregnancy rate was higher when ovulation induction was done using combination of clomiphene and letrozole but difference was not statistically significant. Mean number of cycles required for conception similar in both groups. Trial registration number CTRI no: CTRI/2020/06/025688