A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome

Objective To evaluate whether a combination of letrozole and clomiphene citrate (CC) results in higher ovulation rates than letrozole alone in infertile women with polycystic ovary syndrome (PCOS). Design Open-label randomized controlled trial. Setting Academic medical center using two clinic sites. Patient(s) Women 18–40 years of age with a diagnosis of infertility and PCOS as defined by the Rotterdam criteria and no other known cause of infertility. Interventions(s) Participants were randomized in a 1:1 ratio, stratified by age and body mass index, to either 2.5 mg letrozole alone or the combination of 2.5 mg letrozole and 50 mg CC daily on cycle days 3–7 for one treatment cycle. Main Outcome Measure(s) Ovulation defined as mid-luteal serum progesterone concentration ≥3 ng/mL. Result(s) Seventy patients were randomized: 35 to letrozole alone and 35 to letrozole and CC. Results were analyzed according to the intention-to-treat principle. Women who received the combination of letrozole and CC had a statistically higher ovulation rate compared with those who received letrozole alone (27 of 35 women [77%] vs. 15 of 35 women [43%]). There were no serious adverse events or multiple-gestation pregnancies in either group. The side-effects profile was similar in the two treatment groups. Conclusion(s) The combination of letrozole and CC was associated with a higher ovulation rate compared with letrozole alone in women with infertility and PCOS. Further studies are needed to evaluate the effect on live birth rate. Clinical Trial Registration Number NCT02802865.