Trial design and protocol of randomized controlled trial comparing the efficacy of combined letrozole and clomiphene versus only letrozole as a method of ovulation induction in women with polycystic ovarian syndrome (CCLOP trial)

Abstract

Background: Both clomiphene (CC) and letrozole are commonly used oral ovulation induction agents, with different mechanism of action. Apart from letrozole or CC, options for ovulation induction in polycystic ovarian syndrome (PCOS) patients are limited and thus leaving the use of gonadotropin injections as the only option of ovulation induction in these patients. The objective of this study is to evaluate the efficacy of combined therapy of letrozole and CC compared to the use of letrozole alone to achieve ovulation in infertile women with PCOS. Methods: This will be a single-centre, double arm, triple-blind randomized controlled trial. The study was conducted after taking approval from institutional ethics committee and was prospectively registered with the clinical trials registry- India. Women were randomly assigned to receive a combination of 2.5 mg letrozole and placebo daily or a combination of 2.5 mg letrozole and 50 mg CC daily on cycle days 3–7 for one treatment cycle. Conclusions: If combination of clomiphene and letrozole is proved to be more efficacious than letrozole alone, there will be several breaks through advantages in the management of infertility. The novel method of ovulation induction with combined letrozole and clomiphene will bring down overall cost of infertility treatment. Trial registration: The study is prospectively registered with the clinical trials registry- India CTRI/2020/09/028012.