Effect of Letrozole, Berberine, or Their Combination for Infertility in Women with Polycystic Ovary Syndrome:Statistical Analysis Plan for a Multicenter Randomized Controlled Trial

Introduction: Letrozole showed higher ovulation and live birth rates than clomiphene in infertile women with polycystic ovary syndrome (PCOS). Berberine, a major active component of Chinese herbal medicine rhizomacoptidis, has been used to improve insulin resistance to facilitate ovulation induction in women with PCOS, but there is no study reporting the live birth or its potential as a complementary treatment to letrozole. We aim to determine the efficacy of letrozole with or without berberine in achieving live births among 644 infertile women with PCOS in Mainland China. Methods and analysis: This is a prospective, randomized, multicentre, double-blinded, controlled design. Infertile women with PCOS were randomized into three-arm, letrozole and berberine, letrozole and berberine placebo, letrozole placebo and berberine. Data and blood were collected at baseline, the third month and sixth month after treatment, or immediately were collected if subject was pregnant. Statisticians and clinical investigators were blinded to treatment allocation and treatment related study results until the central database was locked for final data extraction and analysis determined. The statistical analysis plan described basic analysis principles, methods commonly encountered in data analysis issues, and the specific statistical procedures for analyzing the primary, secondary, and safety outcomes. Ethics and dissemination: The study was approved by the ethics committee of the First Affiliated Hospital, Heilongjiang University of Chinese Medicine. The study findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration: Chinese Clinical Trial Registry:ChiCTR-TRC-09000376. ClinicalTrials.gov identifier:NCT01116167.