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 China's Mainland.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:Chi CTR-TRC-09000376.Clinical Trials.gov identifier:NCT01116167.

Evidence-based interventions of threatened miscarriage

Threatened miscarriage is the commonest complication of early pregnancy and affects about 20% of pregnancies. It presents with vaginal bleeding with or without abdominal cramps. Increasing age of women, smoking, obesity or polycystic ovary syndrome(PCOS) and a previous history of miscarriage are risk factors for threatened miscarriage. The pathophysiology has been associated with changes in levels of cytokines or maternal immune dysfunction. Clinical history and examination, maternal serum biochemistry and ultrasound findings are important to determine the treatment options and provide valuable information for the prognosis. Bed rest is the commonest advice, but there is little evidence of its value. Other options include progesterone, human chorionic gonadotropin(HCG) and muscle relaxants. The complementary and alternative medicine(CAM) therapies such as acupuncture and Chinese herbs have also been tried. There is some evidence from clinical studies indicating that CAM therapies may reduce the rate of miscarriage, but the quality of studies is poor. Thus, further double-blind,randomized-controlled trials are necessary to confirm its effectiveness, especially acupuncture and Chinese herbs.