Letrozole, berberine, or a combination for infertility in Chinese women with polycystic ovary syndrome: a multicentre, randomised, double-blind, placebo-controlled trial

• Published in: The Lancet (British edition) 2015-10, Vol.386, p.S70-S70
• Main Authors: Wu, Xiao-Ke, Prof, Wang, Yong-Yan, Liu, Jian-Ping, Hou, Li-Hui, Gao, Ya-Qin, Du, Shao-Min, Yan, Ying, Zhang, Jin-Feng, Xue, Hui-Ying, Li, Wei-Li, Liang, Rui-Ning, Tan, Zhen-Yu, Fu, Jin-Ying, Ma, Hong-Xia, Shao, Xiao-Guang, He, Feng-Jie, An, Mu-Er, Li, Pei-Lin, Ding, Cai-Fei, Li, Xiao-Bin, Shen, Xian-Ji, Yu, Guang-Zhu, Tian, Feng, Xie, Yan-Ming, Silver, Robert M, Stener-Victorin, Elisabet, Ng, Ernest HY
• Format: Article
• Language: English
• Subjects: Birth rate; Births; Chinese medicine; Discipline; Fertility; Folk medicine; Herbal medicine; Infertility; Internal Medicine; Polycystic ovary syndrome; Technicians
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(15)00651-0

Abstract Background Letrozole is superior to clomiphene in infertile women with polycystic ovary syndrome and leads to higher ovulation and live birth rates. Berberine, a major active component of Chinese herbal medicine Rhizoma coptidis and found in Cortex Phellodendri and Cortex Berberidis in the rest of the world, has similar but even more profound metabolic effects than metformin. Our hypothesis was that a combination of letrozole and berberine would result in a higher live birth rate than letrozole or berberine alone in infertile women with polycystic ovary syndrome. Methods In this multicentre, randomised, double-blind, placebo-controlled trial in 19 participating centres in mainland China, we compared the effect of three interventions for up to six menstrual cycles: letrozole plus berberine placebo (letrozole group), berberine plus letrozole placebo (berberine group), or the combination of letrozole and berberine (combination group). The randomisation (1:1:1) was done through a web-based computer program operated by an independent data center in the China Academy of Chinese Medical Sciences. Participants, investigators, doctors, laboratory technicians, and data analysers were masked to the assignments. Eligible women (age 20–40 years) had polycystic ovary syndrome, as defined by the Rotterdam criteria, had at least one open Fallopian tube and normal uterine cavity, and had at least 1 year of infertility. Berberine or berberine placebo were administrated orally at a daily dose of 1·5 g for 6 months. Patients received an initial dose of 2·5 mg of letrozole or placebo on days 3–7 of the first three treatment cycles. This dose was increased to 5 mg letrozole or placebo on days 3–7 of the last three treatment cycles if not pregnant. Couples were instructed to have regular intercourse two to three times a week until becoming pregnant. The primary outcome was live birth rate after intervention for up to six menstrual cycles. We used either a χ2 test or Fisher's exact test a two-sided significance level of 0·05 to test differences between groups. Data were analysed according to the intention-to-treat principle. This study was approved by an Ethics Committee (2009LL-001) at First Affiliated Hospital in Heilongjiang University of Chinese Medicine. This trial is registered at Chinese Clinical Trials Registration, identifier ChiCTR-TRC-09000376, and at ClinicalTrials.gov , number NCT01116167 . All participants provided written informed consent. Findings We enro