Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis

• Published in: BMJ (Online) Vol. 356; p. j138
• Main Authors: Wang, Rui, Kim, Bobae V, van Wely, Madelon, Johnson, Neil P, Costello, Michael F, Zhang, Hanwang, Ng, Ernest Hung Yu, Legro, Richard S, Bhattacharya, Siladitya, Norman, Robert J, Mol, Ben Willem J
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 31.01.2017; BMJ Publishing Group LTD; BMJ Publishing Group Ltd
• Subjects: Anovulation - drug therapy; Anovulation - physiopathology; Birth; Clinical trials; Clomiphene; Clomiphene - therapeutic use; Drilling; Drug therapy; Drug Therapy, Combination; Female; Gonadotropins; Humans; Infertility, Female - drug therapy; Infertility, Female - physiopathology; Laparoscopy; Letrozole; Meta-analysis; Metformin; Metformin - therapeutic use; Network Meta-Analysis; Nitriles - therapeutic use; Ovulation; Ovulation Induction - methods; Pituitary (anterior); Placebos; Pregnancy; Pregnancy Rate; Reviews; Systematic review; Treatment Outcome; Triazoles - therapeutic use
• ISSN: 0959-8138; 1756-1833; 1756-1833
• DOI: 10.1136/bmj.j138

AbstractObjectiveTo compare the effectiveness of alternative first line treatment options for women with WHO group II anovulation wishing to conceive.DesignSystematic review and network meta-analysis.Data sourcesCochrane Central Register of Controlled Trials, Medline, and Embase, up to 11 April 2016.Study selectionRandomised controlled trials comparing eight ovulation induction treatments in women with WHO group II anovulation: clomiphene, letrozole, metformin, clomiphene and metformin combined, tamoxifen, gonadotropins, laparoscopic ovarian drilling, and placebo or no treatment. Study quality was measured on the basis of the methodology and categories described in the Cochrane Collaboration Handbook. Pregnancy, defined preferably as clinical pregnancy, was the primary outcome; live birth, ovulation, miscarriage, and multiple pregnancy were secondary outcomes.ResultsOf 2631 titles and abstracts initially identified, 54 trials reporting on 7173 women were included. All pharmacological treatments were superior to placebo or no intervention in terms of pregnancy and ovulation. Compared with clomiphene alone, both letrozole and the combination of clomiphene and metformin showed higher pregnancy rates (odds ratio 1.69, 95% confidence interval 1.33 to 2.14; 1.71, 1.28 to 2.27; respectively). Letrozole led to higher live birth rates when compared with clomiphene alone (1.67, 1.11 to 2.49). Metformin led to lower multiple pregnancy rates compared with clomiphene alone (0.22, 0.05 to 0.93).ConclusionsIn women with WHO group II anovulation, letrozole and the combination of clomiphene and metformin are superior to clomiphene alone in terms of pregnancy. Compared with clomiphene alone, letrozole is the only treatment showing a significantly higher rate of live birth.Systematic review registrationPROSPERO CRD42015027579.Readers’ noteThis is the second version of this paper. The original version was corrected following the retraction of two studies and removal of another which were ineligible (references 40, 41, and 75 of the original paper). These studies are not shown in this version. A tracked changes version of the original version is attached as a supplementary file to the correction notice, which explains the issue further.