title: Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis
abstract: To compare the effectiveness of alternative first line treatment options for women with WHO group II anovulation wishing to conceive.
  
  
  
  Systematic review and network meta-analysis.
  
  
  
  Cochrane Central Register of Controlled Trials, Medline, and Embase, up to 11 April 2016.
  
  
  
  Randomised 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.
  
  
  
  Of 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).
  
  
  
  In 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.
  
  
  
  PROSPERO CRD42015027579.
  
  
  
  This 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.
authors.affiliation: Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, North Adelaide, Australia r.wang@adelaide.edu.au.|Reproductive Medicine Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, North Adelaide, Australia.
authors.forename: Bobae V
authors.initials: BV
authors.lastname: Kim
authors.affiliation: Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Madelon
authors.initials: M
authors.lastname: van Wely
authors.affiliation: Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, North Adelaide, Australia.|Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand.
authors.forename: Neil P
authors.initials: NP
authors.lastname: Johnson
authors.affiliation: School of Women's and Children's Health, University of New South Wales, Sydney, Australia.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Costello
authors.affiliation: Reproductive Medicine Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hanwang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynaecology, University of Hong Kong, Hong Kong, China.
authors.forename: Ernest Hung Yu
authors.initials: EH
authors.lastname: Ng
authors.affiliation: Department of Obstetrics and Gynecology, Penn State College of Medicine, Hershey, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Legro
authors.affiliation: Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Siladitya
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, North Adelaide, Australia.|FertilitySA, Adelaide, Australia.|NHMRC (National Health and Medical Research Council) Centre for Research Excellence in Polycystic Ovary Syndrome, Adelaide, Australia.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Norman
authors.affiliation: Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, North Adelaide, Australia.|South Australian Health and Medical Research Institute, Adelaide, Australia.
authors.forename: Ben Willem J
authors.initials: BW
authors.lastname: Mol
mesh_terms: D005260:Female; D006801:Humans; D011247:Pregnancy; D000858:Anovulation / Q000188:drug therapy / Q000503:physiopathology; D002996:Clomiphene / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D007247:Infertility, Female / Q000188:drug therapy / Q000503:physiopathology; D000077289:Letrozole; D008687:Metformin / Q000627:therapeutic use; D009570:Nitriles / Q000627:therapeutic use; D010062:Ovulation Induction / Q000379:methods; D018873:Pregnancy Rate; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D002996:Clomiphene; D000077289:Letrozole; D008687:Metformin; D009570:Nitriles; D014230:Triazoles