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BMJ. 2017 Jan 31;356:j138. doi: 10.1136/bmj.j138.

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

Author information

1
Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, North Adelaide, Australia r.wang@adelaide.edu.au.
2
Reproductive Medicine Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
3
Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, North Adelaide, Australia.
4
Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands.
5
Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand.
6
School of Women's and Children's Health, University of New South Wales, Sydney, Australia.
7
Department of Obstetrics and Gynaecology, University of Hong Kong, Hong Kong, China.
8
Department of Obstetrics and Gynecology, Penn State College of Medicine, Hershey, USA.
9
Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
10
FertilitySA, Adelaide, Australia.
11
NHMRC (National Health and Medical Research Council) Centre for Research Excellence in Polycystic Ovary Syndrome, Adelaide, Australia.
12
South Australian Health and Medical Research Institute, Adelaide, Australia.

Abstract

OBJECTIVE:

 To compare the effectiveness of alternative first line treatment options for women with WHO group II anovulation wishing to conceive.

DESIGN:

 Systematic review and network meta-analysis.

DATA SOURCES:

 Cochrane Central Register of Controlled Trials, Medline, and Embase, up to 11 April 2016.

STUDY SELECTION:

 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.

RESULTS:

 Of 2631 titles and abstracts initially identified, 57 trials reporting on 8082 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 1.58, 95% confidence interval 1.25 to 2.00; 1.81, 1.35 to 2.42; respectively) and ovulation rates (1.99, 1.38 to 2.87; 1.55, 1.02 to 2.36; respectively). Letrozole led to higher live birth rates when compared with clomiphene alone (1.67, 1.11 to 2.49). Both letrozole and metformin led to lower multiple pregnancy rates compared with clomiphene alone (0.46, 0.23 to 0.92; 0.22, 0.05 to 0.92; respectively).

CONCLUSIONS:

 In women with WHO group II anovulation, letrozole and the combination of clomiphene and metformin are superior to clomiphene alone in terms of ovulation and pregnancy. Compared with clomiphene alone, letrozole is the only treatment showing a significantly higher rate of live birth.

SYSTEMATIC REVIEW REGISTRATION:

 PROSPERO CRD42015027579.

PMID:
28143834
PMCID:
PMC5421445
DOI:
10.1136/bmj.j138
[Indexed for MEDLINE]
Free PMC Article

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