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

Rui Wang, Bobae V Kim, Madelon van Wely, Neil P Johnson, Michael F Costello, Hanwang Zhang, Ernest Hung Yu Ng, Richard S Legro, Siladitya Bhattacharya, Robert J Norman, Ben Willem J Mol

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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.

Original languageEnglish
Article numberj138
JournalBritish Medical Journal (Clinical Research Ed.)
Volume356
DOIs
Publication statusPublished - 31 Jan 2017

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letrozole
Anovulation
Clomiphene
Metformin
Ovulation
Live Birth
Pregnancy
Multiple Pregnancy
Therapeutics
Pregnancy Rate
Placebos
Network Meta-Analysis
Ovulation Induction
Birth Rate
Spontaneous Abortion
Tamoxifen
Gonadotropins
Randomized Controlled Trials
Odds Ratio
Pharmacology

Cite this

Wang, R., Kim, B. V., van Wely, M., Johnson, N. P., Costello, M. F., Zhang, H., ... Mol, B. W. J. (2017). Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis. British Medical Journal (Clinical Research Ed.), 356, [j138]. https://doi.org/10.1136/bmj.j138

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

In: British Medical Journal (Clinical Research Ed.), Vol. 356, j138, 31.01.2017.

Research output: Contribution to journalArticle

Wang, R, Kim, BV, van Wely, M, Johnson, NP, Costello, MF, Zhang, H, Ng, EHY, Legro, RS, Bhattacharya, S, Norman, RJ & Mol, BWJ 2017, 'Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis', British Medical Journal (Clinical Research Ed.), vol. 356, j138. https://doi.org/10.1136/bmj.j138
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. / Treatment strategies for women with WHO group II anovulation : systematic review and network meta-analysis. In: British Medical Journal (Clinical Research Ed.). 2017 ; Vol. 356.
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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.",
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AU - Wang, Rui

AU - Kim, Bobae V

AU - van Wely, Madelon

AU - Johnson, Neil P

AU - Costello, Michael F

AU - Zhang, Hanwang

AU - Ng, Ernest Hung Yu

AU - Legro, Richard S

AU - Bhattacharya, Siladitya

AU - Norman, Robert J

AU - Mol, Ben Willem J

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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N2 - 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.

AB - 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.

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