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

doi:10.1136/bmj.j138

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 language	English
Article number	j138
Number of pages	11
Journal	British Medical Journal (Clinical Research Ed.)
Volume	356
DOIs	https://doi.org/10.1136/bmj.j138
Publication status	Published - 31 Jan 2017

Bibliographical note

Funding: The work was supported by an Australian government research training programme scholarship (held by RW) and the Australian National Health and Medical Research Council funded Centre for Research Excellence in Polycystic Ovary Syndrome (APP1078444).

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Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis
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Siladitya Bhattacharya
- School of Medicine, Medical Sciences & Nutrition, Applied Health Sciences - Dugald Baird Chair in Women's Health
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Centre for Women’s Health Research
Person: Clinical Academic

Cite this

Wang, R., Kim, B. V., van Wely, M., Johnson, N. P., Costello, M. F., Zhang, H., Ng, E. H. Y., Legro, R. S., Bhattacharya, S., Norman, R. J., & 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, Article j138. https://doi.org/10.1136/bmj.j138

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

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.",

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

note = "Funding: The work was supported by an Australian government research training programme scholarship (held by RW) and the Australian National Health and Medical Research Council funded Centre for Research Excellence in Polycystic Ovary Syndrome (APP1078444).",

year = "2017",

month = jan,

day = "31",

doi = "10.1136/bmj.j138",

language = "English",

volume = "356",

journal = "British Medical Journal (Clinical Research Ed.)",

issn = "0267-0623",

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T1 - Treatment strategies for women with WHO group II anovulation

T2 - systematic review and network meta-analysis

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 - Funding: The work was supported by an Australian government research training programme scholarship (held by RW) and the Australian National Health and Medical Research Council funded Centre for Research Excellence in Polycystic Ovary Syndrome (APP1078444).

PY - 2017/1/31

Y1 - 2017/1/31

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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DO - 10.1136/bmj.j138

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C2 - 28143834

SN - 0267-0623

VL - 356

JO - British Medical Journal (Clinical Research Ed.)

JF - British Medical Journal (Clinical Research Ed.)

M1 - j138

ER -

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

Abstract

Bibliographical note

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Siladitya Bhattacharya

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