Role Of Metformin For Ovulation Induction In Infertile Patients With Polycystic Ovary Syndrome (PCOS)

Publication Date: September 1, 2017
Last Updated: March 14, 2022

Summary

There is good evidence that metformin alone vs placebo increases the ovulation rate in women with PCOS. (, A)
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There is insufficient evidence to suggest that metformin alone increases pregnancy rates or live-birth rates compared with placebo. (, C)
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There is fair evidence from one, large well-designed RCT that metformin alone is less effective than CC alone for the achievement of ovulation induction, clinical pregnancy, and live birth in women with PCOS. (, B)
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There is insufficient evidence to suggest that metformin alone increases pregnancy or live-birth rates compared with letrozole alone. (, C)
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There is fair evidence based on one well-designed trial in support of letrozole for ovulation induction. (, B)
Therefore, letrozole is a reasonable first-line agent for ovulation induction in PCOS patients.
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There is good evidence that metformin in combination with CC improves ovulation and clinical pregnancy rates but does not improve live-birth rates compared with CC alone in women with PCOS. (, A)
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There is fair evidence from one RCT that pretreatment with metformin for at least 3 months followed by the addition of another ovulation-inducing drug increases live-birth rate. (, B)
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There is fair evidence that CC-metformin improves ovulation and pregnancy rates compared with CC alone in CC‒resistant PCOS women. (, B)
However, more studies are needed to determine whether there may be subgroups of women (e.g., specific BMI, ethnicity, absence of insulin resistance, etc.) with PCOS and CC resistance for which CC-metformin provides the most benefit over CC alone.
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There is fair evidence that overall pregnancy rates are not different with CC-metformin, CC-LOD, or LOD alone in women with CC‒resistant PCOS. (, B)
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There is insufficient evidence regarding pregnancy rate or live-birth rate with the use of metformin alone compared with LOD for ovulation induction in CC‒resistant PCOS patients. (, C)
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There is insufficient evidence to compare metformin plus CC to aromatase inhibitors alone or metformin plus aromatase inhibitors for ovulation induction in CC‒resistant women. (, C)
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There is insufficient or conflicting evidence regarding metformin use combined with CC compared with gonadotropins for ovulation induction in women with CC‒resistant PCOS. (, C)
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There is fair evidence that metformin used while attempting pregnancy and stopped at the initiation of pregnancy does not affect the rate of miscarriage. (, B)
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There is insufficient evidence to recommend metformin during pregnancy to reduce the chance of miscarriage. (, C)
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There is good evidence that metformin alone does not increase the rate of multiple pregnancy. (, A)
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While there is no evidence of an effect (either increase or decrease) on multiple pregnancy rates in cycles using combination CC plus metformin vs CC alone, there remains insufficient data on this matter due to lack of adequate power to detect a difference. (, C)
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There is insufficient evidence of a reduced risk for multiple pregnancy with the addition of metformin to FSH compared with FSH alone. (, C)
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There is insufficient good-quality evidence to determine if metformin is more effective in non-obese or obese women with PCOS. (, C)
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Recommendations

Metformin alone should not be used as first-line therapy for ovulation induction in women with PCOS, since ovulation induction agents such as CC or letrozole are more effective. CC alone or letrozole alone are reasonable first-line agents for ovulation in women with PCOS. Combination therapy with CC may be beneficial in women who are resistant to CC alone. While metformin alone is not likely to increase live-birth rate in women seeking pregnancy in the short term, utilizing metformin in individualized cases of PCOS with the goal of improving ovulation rates over the long term may be of benefit. In the context of increased ovulation rate and overall improved insulin resistance on metformin, the subsequent addition of other ovulation-inducing agents may be beneficial in increasing pregnancy rates, although there is insufficient evidence of an increase in live-birth rates. These data suggest that individualization of treatment may be warranted, particularly in younger women with PCOS. Additional large, adequately powered randomized trials are needed in carefully defined populations of women with various forms of PCOS (i.e., phenotype specified) to determine in whom the use of metformin may be of benefit.
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Recommendation Grading

Overview

Title

Role Of Metformin For Ovulation Induction In Infertile Patients With Polycystic Ovary Syndrome (PCOS)

Authoring Organization

American Society for Reproductive Medicine

Publication Month/Year

September 1, 2017

Last Updated Month/Year

January 17, 2024

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

The goal of this guideline is to provide recommendations for the use of metformin for ovulation induction in women with PCOS desiring pregnancy. For the purposes of this document, all patients had PCOS unless otherwise indicated.

Target Patient Population

Infertile patients with polycystic ovary syndrome

Inclusion Criteria

Female, Adult

Health Care Settings

Ambulatory, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Management

Diseases/Conditions (MeSH)

D007246 - Infertility, D007247 - Infertility, Female, D011085 - Polycystic Ovary Syndrome, D008687 - Metformin

Keywords

polycystic ovary syndrome (PCOS), infertility, metformin