Efficacy and safety of metformin in pregnant women with polycystic ovary syndrome: a systematic review with meta-analysis of randomized and non-randomized controlled trials

Abstract

Objective

To evaluate the efficacy and safety of using metformin in pregnant women with polycystic ovarian syndrome (PCOS) and to explore the most effective and safe protocol by using a meta-analysis method.

Methods

Medline, EMBASE, Cochrane Library, and other databases were searched for randomized controlled trials and prospective cohort studies enrolling pregnant women with PCOS on receiving metformin or placebo or nothing. Subgroup analyses were undertaken.

Results

A total of 17 studies involving 2899 patients were included. Compared with control group, the use of metformin significantly reduced the incidence of preterm delivery (cumulative rate 3.86% vs 9.19%, relative risk (RR), 0.42 [95% confidence interval (CI), 0.25–0.71,]; p = .001), early miscarriage (cumulative rate 6.58% vs 18.35%, RR, 0.40 [95% CI, 0.20–0.78]; p = .007), gestational diabetes (cumulative rate 12.86% vs 22.91%, RR, 0.48 [95% CI, 0.26–0.89]; p = .02), and pre-eclampsia (cumulative rate 4.95% vs 7.72%, RR, 0.61 [95% CI, 0.40–0.93]; p = .02), the need for insulin treatment throughout pregnancy (cumulative rate 2.14% vs 5.12%, RR, 0.43 [95% CI, 0.22–0.85]; p = .01), and weight gain of pregnant women (mean difference, −2.45, [95% CI, −3.04 to −1.85]; p < .00001).

Conclusions

The use of metformin in pregnant women with PCOS can significantly reduce maternal complications. No significant difference was observed in serious maternal adverse events. The efficacy and safety of metformin are worthy of recognition.

摘要

目的：评价二甲双胍治疗多囊卵巢综合征（PCOS）孕妇的疗效和安全性, 并采用Meta分析的方法探讨最有效、最安全的方案。

方法：在 Medline、EMBASE、Cochrane 图书馆和其他数据库中搜索随机对照试验和前瞻性队列研究, 这些研究招募了 PCOS 孕妇分为接受二甲双胍或安慰剂或不接受任何治疗组进行分析。

结果：共纳入 17 项研究, 涉及 2899 名患者。与对照组相比, 使用二甲双胍显著降低了早产的发生率（累积率 3.86% vs 9.19%, 相对风险 (RR), 0.42 [95% 置信区间 (CI), 0.25–0.71, ]；p=.001) , 早期流产（累积率 6.58% vs 18.35%, RR, 0.40 [95% CI, 0.20–0.78]；p=.007）, 妊娠期糖尿病（累积率 12.86% vs 22.91%, RR, 0.48 [95% CI, 0.26–0.89]；p=.02）和先兆子痫（累积发生率 4.95% vs 7.72%, RR, 0.61 [95% CI, 0.40–0.93]；p=.02）, 整个孕期需要胰岛素治疗（累积率 2.14% vs 5.12%, RR, 0.43 [95% CI, 0.22–0.85]; p=.01), 和孕妇体重增加 (平均差2.45, [95% CI, 3.04 to 1.85]; p<. 00001)。

结论：PCOS孕妇使用二甲双胍可显著减少产妇并发症。在严重的孕产妇不良事件中未观察到显著差异。二甲双胍的疗效和安全性值得肯定。

Keywords:

• Metformin
• polycystic ovary syndrome
• pregnant women
• meta-analysis

关键词:

• 二甲双胍
• 多囊卵巢综合征
• Meta分析

Acknowledgment

The authors thank Dr. Jixiang Tan for the statistical assistance.

Ethical approval and consent to participate

This article does not contain any studies with human participants or animals performed by any of the authors.

Author contributions

Conceived and designed the study: QZ and JH; selected the references: QZ and JH; extracted the data: QZ and JH; analyzed and interpreted data: QZ and JH; wrote the paper: QZ; provided critical revisions: JH; approved the final version of the manuscript: QZ and JH.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Data availability statement

This research is a meta-analysis of available studies conducted by searching electronic databases.