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. 2022 Apr;10(7):418.
doi: 10.21037/atm-22-909.

Effects of metformin on pregnancy outcome, metabolic profile, and sex hormone levels in women with polycystic ovary syndrome and their offspring: a systematic review and meta-analysis

Daiyu Zhu  1   2   3   4 , Yan Chen  1   2   3 , Jianfeng Huang  4 , Hongxia Deng  1   2   3 , Xiaoyang Shen  1   2   3 , Danhua Lu  1   2   3 , Liangzhi Xu  1   2   3
Affiliations

Effects of metformin on pregnancy outcome, metabolic profile, and sex hormone levels in women with polycystic ovary syndrome and their offspring: a systematic review and meta-analysis

Daiyu Zhu et al. Ann Transl Med. 2022 Apr.

Abstract

Background: Researches of the efficacy and safety of metformin on long-term pregnancy outcomes remains conflicted. We performed an updated systematic review and meta-analysis to systematically investigate the effect of metformin treatment on pregnancy outcome, metabolic profile, and sex hormone characteristics in women with polycystic ovary syndrome (PCOS) and their offspring.

Methods: The PubMed, Embase, and Cochrane Library databases were searched from inception to July 10, 2021 with the keywords "metformin", "PCOS", and "pregnancy". Randomized controlled studies reported pregnant related outcomes after metformin intervention among PCOS women were included, while abstracts and reviews were excluded. Two authors independently identified trials, extracted data and assessed risk of bias with Cochrane Reviewer's Handbook 5.0. Random effects models were used to evaluate the pooled risk ratios (RR) and 95% confidence intervals (95% CI) of pregnancy outcome, metabolic profile, and sex hormone levels.

Results: Eighteen studies were included. The majority of trials were in medium methodological quality. In terms of pregnancy complications among women with PCOS, metformin treatment was associated with a significantly reduced risk of preterm delivery (RR =0.37, 95% CI: 0.23-0.61), pregnancy-induced hypertension (PIH) and preeclampsia (RR =0.45, 95% CI: 0.24-0.83) and macrosomia (RR =0.26, 95% CI: 0.11-0.64). In terms of offspring, metformin significantly associated with larger head circumference (MD =0.29, 95% CI: 0.13-0.45) and higher long-term body mass index (BMI) measures (MD =0.37, 95% CI: 0.17-0.56). In terms of metabolic profile and sex hormone characteristics, a significant decrease in homeostatic model assessment for insulin resistance (HOMA2-IR) scores was found in mothers (MD =-0.32, 95% CI: -0.63 to -0.02), whereas a significant increase of sex hormone binding globulin (SHBG) levels was detected in offspring (MD =0.33, 95% CI: 0.01-0.65).

Discussion: Although the relative low quality of randomized controlled trials (RCTs) and limited results made it difficult to draw a definite conclusion, our study showed that metformin treatment during pregnancy can reduce the risk of pregnancy complications but may have impacts on increasing SHBG levels and long-term BMI in offspring.

Keywords: Metformin; offspring; polycystic ovary syndrome (PCOS); pregnant outcomes.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-909/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Flow chart of the included studies.
Figure 2
Figure 2
Effect of continual metformin treatment in pregnancy on perinatal outcomes in women with PCOS. PCOS, polycystic ovary syndrome.
Figure 3
Figure 3
Effect of continual metformin treatment on birth anthropometrics in offspring.
Figure 4
Figure 4
Effect of continual metformin treatment on birth outcomes in offspring.
Figure 5
Figure 5
Effect of continual metformin treatment in pregnancy on metabolic health in women with PCOS. PCOS, polycystic ovary syndrome.
Figure 6
Figure 6
Effect of continual metformin treatment in pregnancy on sex hormone levels in women with PCOS. PCOS, polycystic ovary syndrome.
Figure 7
Figure 7
Effect of continual metformin treatment on sex hormone levels in offspring.
Figure 8
Figure 8
Effect of continual metformin treatment on metabolic health in offspring.
See this image and copyright information in PMC

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