Zhu Daiyu, Chen Yan, Huang Jianfeng, Deng Hongxia, Shen Xiaoyang, Lu Danhua, Xu Liangzhi
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
Reproductive Endocrinology and Regulation Laboratory, West China Second University Hospital, Chengdu, China.
Ann Transl Med. 2022 Apr;10(7):418. doi: 10.21037/atm-22-909.
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.
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.
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).
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.
二甲双胍对长期妊娠结局的有效性和安全性研究仍存在争议。我们进行了一项更新的系统评价和荟萃分析，以系统地研究二甲双胍治疗对多囊卵巢综合征（PCOS）女性及其后代的妊娠结局、代谢谱和性激素特征的影响。
检索PubMed、Embase和Cochrane图书馆数据库，时间跨度从建库至2021年7月10日，关键词为“二甲双胍”、“PCOS”和“妊娠”。纳入报道PCOS女性接受二甲双胍干预后妊娠相关结局的随机对照研究，排除摘要和综述。两名作者独立识别试验、提取数据并使用Cochrane评价员手册5.0评估偏倚风险。采用随机效应模型评估妊娠结局、代谢谱和性激素水平的合并风险比（RR）和95%置信区间（95%CI）。
纳入18项研究。大多数试验方法学质量中等。在PCOS女性的妊娠并发症方面，二甲双胍治疗与早产风险显著降低相关（RR =0.37，95%CI：0.23 - 0.61）、妊娠高血压（PIH）和先兆子痫（RR =0.45，95%CI：0.24 - 0.83）以及巨大儿（RR =0.26，95%CI：0.11 - 0.64）。在后代方面，二甲双胍与更大的头围显著相关（MD =0.29，95%CI：0.13 - 0.45）以及更高的长期体重指数（BMI）测量值相关（MD =0.37，95%CI：0.17 - 0.56）。在代谢谱和性激素特征方面，母亲的胰岛素抵抗稳态模型评估（HOMA2 - IR）得分显著降低（MD = - 0.32，95%CI： - 0.63至 - 0.02），而后代的性激素结合球蛋白（SHBG）水平显著升高（MD =0.33，95%CI：0.01 - 0.65）。
尽管随机对照试验（RCT）的质量相对较低且结果有限，难以得出明确结论，但我们的研究表明，孕期使用二甲双胍可降低妊娠并发症风险，但可能对后代SHBG水平升高和长期BMI有影响。
