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Abstract The results of studies that assessed the impact of metformin treatments on gestational diabetes mellitus (GDM) in patients with polycystic ovary syndrome (PCOS) are inconclusive. In addition, the impact of time and duration of metformin therapy for an optimum reduction of GDM has not been reported in these studies. This study aimed to summarize current knowledge regarding the effect of metformin-therapy before conception versus throughout pregnancy on the risk of GDM in women with PCOS. PubMed, Scopus, Google Scholar and ScienceDirect databases were searched to identify relevant studies. Both fixed and random effect models were used. Subgroup analyses were performed based on the on the study methodology. The association between the PCOS status and GDM was assessed using the univariate and multiple meta-regression analysis adjusted by the BMI and metformin therapy. Forty-eight of 1397 identified studies were included involving 5711 PCOS patients and 20,296 controls. Regardless of metformin therapy, the prevalence of GDM diagnosed in the second trimester among women with PCOS was significantly higher than healthy controls that was independent of obesity. Including all studies, the increased risk of GDM among women with PCOS, compared to healthy controls, disappeared after the adjustment of metformin-therapy (β = 0.08, 95% CI 0.04, 0.2; p = 0.624). By excluding observational studies as a source of bias, the prevalence of GDM among women with PCOS treated using metformin before conception till the end of pregnancy did not differ from treated just before conception (β = − 0.09, 95% CI − 0.2, 0.02; p = 0.092) or those without metformin therapy (β = − 0.05, 95% CI − 0.07, 0.04; p = 0.301). The results remained unchanged after the subgroup analysis based on the methodology of RCTs and non-RCTs studies. The main body of literature in the current meta-analysis was observational, which may be mixed with some sources of bias. Also, a lack of well-designed and high quality interventional studies means that the findings should be interpreted with cautious. In this respect, decisions regarding the continuation or discontinuation of metformin therapy in women with PCOS are somewhat arbitrary and can be made individually based on the patient’s condition given the presence or absence of other GDM risk factors. Additional well-designed RCTs still need for precise recommendation.

Abstract Background The absence of universal gold standards for screening of gestational diabetes (GDM) has led to heterogeneity in the identification of GDM, thereby impacting the accurate estimation of the prevalence of GDM. We aimed to evaluate the effect of different diagnostic criteria for GDM on its prevalence among general populations of pregnant women worldwide, and also to investigate the prevalence of GDM based on various geographic regions. Methods A comprehensive literature search was performed in PubMed, Scopus and Google-scholar databases for retrieving articles in English investigating the prevalence of GDM. All populations were classified to seven groups based-on their diagnostic criteria for GDM. Heterogeneous and non-heterogeneous results were analyzed using the fixed effect and random-effects inverse variance model for calculating the pooled effect. Publication bias was assessed by Begg’s test. The Meta-prop method was used for the pooled estimation of the prevalence of GDM. Meta-regression was conducted to explore the association between prevalence of GDM and its diagnostic criteria. Modified Newcastle–Ottawa Quality Assessment Scale for nonrandomized studies was used for quality assessment of the studies included; the ROBINS and the Cochrane Collaboration’s risk of bias assessment tools were used to evaluate the risk of bias. Results We used data from 51 population-based studies, i.e. a study population of 5,349,476 pregnant women. Worldwide, the pooled overall-prevalence of GDM, regardless of type of screening threshold categories was 4.4%, (95% CI 4.3–4.4%). The pooled overall prevalence of GDM in the diagnostic threshold used in IADPSG criteria was 10.6% (95% CI 10.5–10.6%), which was the highest pooled prevalence of GDM among studies included. Meta-regression showed that the prevalence of GDM among studies that used the IADPSG criteria was significantly higher (6–11 fold) than other subgroups. The highest and lowest prevalence of GDM, regardless of screening criteria were reported in East-Asia and Australia (Pooled-P = 11.4%, 95% CI 11.1–11.7%) and (Pooled-P = 3.6%, 95% CI 3.6–3.7%), respectively. Conclusion Over the past quarter century, the diagnosis of gestational diabetes has been changed several times; along with worldwide increasing trend of obesity and diabetes, reducing the threshold of GDM is associated with a significant increase in the incidence of GDM. The harm and benefit of reducing the threshold of diagnostic criteria on pregnancy outcomes, women’s psychological aspects, and health costs should be evaluated precisely.