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Our study aims to compare the effect of metformin, inositol and their combinations on the efficiency in improving outcomes of assisted reproductive technologies in women with PCOS. PubMed, The Cochrane Library, ClinicalTrials.gov, Embase, MEDLINE. The search was performed on studies published before November 14, 2021, to identify articles evaluating the effectiveness of treatment metformin and inositol on ART outcomes. The systematic review was conducted according to the PRISMA 2020 checklist and registered in the PROSPERO 2021 CRD42021287887. Randomized controlled trials (RCTs) in English that compared metformin or inositol or metformin + inositol treatment with placebo or no treatment in women with PCOS undergoing assisted reproduction were included. In addition, RCTs with comparison combination and single metformin or inositol treatment were also included. 35 RCTs were included for qualitative analysis reporting on 4668 participants. In group of Metformin treatment were included 1891 patients, in Myo-inositol group − 281, in inositol + metformin group were included 110 participants and in control group (placebo or absence of treatment) − 1865 women with PCOS. 5 meta-analyses were performed. CPR in comparison of metformin and placebo in 1312 patients were higher in metformin group (RR = 1.30, 95% CI: 1.12 to 1.50,  p  = 0.0004). OHSS was less in metformin (RR = 0.34, 95% CI: 0.17 to 0.69,  p  = 0.003). However, LBR were not statistically significant (RR = 1.12, 95% CI: 0.93 to 1.36,  p  = 0.24). In comparison of inositol and no treatment there was also no difference in CPR (RR = 1.37, 95% CI: 0.79 to 2.38,  p  = 0.26). As for metformin and inositol meta-analysis in 220 patients with PCOS, CPR were higher in inositol group (RR = 1.52, 95% CI: 1.05 to 2.18,  p  = 0.03). Combination treatment included only two RCTs and was illegible for meta-analysis. To our knowledge, it is the first meta-analysis that estimates inositol treatment compared to metformin. Based on our systematic review and meta-analysis, metformin seems to be a good option for improving ART outcomes in women with PCOS. However, it is not clear whether inositol usage is adequate. Nevertheless, we need more clinical trials of good quality to answer all questions thoroughly.

Effectiveness of inositol, metformin and their combination in women with PCOS undergoing assisted reproduction: systematic review and meta-analysis