Abstract
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by ovulatory dysfunction and hormonal imbalance, often leading to infertility. Cangfu Daotan Decoction (CFDTT, Atractylodis Rhizoma, Cyperi Rhizoma, Pinelliae Rhizoma, Poria, Pericarpium Citri Reticulatae, Glycyrrhizae Radix et Rhizoma, Arisaema cum Bile, Aurantii Fructus) is a traditional Chinese herbal formula commonly used to treat PCOS-related infertility, with its pathogenesis attributed to phlegm-dampness obstruction. There is an urgent need for a systematic evaluation of its efficacy and safety. OBJECTIVE: To evaluate the efficacy, safety, and potential mechanisms of CFDTT in treating PCOS-related infertility, providing evidence for clinical application and future research. METHODS: Seven databases were searched to identify randomized controlled trials (RCTs) evaluating CFDTT for PCOS-related infertility. Data were analyzed using meta-analysis, subgroup analysis, sensitivity analysis, publication bias testing (funnel plot, Egger's test, trimming and filling method), and evidence quality assessment (GRADE). RESULTS: A total of 19 RCTs involving 2,181 participants were identified. CFDTT combined with conventional pharmacotherapy was superior to conventional pharmacotherapy alone in improving ovulation rate, pregnancy rate, ovarian volume, dominant follicle count, and endometrial thickness. However, due to high heterogeneity and methodological limitations, the overall certainty of the evidence was low to very low. Only two trials directly compared CFDTT with conventional pharmacotherapy, reporting no significant differences in pregnancy rate or endometrial thickness, but the evidence was limited to a single study. Safety data are inadequately reported: 73.7% of trials did not provide information on adverse events, and laboratory monitoring data are scarce. Existing evidence suggests that CFDTT does not increase the risk of adverse events and may reduce the risk of ovarian hyperstimulation syndrome (OHSS) or luteinized unruptured follicle syndrome (LUFS), but organ toxicity cannot be ruled out. Publication bias exists for some outcomes, but sensitivity analyses confirmed the robustness of key findings. CONCLUSION: This meta-analysis provides preliminary evidence supporting the use of CFDTT as an adjunctive therapy for infertility associated with PCOS, suggesting potential synergistic effects when combined with conventional pharmacotherapy. While the efficacy of CFDTT monotherapy appears comparable to that of conventional pharmacotherapy, the available evidence remains highly limited. However, the included studies exhibit substantial methodological shortcomings, including a high risk of bias, considerable heterogeneity, and significant gaps in safety monitoring. Consequently, the current findings regarding the efficacy and safety of CFDTT should be interpreted with caution, and further validation through well-designed, large-scale, prospective randomized controlled trials is essential to confirm these results. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/recorddashboard CLINICAL TRIAL REGISTRATION: Since this study is a meta-analysis rather than a clinical trial, registration with a clinical trial registry is not required.