Effects of the commercial Chinese polyherbal preparation Zishen Yutai Pill on the pregnancy outcomes in women undergoing in vitro fertilization-embryo transfer: a systematic review and meta-analysis of randomized controlled trials

Aim of the Study: fertilization-embryo transfer (IVF-ET). Methods: Electronic databases (PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP, and CBM) were systematically searched from inception to 12 February 2025. The primary outcome measure was the clinical pregnancy rate. The secondary outcomes were live birth rate, biochemical pregnancy rate, miscarriage rate, implantation rate, endometrial thickness and number of oocytes retrieved. The ROB2 tool was used to assess the risk of bias, the data were pooled using Review Manager 5.3, and the pooled data were presented in terms of risk ratio (RR) or mean difference (MD) with a confidence interval of 95%. GRADE was used to evaluate the quality of the evidence. In addition, we performed sensitivity analysis, used Stata 17.0 for Egger's test and constructed funnel plots to assess publication bias. Results: Eighteen RCTs (5,660 participants) were included. Compared to the control group, ZYP significantly improved the clinical pregnancy rate (RR = 1.22, 95% CI: 1.15-1.30, P < 0.00001), live birth rate (RR = 1.25, 95% CI: 1.15-1.36, P < 0.00001), biochemical pregnancy rate (RR = 1.13, 95% CI: 1.05-1.22, P = 0.002), and implantation rate (RR = 1.19, 95% CI: 1.11-1.27, P < 0.00001). Subgroup analysis suggested that the combination of biomedicine was more effective than ZYP alone. Additionally, ZYP was associated with a lower miscarriage rate (RR = 0.75, 95% CI: 0.63-0.88, P = 0.0005). ZYP also increased endometrial thickness on the day of transfer (MD = 1.06, 95% CI: 0.61-1.51, P < 0.00001) and the number of oocytes retrieved (MD = 0.77, 95% CI: 0.09-1.45, P = 0.03), though significant heterogeneity was observed for these two outcomes. The GRADE assessment indicated that the quality of evidence for all outcomes was very low. Regarding safety, only 5 of 18 studies reported adverse events. Among the 4 studies with quantifiable data (589 participants), all events were mild and self-limiting (e.g., nausea, constipation, rash), with incidence rates of 11.1% (27/244) in the ZYP group and 5.8% (20/345) in the control group. No serious adverse events were reported. Formal statistical comparison was not performed owing to the limited number of reporting studies and heterogeneous documentation methods. Conclusion: As an adjunctive treatment, ZYP appears to improve multiple pregnancy outcomes among women undergoing IVF. However, due to the limited certainty of evidence and the incomplete methodological reporting in the included studies, these findings do not support immediate changes in clinical practice and should be regarded as exploratory. Large-scale, double-blind RCTs with standardized ZYP protocols are needed to confirm these findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251030089, identifier CRD420251030089.