Efficacy and Safety of Traditional Chinese Medicine in the Treatment of Immune Infertility Based on the Theory of “Kidney Deficiency and Blood Stasis”: A Systematic Review and Meta-Analysis

Objective This study aims to evaluate the efficacy and safety of traditional Chinese medicine (TCM) therapy of tonifying kidney and activating blood circulation (TKABC) based on the theory of “kidney deficiency and blood stasis” for the treatment of immune infertility.Methods Six electronic databases, including the Cochrane Library, PubMed, EMBASE, the China National Knowledge Infrastructure, Wanfang Data, and VIP information database, were searched from inception to January 2021 to identify eligible studies of randomized controlled trials (RCTs). The primary outcome measurements were the total effective rate and pregnancy rate, and the secondary outcome measurements included the negative conversion rate of serum antibodies and the incidence of adverse effects. The quantitative synthesis was performed using the Review Manager 5.3 software. The chi-square statistic and I 2 statistic were employed to investigate statistical heterogeneity. The fixed-effects model was used for a low heterogeneity ( I 2  < 50%), and the random-effects model was applied if heterogeneity was moderate (50% <  I 2  < 75%). Funnel plots were used to evaluate potential reporting bias when more than ten eligible studies were included.Results Thirteen RCTs involving 1298 patients with immune infertility of kidney deficiency and blood stasis were included. Compared with conventional group, TCM TKABC therapy showed a significant improvement on the total effective rate (RR: 1.38; 95% CI: 1.30,1.47; and I 2  = 0%), pregnancy rate (RR: 2.04; 95% CI: 1.73, 2.40; and I 2  = 30%), negative conversion rates of AsAb (RR: 1.42; 95% CI: 1.12,1.79; and I 2  = 62%), AEmAb rates (RR: 1.21; 95% CI: 1.04,1.41; and I 2  = 0%), and AhCGAb with less adverse effects (RR: 0.24; 95% CI: 1.73, 2.40; and I 2  = 55%). However, the negative conversion rate of AoAb and ACAb showed no significant statistical difference.Conclusions Our review suggests that TCM TKABC therapy based on the theory of kidney deficiency and blood stasis appears to be an effective and safe approach for patients with immune infertility. However, the methodological quality of included RCTs was unsatisfactory, and it is necessary to verify its effectiveness with more well-designed and high-quality multicenter RCTs.