Effect of Yiqi Bushen Shugan Huoxue Decoction on impaired endometrial receptivity associated with ovarian stimulation: A clinical trial, modular pharmacology, molecular docking, and experiment-based study.

Abstract

Endometrial receptivity plays a critical role in pregnancy, while controlled ovarian hyperstimulation (COH) - widely used for infertile patients - could impair endometrial receptivity and subsequent pregnancy outcomes. This study aims to explore the effect of Yiqi Bushen Shugan Huoxue Decoction (YBSHD) on impaired endometrial receptivity in patients with unexplained infertility (UI) undergoing COH and to determine the mechanism for it through modular pharmacology, molecular docking, and a murine model. First, we retrospectively studied 422 patients with UI who underwent COH to get pregnant. Results indicated that the live birth rate significantly increased in the YBSHD group. Second, a systematic network pharmacology analysis was performed to screen the ingredients and possible targets of YBSHD. The main targets concerning YBSHD and endometrial receptivity involved pathways including hormone regulation, inflammatory responses, and apoptosis. The active components of quercetin and kaempferol from YBSHD exhibited a strong binding affinity to key molecules, including BCL2, ESR1, IL6, IL1B, and TNF. Third, YBSHD improved endometrial receptivity in a murine COH model. Compared to the COH group, the number of embryo implantations and endometrial pinopodes significantly increased in the YBSHD group, indicating improved endometrial receptivity. YBSHD improved the local immune microenvironment in COH mice by regulating excessive hormone secretion, gene expression of inflammatory factors, and proportions of neutrophils and macrophages. Moreover, YBSHD inhibited apoptosis in the ovaries and uteruses of COH mice. In summary, YBSHD could increase the live birth rate in patients with UI, mainly because it can inhibit inflammation and cell apoptosis, thereby improving endometrial receptivity.