Sun's Bushen Huayu Formula Restores Fertility in Endometriosis by Modulating Th1 and Th2 Cytokine Balance in Clinical and Animal Models

Endometriosis (EMs) is a common gynecological disorder frequently associated with infertility, yet the underlying immune mechanisms remain poorly understood. Sun's Bushen Huayu Formula (BSHYF) has been clinically applied to improve fertility in patients with EMs, but its immunological mechanism remains unclear. This study investigated whether BSHYF alleviates EMs-related infertility by modulating the Th1/Th2 cytokine balance. A total of 80 serum samples from women with or without EMs were analyzed and further stratified into pregnancy and infertility groups (n = 20 each). Levels of IFN-γ and IL-4 were measured by ELISA, and the IFN-γ/IL-4 ratio was calculated. In parallel, an EMs rat model was established and divided into four groups: control, EMs, EMs + BSHYF, and EMs + aspirin. After treatment, fertility outcomes were evaluated, and flow cytometry was performed to assess Th1 (IFN-γ⁺) and Th2 (IL-4⁺) lymphocyte proportions. Clinically, EM patients-particularly those with infertility-showed a significantly elevated IFN-γ/IL-4 ratio compared with controls. In the animal model, BSHYF treatment improved the pregnancy rate from 20% to 50% and effectively corrected the Th1/Th2 imbalance. Notably, BSHYF demonstrated a stronger immunoregulatory effect on Th1/Th2 cytokine balance than aspirin, accompanied by improved reproductive performance. These findings indicate that BSHYF may alleviate infertility associated with EMs by restoring Th1/Th2 cytokine homeostasis, providing new mechanistic insights into immunomodulation and supporting its therapeutic potential as a complementary approach for EMs-related infertility.