Effect of Xiaonang Yusi decoction () on IVF outcomes in patients with phlegm-dampness type PCOS: a prospective cohort study with supporting metabolomics, network pharmacology, and molecular docking analysis.

OBJECTIVE

To evaluate the clinical efficacy of Xiaonang Yusi decoction (XNYSD, ) in patients with phlegm-dampness type polycystic ovary syndrome (PCOS) undergoing in vitro fertilization and embryo transfer (IVF-ET), and to investigate its underlying mechanism by examining the arachidonic acid (AA) metabolic pathway.

METHODS

Women undergoing IVF-ET were divided into a treatment group (TCM treatment), a phlegm-dampness PCOS group, and a tubal factor control group (n = 32 each); all received a GnRH antagonist protocol. The study evaluated IVF-ET laboratory and clinical outcomes, alongside changes in TCM syndrome scores. To elucidate the therapeutic mechanism, follicular fluid AA metabolites were quantified by targeted metabolomics. These data were integrated with a network pharmacology analysis to link the active ingredients of Xiaonang Yusi decoction, PCOS targets, and differential metabolites. A protein-protein interaction (PPI) network was then constructed (STRING) and analyzed for GO/KEGG enrichment (DAVID) to systematically clarify the treatment's mode of action.

RESULTS

Clinical findings demonstrate that Traditional Chinese Medicine (TCM) intervention significantly ameliorates phlegm-dampness symptoms in PCOS patients, with marked improvements in embryo implantation rate (52.0% vs. 28.0%), clinical pregnancy rate (67.9% vs. 29.0%), and ongoing pregnancy rate (60.7% vs. 29.0%) (all p < 0.05), while showing no significant intergroup differences in early miscarriage rates (p > 0.05). Metabolomic profiling revealed significantly elevated levels of four arachidonic acid metabolites, including 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), in follicular fluid of PCOS patients compared to controls (p < 0.05), with TCM treatment effectively reducing 15(S)-HETE concentrations (p < 0.05). Network pharmacological analysis suggests that Xiaonang Yusi Decoction may modulate PCOS pathophysiology through targeting 15(S)-HETE-mediated pathways, acting on core targets including ESR1 and SIRT1, and influencing critical signaling pathways such as cancer-related pathways, lipid metabolism, and PI3K-Akt signaling. Molecular docking results show favourable interactions, indicating the active compound can spontaneously bind and modulate multiple key targets.

CONCLUSION

Xiaonang Yusi Decoction significantly improves TCM syndrome manifestations and IVF-ET outcomes in phlegm-dampness PCOS patients, enhancing embryo quality and pregnancy rates. The therapeutic effects appear mediated through regulation of arachidonic acid metabolites, particularly 15(S)-HETE, in follicular fluid. Network pharmacology analysis has preliminarily elucidated the underlying mechanisms, providing novel evidence for TCM-based PCOS treatment strategies.