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

## TL;DR

Xiaonang Yusi decoction improves IVF outcomes in PCOS patients with phlegm-dampness syndrome by reducing harmful metabolites and enhancing pregnancy rates.

## Contribution

This study provides novel evidence linking Xiaonang Yusi decoction to improved IVF outcomes via regulation of arachidonic acid metabolites and key signaling pathways.

## Key findings

- TCM treatment significantly improved embryo implantation, clinical pregnancy, and ongoing pregnancy rates in PCOS patients.
- Metabolomic analysis showed reduced 15(S)-HETE levels in follicular fluid following TCM intervention.
- Network pharmacology suggests Xiaonang Yusi decoction modulates PCOS via ESR1, SIRT1, and lipid metabolism pathways.

## Abstract

To evaluate the clinical efficacy of Xiaonang Yusi decoction (XNYSD, 消囊育嗣汤) 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.

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.

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.

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.