Efficacy of Acupoint Application on In Vitro Fertilization Outcome in Patients with Polycystic Ovary Syndrome: A UHPLC-MS-Based Metabolomic Study

OBJECTIVE: To explore the clinical effect of acupoint application on the outcome of in vitro fertilization-embryo transfer (IVF-ET) in patients with polycystic ovary syndrome (PCOS) of the phlegm-dampness type and elucidate its possible mechanism of action from the perspective of follicular fluid metabolomics. METHODS: A total of 90 patients undergoing IVF-ET due to infertility were selected and divided into three groups: the treatment group (PCOS with acupoint application, n = 30), the control group (PCOS without acupoint application, n = 30), and the normal group (non-PCOS, n = 30). All patients received a gonadotropin-releasing hormone agonist (GnRH-a) long protocol for controlled ovarian hyperstimulation (COH). Among them, the treatment group was also given the acupoint application from the day of pituitary downregulation to the day of the human chorionic gonadotrophin (hCG) trigger. Ultrahigh-performance liquid chromatography connected with quadrupole time-of-flight mass spectrometry (UHPLC-MS) was adopted for untargeted metabolomic analysis of follicular fluid collected from the three groups of patients on the day of oocyte pick-up (OPU). The significantly differential metabolites were screened using univariate and multivariate statistical analysis, and the related metabolic pathways were identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS: Metabolomic analysis showed that the treatment group's follicular fluid samples were aggregated with the normal group and separated from the control group. A total of 34 significantly differential metabolites were found in the follicular fluid of patients with phlegm-dampness PCOS and normal people. With the intervention of acupoint application, seven metabolites (pseudouridine, phenol, 2-oxoadipic acid, 9R,10S-EpOME, DL-lactate, nicotinamide, and DL-indole-3-lactic acid) were all downregulated, mainly involving the pathways of pyruvate metabolism, nicotinate and nicotinamide metabolism, protein digestion and absorption, biosynthesis of amino acids, and pyrimidine metabolism. CONCLUSIONS: Acupoint application can effectively improve the clinical symptoms and the outcome of IVF-ET treatment in patients with PCOS of the phlegm-dampness type, and its mechanism of action may be related to the regulation of the pathways of pyruvate metabolism, nicotinate and nicotinamide metabolism, protein digestion and absorption, biosynthesis of amino acids, and pyrimidine metabolism.