Metabolomic profiling of follicular fluid reveals unique pathways in endometriosis and infertility etiologies: a pilot study.

PURPOSE: This study investigates metabolic profiles in follicular fluid of patients with endometriosis (EM), polycystic ovary syndrome (PCOS), tubal blockage (TB), and unexplained infertility (UEI), assessing their associations with follicular development and in vitro fertilization (IVF) outcomes. It aims to identify metabolic alterations and potential biomarkers for EM diagnosis and personalized reproductive strategies.

METHODS

Follicular fluid samples were collected from 12 infertility patients (3 EM, 3 PCOS, 3 TB, and 3 UEI) undergoing IVF. Metabolomic profiling was performed using liquid chromatography-mass spectrometry (LC-MS), followed by pathway enrichment analysis to identify key metabolic pathways. Statistical analyses were conducted to compare metabolic profiles across groups, assess correlations with follicular development rate (FDR), and evaluate potential biomarkers for EM diagnosis.

RESULTS

EM patients showed significant metabolic changes, including reduced steroid biosynthesis and elevated thiamine metabolism metabolites, linked to lower FDR. Oxidative stress markers (3-chloro-L-tyrosine, 8-oxoerythraline) were elevated and negatively correlated with FDR. A predictive model identified D-mannosamine, D-galacturonic acid, and 3-chloro-L-tyrosine as potential EM biomarkers with high diagnostic accuracy.

CONCLUSION

This study reveals distinct metabolic disruptions in the follicular fluid of EM patients, particularly in steroid biosynthesis and thiamine metabolism pathways, which are linked to impaired follicular development. The identification of specific metabolites as potential biomarkers for EM provides a foundation for developing diagnostic approaches that minimize the need for additional invasive procedures and support personalized assisted reproductive technology (ART) strategies. This pilot study requires further validation to confirm these findings and translate them into clinical practice.