A Pilot Study Beyond Ovarian Reserve: How AMH Levels Shape the Proteomic and Metabolic Landscape of the Follicle.

PURPOSE: The follicular fluid (FF) microenvironment critically influences oocyte development, with Anti-Müllerian Hormone (AMH) serving as a primary marker of ovarian reserve. This exploratory pilot study investigates the biochemical and proteomic shifts across the AMH spectrum to provide initial insights into potential targeted intrafollicular strategies. METHODS: FF samples from 49 patients undergoing assisted reproduction were grouped into Low-, Normal-, and High-AMH groups. Oxidative stress, antioxidant capacity, and metabolic indicators (lactate, adiponectin) were analyzed. Proteomic profiling was performed via LC-ESI-MS/MS, followed by STRING network and Spearman correlation analyses. RESULTS: Distinct molecular shifts occurred across groups. The High-AMH group showed a marked oxidative imbalance. Conversely, the Low-AMH group exhibited a distinct signature with higher lactate, lower adiponectin, and downregulated immunoglobulins, alongside upregulated HRG, ITIH3, and GPLD1. Positive correlations between adiponectin and immunoglobulins in Low-AMH subjects suggest that metabolic and immune-related factors may be coordinately regulated. CONCLUSIONS: This study suggests that AMH levels are associated with specific follicular microenvironment shifts. Low AMH levels appear linked to a distinct profile characterized by immune and metabolic alterations. These findings provide an exploratory foundation for future larger-cohort investigations into follicular homeostasis.