Differences in follicular fluid kynurenic acid and 9,10-DiHOME levels between controlled ovarian stimulation and modified natural ART cycles

This study investigates the impact of assisted reproductive technology (ART) protocols, specifically modified natural cycle (MNC) and controlled ovarian stimulation (COS), on Kynurenine metabolism and bioactive lipid mediators. Follicular fluid (FF) samples from 28 participants (MNC: 14, COS: 14) were analyzed using targeted and untargeted liquid chromatography-tandem mass spectrometry, alongside evaluation of baseline reproductive hormones. A significant reduction in Kynurenic acid (KA) levels (p = 0.0088) was observed in the COS group, while other Kynurenine pathway metabolites such as L-Kynurenine (Kyn), 3-Hydroxykynurenine, and Tryptophan (Trp) remained unchanged. KA/Kyn and KA/Trp ratios were also unchanged, suggesting no major alteration in overall Kynurenine aminotransferase (KAT)-associated pathway activity between the groups. A targeted analysis of oxylipins revealed a significant decrease of 9,10-dihydroxy-12-octadecenoic acid (9,10-DiHOME) in COS samples (p < 0.0001), whereas levels of 12,13-DiHOME, 13-HODE, DiHETEs, and 8-Iso-prostaglandin E₂ showed no significant differences. The parallel reduction of KA and 9,10-DiHOME in COS cycles indicates that differences in the intensity of ovarian stimulation are associated with alterations in the follicular immunometabolic environment. Further research is needed to evaluate the functional relevance of these changes for oocyte quality and reproductive outcomes.