Oya Korkmaz, Seda Karabulut, Pelin Macit
Ovarian response to controlled ovarian stimulation varies considerably among women and may be influenced by inflammatory activity within the follicular microenvironment. To examine the relationship between ovarian response and follicular inflammatory activity by evaluating IL-1β, IL-17, and IL-18 levels, granulosa cell expression, and markers of chromatin integrity and apoptosis in IVF cycles. A total of 150 women undergoing controlled ovarian stimulation were grouped as low, normal, or high ovarian response (n = 50 each). Follicular fluid cytokine levels were measured by ELISA/CLIA, granulosa cell cytokine expression was assessed immunohistochemically, and chromatin integrity and DNA fragmentation were evaluated using Toluidine Blue and TUNEL assays. Follicular fluid levels and granulosa cell immunopositivity of IL-1β, IL-17, and IL-18 increased progressively from low to high ovarian response groups (p < 0.05). Chromatin integrity was best preserved in the normal responder group, whereas both Toluidine Blue–positive and TUNEL-positive granulosa cell ratios were significantly higher in low and high responders (p < 0.01). IL-18 levels showed positive correlations with oocyte number, serum estradiol levels, and MII oocyte ratio (p < 0.05). Notably, granulosa cell IL-18 expression was inversely correlated with DNA fragmentation, suggesting a potential cytoprotective role under physiological inflammatory conditions. These findings demonstrate that follicular cytokine balance is closely associated with ovarian response and granulosa cell integrity during IVF. IL-18 emerges as a key regulator linking physiological inflammation to oocyte competence, highlighting its potential relevance for individualized ovarian stimulation strategies.