Differences of pro-inflammatory and cell apoptosis markers between patients with normal and poor ovarian response during in vitro fertilization program Running Titel: Pro-inflammatory markers in IVF patients

Abstract This study aimed to compare pro-inflammatory (Interleukin-6; IL-6 and TNF-α) and cell apoptosis (GABRA-1) markers in patients with normal ovarian response (NOR) and poor ovarian response (POR) to ovarian stimulation during in vitro fertilization (IVF) treatment. A cross-sectional study was conducted with 27 patients (NOR = 16 and POR = 11). Pleiotropic cytokine IL-6 levels in follicular fluid were determined by enzyme-linked immunosorbent assay. Relative expression levels of TNF-α and GABRA-1 related genes were determined in cumulus cells by reverse transcription-quantitative polymerase chain reaction. TNF-α levels were significantly higher in POR group compared to NOR group (POR = 7.1 ± 1.9 and NOR = 2.4 ± 1.5, P < 0.001). Additionally, positive correlation was noted between TNF-α relative expression levels and factors associated with ovarian response, including levels of anti-müllerian hormone (AMH) (r² = 0.69, P = 0.008), antral follicle count (r² = 0.73, P < 0.001) and number of retrieved oocytes (r² = 0.74, P < 0.001). However, IL-6 and GABRA-1 levels did not differ between cohorts. In conclusion, TNF-α presents significantly different between NOR and POR patients, suggesting its crucial role in ovarian response during IVF treatment. This finding provides an opportunity for further study of POR pathogenesis.