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    NF-?B as an Inflammatory Biomarker in Thin Endometrium: Predictive Value for Live Birth in Recurrent Implantation Failure
    (Mdpi, 2025) Kali, Zercan; Karli, Pervin; Tanilir, Fatma; Kirici, Pinar; Ege, Serhat
    Background: Recurrent implantation failure (RIF) poses a major challenge in assisted reproductive technologies, with thin endometrium (<= 7 mm) being a frequently observed yet poorly understood condition. Emerging evidence implicates nuclear factor-kappa B (NF-kappa B), a key transcription factor in inflammatory signaling, in impaired endometrial receptivity. However, its clinical relevance and prognostic value for live birth outcomes still need to be fully elucidated. Objective: We aim to evaluate the expression levels of endometrial NF-kappa B in patients with RIF and thin endometrium and to determine its potential as a predictive biomarker for live birth outcomes following IVF treatment. Methods: In this prospective case-control study, 158 women were categorized into three groups: Group 1 (RIF with thin endometrium, <= 7 mm, n = 52), Group 2 (RIF with normal endometrium, >7 mm, n = 38), and fertile controls (n = 68). NF-kappa B levels were assessed using ELISA and immunohistochemical histoscore. Pregnancy outcomes were compared across groups. ROC analysis and multivariable logistic regression were performed to assess the predictive value of NF-kappa B. Results: NF-kappa B expression was significantly elevated in Group 1 compared to Group 2 and controls (p = 0.0017). ROC analysis identified a cut-off value of 7.8 ng/mg for live birth prediction (AUC = 0.72, sensitivity 74%, specificity 75%). Multivariable analysis confirmed NF-kappa B is an independent predictor of live birth (p = 0.045). Histological findings revealed increased NF-kappa B staining in luminal and glandular epithelial cells in the thin endometrium group. Conclusions: Increased endometrial NF-kappa B expression is associated with thin endometrium and reduced live birth rates in RIF patients. NF-kappa B may serve not only as a biomarker of pathological inflammation but also as a prognostic tool for treatment stratification in IVF. Based on findings in the literature, the therapeutic targeting of NF-kappa B may represent a promising strategy to improve implantation outcomes.
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    PTX3 as a key modulator of functional ovarian response in PCOS: evaluation alongside TSG-6 and ITI
    (Bmc, 2025) Kali, Zercan; Karabulut, Umran; Memur, Tuba; Cagiran, Fatma Tanilir; Mavral, Nihal; Kirici, Pinar
    ObjectiveTo investigate the relationship between follicular fluid pentraxin 3 (PTX-3) levels and ovarian response, embryo quality, and insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS) undergoing IVF/ICSI.MethodsA total of 130 women were enrolled and categorized into three groups: lean PCOS (n = 43), overweight PCOS (n = 42), and unexplained infertility (UEI, n = 45). Patients with endocrine disorders, chronic inflammatory diseases, or recent hormonal therapy (within 3 months) were excluded. Follicular fluid (FF) and serum PTX-3 levels were measured using ELISA. Subgroup analyses were performed according to BMI and HOMA-IR status. Correlations between FF PTX-3 and clinical, hormonal, and embryological parameters were assessed. ROC curve analysis and multivariate linear regression were used to evaluate the diagnostic and predictive value of FF biomarkers for follicular output rate (FORT).ResultsFF PTX-3 levels were significantly higher in both lean (23.31 +/- 1.33 ng/mL) and overweight PCOS patients (12.54 +/- 1.05 ng/mL) compared to UEI controls (7.01 +/- 0.54 ng/mL; p = 0.029). Notably, PTX-3 remained elevated in lean PCOS despite a lower BMI, supporting its role in intrinsic ovarian inflammation. FF PTX-3 showed significant positive correlations with total testosterone (r = 0.580), AFC (r = 0.598), and oocyte count (r = 0.532), but was inversely associated with high-quality embryo number (r = - 0.482), 2PN count (r = - 0.312), and FORT (r = - 0.418). ROC analysis demonstrated moderate diagnostic performance of PTX-3 for predicting suboptimal FORT (AUC = 0.77; cut-off: 20.4 ng/mL). In multivariate analysis, FF PTX-3 (beta = - 0.65, p = 0.001), TSG-6 (beta = - 0.42), and ITI (beta = - 0.37) were independent negative predictors of FORT, while AFC was positively associated.ConclusionElevated follicular PTX-3 levels are linked to hyperandrogenism and ovarian reserve in PCOS, but may impair embryo quality and functional follicular response. PTX-3 may serve as a potential biomarker of ovarian inflammation and compromised oocyte competence, independent of BMI or systemic insulin resistance.