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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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    Noninvasive assessment of classic and high PPROM using cervicovaginal podocalyxin and nephrin: Findings from a prospective observational study
    (Lippincott Williams and Wilkins, 2025) Kali, Zercan; Karli, Pervin; Karabulut, Ümran; Çağiran, Fatma Tanilir; Kirici, Pinar; Ege, Serhat
    This study assesses the diagnostic and prognostic value of cervicovaginal amniotic fluid (CVAF) podocalyxin (PDX) and nephrin levels in pregnancies with classic and high preterm premature rupture of membranes (PPROM), focusing on neonatal outcomes. This prospective study included 144 singleton pregnancies between 22 and 34 weeks, classified as classic PPROM (n = 74), high PPROM (n = 32), and controls (n = 38). CVAF and serum samples were analyzed using enzyme-linked immunosorbent assay to quantify PDX and nephrin levels. Receiver operating characteristic curves evaluated diagnostic performance. Logistic regression identified predictors of respiratory distress syndrome and bronchopulmonary dysplasia. CVAF PDX and nephrin levels were significantly higher in the classic PPROM group (35.05 ± 5.55 and 12.88 ± 3.85 ng/mL, respectively) compared to high PPROM and control groups. Receiver operating characteristic analysis demonstrated excellent diagnostic performance for distinguishing classic PPROM, with area under the curve values of 0.92 (95% confidence interval [CI]: 0.88–0.96) for PDX and 0.93 (95% CI: 0.89–0.97) for nephrin. In multivariable logistic regression, elevated PDX was independently associated with bronchopulmonary dysplasia (odds ratio = 1.32, 95% CI: 1.10–1.59), while elevated nephrin predicted respiratory distress syndrome (odds ratio = 1.18, 95% CI: 1.02–1.36). These findings support their utility as noninvasive biomarkers for both diagnosis and risk stratification in PPROM. CVAF PDX and nephrin demonstrated significant diagnostic and prognostic value in differentiating PPROM subtypes and may be useful for neonatal risk stratification. These findings suggest that CVAF PDX and nephrin levels may serve as noninvasive tools for early identification of high-risk PPROM cases, potentially guiding timely intervention and targeted neonatal care. © 2025