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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
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    Prediction of Possible Adverse Effects of Gestational Diabetes Mellitus on Maternal and Fetal Glomeruli by Urine and Amniotic Fluid Podocyte Degradation Products
    (Mdpi, 2024) Cagiran, Fatma Tanilir; Mavral, Nihal; Kali, Zercan; Kirici, Pinar
    Objectives: To compare the levels of podocyte damage markers nephrin and podocalyxin in urine samples taken at the time of gestational diabetes mellitus (GDM) diagnosis and at birth. Amniotic fluid podocalyxin (pdx) and nephrin levels were also analyzed to determine whether GDM had an impact on fetal glomeruli. Methods: A total of 50 patients, including 24 patients diagnosed with gestational diabetes and 26 healthy pregnant women whose gestational weeks were matched, were included in the study. GDM was diagnosed with a 75 g oral glucose tolerance test (OGTT). Fresh morning urine samples from patients diagnosed with GDM were collected. The second urine sample was collected with the help of a catheter during birth. Amniotic fluid samples were taken from patients who gave birth by cesarean section. The urinary podocalyxin and nephrin levels were measured via the quantitative sandwich enzyme immunoassay. Albumin-creatinine ratio (uACR) was also calculated in urine samples. Results: Urinary nephrin and pdx levels on the day of GDM diagnosis were similar in the GDM and control groups. Microalbuminuria was detected in only one patient from each group at the time of GDM diagnosis. In the urine samples taken from the time of birth, pdx and nephrin levels of the GDM group were significantly higher than the control group (p < 0.001 for each). While microalbuminuria was detected in five patients (20.8%) at the time of birth in the GDM group, it was detected in only two patients (7.7%) in the control group. In the GDM group, a significant increase was detected between the urine pdx and nephrin levels measured at diagnosis and those measured at birth. In the control group, measurements at baseline and at birth were similar. There was no significant difference between the GDM and control groups in terms of amniotic fluid pdx and nephrin levels. A positive and significant correlation was detected between urinary pdx, nephrin, SBP, and uACR. Conclusions: While GDM triggers podocyte damage in maternal glomeruli, it does not cause significant change in fetal glomeruli.
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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.