Search Results (11,868)

Amniotic oxidative stress in women with vaginal infection but no documented intra-amniotic infection has received little attention. In this prospective cohort study of 90 women undergoing elective cesarean delivery, 45 had symptomatic, culture- or Nugent-confirmed vaginal infection and 45 were asymptomatic controls. Amniotic fluid advanced oxidation protein products (AOPP) and malondialdehyde (MDA) were measured by commercial ELISA. Both were higher in the infection group (median 7.96 versus 5.77 ng/mL and 12.49 versus 7.73 nmol/mL, both p < 0.001), with lower cord blood pH (p = 0.003) and more frequent neonatal intensive care unit (NICU) admission (26.7% versus 4.4%, p = 0.007). AOPP was associated with NICU admission (area under the curve 0.917, 95% CI 0.777 to 0.999), although this rests on 14 events with thresholds derived and evaluated in the same sample. Elevations were largest in the bacterial vaginosis and aerobic bacterial subgroups, but the etiologies did not differ. Both kits were designed for serum and are not validated for amniotic fluid, and 16.7% of MDA measurements fell outside the calibration range, so the MDA results are semi-quantitative. Vaginal infection at cesarean delivery is associated with higher amniotic oxidative stress markers; these findings are exploratory and require external validation. Full article

Background: Fetal growth restriction (FGR) is associated with placental dysfunction and adverse perinatal outcomes. Although insulin-like growth factor-1 (IGF-1) signaling is important for placental and fetal development, the mRNA expression, immunopositivity and potential biological significance of specific IGF-1 isoforms in FGR remain incompletely characterized. This study investigated placental IGF-1Eb mRNA expression and immunopositivity in FGR pregnancies compared with appropriate-for-gestational-age (AGA) pregnancies. Methods: A total of 62 third-trimester human placentas were analyzed, including 47 from pregnancies complicated by FGR and 15 from pregnancies with AGA fetal growth. The mRNA expression of the IGF-1Eb isoform was assessed by reverse-transcription quantitative PCR in a subset of 28 fresh placental samples. IGF-1Eb protein immunoreactivity was assessed in paraffin-embedded tissue sections. Histopathological lesions were classified according to the Amsterdam criteria, and associations with clinical, demographic, and pathological parameters were evaluated using appropriate statistical analyses. Results: IGF-1Eb mRNA expression did not differ significantly between the FGR and AGA groups. In contrast, significant differences in IGF-1Eb immunoreactivity were observed in selected placental compartments. Moderate immunoreactivity in the perivillous syncytiotrophoblast was more frequent in FGR placentas and was associated with histological features of maternal vascular malperfusion, as well as with gestational age, neonatal birth weight, placental weight, maternal body mass index, and fetal sex. Increased IGF-1Eb immunopositivity was also observed in the endothelium of maternal decidual and fetal villous vessels in FGR placentas. No significant differences were observed in IGF-1Eb immunoreactivity in the extravillous trophoblast. Conclusions: In this observational study, placental IGF-1Eb protein immunoreactivity, but not mRNA expression, differed between FGR and AGA pregnancies in selected placental compartments. These findings indicate compartment-specific differences in IGF-1Eb protein immunoreactivity, associated with FGR and placental pathological features. However, the observational and cross-sectional design does not establish causality or a functional role for IGF-1Eb in placental dysfunction. Larger prospective studies incorporating functional validation are required to clarify the biological significance of these findings. Full article

Background: Romania has one of the highest cervical cancer incidence and mortality rates in the European Union (EU) and one of the lowest levels of screening participation. We examined eight years of screening activity at an accredited centre in Bihor County, north-western Romania, encompassing the pre-pandemic period (2018–2019), the COVID-19 pandemic (2020–2021), the post-pandemic recovery (2022–2023) and the transition from primary cytology to primary human papillomavirus (HPV) DNA screening (2024–2025). Methods: This retrospective, single-centre study included 17,807 de-identified screening-episode records collected between 2018 and 2025 at Pelican Clinical Hospital, Oradea. Cytology was the primary screening test in the cytology era (2018–2023), whereas high-risk HPV (HR-HPV) DNA testing (cobas HPV Test, Roche, Pleasanton, CA, USA) with reflex cytology was used in the HPV-primary era (2024–2025). Screening activity was expressed relative to the provider’s registered administrative catchment of 65,978 women. Because quarterly counts were markedly overdispersed, changes in screening volume were analysed using negative-binomial incidence-rate ratios (IRRs) and a segmented negative-binomial interrupted time-series; cytological positivity was evaluated using age-adjusted logistic regression and the Cochran–Armitage trend test. Results: The number of screening episodes recorded over eight years corresponded to 27.0% (95% confidence interval [CI] 26.6–27.3) of the registered catchment, while annual throughput never exceeded 5.2%. Mean monthly screening volume declined from 264.5 tests in the pre-pandemic period (2018–2019) to 88.6 during the pandemic (2020–2021; IRR 0.335, 95% CI 0.177–0.634; 66.5% reduction; p < 0.001), corresponding to an estimated deficit of approximately 3700 tests; the interrupted time-series estimated an immediate 86% reduction at lockdown onset. Activity recovered to 61% of the pre-pandemic rate during the post-pandemic recovery (2022–2023; IRR 0.614, 95% CI 0.482–0.783) and to 90% in the HPV-primary era (2024–2025; IRR 0.898, 95% CI 0.733–1.100), coinciding with the transition to primary HPV screening. All primary HPV tests produced valid results, compared with an annual unsatisfactory-sample rate of 2.9–4.2% during primary cytology. Cytological positivity remained stable during 2018–2023, and the cytological high-grade squamous intraepithelial lesion (HSIL) detection rate per 1000 screened did not change significantly during the pandemic, although absolute HSIL detections declined with screening volume. In 2024–2025, HR-HPV positivity was 22.8% (1301/5700; 95% CI 21.8–23.9), and 47.9% of HPV-positive women had abnormal reflex cytology. Conclusions: The pandemic substantially reduced screening activity at a provider already operating with low throughput relative to its registered catchment. Activity subsequently returned to near pre-pandemic levels during the period coinciding with the introduction of primary HPV screening, which also improved primary-sample adequacy. However, the absence of persistent patient linkage and of follow-up data from colposcopy, histology and treatment precluded estimation of population-based coverage, screening intervals and detection of histologically confirmed cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The findings support population-based invitation and recall, clearly defined age-specific screening and follow-up algorithms, self-sampling, targeted catch-up after pandemic-related delays and longitudinal evaluation using histologically confirmed CIN3+ as the principal clinical endpoint. Full article

Background: Congenital heart block (CHB) is a severe disorder, with an estimated incidence of 1 in 20,000 live births. In most cases, the underlying pathophysiology involves transplacental transfer of maternal anti-Ro/SSA and/or anti-La/SSB antibodies, which are thought to bind to L-type calcium channels on fetal cardiac conduction cells, triggering apoptosis and initiating an inflammatory response that ultimately leads to destruction of the conduction system. Case presentation: We report a case of a dichorionic diamniotic twin pregnancy in which one fetus exhibited complete heart block in the 21st week of gestation, whereas the co-twin showed no abnormalities. The maternal history was notable for multiple autoimmune disorders among first- and second-degree relatives. Serological testing revealed markedly elevated titers of anti-SSA autoantibodies. Following parental decision, the pregnancy was terminated. Macroscopic evaluation of the affected fetal heart showed ventricular dilation, while histopathological examination demonstrated fibrotic and degenerative changes as well as focal calcification in the atrioventricular junctional region. In contrast, the cardiac conduction system of the unaffected fetus was preserved. Discussion: Fetuses of seropositive mothers have a 2–5% first-event risk of developing CHB during gestation. The available literature suggests that the underlying pathophysiology in discordant twin pregnancies likely reflects unequal placental transfer of antibodies in combination with subtle differences in fetal susceptibility and local immune responses. Conclusions: This case illustrates the unpredictable course of anti-SSA-associated CHB in twin pregnancies and highlights the importance of careful fetal cardiac surveillance in seropositive women, even in the absence of a clinically apparent autoimmune disease. Furthermore, the comprehensive histopathological documentation provides additional insight into the pathological basis of CHB. Full article

Background/Objectives: Obesity and excessive gestational weight gain (EGWG) are known risk factors for adverse outcomes in pregnancy, but the comparative risk is less well defined and increasingly relevant in an era of increasing use of weight loss medications. We aimed to determine whether EGWG was associated with adverse maternal and neonatal outcomes, compared with prepregnancy obesity. Methods: Multicenter retrospective cohort study of pregnant patients who delivered a singleton within a single university health system from 2019–2024. Patients with missing prepregnancy body mass index (BMI) data, BMI < 18.5 kg/m², or pregestational diabetes were excluded. Logistic regression with propensity score weights and g-computation were used to evaluate if the incidence of several adverse maternal and neonatal outcomes were impacted by prepregnancy obesity and gestational weight gain (GWG). p values were adjusted for multiple comparisons. Results: Among the 129,615 pregnancies included, 28,516 (22.0%) had prepregnancy obesity, 36,943 (28.5%) were overweight prior to pregnancy, and 64,156 (49.5%) had a normal BMI prior to pregnancy. When compared to patients with obesity, patients with normal prepregnancy BMI and EGWG had a lower risk of adverse maternal and neonatal outcomes, including gestational diabetes, gestational hypertension, preeclampsia, eclampsia, cesarean delivery, and postpartum hemorrhage, as well as large and small for gestational age birthweight, stillbirth, neonatal intensive care unit admission, neonatal mechanical ventilation, respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and sepsis. Beneficial effects were attenuated for patients with overweight prepregnancy BMI or for larger EGWG. Conclusions: Lower prepregnancy BMI, even with the potential unintended consequence of EGWG, may be more favorable than untreated prepregnancy obesity with regard to perinatal outcomes. Full article

Background/Objectives: Individuals with 46,XY disorders of sexual development (DSD) present with incomplete genital masculinization, aberrant gonadal development, and occasional retention of Müllerian duct remnants. Genetic factors play a substantial role in DSD pathogenesis, and whole-exome sequencing has expanded the catalog of candidate variants in recent years. However, the underlying molecular pathways remain incompletely characterized, and the functional relevance of most isolated genetic findings has not been systematically determined. This study aimed to identify and functionally characterize novel NR5A1 variants in DSD. Methods: A heterozygous missense variant NR5A1 c.88T>A (p.Cys30Ser) was identified in two patients with DSD, and initial functional characterization of the variant was performed via immunofluorescence analysis, Western Blotting, RNA sequencing, and quantitative real-time PCR analysis. Results: Wildtype NR5A1 protein localized predominantly to the nucleus, whereas the p.Cys30Ser mutant exhibited dual nuclear and cytoplasmic distribution. Compared with the wildtype, the p.Cys30Ser variant altered the expression of 642 genes, with differentially expressed genes primarily enriched in the neuroactive ligand–receptor interaction pathway. The variant impaired the transactivation of canonical NR5A1 downstream targets, resulting in the marked downregulation of 560 genes including key regulators such as KISS1R, CYP11A1, STAR, GABRP, and GRAMD1D. Conclusions: This study is the first to identify and functionally characterize the NR5A1 p.Cys30Ser variant in the context of DSD. Our findings broaden the mutational spectrum of NR5A1-related DSD and provide new insights into the molecular genetic basis of sexual development disorders. Full article

Background: This study aims to investigate the impact of chronic endometritis (CE) diagnosis and treatment on pregnancy outcomes during hysteroscopic fallopian tube catheterization combined with laparoscopy in infertility patients with pelvic endometriosis (EMS) and proximal tubal obstruction (PTO). Methods: A retrospective study was conducted between July 2020 and March 2022, including patients with PTO who underwent hysteroscopy–laparoscopy. CE was diagnosed via CD138 immunohistochemical staining and treated with oral doxycycline. The study further assessed the prevalence of CE and evaluated the effect of its diagnosis and treatment on pregnancy outcomes. Results: A total of 454 participants with PTO were enrolled, of whom 158 had concomitant pelvic EMS. Among EMS patients, 78 underwent CD138 staining for CE diagnosis (Group A), while the rest were classified as Group B. The incidence of CE in Group A was 62.8%. These affected individuals were treated with doxycycline. The natural pregnancy rate was significantly higher in Group A than Group B (46.2% vs. 26.3%, p = 0.009). The clinical pregnancy rate and live birth rate were higher in Group A, although the differences were not statistically significant. Additionally, Group A demonstrated a significantly higher cumulative natural pregnancy rate (p < 0.05). Notably, the diagnosis and treatment of CE emerged as a protective factor for cumulative natural pregnancy (HR, 1.78; 95% CI, 1.06–2.97; p = 0.028). Conclusions: In infertility patients with pelvic EMS complicated by PTO undergoing hysteroscopic tube catheterization combined with laparoscopy, prioritizing the diagnosis and treatment of CE is crucial for enhancing natural pregnancy outcomes. Full article

Background/Objectives: Hodgkin lymphoma (HL) and primary mediastinal B-cell lymphoma (PMBCL) affect young women, with cure rates exceeding 80%. Treatment-related gonadal insufficiency is recognized for its impact on fertility, yet fertility preservation remains underutilized, and prospective data are limited. The aim of this study is to prospectively evaluate gonadal function in women ≤40 years old with lymphoma undergoing chemotherapy. Methods: Ovarian reserve and endocrine ovarian function were evaluated by sequential measurements of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), progesterone, and estradiol at diagnosis, during, and after chemotherapy. Results: 81 female patients ≤40 years old were enrolled, including 53 with HL and 28 with NHL (16 with PMBCL). HL patients had significantly lower AMH values for their respective age group compared to all other diagnoses (p = 0.05), which was more striking for patients ≤30 years old (p = 0.039), indicating pre-existing reduced ovarian reserve in HL. In HL, both FSH and AMH levels indicate gonadal dysfunction for at least six months post-chemotherapy, with AMH serving as a more sensitive biomarker than FSH. For PMBCL patients treated with R-DA-EPOCH, AMH suppression was noticed, with no evidence of recovery up to 18 months post-treatment. At all time points, the PMBCL patients had significantly lower AMH values compared to the HL patients (AMH6: p = 0.03, AMH12 and AMH18: p = 0.05). AMH emerged as the most sensitive marker of ovarian damage, with pretreatment levels <7 pmol/L predicting impaired ovarian reserve in HL patients. Conclusions: For HL, the pretreatment cut-off of 7 pmol/L could discriminate patients with ovarian insufficiency post-treatment, whereas no statistically significant predictive association was identified in PMBCL. These findings require validation in larger cohorts. Full article

Background: Caesarean section is associated with postoperative pain and wound-related morbidity. Topical agents that promote early wound healing may enhance postoperative recovery. This randomized, placebo-controlled clinical trial evaluated the effect of HealFast Silver Ointment on pain and early wound-healing parameters after Caesarean section. Methods: Two hundred women who underwent Caesarean section were randomly allocated into two groups: a placebo group and a HealFast Silver Ointment group, each consisting of 100 women. The intervention was applied topically three times daily for three weeks. Outcomes were assessed at baseline, week 1, and week 3, and included pain intensity using the Visual Analogue Scale, transepidermal water loss, tissue oxygenation assessment, and wound surface morphology using Visioscan. Results: Baseline characteristics were comparable between groups. At week 3, the Visual Analogue Scale score decreased from 8.13 ± 0.93 to 1.33 ± 0.71 in the treated group, compared with 8.15 ± 1.47 to 7.03 ± 1.95 in the placebo group. Transepidermal water loss decreased from 34.13 ± 6.89 to 6.84 ± 3.99 in the treated group, compared with 32.70 ± 6.67 to 30.77 ± 6.69 in the placebo group. O2C increased from 40.08 ± 6.36 to 57.48 ± 7.19 in the treated group, compared with 40.80 ± 6.70 to 45.00 ± 6.84 in the placebo group. Significant time × group interactions were observed for the main clinical and physiological outcomes. Conclusions: HealFast Silver Ointment was associated with reduced postoperative pain, improved epidermal barrier recovery, increased tissue oxygenation, and improved wound surface morphology during the first three weeks after Caesarean section. Larger registered multicenter trials with longer follow-ups are needed to confirm these findings. Full article

Background and Objectives: Type 2 diabetes mellitus (T2DM), visceral adiposity, and hypertension frequently coexist, but their independent associations with carotid intima–media thickness (cIMT) remain uncertain. We compared cardiometabolic profiles by diabetes status and evaluated adjusted associations with cIMT. Materials and Methods: This retrospective cross-sectional study included 147 adults admitted to Clinical CF Hospital Timișoara between 1 July 2025 and 30 June 2026. Bilateral cIMT was available in 141 patients. Group comparisons, Spearman correlation, and heteroscedasticity-robust multivariable linear regression were performed. Results: T2DM was present in 39 patients (26.5%), hypertension in 125 (85.0%), and obesity in 120 (81.6%). Compared with participants without diabetes, those with T2DM had higher homeostasis model assessment of insulin resistance (HOMA-IR; 4.11 vs. 3.08; p = 0.005) and fasting glucose (6.60 vs. 5.06 mmol/L; p < 0.001), but lower total cholesterol (205.2 vs. 225.9 mg/dL; p = 0.009) and non-high-density lipoprotein cholesterol (156.5 vs. 176.6 mg/dL; p = 0.006). These lower lipid values may reflect treatment or other residual confounding and should not be interpreted as an intrinsic T2DM phenotype. Mean cIMT was numerically higher in T2DM (0.619 vs. 0.592 mm; p = 0.284). Visceral fat area correlated with cIMT before adjustment (ρ = 0.237; p = 0.005), but not after adjustment. Age (β = 0.057 mm/decade; p < 0.001) and hypertension (β = 0.046 mm; p = 0.042) retained adjusted associations with cIMT. Conclusions: T2DM identified metabolic dysregulation, whereas age and hypertension showed the strongest adjusted associations with cIMT. Visceral adiposity showed an unadjusted but not independent association, supporting comprehensive cardiovascular risk assessment and rigorous blood pressure management. Full article

Background: Maternal anti-D antibody titers are routinely used for risk stratification in RhD alloimmunization before the development of fetal anemia. However, their association with disease severity and perinatal outcomes among pregnancies that have already progressed to severe fetal anemia requiring intrauterine transfusion (IUT) remains unclear. This study aimed to investigate the association between maternal anti-D antibody titers, disease severity, and perinatal outcomes in pregnancies complicated by severe RhD alloimmunization requiring IUT. Methods: This retrospective cohort study included 38 RhD-alloimmunized pregnancies complicated by severe fetal anemia and managed with IUT at a tertiary referral center between January 2017 and December 2022. Maternal characteristics, anti-D antibody titers, presence of hydrops fetalis, IUT characteristics, delivery data, neonatal outcomes, and mortality were evaluated. Maternal anti-D antibody titers were analyzed in relation to disease severity and perinatal outcomes. Results: Hydrops fetalis was present in 24 fetuses (63.2%). The mean maternal age was 30.3 ± 4.8 years, and the mean gestational age at diagnosis was 23.5 ± 5.8 weeks. Maternal anti-D antibody titers were significantly higher in pregnancies complicated by hydrops fetalis than in non-hydropic pregnancies (p = 0.014). No significant associations were observed between maternal anti-D antibody titers and intrauterine fetal demise, neonatal mortality, neonatal intensive care unit admission, Apgar scores, or the number of IUT procedures. Conclusions: Among pregnancies with severe RhD alloimmunization requiring intrauterine transfusion, higher maternal anti-D antibody titers were associated with hydrops fetalis, suggesting an association with disease severity. However, no statistically significant associations were observed between maternal anti-D antibody titers and other evaluated perinatal outcomes in this high-risk cohort. These findings indicate that, once severe fetal anemia requiring IUT has developed, maternal anti-D antibody titers should be interpreted alongside fetal Doppler surveillance and comprehensive clinical assessment rather than as independent predictors of perinatal prognosis. Full article

Background: Opioid use during pregnancy is linked to preterm birth, fetal growth restriction, and Neonatal Opioid Withdrawal Syndrome. While the placenta is the primary regulator of the uterine environment, the precise molecular mechanisms by which opioids dismantle placental function remain poorly defined. Methods: The transcriptomic landscape of opioid-exposed human placentas from a unique Hawai’i-based cohort was characterized. Results: Transcriptional signatures were defined by genes involved in translational inhibition and metabolic attenuation. Integrative network modeling predicted a prominent stress-signaling hub centered on p38 Mitogen-Activated Protein Kinase and Extracellular Signal-Related Kinase 1/2, paralleling a broad suppression of ribosomal protein transcripts (Ribosomal Protein 27S, -29, and -39). This response was further characterized by the inhibition of the Myelecytomatosis Proto-Oncogene regulatory hub, predicting a loss of mitochondrial phosphate transport through associated genes (via Solute Carrier Family 25A3) and cell-cycle progression (via S-Phase Kinase-Associated Protein 1). Additionally, the genes in this model suggested upregulation of antisense regulatory brakes, such as RAP2C Antisense RNA 1, which might further reinforce this inhibitory state. Conclusion: The findings suggest that prenatal opioid exposure is associated with the disruption of placental homeostasis. This may be coordinated by protein synthesis and bioenergetic flux, as inferred from the modeled eukaryotic Translation Initiation Factor-mediated Integrated Stress Response. These findings establish a localized, clinical baseline of human placental stress, highlighting candidate molecular regulatory nodes to guide future mechanistic studies and biomarker discovery in exposed pregnancies. Full article

Background/Objectives: MicroRNAs released into spent culture medium (SCM) may reflect embryo developmental status, but their relationship with blastocyst morphology and time-lapse morphokinetic behavior remains incompletely understood. This prospective study aimed to investigate whether selected SCM microRNAs are associated with blastocyst morphological grade and early morphokinetic dynamics in human embryos. Methods: A total of 432 SCM samples were collected from embryos cultured in a time-lapse incubation system between October 2018 and July 2020. Blastocysts were classified as good, fair, or poor quality according to morphological grading. The expression levels of six candidate microRNAs, including miR-182-5p, miR-302a-3p, miR-372-3p, miR-373-3p, miR-518a-3p, and miR-519d-3p, were quantified using real-time quantitative polymerase chain reaction. Associations between microRNA expression, embryo morphology, and morphokinetic parameters were analyzed using GEE, multivariate logistic regression, and receiver operating characteristic (ROC) analysis. Results: After accounting for within-patient clustering using GEE, good-quality embryos showed significantly lower expression of miR-372-3p and miR-373-3p than poor-quality embryos. On multivariate logistic regression, lower miR-372-3p expression remained independently associated with optimal t5–t2 interval after adjustment, whereas its associations with optimal CC3 and the combined outcomes were attenuated. ROC analysis demonstrated modest discriminatory ability for miR-372-3p alone (AUC = 0.644), whereas embryo morphology alone achieved an AUC of 0.731, and the combined model incorporating morphology and miR-372-3p reached the highest AUC of 0.752. Conclusions: These findings suggest that SCM microRNA expression is associated with embryo development. In particular, reduced miR-372-3p expression may reflect more favorable blastocyst morphology and early developmental dynamics, supporting its potential as an adjunctive molecular indicator of embryo quality. Further validation incorporating embryo ploidy status and clinical outcomes is warranted before clinical application. Full article

Background: Abnormal uterine bleeding (AUB) caused by adenomyosis can result in significant iron-deficiency anemia. Given that transvaginal ultrasound (TVUS) is commonly performed during routine examinations, its assessment may facilitate preemptive treatment. Methods: In this study, TVUS images from patients with surgically confirmed adenomyosis were preprocessed to minimize intra- and inter-scan variability. Radiomics features were extracted using PyRadiomics to train automated machine-learning classifiers under k-fold nested cross-validation. Multiple dataset configurations were evaluated, including feature extraction from a custom region-of-interest (ROI) of the uterine corpus, whole-image features adjusted for uterine size, and supplementary variables from complete blood counts (CBC). Results: Radiomics-centered models demonstrated modest discrimination (mean accuracy 0.606–0.618). While incorporating CBC variables with radiomics features substantially improved performance compared to radiomics alone, models trained exclusively on CBC data yielded overall higher results. Conclusions: These findings indicate that quantitative features derived from routine TVUS provide modest complementary information for predicting anemia. While they do not offer clear incremental value when highly discriminatory clinical data (CBC) are available, TVUS radiomics may serve as a supplementary diagnostic tool in settings where blood tests are incomplete or unavailable. Further validation in larger, multi-institutional cohorts with patient-level separation is warranted. Full article