Search Results (131)

Objectives: To evaluate perinatal, obstetric, and early functional outcomes following totally percutaneous fetoscopic repair of open spina bifida (OSB) using the skin-over-biocellulose for antenatal fetoscopic repair (SAFER) technique. Methods: This retrospective cohort study included all fetuses who underwent totally percutaneous fetoscopic repair of OSB at a single tertiary referral center between September 2018 and March 2026. Eligibility was based on predefined clinical criteria. Data on maternal, fetal, operative, and neonatal outcomes were collected. The primary outcomes included perinatal and obstetric results, need for cerebrospinal fluid (CSF) diversion within the first year of life, and early functional outcomes, including motor improvement and ambulation. Exploratory analyses were performed to assess associations between procedural factors and obstetric outcomes. Results: Twenty-two fetuses underwent fetoscopic repair. The procedure was completed in 95% of cases. Median gestational age at surgery was 28.2 weeks. Preterm prelabor rupture of membranes (PPROM) occurred in 68% of cases, and the median gestational age at delivery was 32.7 weeks. All fetuses were live-born, with no neonatal deaths. Maternal outcomes were favorable, with no maternal mortality and no ICU admissions. Vaginal delivery was achieved in 50% of cases, with no uterine rupture or dehiscence. The rate of CSF diversion within the first year was 31.8%. Reversal of hindbrain herniation was observed in 95% of cases. A motor improvement of ≥2 levels was achieved in 68% of patients, with no cases of functional deterioration. Community ambulation at ≥24 months was observed in 53% of cases with available follow-up. Conclusions: Totally percutaneous fetoscopic repair of OSB using the SAFER technique was associated with favorable perinatal, obstetric, and early functional outcomes in this single-center cohort. The high incidence of PPROM and subsequent preterm delivery remains an obstetrical challenge. Maternal safety profile, including the preservation of uterine integrity for vaginal delivery, and the early neurological benefits were encouraging. Our results support the feasibility of this approach and highlight the absolute necessity of multidisciplinary expertise and structured training. Full article

Background: Mechanical trauma during pregnancy from motor vehicle accidents, falls, and maternal seizures poses significant risks to fetal development. The fetus is protected by multiple hierarchical layers including the uterine wall, amniotic fluid, and cerebrospinal fluid surrounding the brain. Despite the clinical significance of maternal trauma occurring in approximately six to eight percent of pregnancies, previous computational studies have focused primarily on amniotic fluid protection while treating the fetus as a homogeneous structure, without examining the nested protective architecture comprising both amniotic fluid and cerebrospinal fluid as an integrated system. Methods: This investigation implements a nested fluid–structure interaction framework simultaneously capturing three hierarchically organized systems: the uterine wall interacting with amniotic fluid, amniotic fluid interacting with the fetal body, and the cranial system comprising skull, cerebrospinal fluid, and brain tissue. The computational architecture employs smoothed particle hydrodynamics for fluid domains coupled with finite element methods for solid structures. Boundary conditions representing traumatic forces were obtained through experimental protocols using an instrumented medical simulation mannequin performing seizure movements. Results: Computational simulations predicted that amniotic fluid absorbed the majority of impact forces through hydraulic cushioning, while cerebrospinal fluid provided additional stress reduction through pressure redistribution, with model predictions suggesting total stress reduction exceeding ninety percent. Peak fetal brain stress values predicted by the model were below injury thresholds reported in adult neural tissue literature, though direct applicability of these thresholds to fetal tissue remains uncertain. The fetal brain exhibited minimal movement relative to the skull despite complex force cascades. Stress distributions showed elevated values in the frontal lobe and brainstem, though magnitudes remained within ranges that the model suggests may be tolerable. Conclusions: Computational modeling suggests that the nested fluid protection architecture operates as an integrated hierarchical system providing potential mechanical protection through sequential energy dissipation. These findings represent model predictions requiring experimental and clinical validation before translation to clinical practice. Full article

Repeat breeder (RB) cows fail to conceive after three or more breeding attempts, yet the uterine factors contributing to this condition remain unclear. Here, we compared uterine fluid composition, endometrial cell responses to uterine fluid, and uterine microbiota between normal pregnant (Normal) and RB cows. Uterine fluid was collected from multiparous Holstein cows classified as Normal (n = 5; conception within three breeding attempts) or RB (no conception after four attempts); RB cows were classified as RB-Rec (n = 4; conceived after uterine lavage) or RB-NoRec (n = 3; did not conceive after uterine lavage). Uterine fluids were applied to bovine endometrial cells, and microbiota composition was analyzed. Concentrations of lipopolysaccharide in the uterine fluid did not differ between the three groups, and uterine fluid from both RB groups significantly increased C-X-C motif chemokine ligand 8 secretion relative to the Normal group. RNA-seq revealed distinct endometrial cell responses to RB-NoRec uterine fluid, with enrichment of immune-related pathways including phagosome, ferroptosis, and cellular senescence. Uterine microbiota profiles differed among groups, with short-chain fatty acid-producing genera (e.g., Fusicatenibacter and Dorea) predominant in Normal cows and inflammation-associated genera (e.g., Trueperella and Helicobacter) predominant in RB-NoRec cows. These data indicate that uterine fluid properties and microbiota composition vary with reproductive status and may modulate endometrial immune activation associated with fertility outcomes. Full article

Prostaglandin E₂ (PGE₂) plays a critical role in regulating uterine endometrial function and supporting embryonic development during early pregnancy in ruminants. However, its precise roles in shaping the uterine microenvironment remain unclear. Herein, 1 mg PGE₂ was infused daily into the uterus of dairy heifers from days 12 to 14 of the estrus cycle. ULF was subsequently collected for integrated proteomic, metabolomic, and targeted lipidomic analyses. In addition, bovine endometrial epithelial cells were used to evaluate the effects of PGE₂ on epithelial adhesion and responsiveness to interferon tau (IFNT). PGE₂ infusion resulted in 909 differentially abundant proteins (DAPs), which are primarily associated with early embryonic development, immune regulation, and cell adhesion. Untargeted metabolomics analysis identified 587 altered metabolites, which were enriched in sphingolipid, arachidonic acid, phenylalanine, and tryptophan metabolism. Proteomic–metabolomic analyses showed that these alterations were primarily associated with early embryonic development, immune regulation, and cell adhesion. Targeted lipidomic analysis showed a global reduction in lipid accumulation, with glycerophospholipid metabolism and choline metabolism most significantly affected. In vitro, PGE₂ reduced epithelial microvilli density, increased osteopontin (OPN) expression, and decreased the expression of junctional proteins (zona occludens-1 (ZO-1), E-cadherin (CDH1), and fibronectin 1 (FN1)). Moreover, PGE₂ enhanced the responsiveness of bEECs to IFNT by interferon alpha/beta receptor 1 (IFNAR1) and IFNAR2, and prostaglandin E receptor 4 (PTGER4) was identified as the primary receptor mediating this response. Collectively, these findings suggest that PGE₂ may modulate lipid metabolism and adhesion-related processes in the endometrium and influence endometrial responsiveness to IFNT, providing insights into molecular mechanisms associated with pregnancy establishment in dairy cows. Full article

With the rapid development of omics technologies, metabolomics and lipidomics have become important tools for elucidating the molecular basis of reproductive performance in livestock. These approaches, which focus on small metabolites and lipid species, provide valuable insights into dynamic interactions between genes, proteins, and the environment, offering a high level of sensitivity. This review summarizes key methodological advances in metabolomics and lipidomics and their applications to gametogenesis, oocyte maturation, embryo development, and pregnancy maintenance. It highlights how metabolic and lipid pathways, particularly those involving energy metabolism, redox regulation, lipid remodeling, and cell–cell signaling, affect reproductive cell quality. This review further integrates biomarkers identified from semen, follicular fluid, oocytes, embryos, and uterine tissues, highlighting their potential roles in fertility assessment. Together, these insights enhance our understanding of metabolic regulation in reproduction and support the effective application of metabolomics and lipidomics in improving livestock fertility. Full article

Endometriosis is a common gynecological pathology, with an incidence of nearly 10% in patients of reproductive age, and is still underdiagnosed. A thorough and well-spread diagnostic study of endometriosis based on epigenetic factor dysregulation can highlight potential areas for improvement. To quantify the potential and utility of non-invasive tools in the early diagnosis of endometriosis, an overview of current knowledge on epigenetic factors, based on DNA and RNA, is presented. Among these tools, it is important to highlight the role of miRNAs (microRNAs), cfDNA (cell-free DNA), and rRNAs (ribosomal RNAs), which are small molecules involved in endometriosis and numerous other pathologies. To evaluate their potential and utility in endometriosis, a salivary miRNA diagnostic test was conducted, the cfDNA methylation patterns of fragmented DNA circulating in bodily fluids (e.g., plasma) were analyzed, and cervical and uterine microbiomes were profiled for bacterial rRNA in patients with clinical suspicion of incipient endometriosis. Specific molecular profiles associated with endometriosis were analyzed. The first profile, a 109-miRNA saliva signature, was validated as a product of miRNA biomarkers and artificial intelligence modeling. In addition, peripheral blood cfDNA methylation biomarkers were identified by investigating nine genes in a molecular signature that requires validation. A profile was also obtained from cervical swabs and uterine washes, including molecular analysis of 16S rRNA amplicon sequencing to evaluate alterations in the cervical bacterial community. This review aims to optimize the integration of a non-invasive diagnostic tool for early endometriosis diagnosis. Genetic biomarkers can be correlated with clinical factors to improve diagnostic accuracy. Of the assessed diagnostic tools, salivary miRNA tests, a peripheral blood cfDNA methylation biomarker, and a microbiome rRNA signature may be useful for early diagnosis of endometriosis, as well as, implicitly, therapeutic attitude and follow-up. Full article

Endometrial cancers (ECs) are mainly adenocarcinomas arising from the uterine endometrium. In this work, we employed data-independent acquisition (DIA) mass spectrometry (MS)-based label-free quantification (LFQ-MS) proteomics to analyze the proteome of tissue washings collected from 25 control (CTRL) subjects, 25 patients with low-grade type 1 endometrial cancer (EC), and 24 patients with high-grade type 1 EC. Following quantification and statistical analysis, we identified 42 proteins able to discriminate CTRL from EC patients, and 151 proteins differentiating high-grade EC cases from low-grade EC cases. Notably, PRRC2A and SYDE2 effectively distinguished both EC patients from controls and advanced EC cases from low-grade EC cases. Validation by Western blot analysis in an independent cohort comprising 19 CTRL patients, 19 patients with low-grade EC, and 19 patients with high-grade EC confirmed the upregulation of PRRC2A and SYDE2. These proteins are implicated in the translocation of SLC2A4, the regulation of MECP2, and extracellular matrix (ECM) proteoglycan pathways, all of which are associated with tumor growth. Our results demonstrate that DIA-based proteomic analysis of tissue washings enables the identification of potential biomarkers for endometrial cancer (EC). Moreover, this study highlights tissue washings as a promising biological fluid for biomarker discovery in EC. Full article

Uterus masculinus is a rare disorder of sexual development in males, characterized by the presence of tubular female genitalia. Diagnostic imaging reports of infected uterus masculinus are limited. We describe the ultrasonographic and computed tomographic findings in three dogs, all presenting with abdominal distension, pain, and systemic infection. Imaging consistently revealed a fluid-filled, bicornuate structure arising from the prostate. In two dogs, the horns extended through the inguinal rings to the scrotal testes; in the third, with a prior left orchiectomy, both horns were intra-abdominal, the right ending in a peritoneal mass. Surgery and histopathology confirmed infected uterus masculinus, with Escherichia coli isolated from urine in all dogs and from the structure in two. Two dogs had Leydig cell tumors, one with concurrent uterine neoplasia; the third had an ovarian or ovotesticular granulosa cell tumor. Although rare, infected uterus masculinus is potentially life-threatening and should be considered in male dogs with abdominal pain, distension, or systemic infection. This is the first case series describing combined ultrasonographic and tomographic features of infected uterus masculinus, including novel findings such as cervix-like mural narrowing and fluid–fluid levels. It is also the first imaging description of an ovarian or ovotesticular tumor in a dog with uterus masculinus. Full article

Endometriosis impairs fertility by interfering with ovarian function, embryonic development, and endometrial receptivity. Extracellular vesicles (EVs) are recognised as non-invasive biomarkers that may indicate biological processes based on their lipid, protein, and microRNA composition. This narrative review synthesises current data on extracellular vesicle (EV) signatures in serum/plasma, menstrual blood, follicular fluid, and uterine fluid in endometriosis patients using assisted reproductive technology (ART). We highlight critical EV-mediated processes, such as progesterone signalling, fibrosis, angiogenesis, inflammation, and metabolism, and their associations with oocyte competence, embryo development, and implantation. Certain EV-miRNA profiles, including miR-22-3p, miR-320a, the miR-200 family, and miR-145-5p, have shown use for diagnostic and prognostic purposes in various investigations. These characteristics are associated with live birth, implantation, and blastocyst quality. We propose a clinical framework that incorporates (i) menstrual-blood EVs for non-invasive endotyping, (ii) serum/plasma EV profiling for baseline risk stratification, and (iii) pre-transfer uterine-fluid EV evaluation to inform embryo-transfer decisions. Translation requires standardisation, cycle phase control, and prior validation. EVs may serve as a beneficial instrument for personalised in vitro fertilisation operations for ladies experiencing infertility due to endometriosis. Full article

Background: Preterm birth (PTB) remains a leading cause of neonatal morbidity and mortality worldwide. Inflammatory cytokines, particularly IL-6, are central to PTB pathogenesis. Lactoferrin (LF), an iron-binding glycoprotein with antimicrobial and immunomodulatory properties, has been proposed as a potential protective factor against PTB. This narrative review aimed to synthesize current evidence on LF supplementation and its effects on inflammation, cytokine modulation, biochemical markers, and obstetric outcomes related to PTB. Methods: Eight clinical studies involving pregnant women at risk of PTB were included. LF was administered orally, vaginally, or through combined regimens, with variations in dosage and duration. Reported outcomes encompassed inflammatory markers, cervical and uterine parameters, oxidative stress biomarkers, and obstetric or neonatal endpoints. Results: Across the studies, LF supplementation was consistently associated with reduced pro-inflammatory cytokines, improvements in cervical length and uterine activity, and favorable changes in oxidative stress markers. Clinically, supplementation was linked with prolonged gestation, fewer preterm births, and reduced neonatal intensive care admissions. Immunological analyses further suggested a positive modulation of cytokine profiles in amniotic fluid. Conclusions: LF appears to exert multifaceted immunomodulatory effects that mitigate inflammation and support pregnancy maintenance. Although findings point to its potential role in PTB prevention, they should be interpreted with caution given the limited and heterogeneous evidence. Further large-scale, multicenter randomized trials are needed to confirm efficacy and to establish optimal dosage, route, and timing of administration. Full article

Background/Objectives: Adnexal masses are commonly encountered in the routine practice of gynecologists, and transvaginal ultrasonography is the preferred imaging modality for assessing the masses in size and complexity. There has been a notable lack of focus on comparative studies concerning benign adnexal tumors. This study aimed to define and compare the specific morphological and vascular characteristics of ovarian mature cystic teratomas (MCTs) and endometriomas using transvaginal ultrasound and Doppler analysis. Methods: This retrospective analysis included 93 patients who underwent surgical intervention for benign adnexal masses at the Obstetrics and Gynecology Clinic Narodni Front from 1 January 2020 to 1 January 2022. Morphological parameters included the appearance of tumors, the largest diameter, volume, capsule thickness, and the presence of fluid in the pouch of Douglas. Hemodynamic parameters included the localization and quantity of blood vessels within the mass, Resistance Index (RI), peak systolic velocity (Vmax), and end-diastolic velocity (Vmin) within detectable tumor vessels. Flow was also assessed in the uterine arteries, calculating the AURI (uterine artery RI) on both the tumor and contralateral sides. Results: There were 46 patients with ovarian mature cystic teratomas, as well as 46 patients with endometriomas; 1 patient presented with both tumors. There were significant differences in ultrasonographic morphological appearance between the two groups. MCTs most frequently presented as multilocular solid cysts (51.0%) or unilocular solid cysts with hyperechoic content (20.4%). Conversely, the majority of endometriomas were classified as unilocular cysts with ground-glass echogenicity (45.5%). A significant difference was identified in the RI of intracystic vessels and the RI of the ipsilateral uterine artery (AURI). Endometriomas presented elevated RI values (0.57 vs. 0.54, p = 0.04) and reduced AURI (0.81 vs. 0.83, p = 0.02) compared to teratomas. Conclusions: These findings confirm that specific morphological and Doppler parameters, particularly the RI and AURI, can assist in distinguishing between endometriomas and mature cystic teratomas. This suggests a potential role for Doppler analysis in improving diagnostic precision for common benign adnexal tumors in clinical practice. Full article

Objective: To identify distinctive 18F-FDG positron emission tomography (PET)/computer tomography (CT) features of gastric-type endocervical adenocarcinoma (GAS) that differentiate it from squamous cell carcinoma (SCC) and usual-type endocervical adenocarcinoma (UEA), as well as to correlate these findings with pathological characteristics. Methods: Patients treated between December 2018 and December 2024 were retrospectively reviewed. The study included 12 GAS, 48 SCC, and 30 UEA cases. Evaluated parameters included tumor morphology, cystic components, uterine cavity fluid, N/M staging, tumor diameter, the cervical lesion maximum standardized uptake value (SUVmax), and the tumor-to-liver maximum standardized uptake ratio (T/L SUVmax). Results: GAS predominantly exhibited diffuse infiltrative growth (11/12), in contrast to mass-like growth observed in SCC (37/48) and UEA (24/30) (both p < 0.001). Cystic components, uterine cavity fluid, and peritoneal metastasis occurred significantly more frequently in GAS (12/12, 11/12, 5/12, respectively) compared to SCC and UEA (all p < 0.001). Elevated CA19-9 levels were more common in GAS (9/12) compared with SCC (p < 0.001). Tumor diameter did not differ significantly among the groups (p > 0.05). SUVmax and T/L SUVmax values were significantly lower in GAS (7.5 ± 3.8 and 2.5 ± 1.6, respectively) than in UEA (19.1 ± 11.4 and 5.7 ± 3.4) and SCC (17.4 ± 6.7 and 5.5 ± 2.6) (all p < 0.001). Conclusion: The clinical characteristics of GAS include infiltrative tumor growth, fluid accumulation in the uterine cavity, frequent formation of microcystic or macrocystic components, peritoneal metastasis, and elevated CA19-9 levels. In this cohort, SUVmax and T/L SUVmax values in GAS were significantly lower than those observed in SCC and UEA. Full article

Exosomes have been shown to play an important role in embryo implantation, but the mechanism is still unclear. This study aimed to investigate the functional roles of lncRNAs in intrauterine exosomes in goat pregnancy. We used RNA-seq to identify the lncRNA profiles of exosomes obtained from goat uterine rinsing fluid at 5, 15, and 18 days of gestation. In addition, we performed weighted gene co-expression network analysis based on differentially expressed mRNAs (DEMs) and lncRNAs (DELs). Functional enrichment analyses of gene modules were conducted using Gene Ontology classification (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. A lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) regulatory network was constructed based on predictive interaction derived from miRTarBase, miRDB and RNAhybrid databases. Altogether, 831 DELs were identified. GO and KEGG analysis showed that the target genes were enriched in processes associated with embryo implantation, such as signaling receptor activity, binding and immune response. Nine functional co-expression modules were enriched in various biological processes, such as metabolic pathways, protein transport, cell cycle and VEGF signaling pathway. Additionally, 12 lncRNA-mediated ceRNA networks were constructed. Our results demonstrate that exosomal lncRNAs in uterine flushing fluid exhibit dynamic changes across gestational stages and play an important role in regulating the uterine microenvironment during embryo implantation. These findings provide a foundational basis for screening exosome-derived lncRNAs that influence embryo implantation and contribute to elucidating the mechanistic roles of lncRNAs in exosome-mediated processes during early pregnancy. Full article

Preterm labour (PTL) affects about 11% of all deliveries world-wide. It is a major cause of perinatal morbidity and mortality. Although the precise cause is unknown in about 50% of cases, infections are thought to be a major contributing factor. These infections are more common in earlier preterm deliveries. While some women with these infections will manifest the classical features of fever, tachycardia (maternal and/or fetal), leucocytosis, raised biomarkers of infections, and uterine tenderness/irritation, others will be asymptomatic. Some of the women may develop a short/dilating cervix without any obvious contractions. Identifying such women is potentially challenging. Evidence has shown that a condensation of echogenic particles just above the cervix—amniotic fluid (AF) sludge, identified by ultrasound—is a marker for microbial invasion of the amniotic cavity (MIAC) and preterm birth (PTB) in both asymptomatic and symptomatic women (including those with a short or normal cervix). Those with a short cervix with AF sludge have a significantly greater risk of progression to PTB. Treatment with antibiotics has been shown in some but not all case series to result in a resolution of the sludge and either a delay or prevention of PTB. The widely varied results from treatment could be related to the antibiotics used and the route of administration. The use of the parenteral combination of clindamycin, a cephalosporin, and metronidazole has been shown to be more effective compared to azithromycin. Here we review the literature on the relationship between the sludge and PTB and conclude (1) that the AF sludge is an ultrasound marker of MIAC and PTL and (2) that following its diagnosis, appropriate counselling should be offered and the triple antibiotic combination offered. We suggest that randomised trials should be undertaken to determine the most efficacious antibiotic combination. Full article

This study applies Computational Fluid Dynamics (CFD) and mathematical modeling to examine uterine and umbilical arterial blood flow during pregnancy, providing a more detailed understanding of hemodynamic changes across gestation. Statistical analysis of Doppler ultrasound data from a large cohort of more than 200 pregnant women (in the second and third trimesters) reveals significant increases in the umbilical arterial peak systolic velocity ($PSV$) between the 22nd and 30th weeks, while uterine artery velocities remain relatively stable, suggesting adaptations in vascular resistance during pregnancy. By combining the Navier–Stokes equations with Doppler ultrasound-derived inlet velocity profiles, we quantify several key fluid dynamics parameters, including time-averaged wall shear stress ($TAWSS$), oscillatory shear index ($OSI$), relative residence time ($RRT$), Reynolds number ($Re$), and Dean number ($De$), evaluating laminar flow stability in the uterine artery and secondary flow patterns in the umbilical artery. Since blood exhibits shear-dependent viscosity and complex rheological behavior, modeling it as a non-Newtonian fluid is essential to accurately capture pulsatile flow dynamics and wall shear stresses in these vessels. Unlike conventional imaging techniques, CFD offers enhanced visualization of blood flow characteristics such as streamlines, velocity distributions, and instantaneous particle motion, providing insights that are not easily captured by Doppler ultrasound alone. Specifically, CFD reveals secondary flow patterns in the umbilical artery, which interact with the primary flow, a phenomenon that is challenging to observe with ultrasound. These findings refine existing hemodynamic models, provide population-specific reference values for clinical assessments, and improve our understanding of the relationship between umbilical arterial flow dynamics and fetal growth restriction, with important implications for maternal and fetal health monitoring. Full article