Search Results (851)

Apical periodontitis is a common inflammatory oral condition and a major cause of endodontic treatment need. The present retrospective clinical study aimed to evaluate the frequency, distribution, and radiographic healing of teeth diagnosed with apical periodontitis following primary endodontic treatment or nonsurgical retreatment within a specific patient cohort. Consecutive patients presenting for endodontic treatment at the study clinic between 2020 and 2021 were screened for inclusion. Eligible cases were those in which patients provided written informed consent, presented with periapical inflammatory pathology, and underwent conservative endodontic treatment. Exclusion criteria were incomplete data, non-functional or non-restorable teeth, third molars, pregnancy, probing depth ≥ 4 mm, radiographic bone loss, pathologic tooth mobility due to attachment loss, periodontal involvement of the lesion, and primary dentition. A total of 277 teeth, all diagnosed with apical periodontitis at baseline, were included. Some patients contributed more than one tooth. All treatments were performed by a single operator according to a standardized clinical protocol, including uniform diagnostic criteria, chemo-mechanical preparation, irrigation regimen, obturation technique, and radiographic follow-up at 12 and 24 months. Periapical healing was assessed radiographically using the Periapical Index (PAI). Within this cohort, elderly patients significantly represented the largest proportion of those treated (p < 0.001). Maxillary teeth also comprised a significantly higher proportion of cases than mandibular teeth (55.2% vs. 44.8%). The mean initial PAI score was 3.37 ± 0.9 points, with a median of 3 points, and the final score was 1.31 ± 0.93 points, with a median of 1 point. Radiographic healing was observed in 56.68% of cases at 12 months and in 84.84% of cases at 24 months. Primary endodontic treatment and nonsurgical retreatment of teeth with apical periodontitis in this selected patient population were associated with substantial radiographic improvement over a 24-month follow-up period. These findings support the value of standardized endodontic management and longitudinal radiographic monitoring. Full article

Background/Objectives: The soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is an established biomarker in the diagnosis of preeclampsia; however, its significance outside overt hypertensive disorders of pregnancy remains unclear. Emerging evidence suggests that angiogenic imbalance may reflect subclinical placental dysfunction even in otherwise low-risk pregnancies. To investigate associations between the sFlt-1/PlGF ratio and maternal and neonatal outcomes in a low-risk term obstetric population, beyond established diagnostic cut-offs. Methods: This prospective cohort study included 87 women with singleton term pregnancies. Serum sFlt-1 and PlGF concentrations were measured at hospital admission before delivery, and the sFlt-1/PlGF ratio was calculated. The primary outcome was estimated blood loss at delivery. Secondary maternal outcomes included postpartum hemoglobin decline, uterine atony, and fibrinogen concentration. Neonatal outcomes included birthweight, umbilical artery pH, and bilirubin concentration. Multivariable regression models were used to evaluate associations between the ln-transformed sFlt-1/PlGF ratio and outcomes after adjustment for prespecified maternal and obstetric covariates. Results: Each doubling of the sFlt-1/PlGF ratio was associated with greater estimated peripartum blood loss (+78.0 mL, 95% CI 42.1–113.9; p < 0.001), a larger postpartum hemoglobin decline (+0.078 g/dL, 95% CI 0.008–0.148; p = 0.030), lower fibrinogen concentration (−20.7 mg/dL, 95% CI −30.5 to −10.9; p < 0.001), and lower neonatal birthweight (−64.6 g, 95% CI −102.0 to −27.2; p = 0.001). No significant associations were observed for uterine atony, premature rupture of membranes, or umbilical artery pulsatility index above the 75th centile. Conclusions: In low-risk term pregnancies, higher sFlt-1/PlGF ratios were associated with greater estimated peripartum blood loss, lower fibrinogen concentrations, and lower neonatal birthweight. These findings support the hypothesis that variation in angiogenic balance may reflect subclinical placental dysfunction even in apparently uncomplicated pregnancies. Further prospective studies are needed to validate these exploratory observations and determine their clinical relevance. Full article

In small ruminants, up to 40% of fertilized ova are lost during early gestation due to inadequate progesterone. This study evaluated post-transfer progestogen supplementation in goats. A total of 207 thawed embryos were transferred into 111 recipients assigned to progestogen-supplemented (n = 37) or non-progestogen-supplemented (n = 74) groups. Pregnancy and embryo survival did not differ between treatments (p > 0.05). However, fetal and neonatal survival were significantly lower in supplemented goats (29%) compared with non-supplemented goats (100%; p < 0.05). Infectious causes were excluded. Possible mechanisms postulated in fetal losses comprise a sharp decline in progesterone after sponge removal or increased oxytocin and prostaglandin due to vaginal mechanical stimulation, inducing luteolysis. In conclusion, intravaginal progestogen supplementation is not recommended for recipient goats in embryo transfer programs. Full article

Neospora caninum is a major cause of reproductive failure in cattle, responsible for epidemic abortion outbreaks that inflict annual billion-dollar losses on the global livestock industry. In water buffaloes (Bubalus bubalis), however, a phylogenetically close relative often raised in the same environments, the same parasite typically establishes a subclinical persistent infection with markedly lower rates of clinical abortion. This review inverts the traditional narrative by arguing that the key to next-generation control strategies lies in understanding the tolerant host (buffalo) rather than solely the susceptible host (cattle). By dissecting this “Neospora paradox”, we explore the molecular and immunological crosstalk that dictates pregnancy outcomes. We examine the parasite’s invasion proteins, revealed by CRISPR-Cas9 screens, and the maternal–fetal interface, where the balance between immune tolerance and parasite control determines the fate of pregnancy. We also compare N. caninum with the related zoonotic parasite Toxoplasma gondii to highlight how differential host immune recognition shapes infection outcomes. Finally, we propose that deciphering the buffalo’s successful equilibrium with N. caninum can illuminate novel pathways for vaccines and immunotherapeutic strategies, transforming the management of neosporosis worldwide. Full article

Objectives: This study aimed to compare the aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and fibrosis-5 index (FIB-5) between women with threatened miscarriage and healthy pregnant controls, and to evaluate their discriminative performance. Methods: This single-center retrospective case–control study included 100 women with threatened miscarriage and 100 gestational-age-matched healthy pregnant controls within the first 12 weeks of gestation. Demographic, obstetric, ultrasonographic, and laboratory data were retrieved from electronic records. APRI, FIB-4, and FIB-5 were calculated from routine laboratory parameters. Group comparisons, binary logistic regression, and ROC analyses were performed. Results: AST, ALT, ALP, APRI, and FIB-4 were higher, while hemoglobin, platelet count, albumin, and FIB-5 were lower in the threatened miscarriage group (all p < 0.001). APRI (OR = 6.937), FIB-4 (OR = 89.114), and FIB-5 (OR = 0.766) were independently associated with case status. FIB-4 showed the highest discriminative performance (AUC = 0.929), followed by APRI (AUC = 0.903) and FIB-5 (AUC = 0.761). Conclusions: APRI and particularly FIB-4 showed good apparent discrimination between women with threatened miscarriage and healthy controls in this retrospective dataset. However, these indices should be interpreted as exploratory laboratory-derived markers rather than disease-specific biomarkers until validated in prospective multicenter studies. Full article

Background: Precision medicine aims to improve early, individualized risk stratification using biologically relevant biomarkers. In early pregnancy, markers reflecting placental function remain limited. Kisspeptin, a placentally derived peptide that rises during normal gestation, has emerged as a potential indicator of pregnancy viability. Objectives: We aimed to evaluate evidence on maternal serum kisspeptin levels and placental KISS1/KISS1R expression in early pregnancy loss, and to assess its potential relevance as a precision biomarker within personalized pharmacy and individualized monitoring frameworks. Methods: A systematic search of PubMed, Scopus, Web of Science, and Google Scholar (up to 2025) was conducted according to the PRISMA 2020 guidelines. Studies assessing circulating kisspeptin and/or placental expression in early pregnancy loss versus viable pregnancies were included. A formal meta-analysis was not performed due to substantial heterogeneity in study design, biological material, assay methods, gestational age, and outcome reporting formats. Under these conditions, quantitative pooling was considered methodologically inappropriate; therefore, qualitative synthesis was performed. Results: Six studies met the inclusion criteria. Most reported significantly lower maternal serum kisspeptin levels in early pregnancy loss, with good discriminatory accuracy. Immunohistochemical analyses showed reduced placental and choriodecidual KISS1/KISS1R expression in miscarriage and recurrent pregnancy loss, indicating disrupted local signaling. Concordant systemic and tissue findings suggest that circulating kisspeptin reflects placental dysfunction. Conclusions: Kisspeptin appears to be a promising precision biomarker for monitoring early pregnancy viability and supporting individualized pharmaceutical care. Standardized assays and large prospective studies are needed before routine clinical implementation. Full article

Chronic exposure to fine particulate matter (PM_2.5) derived from wood combustion represents a major environmental health burden, particularly during pregnancy. However, the impact of pregestational and gestational (PM_2.5) exposure on the maternal great vasculature remains largely unexplored. This study evaluates the effects of wood smoke-derived (PM_2.5) on the structural architecture of the maternal aortic arch and associated hemodynamic changes during pregnancy in second-generation Sprague–Dawley rats. Animals were allocated into four groups (n = 12) according to filtered (FA) or non-filtered air (NFA) exposure during pregestational and gestational periods: FA/FA, FA/NFA, NFA/FA, and NFA/NFA. Morphometric analysis revealed significant reductions in tunica media (p = 0.0251) and adventitia thickness (p = 0.0014) in exposed groups, without changes in integrated optical density, suggesting alterations in elastic matrix organization without evidence of net mass loss. Histological analysis supported exposure-dependent structural heterogeneity, including elastic lamellae fragmentation and extracellular matrix disorganization. Each exposed group exhibited a distinct systolic blood pressure trajectory across gestation, with FA/NFA reaching the highest values at day 18 (151.0 ± 17.0 mmHg) and NFA/FA displaying sustained elevations despite gestational low-exposure conditions. Principal component analysis (49.2% explained variance) revealed a structured multivariate distribution of vascular and hemodynamic variables across exposure conditions, consistent with an exposure-window-dependent pattern. These findings suggest that (PM_2.5) exposure is associated with coordinated structural and hemodynamic changes in the aortic arch and support the hypothesis that the pregestational period may represent a window of increased susceptibility. Full article

Pregnancy-associated hemodynamic overload and hormonal changes induce hypertrophy and metabolic remodeling of the maternal heart. Mitochondrial motility, mediated by ras homolog family member T (RHOT) 1 and RHOT2, is essential for cardiac adaptation to increased workload, cardiomyocyte hypertrophy, and sarcomere maturation. To test the hypothesis that Rhot1/2 expression is required for pregnancy- and postpartum-associated adaptations of the maternal heart, female mice with tamoxifen-inducible, cardiomyocyte-selective deletion of Rhot1 and Rhot2 (iRhot1/2-KO) were mated. Following gene deletion in adult mice, cardiac tissue and function were analyzed after three to five successive pregnancies and postpartum nursing periods. Age-matched nulliparous iRhot1/2-KO mice and age-matched mice expressing Rhot1 and Rhot2 served as controls. Motility of mitochondria isolated from iRhot1/2-KO hearts was impaired, as determined by the number of mobile mitochondria in an in vitro motor protein-driven single mitochondrion motility assay performed on surface-immobilized microtubules. Despite loss of Rhot1/2 expression, contractile function assessed by transthoracic echocardiography, mRNA expression of peripartum-associated heart failure markers, cardiac structure, mitochondrial morphology, mitochondrial enzymatic activity, and mitochondrial DNA content were all comparable to controls expressing Rhot1/2 at the investigated time points. RNA sequencing-based gene profiling identified a transcriptional program through which RHOT proteins preserve cardiac energetic and contraction gene expression during pregnancy and postpartum. Together, cardiomyocyte-selective loss of Rhot1/2 expression in the adult heart does not cause peripartum-associated heart failure, despite reduced cardiac energetic and contraction gene expression. Full article

Background and Objectives: Robotic-assisted tubal reanastomosis (RATR) remains a clinically relevant option for selected women seeking fertility after sterilization. In the era of IVF, surgical reversal continues to be discussed because it may restore the possibility of spontaneous conception rather than offering only cycle-dependent treatment. However, the available evidence on RATR is heterogeneous and derives predominantly from observational studies. The aim of this narrative review with a structured literature search was to synthesize the published evidence on the operative, reproductive, and economic outcomes of RATR and to contextualize its role in contemporary fertility counseling. Materials and Methods: A structured literature search of PubMed/MEDLINE, Scopus, and Google Scholar was performed from database inception to 20 December 2025. Data were synthesized descriptively without meta-analysis. Primary robotic clinical studies were interpreted separately from secondary and contextual publications. Results: In total, 16 studies were included in our study. The evidence base comprised predominantly retrospective cohorts and case series; no randomized controlled trials were identified. Reported tubal patency endpoints in robotic cohorts ranged from 81.0% to 94.1%, although denominators differed across studies and were reported either per patient or per tube. Reported pregnancy outcomes ranged from 25% to 80%, reflecting substantial heterogeneity in patient selection, follow-up duration, and outcome definitions. When woman-level delivery or live-birth outcomes were explicitly reported, they were generally encouraging in selected series, although not uniformly defined. Estimated blood loss was usually minimal when reported, and conversion to laparotomy was uncommon. Any comparison with IVF was indirect because no contemporary head-to-head comparative studies were identified. Economic data were sparse, institution-specific, and methodologically heterogeneous. Conclusions: Available observational evidence suggests that RATR is a feasible minimally invasive option for fertility restoration in carefully selected women after sterilization. However, the evidence base remains limited by retrospective design, small cohorts, heterogeneous outcome reporting, variable follow-up, and indirect comparison with IVF. RATR should be considered within individualized fertility counseling rather than as a universal alternative to IVF. Prospective comparative studies with standardized outcome definitions, transparent reporting of prognostic factors, and robust economic evaluation are needed. Full article

Pregnancy represents a critical eco-biological window during which maternal physiology integrates environmental exposures, lifestyle factors, and interconnected microbial ecosystems to shape fetal development and long-term health. From a One Health perspective, defined here as the interconnection between maternal health, environmental determinants, and microbial ecosystems across generations, the maternal microbiome functions as a dynamic interface linking the external environment to the intrauterine milieu, translating ecological signals into immunological, metabolic, and neuroendocrine pathways that influence placental function and developmental programming. Across gut, vaginal, oral, and mammary niches, maternal microbial communities operate as an integrated network regulating systemic inflammation, metabolic homeostasis, and the production of bioactive metabolites, including short-chain fatty acids, bile acids, and tryptophan derivatives. This review proposes an integrated systems framework in which pregnancy is viewed as a transient ecological system shaped by ten interconnected maternal determinants, encompassing microbial niches, nutrition, lifestyle factors, medical interventions, mode of delivery, and postnatal microbial transmission, that converge on shared microbiome-mediated signaling pathways affecting fetal and neonatal immune, metabolic, and neurodevelopmental trajectories. Broader macro-environmental drivers, including biodiversity loss, urbanization, pollution, and industrialized lifestyles, are considered as upstream modulators of maternal microbial ecology within a One Health context. A systems model is presented to illustrate how environmental inputs are biologically transduced through maternal microbial networks to influence placental function, fetal development, and early-life health trajectories. Framing pregnancy as an integrated eco-biological continuum highlights the maternal microbiome as a central hub of intergenerational health and may support microbiome-informed preventive strategies and public health approaches aimed at reducing the burden of non-communicable diseases (NCDs) of early-life origin. Full article

Recurrent intrauterine adhesions (IUA) and refractory thin endometrium are associated with impaired endometrial regeneration, reduced implantation, and poor live birth outcomes. Regenerative therapy using mesenchymal stromal cells (MSCs) has shown promising results; however, factors associated with reproductive success remain unclear. In this prospective, single-centre, single-arm uncontrolled observational study, 35 women with recurrent IUA and thin endometrium (<7 mm) unresponsive to standard surgical and hormonal therapy received combined subendometrial and systemic administration of placenta-derived MSCs. The primary endpoint was live birth. Secondary endpoints included clinical pregnancy rate, time to pregnancy, endometrial thickness changes, uterine blood flow (resistance index, RI), and anti-Müllerian hormone (AMH) levels. Univariable logistic regression was performed to identify factors associated with live birth. Clinical pregnancy occurred in 13/35 patients (37.1%), and live birth was achieved in 11/35 (31.4%). Median time to pregnancy was 7 (5–8) months. Shorter duration of infertility or prior pregnancy loss (OR 1.55 per year; 95% CI 1.10–2.57), AFS stage I adhesions (OR 6.8; 95% CI 1.1–42; p = 0.04), lower baseline RI in uterine, arcuate and radial arteries, and higher baseline AMH (OR 2.59 per doubling; 95% CI 1.15–6.89) were significantly associated with live birth. Endometrial thickness increased after therapy but was not significantly associated with live birth. No severe adverse events were observed. Placenta-derived MSC therapy was followed by live birth in 31.4% of women with recurrent IUA and refractory thin endometrium. A shorter duration of reproductive disorders, less severe adhesions, lower baseline RI in uterine, arcuate and radial arteries, and higher AMH levels were associated with live birth after treatment and may help identify patients with a more favourable reproductive prognosis in future controlled studies. Full article

Recurrent pregnancy loss (RPL) is a multifactorial reproductive disorder with important genetic, endocrine, immune, and metabolic determinants. Growing evidence links vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms to pregnancy complications, including RPL. A narrative review was conducted via a literature search in major databases: PubMed, EMBASE, Scopus, and Web of Science from January 2010 to January 2026, which synthesized observational studies on maternal 25-hydroxyvitamin D [25(OH)D] status and/or VDR polymorphisms in RPL, with predefined eligibility criteria and qualitative risk-of-bias assessment. Most studies focused on FokI (rs2228570) and the 3′ regulatory block BsmI/ApaI/TaqI. FokI is the most extensively studied VDR variant in RPL and showed the most consistent directional association compared with other variants, particularly in Asian and Middle Eastern populations, though the effect varied by study design, ancestry, and covariate adjustment. Contrary to that, investigations of BsmI/ApaI/TaqI loci were not consistent due to ancestry-specific linkage disequilibrium (LD). Genotype and vitamin D interaction effects were scarcely studied, with stratified analyses indicating a more significant genotype effect under vitamin D deficiency. From clinical practice perspectives, VDR polymorphisms may explain why some patients with RPL have a poor response to standard vitamin D supplementation. Women with the FokI f allele polymorphism associated with lower VDR activity require higher vitamin D dosing or earlier immunomodulatory support to achieve adequate endometrial receptivity. VDR variation, particularly FokI, may contribute to RPL susceptibility within an endocrine–immune–metabolic framework. Clinical translation will require standardized RPL definitions, concurrent 25(OH)D assessment, robust control for confounders, and analytical models that account for gene–environment interactions. Full article

Objectives: To evaluate the presence and dominance of Lactobacillus in the endometrial microbiome and their age-related associations in a large group of Bulgarian patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) who attend our clinic. Methods: This retrospective study included 199 patients (mean age: 35.69 ± 5.16) with RIF (n = 103) and RPL (n = 96) who visited our fertility clinic between October 2019 and November 2022. Endometrial samples were analyzed using real-time PCR for target DNA sequences. Results: Overall, 62.8% (n = 125) exhibited an absence of Lactobacilli in their endometrial samples, with 63.1% (n = 65) of the RIF group and 62.5% (n = 60) of the RPL group showing a lack of Lactobacilli, with no statistically significant difference between the groups (p = 0.926). A Lactobacillus-dominant microbiome was found in 23.6% of the entire cohort (n = 47), 25.2% of the RIF group (n = 26) and 21.9% of the RPL group (n = 21). A reduced abundance of Lactobacilli was identified in 13.5% of the cohort (n = 27), though to differing degrees. There was no significant relationship between the abundance of Lactobacilli and belonging to the RIF or RPL group. A statistically significant difference was found in the mean age of two groups in cases with a Lactobacillus-dominant microbiome (mean age of 36.4 ± 4.8 years in the RIF group and 32.5 ± 3.5 years in the RPL group) (p = 0.004). Conclusions: Our findings demonstrate a high prevalence of non-Lactobacillus-dominant microbiomes in a large group of Bulgarian patients with RIF and RPL and significant age-related Lactobacillus changes in the microbiome of patients with RPL. These results point to the potential role of the uterine microbiome and support the need for further prospective studies, especially in cases of advanced maternal age. Full article

Background: Recurrent pregnancy loss (RPL) remains etiologically unexplained in 40–50% of cases following standard diagnostic workup. Non-criteria antiphospholipid antibodies (non-criteria aPL) are increasingly considered potential markers of seronegative obstetric antiphospholipid syndrome (APS); however, their diagnostic value in this clinical setting requires further investigation. Objective: To assess the diagnostic value of non-criteria aPL in women with RPL and to construct an exploratory immunological scoring model for diagnostic stratification. Methods: Antiphospholipid antibody detection was performed using a single-measurement semi-quantitative line immunoblot assay (Anti-Phospholipid 10 Dot, Generic Assays, Germany). Statistical analysis included χ², Fisher’s exact test, Mann–Whitney U test, binary logistic regression, and ROC analysis. Results: Statistically significant associations with RPL were observed for anti-prothrombin antibodies (OR = 11.1; 95% CI 1.8–68.0; p = 0.022 [Haldane–Anscombe correction]), anti-annexin V (OR = 4.28; 95% CI 1.18–15.6; p = 0.023), and anti-β₂GP I (OR = 3.31; 95% CI 1.18–9.28; p = 0.019). The exploratory composite immunological score demonstrated moderate discriminatory performance (AUC = 0.701; 95% CI 0.588–0.814; p = 0.005). The overall logistic regression model was statistically significant (χ² = 8.564; p = 0.036), although none of the individual predictors retained independent significance, indicating a contribution of cumulative immunological burden rather than any single marker. Conclusions: In this single-center cross-sectional study, non-criteria aPL were frequently detected in women with RPL and were statistically associated with the condition. The findings should be interpreted as hypothesis-generating only, given the cross-sectional design, single-measurement immunoblot, small control group, and absence of external validation. Confirmation in larger prospective multicenter cohorts using ELISA-based assays with the internationally recommended 12-week repeat measurement is required before any clinical implementation. Full article

Background: Cervical pregnancy and cesarean scar pregnancy are rare forms of non-tubal ectopic pregnancy associated with a high risk of severe hemorrhage, surgical intervention, and potential loss of fertility. We describe a unique case of sequential abnormal implantation in which a cervical pregnancy was followed by a cesarean scar pregnancy one year later. The occurrence of two distinct forms of non-tubal ectopic pregnancy in a single patient represents an exceptionally uncommon clinical scenario, underscoring the importance of early diagnosis and carefully planned treatment. Case presentation: A 39-year-old woman, gravida 4 para 3, was diagnosed with two distinct non-tubal ectopic pregnancies over a 1-year period. The first pregnancy was implanted in the cervical canal, whereas the second was located within the cesarean section scar. In each episode, the diagnosis was established early by transvaginal ultrasound. As the patient was hemodynamically stable and wished to preserve fertility, minimally invasive hysteroscopic evacuation was performed in both pregnancies. The procedures were completed without significant intraoperative bleeding, and no additional hemostatic interventions were required. Follow-up serum β-hCG levels became negative after treatment, confirming complete resolution of pregnancies. Conclusions: This case demonstrates that early ultrasonographic diagnosis and careful individualized management may enable successful fertility-preserving treatment even in exceptionally rare cases. It also supports the potential role of minimally invasive approaches in selected hemodynamically stable patients and highlights the need for standardized management protocols for cervical and cesarean scar pregnancy. Full article