Medicine and Pharmacology

Abstract: Background/Objectives: Menopausal hormone therapy (MHT) and alendronate improve bone mineral density (BMD), but their comparative effects on trabecular bone score (TBS) are unclear. We compared 12-month changes in TBS and site-specific BMD in postmenopausal women treated with MHT or alendronate. Methods: This retrospective cohort included 172 treatment-naïve postmenopausal women with newly diagnosed osteoporosis who initiated MHT (n=87) or alendronate 70 mg/week (n=85). Complete baseline and approximately 12-month DXA/TBS data were available for 164 women (MHT, n=83; alendronate, n=81). The primary outcome was the adjusted between-group difference in lumbar spine TBS at follow-up, assessed by analysis of covariance. Results: The adjusted MHT-minus-alendronate difference in TBS was 0.023 (95% CI, 0.010–0.036; P<0.001). TBS showed no significant within-group change with MHT (0.002 ± 0.044; P=0.699) but decreased with alendronate (−0.018 ± 0.040; P<0.001). BMD increased significantly in both groups, with greater gains with alendronate at the lumbar spine (adjusted difference, −0.014 g/cm²; 95% CI, −0.019 to −0.009; P<0.001), femoral neck (−0.005 g/cm²; 95% CI, −0.009 to −0.001; P=0.013), and total hip (−0.007 g/cm²; 95% CI, −0.011 to −0.003; P<0.001). Conclusions: Both treatments improved BMD, but alendronate produced larger gains, whereas no significant within-group change in TBS was observed with MHT. These findings suggest discordant treatment-related changes in BMD and TBS and warrant cautious interpretation because of the observational design and limitations of serial TBS monitoring.

Abstract: Preeclampsia (PE), a multi-system disorder, is not confined to the puerperium and may represent a sentinel event leading to increased maternal risk for future cardiovascular disease (CVD). Early-onset PE appears to carry a distinct, and possibly more pronounced, vascular signature than late-onset PE. Accumulating data consistently link previous early-onset PE, to an elevated lifetime risk of CVD. Arterial stiffness (AS), most commonly quantified by carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AIx, or AIx corrected to a heart rate of 75 beats per minute, AIx-75), is an established, independent predictor of CVD in the general population and has therefore attracted interest as a candidate marker for postpartum CVD risk stratification. However, whether AS remains elevated once the puerperium has resolved, has been a persistently unsettled question. Existing literature is inconclusive regarding the association between postpartum AS measurements and previous early-onset PE. This comprehensive review synthesizes the available literature on oscillometric AS measurements before and after delivery in pregnancies complicated by early-onset PE and attempts to quantify the differences between ante- and postpartum oscillometric AS measurements. Although not a systematic review, this quantitative review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and MOOSE (Meta-Analysis of Observational Studies in Epidemiology) guidelines. The study protocol was registered at PROSPERO (Prospective Register of Systematic Reviews System) (ID CRD42020167749) a priori. Only longitudinal studies reporting on both pregnancies complicated by early-onset PE (case group) and normotensive pregnancies (control group) were included. cf-PWV, Alx and Alx-75 were assessed both ante- and postpartum. Quantitative synthesis was performed for indices presented among at least 2 studies. Data were presented as standardized mean differences (SMDs) and 95% confidence intervals (95%CIs). Overall, from 14 citations of relevance, 3 studies with a total of 35 cases and 155 controls fulfilled the inclusion/exclusion criteria. In pregnancies complicated by early-onset PE assessed both ante- and postpartum with either cf-PWV (SMD: -0.61, 95%CI: -1.3 to 0.07) and/or Alx (SMD: -0.32, 95%CI: -2.83 to 2.2) and/or Alx-75 (SMD: -0.61, 95%CI: -1.27 to 0.05), there was no statistically significant difference in AS measurements. In conclusion, current literature suggests that AS measurements (cf-PWV, AIx and AIx-75) are not significantly altered in pregnancies complicated by early-onset PE. Alx and Alx-75 should be further evaluated. Substantial heterogeneity in study design, small sample sizes, and inconsistent postpartum follow-up windows continue to limit firm conclusions, underscoring the need for larger, standardized, and adequately powered longitudinal studies before AS measurements can be recommended for routine postpartum CVD risk stratification.

Abstract: Endometriosis is a systemic, estrogen dependent neuroinflammatory-mediated disease affecting approximately 10-15% of women of reproductive age. Clinical manifestations include chronic pelvic pain (CPP), dysmenorrhea, dyspareunia, dyschezia, dysuria, and infertility. Endometriosis-associated pain is multifactorial and comprises overlapping nociceptive, neuropathic, and nociplastic pain phenotypes driven by persistent inflammation, neuroangiogenesis, peripheral nerve involvement, and central sensitization (CS). These mechanisms may sustain pain beyond lesion excision, highlighting the importance of pelvic nervous system (PNS) involvement. This narrative review examines the role of neuropelveology (NP) in endometriosis, focusing on pain mechanisms, diagnostic implications, and surgical decision making. NP integrates pelvic neuroanatomy and neurophysiology into structured neurological assessment, pain mapping, symptom localization, and nerve sparing surgery. Current evidence suggests that NP may complement conventional evaluation in selected patients with refractory pain, neuropathic symptoms, discordance between symptom severity and imaging findings, or suspected involvement of the sacral plexus or sciatic nerve. Recognizing distinct pain phenotypes may support individualized treatment planning by balancing lesion excision with neural preservation and identifying patients who may benefit from multidisciplinary pain management, rehabilitation, neurolysis, or neuromodulation. Although current evidence remains limited, NP should be considered a complementary framework rather than a replacement for established endometriosis management. Prospective multicenter studies using standardized diagnostic criteria and long-term functional outcomes are needed to define its clinical utility.

Abstract: Background: Current guidelines by the American College of Obstetrics and Gynecology require a two-step procedure for diagnosis of gestational diabetes (GD). This two-step procedure is challenging in resource limited settings. We determined if electrocardiography (ECG) done combined with artificial intelligence techniques can predict GD to provide a non-invasive, early gatekeeper strategy for GD risk stratification. Methods: Data for this study came from the Markers of Early Risk-stratification of Gestational Diabetes (MERGD) study and included 10s, 12-lead ECGs collected at the first antenatal visit. Patients were invited to undergo GCT at 24-28 weeks and, if required, an OGTT was conducted. GCT result was considered positive if the 1-hour, 50g glucose load blood glucose level was ≥130 mg/dL. ECGs were preprocessed, filtered, and a synthetic dataset was generated by using features from autoencoders, device-reported variables and heart rate variability parameters. A random forest model (RF-ECG) was trained on the synthetic data and validated first by 10-fold cross-validation, then on a held-out test of the synthetic data and finally on the original data not seen by the model. Results: Total 1,036 quality checked, preprocessed ECGs were used in the study. A total of 123 (11.87%) women developed GD. The fully trained RF-ECG model provided validation performance as follows: 78.28% accuracy, 87.80% sensitivity, 77.00% specificity and a likelihood ratio of positive test of 3.82. The RF-ECG model outperformed existing models of GD risk stratification. Importance metric identified 40 features as contributory to the model’s diagnostic logic. Conclusions: ECGs can accurately predict the likelihood of GD ahead of the final diagnosis. If supported by external validation in future studies, our approach can help noninvasively identify GD risk early during pregnancy in resource limited settings.

Abstract: Background: Maternal overweight, obesity, and inappropriate gestational weight gain (GWG) are increasingly recognized as major contributors to adverse pregnancy outcomes worldwide. Elevated pre-pregnancy body mass index (BMI) is associated with gestational diabetes mellitus (GDM), hypertensive disorders, cesarean delivery, fetal overgrowth, and long-term cardiometabolic risks for both mother and child. Regional contemporary data from Bulgaria remain limited. Objective: To evaluate trends in maternal obesity and gestational weight gain among pregnant women in Southeastern Bulgaria between 2021 and 2025, using a regional cohort from Burgas, and to assess associations with maternal and neonatal outcomes. Methods: This retrospective cohort study included 1,176 singleton pregnancies registered for antenatal follow-up at MC Prime Clinic – Dr. Kirovakov Ltd., Burgas, Bulgaria, between January 2021 and December 2025. Women were classified according to World Health Organization BMI categories as underweight, normal weight, overweight, and obese. Gestational weight gain was categorized as below, within, or above Institute of Medicine recommendations. Maternal and neonatal outcomes were analyzed using comparative statistics and multivariable logistic regression. Results: The mean maternal age was 30.8 ± 5.4 years, and the mean pre-pregnancy BMI was 25.1 ± 4.8 kg/m². BMI distribution was: underweight 7.6%, normal weight 49.8%, overweight 27.9%, and obesity 14.7%. Overall, 42.6% of women entered pregnancy overweight or obese. Mean total GWG was 13.2 ± 5.6 kg. Excessive GWG occurred in 39.0% of women, while only 39.6% remained within recommended ranges. Excessive GWG was significantly more common among obese women (52.8%) than among women with normal BMI (34.7%, p<0.001). Compared with women of normal BMI, obese women had significantly higher rates of gestational diabetes mellitus (16.7% vs 5.8%), hypertensive disorders (12.9% vs 4.2%), preeclampsia (8.4% vs 2.1%), cesarean delivery (47.4% vs 28.6%), macrosomia (14.5% vs 6.1%), and preterm birth (10.7% vs 6.9%) (all p<0.05). In multivariable analysis, maternal obesity independently predicted GDM (aOR 2.94, 95% CI 1.82-4.73), preeclampsia (aOR 3.18, 95% CI 1.87-5.39), cesarean delivery (aOR 2.11, 95% CI 1.42-3.14), macrosomia (aOR 2.46, 95% CI 1.51-4.01), and preterm birth (aOR 1.67, 95% CI 1.02-2.74). Conclusions: Maternal obesity and excessive gestational weight gain were highly prevalent among pregnant women in Southeastern Bulgaria during 2021-2025 and were strongly associated with adverse maternal and neonatal outcomes. These findings support the need for preconception counseling, individualized antenatal weight management, and targeted regional public health strategies.

Abstract: Background. Malignancy risk in hysteroscopic polypectomy specimens rises with age and postmenopausal status, but decade-stratified absolute rates from large, unselected cohorts remain scarce. Objective. To estimate decade-specific absolute malignancy rates and to determine how postmenopausal bleeding and other procedural indications modify that risk. Methods. Retrospective multicenter cohort with SNOMED-coded histology. All hysteroscopic polypectomies at five Assuta Medical Center sites from January 2019 to April 2026 with a linked histology result (n = 9,269; 75.1% of a base cohort of 12,339). Primary outcome: histologically confirmed endometrial malignancy. Multivariable logistic regression adjusted for weight category, hospital site, and calendar year. Results. The overall malignancy rate was 1.63% (151/9,269), increasing monotonically with age: 0.45% (under 50 years), 1.25% (50–59), 3.79% (60–69), and 4.58% (70 or older). Adjusted odds ratios versus the reference group were 2.02 (95% CI, 1.13–3.60), 5.77 (95% CI, 3.39–9.83), and 8.03 (95% CI, 4.51–14.30). Postmenopausal bleeding carried a malignancy rate of 6.32%; among women aged 70 or older presenting with postmenopausal bleeding, the rate reached 13.1%. Non-postmenopausal abnormal uterine bleeding was not associated with excess risk (0.36%). Weight over 80 kg was an independent predictor (adjusted OR, 3.05; 95% CI, 1.92–4.84). Conclusions. Malignancy risk rises more than tenfold across age groups. Postmenopausal bleeding carries substantially higher risk than other uterine bleeding indications, while non-postmenopausal bleeding carries none. Age and postmenopausal bleeding status, considered jointly, are the most clinically useful predictors for stratifying histological examination decisions.

Abstract: Important gaps remain in our understanding of the composition of the vaginal virome, its interactions with the bacterial microbiome and the host immune system, and its implications for vaginal homeostasis, human papillomavirus (HPV) persistence, and obstetric outcomes. The vaginal virome is a dynamic component of the female genital ecosystem, comprising eukaryotic viruses, bacteriophages, and endogenous viral elements. Recent evidence suggests that alterations in viral composition and diversity may influence the stability of the vaginal microbiome and mucosal immune responses, thereby increasing susceptibility to clinically relevant disorders. Increased viral diversity has been associated with vaginal dysbiosis, persistent HPV infection, and adverse pregnancy outcomes, including preterm birth. In parallel, bacteriophage-based therapies and recombinant endolysins have shown promise for the selective treatment of bacterial biofilms associated with bacterial vaginosis. The vaginal virome is an integral component of the microbial ecology of the female genital tract. A better understanding of its interactions with the bacterial microbiome and the host immune system may facilitate the development of diagnostic biomarkers and innovative therapeutic strategies for precision medicine in women's health.

Abstract: Objective: Ovarian, fallopian tube, and primary peritoneal cancers are the deadliest gynecological malignancies, largely due to delayed diagnosis, tumor heterogeneity, and lack of effective methods for early detection. Increasing evidence suggests that most high-grade serous ovarian carcinomas originate from the fallopian tube epithelium. Consequently, recent studies have focused on fallopian tube cytology and its correlation with histological findings. We aimed to evaluate the exploratory diagnostic performance of ex vivo fallopian tube cytology and the CytoSaLPs score for detecting adnexal malignancies in women undergoing salpingectomy. Methods: We conducted a prospective observational study including 304 women undergoing salpingectomy or salpingo-oophorectomy for benign or malignant gynecological indications between 2020 and 2023. Ex vivo cytological brushing of the fimbrial end was performed before fixation. The primary endpoint was diagnostic accuracy compared with histology. Secondary endpoints included evaluation of the CytoSaLPs score using receiver operating characteristic analysis. Results: 491 speciments were obtained. Cytological findings were correlated with histology, demonstrating the diagnostic value of tubal cytology. For fallopian tubes, cytology showed a sensitivity of 94.4%, specificity of 71.0%. and accuracy of 72.7%. Ovarian cytology showed lower sensitivity (72.9%) and specificity (70.7%). For the adnexa as a single entity, sensitivity was 76.5% and specificity 70.7%. ROC analysis demonstrated strong performance of the CytoSaLPs Score for fallopian tubes (AUC 82.9%), moderate performance for ovaries (AUC 63.4%), and fair performance for adnexa overall (AUC 69.9%). Conclusion: This exploratory proof-of-concept study suggests that ex vivo fallopian tube cytology combined with the CytoSaLPs score may represent a promising adjunctive approach for future early detection strategies. External validation is required before clinical implementation.

Abstract: Background: Pelvic organ prolapse (POP) and stress urinary incontinence (SUI) are common pelvic floor disorders with multifactorial etiology. This study aimed to identify demographic, anthropometric, and obstetric factors associated with POP and SUI. Methods: A retrospective cross-sectional study was conducted among 5,477 women attending a tertiary urogynecological outpatient clinic between 2016 and 2025. The study group included 4,333 women diagnosed with POP or SUI, while 1,144 women with other gynecological conditions served as controls. Associations between age, body mass index (BMI), smoking, and obstetric history were evaluated using multivariable logistic regression and the U-Smile predictive method. Results: Increasing age was independently associated with a higher risk of pelvic floor disorders (OR = 1.02; 95% CI: 1.01–1.02; p < 0.0001). Overweight was associated with a reduced likelihood of POP/SUI compared with normal BMI (OR = 0.85; 95% CI: 0.73–1.00; p = 0.0444). Each additional full-term pregnancy was associated with a 35% reduction in the odds of pelvic floor disorders (OR = 0.65; 95% CI: 0.60–0.69; p < 0.0001). Underweight, obesity, preterm birth, miscarriage, and smoking were not independent predictors. Conclusions: Age, overweight status, and the number of full-term pregnancies were the strongest independent predictors of POP and SUI. Further studies are needed to clarify the unexpected protective associations observed for overweight and term pregnancies.

Abstract: Background/Objectives: Persistent infection with high-risk HPV genotypes accounts for the development of a substantial portion of anogenital and oropharyngeal malignancies. Patients with primary and secondary immunodeficiency or those receiving immunosuppressive therapy, including transplant recipients and patients affected by rare diseases, are vulnerable to particularly severe clinical manifestations of infection. While HPV vaccination constitutes primary prevention, patients with HPV-associated disease remain at risk of reinfection or subsequent infection with alternative genotypes following surgical treatment and may benefit from peri-operative vaccination regimens. This study aimed to evaluate long-term outcomes of HPV vaccination following surgical management of condyloma acuminata in patients with concurrent high-risk genotype infection. Methods: 350 patients with condyloma acuminata and HPV-16 or -18 co-infection confirmed by histopathological examination and PCR genotyping (oral cavity, vulva, vagina, penis, anoderma), including a subgroup with primary or acquired immunodeficiency or chronic immunosuppressive regimens, underwent surgical treatment, receiving simultaneous immunization with the first dose (subsequent completion of full regimen over 12 months) of the bivalent Cervarix vaccine (170 patients) or the quadrivalent Gardasil vaccine (180 patients). A follow-up examination including HPV genotyping (16/18/31/35) was performed after 6 and 12 months following regimen completion. After 36 months a standard clinical examination was performed, and in doubtful cases, supplemented with genotyping with biopsy/cytology. Observation was continued in subsequent years (5, 10, and >15 years). Results: Condyloma acuminata requiring removal were observed in 5% of the patients in follow-up at 36 months, with no significant statistical difference between vaccine groups. No cellular atypia or malignant transformation in the form of squamous cell carcinoma was observed. Genotyping did not detect HPV-16/18/31/35 infection in the follow-up examinations. Conclusions: In this uncontrolled, single-arm cohort, peri-operative initiation of either the bivalent or quadrivalent HPV vaccine was associated with a low rate of clinically apparent condyloma acuminata recurrence and no detectable HPV-16/18/31/35 infection during follow-up.

Abstract: Purpose: To review how standardized ultrasound-based risk stratification and artificial-intelligence (AI) governance have reshaped early diagnostic pathways for ovarian cancer. Materials and Methods: We performed a critical narrative review of milestones in transvaginal ultrasound, IOTA descriptors, ADNEX, O-RADS US/MRI, population screening trials and AI reporting/governance standards. Priority was given to evidence that used external validation, calibration or explicit links between risk categories and clinical management. Results: Population screening with CA-125 and ultrasound has not reduced mortality in average-risk women; therefore, the highest near-term value lies in triage once an adnexal lesion is detected. IOTA/ADNEX and O-RADS translate sonographic descriptors into reproducible probabilities and management categories; O-RADS MRI is useful for sonographically indeterminate lesions. AI may support segmentation, structured reporting and triage, but high discrimination is insufficient without external validation, calibration, transportability testing, decision-curve analysis and subgroup monitoring. Conclusion: Earlier and safer decisions are more likely to come from living standards - structured ultrasound reporting, calibrated risk models, MRI arbitration, auditable AI updates and equity-aware monitoring - than from population screening alone.

Abstract: Prenatal detection of agenesis of corpus callosum (CC) anomalies is a challenge. Although a correct diagnosis of anomalies of the CC requires direct examination of the CC in the mid-sagittal plane of the fetal brain, the international guidelines on mid-trimester morphology scan do not recommend such direct examination of the CC in low-risk populations because of the associated technical difficulties. Recently, routine direct assessment of the CC with the mid-sagittal view has been recommended by several international experts in a consensus statement. The implementation of such routine direct assessment is not easy given the difficulties encountered in obtaining the mid-sagittal view of the CC. As such, it is the time to revisit the various two-dimensional and three-dimensional ultrasound techniques with a view to improve visualisation of the CC. The aim of this narra-tive review article is to discuss the use of various prenatal ultrasound screening methods of CC anomalies in-cluding standard axial views, a more detailed axial views, the mid-sagittal view, transvaginal approach, and 3D reconstruction. New insights on screening methods, and a pragmatic approach are also shared.

Abstract: Objective: To determine whether a high concentration of oxygen and hyaluronic acid applied vaginally in the two weeks preceding embryo transfer may increase implantation rates in human IVF. Design: Oxygen was applied vaginally in 3 x 15 minute sessions in the two weeks prior to embryo transfer at a pressure of 1bar at a flow of 2 litres /minute containing 0.2% of sodium hyaluronate. Subjects: 377 women (average age in the control group 38.0yrs and 37.5 yrs in the treated group) with a history of infertility or previous IVF failure undergoing frozen blastocyst transfer. Main Outcome Measures: Implantation rates after homologous and heterologous frozen blastocyst transfer. Results: The treated patients (n = 161) showed a significant increase in implantation rate compared to the control group (n = 216), with the highest significance in the heterologous population. Conclusions: Pre-treating IVF patients with high concentrations of O₂ and hyaluronic acid delivered vaginally in the two weeks preceding transfer statistically improved implantation rates in human IVF following frozen-thawed single blastocyst transfer.

Abstract:

Background/Objectives: Sacrocolpopexy (SP) remains the gold standard for apical pelvic organ prolapse (POP) repair; however, promontory-sparing techniques such as laparoscopic lateral suspension (LLS) and pectopexy (PP) have emerged as alternatives to reduce surgical complexity and potential complications. Comparative evidence among these techniques remains limited. Methods: Single-center prospective cohort study including 312 women undergoing laparoscopic apical POP repair. The primary endpoint was apical recurrence, defined as POP-Q stage ≥ II, point C > 0, or reintervention. Secondary endpoints included compartment-specific recurrence, operative time, and perioperative complications. Anatomical outcomes were assessed using both POP-Q staging and individual POP-Q measurements. Results: Anatomical preoperative heterogeneity reflecting routine clinical practice due to the non-randomized design. No significant differences were observed in apical recurrence rates (p=0.779), point C > 0 (p=0.696) or reintervention rates (p=0.719) between techniques. Anterior compartment outcomes were comparable, although Ba > 0 was more frequent in PP (p=0.005). Posterior compartment recurrence differed, with higher rates in PP compared to SP (p=0.007). Operative time was significantly longer in SP (202.5 ± 61.2 min) than in LLS (113.0 ± 40.3 min) and PP (168.0 ± 48.8 min) (p<0.001). Overall complication rates were similar (p=0.152), although major complications occurred in SP. Conclusions: SP remains the gold standard laparoscopic technique for apical prolapse but entails greater surgical complexity and increased operative time, whereas LLS and PP could be other options to correct the apical defect. Future multicenter randomized trials with long-term follow-up are required to determine definitive equivalence among techniques. Surgical planning should be individualized based on patient risk profile and anatomical considerations.

Abstract: Objective: To assess gut and endometrial microbiota simultaneously in women with unexplained recurrent implantation failure (RIF) and explore the hypothesis of a gut-endometrium microbial axis. Study design: This monocentric observational pilot study included women aged 38 years or younger with RIF and a normal uterine cavity. Paired fecal and endometrial samples were collected on the same day and analyzed by 16S rRNA gene sequencing. Relative abundances of major phyla and alpha-diversity indices were compared between compartments. Results: Twenty-one women were included. Chronic endometritis was documented hysteroscopically in all cases. Gut dysbiosis was observed in 20/21 patients (95.2%), whereas endometrial dysbiosis was found in 16/21 (76.2%); crude agreement between compartments was 71.4%. The intestinal microbiota was dominated by Bacteroidetes (52.8% ± 14.9%) and Firmicutes (33.3% ± 11.0%), whereas the endometrial microbiota was enriched in Firmicutes (64.5% ± 33.5%) and Proteobacteria (30.9% ± 32.3%). Bacteroidetes were significantly more abundant in fecal than endometrial samples (p < 0.001), while Firmicutes were significantly enriched in the endometrium (p = 0.001). All alpha-diversity indices were significantly higher in feces, indicating greater microbial richness and complexity in the gut. Conclusions: In women with RIF, gut and endometrial dysbiosis frequently coexist and show relevant concordance. These data support the hypothesis that endometrial dysbiosis may reflect a broader systemic microbial imbalance rather than an isolated uterine disorder.

Abstract: Objective: To analyze the clinical and sociodemographic profile of patients un-dergoing assisted reproductive techniques (ART) and to assess whether sociodemo-graphic or clinical factors influence access to the different therapeutic modalities available in a public assisted reproduction unit. Materials and Methods: A retrospective study was conducted including 222 pa-tients treated at the Maternal and Child Hospital of Málaga (January–June 2025). So-ciodemographic and clinical variables were analyzed using multivariate models. Results: The mean age was 34.7 years, with a predominance of women aged 35–39 years (46.85%). Most patients were of normal weight (59.17%), non smokers (74.77%), and employed (88.68%). New family models accounted for 23.6% of the co-hort, including 16.67% single mothers by choice (SMC) and 6.94% female couples, high-lighting diversity and equity in reproductive access. Infertility diagnosis and marital status were significantly associated with the technique used (p < 0.001), whereas edu-cational level showed no association. Among clinical diagnoses, structural uterine pa-thology was one of the most frequent (23.02% of valid gynecological histories), together with diminished ovarian reserve and other factors guiding referral to IVF/ICSI and other high complexity techniques. In the multivariate analysis, structural uterine pa-thology showed a trend toward greater use of high complexity techniques without reaching statistical significance (adjusted OR 1.16; 95% CI: 0.48–2.77; p = 0.742), likely due to limited statistical power and a high proportion of missing data (36.94% for infertility diagnosis/duration). Conclusions: In this cohort, the public health system ensured equitable access to ART based on clinical criteria and family models, suggesting that the socioeconomic variables evaluated did not determine the type of treatment received. Access was pri-marily driven by clinical need, underscoring the relevance of the uterine factor as a functional determinant of implantation and therapeutic personalization. Multicenter studies are warranted to evaluate reproductive outcomes and potential hidden inequities.

Abstract: Background and Objectives: High-risk pregnancy is associated with increased vulnerability to psychological distress, yet the protective mechanisms that may buffer this vulnerability remain insufficiently understood. This study examined differences in emotional distress and coping strategies between women with high-risk and low-risk pregnancies and investigated whether active coping and marital satisfaction attenuate associations between negative pregnancy experiences, prenatal depression and perceived stress. Materials and Methods: A cross-sectional study was conducted among 195 pregnant women aged 18–51 years (M = 31.76, SD = 5.32), including 102 women with high-risk pregnancies and 93 women with low-risk pregnancies. Participants completed measures of prenatal depression (EPDS), state anxiety (STAI), perceived stress (PSS-10), pregnancy-related anxiety (PRAS), pregnancy experiences (PES), coping strategies (COPE), and marital satisfaction (CSI). Independent-samples t tests, correlation analyses, partial correlations and moderation analyses were conducted. Results: Women with high-risk pregnancies reported significantly higher levels of prenatal depression (p = 0.032) and pregnancy-related anxiety (p < 0.001) than women with low-risk pregnancies. They also reported lower use of socio-emotional support (p = 0.036) and mental disengagement coping strategies (p = 0.022). Negative pregnancy experiences were positively associated with state anxiety, pregnancy-related anxiety, prenatal depression, and perceived stress after controlling for pregnancy risk status (all p < 0.001). Maladaptive coping strategies were generally associated with higher emotional distress, whereas adaptive coping strategies, particularly positive reinterpretation and planning, were associated with lower levels of prenatal depression and anxiety. Active coping moderated the association between negative pregnancy experiences and perceived stress (β = −0.16, p = 0.016). Marital satisfaction moderated the association between prenatal depression and perceived stress among women with high-risk pregnancies (β = −0.21, p = 0.016). Conclusions: Active coping and marital satisfaction emerged as modifiable protective factors that may attenuate psychological distress during pregnancy. These findings support the integration of psychological screening, coping-focused interventions, and partner involvement into prenatal care, particularly for women experiencing high-risk pregnancies.

Abstract: Background: Idiopathic intrauterine growth restriction (IUGR) is strongly associated with placental dysfunction, impaired spiral uterine artery remodeling, and adverse perinatal outcomes. Although insulin-like growth factor-1 (IGF-1) signaling is essential for placental and fetal development, the role of specific IGF-1 isoforms remains unclear. This study investigated placental IGF-1Eb expression in idiopathic IUGR and its potential as a biomarker of placental dysfunction. Methods: A total of 62 third-trimester human placentas were analyzed, including 47 from pregnancies complicated by idiopathic intrauterine growth restriction (IUGR) and 15 from pregnancies with appropriate-for-gestational-age (AGA) fetal growth, which served as the control group. The mRNA expression levels of the IGF-1Eb isoform were assessed by reverse transcription quantitative PCR in a subset of 28 fresh placental samples. The immunoexpression of IGF-1Eb protein was assessed in paraffin-embedded tissue sections. Histopathological lesions were classified according to the Amsterdam criteria, and correlations with clinical, demographic and pathological parameters were assessed using appropriate statistical analyses. Results: The mRNA expression of the IGF-1Eb isoform in placentas did not differ significantly between the IUGR and AGA groups. In contrast, immunohistochemical analysis revealed statistically significant differences in IGF-1Eb protein expression. The protein localization was cytoplasmic, perimembranous and occasionally nuclear, expressed in the perivillous and extravillous trophoblast, and the endothelium of fetal and maternal vessels. Moderate IGF-1Eb immunoexpression in the perivillous syncytiotrophoblast was observed significantly more frequently in IUGR placentas compared with the AGA group and was associated with histological changes of maternal vascular malperfusion, and with clinical parameters, including gestational age, neonatal birth weight, placental weight, maternal body mass index, and fetal sex. Furthermore, a significant increase in IGF-1Eb immunopositivity was observed in the endothelium of maternal decidual and fetal villous vessels in IUGR placentas. In contrast, no statistically significant differences were recorded in the scores or intensity of IGF-1Eb immunoexpression in the extravillous trophoblast between the two groups. Conclusions: Although total IGF-1Eb mRNA levels remained unchanged, increased protein immunoexpression was associated with idiopathic IUGR in distinct parts of the placenta. In association with histological changes of maternal vascular malperfusion, these findings suggest that IGF-1Eb may serve as a potential marker of placental dysfunction in IUGR pregnancies.

Abstract: Preterm labor is a leading cause of neonatal morbidity and mortality, with inflammation playing a central role in its pathogenesis. This structured literature review summarizes the role of the nuclear factor kappa B (NF-κB) signaling pathway in term and preterm labor and critically evaluates current evidence on natural and synthetic NF-κB modulators as potential therapeutic approaches. To ensure comprehensive identification of relevant studies, a structured literature search informed by PRISMA 2020 reporting recommendations was performed, including studies published through August 2025. Experimental, translational, and review studies were synthesized narratively. NF-κB integrates hormonal, mechanical, infectious, and sterile inflammatory signals in gestational tissues, promoting the expression of pro-inflammatory cytokines, cyclooxygenase-2, prostaglandins, chemokines, and contraction-associated proteins that drive uterine activation. While tightly regulated NF-κB activation is essential for physiological term labor, its premature or excessive activation contributes to inflammation-associated preterm labor. Natural compounds and synthetic agents consistently attenuate excessive NF-κB signaling and downstream inflammatory responses in preclinical models, supporting their potential as candidate therapeutic strategies. However, clinical evidence remains limited. Future research should prioritize tissue-specific, context-dependent modulation of NF-κB and establish the safety, optimal therapeutic windows, and clinical efficacy of NF-κB-targeted interventions during pregnancy.

Abstract: Recent advances in artificial intelligence (AI), especially machine learning (ML), deep learning (DL), natural language processing (NLP) and computer vision have rapidly impacted obstetric care. Key applications include automated ultrasound interpretation (biometry, anomaly detection), AI-enhanced fetal monitoring (cardiotocography), risk stratification (preeclampsia, preterm birth, hemorrhage), labor management (delivery mode prediction), genomic screening (NIPT interpretation), and remote/telehealth tools for monitoring especially in underserved areas. For example, DL models now attain accuracy comparable to experts for fetal ultrasound biometry[1], and FDA-cleared AI tools have achieved >97% detection of congenital heart defects during prenatal screening[2]. However, clinical readiness varies: some technologies (e.g. ultrasound AI tools) are already FDA-cleared[2,3], whereas others remain at proof-of-concept. Across studies, performance metrics (AUC, R2, accuracy) are generally high (often >0.85) but depend on data quality and label definitions[4,5]. Crucial issues include dataset biases, lack of standardization, explainability, and regulatory oversight. This review synthesizes AI technologies, applications, validation (metrics, datasets), deployment (trials, approval, integration), and ethical considerations, and identifies knowledge gaps. Overall, AI shows promise to improve prenatal diagnosis and individualized care, but requires rigorous validation, transparent algorithms, and clinician oversight to ensure safety, equity and trust.