Background/Objectives: The role of the endometrial microbiome in reproductive failure remains incompletely understood. This study aimed to describe the composition of the endometrial microbiome in women evaluated for infertility or recurrent miscarriage. Methods: In this single-center descriptive study, endometrial samples were collected from women evaluated for infertility or recurrent miscarriage. Microbiome profiling was performed using 16S rRNA gene next-generation sequencing. Samples were classified as Lactobacillus-dominant when Lactobacillus spp. accounted for ≥90% of the total bacterial community. Alpha diversity was assessed using the Shannon and Simpson indices, while beta diversity was evaluated using Bray-Curtis dissimilarity, principal coordinates analysis (PCoA), PERMANOVA, and PERMDISP. Results: Of the 60 samples, 20 (33.3%) were Lactobacillus-dominant and 40 (66.7%) were non-Lactobacillus-dominant. Across all samples, Firmicutes was the predominant phylum (76.6%). Non-Lactobacillus-dominant samples showed significantly higher alpha diversity than Lactobacillus-dominant samples for both the Shannon and Simpson indices (p = 1.19 × 10-6 and p = 1.51 × 10-6, respectively), as well as higher observed taxa richness (p = 0.000017). PCoA based on Bray-Curtis dissimilarity demonstrated clear separation between microbiome profiles, supported by PERMANOVA (pseudo-F = 13.87, R2 = 0.193, p = 0.001). PERMDISP showed significantly greater dispersion among non-Lactobacillus-dominant samples (F = 566.94, p < 0.001). Non-Lactobacillus-dominant samples showed greater representation of Enterococcus and Prevotella. Conclusions: In this cohort non-Lactobacillus-dominant communities were more frequent with greater diversity, richness, and compositional heterogeneity than Lactobacillus-dominant communities. These findings highlight the need for larger, standardized studies with appropriate control populations to clarify their clinical significance.

Oxidative stress (OS) is a critical regulator of placental development; however, its specific effects on trophoblast biology remain incompletely elucidated. This narrative review synthesizes evidence derived from studies using human placental tissues and trophoblast cell models to delineate how excessive reactive oxygen species (ROS) disrupt molecular and cellular pathways essential for normal placentation. The literature search was restricted to human-based and in vitro investigations. Across these studies, OS was consistently shown to impair mitochondrial function in trophoblasts, resulting in increased mitochondrial ROS generation, loss of mitochondrial membrane potential, and activation of apoptotic signaling cascades. These mitochondrial disturbances were associated with reduced trophoblast proliferation, migration, and invasion, as well as dysregulation of angiogenic balance. Furthermore, several studies reported alterations in mitophagy, involvement of redox-sensitive pathways such as CYP1A1 and KLF9, and the extracellular release of mitochondrial DNA, which was linked to reduced cell viability and increased necrotic cell death. Collectively, the available evidence indicates that OS interferes with key trophoblast-dependent developmental processes, providing mechanistic insight into the pathogenesis of placental dysfunction observed in pregnancy complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR). Elucidation of these pathways may inform the development of targeted therapeutic strategies aimed at preserving placental function and improving adverse pregnancy outcomes.

OBJECTIVE:The objective of this study is to investigate long-term temporal trends in the size and age structure of the population of women of reproductive age (WRA) in Greece. MATERIALS AND METHODS:Data on the estimated mid-year WRA population (15-44 years) in Greece were obtained from the Hellenic Statistical Authority for the period 1956-2024. For each year, the percentage distribution of the WRA population across five-year age groups was calculated. Temporal trends were assessed using Joinpoint regression analysis, and annual percent changes (APCs) with corresponding 95% confidence intervals (95% CIs) were estimated. RESULTS:The WRA population in Greece fluctuated without a significant overall trend between 1956 and 1974, reaching 2,026,378 in 1968 and declining to 1,883,459 in 1974. Subsequently, it increased by 25% to a historic peak of 2,353,200 in 2000, with significant upward trends during 1974-1987 (APC = 0.7, 95% CI: 0.1 to 1.4) and 1987-1995 (APC = 1.3, 95% CI: 0.3 to 2.0). Since 2000, the WRA population has declined by 28%, reaching a historic low of 1,701,390 in 2024. The decline was modest during 2000-2010 (APC = -0.5, 95% CI: -0.5 to -0.4) but accelerated thereafter, with the WRA population decreasing by 24% between 2010 and 2024 at an almost exponential annual rate of 2.0%. Age-specific analysis revealed progressive aging of the WRA population. The modal age group shifted from 15-19 years during 1975-1988 to 40-44 years since 2010, highlighting a marked shift toward older reproductive ages. CONCLUSIONS:The WRA population in Greece entered a period of marked decline after reaching a historic peak in 2000, with an almost exponential decrease observed after 2010. Greece lost nearly one-quarter of its female population of childbearing age between 2010 and 2024. This demographic contraction was accompanied by pronounced aging of the WRA population, developments that are likely to substantially constrain the future annual number of births in the country.

Endometriosis is a chronic hormone-responsive disorder linked to infertility, usually characterized by the presence of ectopic endometrium in the pelvis that disrupts local homeostasis. Advances in single-cell “omic” methods have revealed the remarkable cellular diversity within the eutopic endometrium and endometriosis lesions, uncovering distinct populations with unique transcriptional and functional profiles. These studies have highlighted alterations in immune cell subsets, stromal and epithelial cell signaling, and intercellular communication networks that collectively impair oocyte quality, embryo development, and endometrial receptivity in women with endometriosis. By dissecting the molecular signatures of individual cells, single-cell approaches provide insights into the mechanisms driving persistent inflammation, impaired angiogenesis, hormonal dysregulation, and immune dysfunction in endometriosis. Importantly, emerging evidence indicates that infertility and reduced assisted reproductive technology (ART) success in endometriosis reflect coordinated cellular and molecular dysfunction rather than solely anatomical abnormalities. Single-cell analyses of oocytes, granulosa cells, and endometrial cell populations demonstrate transcriptomic and epigenetic alterations affecting mitochondrial function, steroid metabolism, immune regulation, and implantation-related signaling pathways, offering a biological explanation for impaired implantation and variable ART outcomes. Integration of these findings with clinical observations supports the concept that endometriosis-associated reproductive failure arises from combined ovarian and endometrial defects detectable at the cellular level. Current single-cell studies highlight candidate biomarker signatures with the potential to improve patient stratification, predict ART outcomes, and guide individualized therapeutic strategies. As these discoveries are refined into clinically applicable biomarker panels, single-cell technologies are poised to bridge mechanistic understanding and precision reproductive medicine, enabling more personalized management approaches aimed at restoring reproductive competence in patients with endometriosis.

In the human reproductive system, extracellular vesicles (EVs) have been recognized as playing a vital role in mediating cell-cell communication. They are considered critical for embryo development, implantation, gamete interaction, and fertilization. The various cargoes carried by EVs, depending on the physiological and pathological state of the cell, include proteins, lipids, nucleic acids, and mitochondrial components. EVs are recognized as critical carriers of redox-related signals and mitochondrial components, linking oxidative stress (OS) to reproductive failure and influencing gamete quality and embryo competence. Although considerable progress has been made, research remains poorly integrated, despite individual omics technologies providing valuable molecular insights. The use of multi-omics technologies, including transcriptomics, proteomics, metabolomics, and microbiome analysis, has been proposed as a global approach to understanding the complexities associated with EVs and discovering new biomarkers associated with infertility. ML and AI have been proposed to identify predictive signatures linked to ART effectiveness and reproductive outcomes, with a strong capacity to handle high-dimensional data. The review aims to provide an overview of current knowledge on EV-mediated redox-mitochondrial signaling in human reproduction, while highlighting the importance of emerging multi-omics and AI technologies for EV-mediated biomarker development. The review discusses the promise of EVs in the development of minimally invasive diagnostic approaches and therapeutic interventions, as well as the challenges in the standardization, integration, and clinical translation of EV-mediated research. In addition, the review proposes integrating computational approaches to better understand molecular pathways involved in the development of next-generation precision medicine in human reproduction.

Background: Miscarriage is defined as the spontaneous loss of a pregnancy before fetal viability and includes all pregnancy losses occurring from conception until 24 weeks of gestation. Recurrent pregnancy loss (RPL) is traditionally defined as three or more consecutive miscarriages. Emerging evidence suggests that both miR-99a and miR-143 may serve as promising biomarkers for recurrent pregnancy loss. Methods: A total of 42 women of reproductive age (18-45 years) were enrolled in this study. The control group consisted of 13 women with no history of recurrent miscarriage, whereas the study group included 29 women diagnosed with spontaneous miscarriages/recurrent implantation failure. Results: Both miR-99a and miR-143 showed significantly lower relative expression in women with recurrent miscarriage/recurrent implantation failure compared with the control group. Conclusions: Despite the relatively small sample size, statistically significant differences in the expression of miR-99a and miR-143 were observed between the case and control groups, with lower relative expression of both miRNAs in the case group. These findings suggest that both microRNAs may be associated with molecular pathways involved in reproductive failure. Furthermore, investigating the expression patterns of miR-99a and miR-143 may contribute to a better understanding of the molecular mechanisms underlying recurrent miscarriage/recurrent implantation failure. Such insights may facilitate the development of genetic risk profiles for women with unexplained pregnancy loss and implantation failure, as well as support the identification of potential therapeutic targets. Further studies are required to determine their potential value as molecular markers and to clarify their functional relevance in reproductive failure.

Endocrine disorders and inherent flaws in oocyte quality are traditional causes of female infertility. Increasing research indicates that structural and biomechanical alterations in the ovarian microenvironment may significantly contribute to reproductive decline. Progressive extracellular matrix remodeling, stromal fibrosis, chronic inflammation, and heightened tissue stiffness seem to affect follicular homeostasis, granulosa–oocyte communication, and ovarian function. Fibro-inflammatory pathways, including transforming growth factor-β (TGF-β), Hippo/YAP-TAZ signaling, oxidative stress, macrophage activation, and mechanotransduction, are increasingly associated with ovarian ageing, polycystic ovary syndrome, reduced ovarian reserve, and unfavourable reproductive outcomes. Here, the term ‘fibro-inflammatory ovary’ is used descriptively to unify these mechanisms rather than as an established clinical entity. Mechanical alterations of the ovarian stroma may affect follicular activation, vascularization, and oocyte competence by altering cellular tension and extracellular matrix dynamics. Our review examines growing findings about ovarian fibrosis and stromal remodeling in female infertility, focusing on molecular causes, mechanobiology, and translational implications for assisted reproduction. Potential diagnostic uses, such as ovarian elastography, and prospective anti-fibrotic therapy techniques are also examined.

Obstetric anal sphincter injuries (OASIs) are serious complications of vaginal delivery and the most frequent cause of postpartum anal incontinence. Underdiagnosis during delivery persists due to limited availability of accurate imaging. Transperineal ultrasound (TPUS) and endoanal ultrasound (EAUS) enable structural assessment of the anal sphincter and have growing roles in triage, repair planning, and follow-up.The aim of the present review is to integrate current evidence on diagnostic value, clinical usefulness, and potential implementation of TPUS and EAUS in gynecologic practice.Ultrasound identifies a high burden of occult sphincter trauma in primiparas with normal clinical assessment with rates close to 25%. EAUS is currently the gold standard for accurate imaging of defects. TPUS has excellent diagnostic performance for external anal sphincter (EAS) defects and is practical for bedside use. Improving the diagnosis of OASIs requires structured post-delivery clinical examination combined with selective use of TPUS as a first-line imaging modality and EAUS in cases of diagnostic uncertainty or suspected complex injury.Immediate postpartum ultrasound may help reduce delayed diagnoses and support timely surgical repair. Key barriers include operator dependence, training, availability, and variable image quality, particularly for routine EAUS in the labor ward.Incorporating ultrasound into postpartum management improves detection and classification of OASIs and subsequently repair and prognosis. Currently, judicious application in high-risk deliveries seems to be an appropriate approach until more evidence from prospective and economic studies is available. New technologies (3D/4D imaging, standardized terminology, and decision-support/AI) hold promise to increase reproducibility and use in everyday clinical practice.

Thrombocytopenia affects up to 10% of pregnant women and represents the second most common blood disorder during pregnancy. Its causes include immune-mediated thrombocytopenia, hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome, preeclampsia (PE), and benign pregnant thrombocytopenia. Diagnosis is crucial because the cause dictates the effect on maternal health, pregnancy management, and neonatal outcomes. This narrative review examines the range of thrombocytopenia during pregnancy, primarily focusing on diagnostic evaluation, underlying pathophysiological causes, and differential diagnosis. In addition, it organizes maternal and fetal complications that might be caused by the condition, such as bleeding, preterm birth, and neonatal thrombocytopenia. Moreover, current patient management based on available evidence and clinical practice is discussed, including immunomodulatory therapies, platelet transfusions, clinical monitoring, and supportive care. A thorough and clinically guided approach to thrombocytopenia in pregnancy is indispensable for maximizing maternal and fetal outcomes and facilitating the personalization of perinatal care.

Adipocytes produce the hormone leptin, a hormone that links energy availability to reproductive function by permitting activation of the hypothalamic-pituitary-gonadal (HPG) axis. Loss-of-function mutations in the long leptin receptor isoform (LEPRb) disrupt intracellular signaling pathways, including the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) pathways, resulting in central leptin resistance and impaired neuroendocrine control of reproduction. Evidence from human monogenic obesity syndromes, animal models, and neuroendocrine studies indicates that LEPRb mutations disrupt hypothalamic circuitry upstream of gonadotropin-releasing hormone (GnRH) neurons, impairing GnRH pulsatility and leading to hypogonadotropic hypogonadism (HH) and infertility. This review synthesizes molecular, translational, and clinical data highlighting the central role of kisspeptin-mediated signaling in leptin-dependent reproductive regulation. Current therapeutic limitations are discussed alongside emerging approaches, including kisspeptin-based therapies and receptor-targeted strategies. Elucidating how LEPRb dysfunction disrupts metabolic-reproductive integration may provide insights into both rare monogenic conditions and common obesity-associated reproductive dysfunction.

Conventional semen analysis frequently fails to identify the underlying pathophysiology of male infertility, which is a complicated clinical disease, especially in cases of idiopathic infertility. A growing body of research indicates that inflammation and oxidative stress (OS) are important and related factors in male reproductive failure. Excessive reactive oxygen species (ROS) promote lipid peroxidation, protein oxidation, mitochondrial dysfunction, and sperm DNA fragmentation, thereby compromising motility, morphology, and fertilizing capacity. Concurrently, pro-inflammatory mediators like interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) are frequently found in the seminal plasma of infertile men and are linked to poor semen parameters and testicular dysfunction. It is crucial that oxidative and inflammatory pathways work together to create a self-sustaining pathophysiological cycle that exacerbates sperm damage and destabilizes the reproductive milieu. The diagnostic significance, clinical suitability, and limitations of oxidative stress and inflammation biomarkers, such as malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), total antioxidant capacity (TAC), and specific inflammatory markers, are critically assessed in this comprehensive review. The lack of established diagnostic thresholds, methodological variation, and translational issues that still restrict their widespread clinical implementation are highlighted in particular. Additionally, the potential contribution of biomarker-guided approaches to focused therapy decisions and individualized patient management is explored. This study examines how oxidative and inflammatory markers may complement conventional male infertility assessments by supporting more precise, mechanism-based approaches in reproductive medicine, while addressing diagnostic readiness and translational limitations.

Background and Objectives: To examine the psychological parameters among pregnant organ transplant recipients that are understudied compared to the physical health of women during post-transplantation pregnancy. Materials and Methods: Systematic review based on PubMed, EMBASE, CINAHL, and PsycInfo that were searched until 15 January 2025. Quality Assessment and meta-aggregation were applied to qualitative studies. Results: Out of 4361 screened unique studies, six are included. Most studies were retrospective and focused on liver, kidney, and heart transplants. Meta-aggregation identified four synthesized findings: “Perception of Pregnancy after Transplantation”, “Concerns about Maternal Physical Health”, “Concerns about Fetal Health”, and “Emotional Burden by Expectant Mothers and Coping Strategies”. The review was constrained by the potential exclusion of relevant studies due to language restrictions and uncontrolled bias in the included studies. Conclusions: Several psychological themes were identified, not all exclusive to transplant recipients. Developing a targeted questionnaire to gather primary data could enhance clinical practice and improve counseling services for this patient population.

Endocrine-disrupting chemicals (EDCs) are a diverse group of environmental pollutants capable of interfering with hormonal and immune system regulation. In recent years, increasing concern has been raised about the effects of chemicals, including bisphenols, phthalates, per- and polyfluoroalkyl substances (PFAS), insecticides, and parabens, on maternal and fetal health, primarily due to their widespread exposure in human populations. Pregnancy represents a critical window characterized by tightly regulated hormonal and immunological adaptations. Emerging evidence suggests that EDC exposure during this period may alter maternal microbiota, disrupt immune responses, and interfere with endocrine signaling. These changes may increase susceptibility to bacterial and viral infections, including bacterial vaginosis, urinary tract infections, and intrauterine infections, all of which are associated with adverse pregnancy outcomes. This review summarizes the current evidence on the sources and mechanisms of exposure to endocrine disruptors during pregnancy and examines the potential biological pathways linking endocrine disruption to the development of infections. Particular emphasis is placed on the interactions between immune regulation, hormonal signaling, and changes in the microbiome, which may contribute to increased susceptibility to infections. A deeper understanding of these complex mechanisms is critical to improve risk assessment, develop effective public health strategies, and ultimately protect maternal and fetal health in an environment of increasing chemical exposure. A literature search was conducted using PubMed/MEDLINE, Scopus, and Web of Science, including studies published up to January 2026.

The pineal gland regulates circadian physiology through the periodic production of melatonin (MLT). In addition to its established role as a chronobiotic agent, MLT regulates redox homeostasis and mitochondrial physiology. Mitochondria and redox-active molecules, particularly reactive oxygen species (ROS), play essential roles in reproduction, including gamete physiology, fertilization, and early embryonic development. Although excessive oxidative stress (OS) impairs fertility, controlled ROS signaling is necessary for normal reproductive function. This comprehensive review synthesizes current evidence regarding MLT as a key intermediary linking circadian signaling with mitochondrial physiology and redox homeostasis. We discuss molecular pathways through which MLT regulates mitochondrial function, including activation of the Nrf2 signaling pathway, modulation of mitochondrial permeability transition, regulation of electron transport chain (ETC) efficiency, and apoptotic signaling. Furthermore, this study investigates MLT’s ability to scavenge free radicals and activate antioxidant defense mechanisms. Moreover, we review novel findings regarding the effects of MLT in experimental animals and humans, assisted reproductive technologies (ART) such as in vitro fertilization (IVF), and consider the translational significance of the hormone as an enhancer of fertility. We also highlight gaps in the literature, including methodological inconsistencies, supraphysiologic doses, and insufficient data from large human cohorts. Lastly, we discuss an integrative model whereby MLT may function as an important regulator of mitochondrial redox balance, with potential implications for reproductive physiology and reproductive outcomes, and propose new avenues for investigation.

Background: Recurrent implantation failure (RIF) remains one of the most challenging presentations in assisted reproductive technology and is characterized by failure to achieve clinical pregnancy despite the transfer of multiple good-quality embryos. Advances in embryo selection and preimplantation genetic testing have highlighted the contribution of endometrial factors to a substantial proportion of otherwise unexplained implantation failures. Methods: This narrative review summarizes current evidence regarding endometrial receptivity, the principal endometrial mechanisms implicated in RIF, contemporary diagnostic approaches, and available therapeutic strategies. Electronic literature searches were conducted using PubMed/MEDLINE, Scopus, ScienceDirect, and the Cochrane Library for publications available up to June 2026. Results: Anatomical, inflammatory, temporal, hormonal, immunological, and vascular endometrial causes of RIF can all be broadly categorized. Progesterone resistance, impaired decidualization, chronic endometritis, microbiome dysbiosis, displacement of the window of implantation, and immune dysregulation represent proposed mechanisms contributing to implantation failure in selected patients. Diagnostic evaluation is most effective when performed using a stepwise approach that prioritizes clinically actionable findings and avoids indiscriminate testing. Management primarily focuses on optimizing hormonal support, whereas immunomodulatory and antithrombotic therapies should be reserved for carefully selected patients. Emerging approaches, including granulocyte colony-stimulating factor, platelet-rich plasma, and microbiome-directed therapies, have shown promising preliminary results in selected patient populations; however, further validation is required. Conclusions: RIF is best regarded as a heterogeneous clinical outcome rather than a single disease entity, reflecting multiple disturbances in endometrial receptivity. Overall, current evidence supports a mechanism-informed approach that integrates targeted diagnostics with individualized, evidence-based therapeutic strategies.

Background/Objectives: During intrauterine development, cell proliferation, differentiation, and apoptosis are strictly regulated for organogenesis to be ensured; disruption of these processes, e.g., by oxidative stress, may lead to congenital anomalies. This systematic review aimed to examine the role of selenium (Se), an important antioxidant, during gestation in the development of congenital anomalies. Methods: To identify relevant original research studies in English, PubMed, Embase, and Cochrane Library were systematically searched up to December 2025. A qualitative synthesis, quality appraisal, and assessment of predefined sources of bias and heterogeneity were performed. Results: 2743 titles and abstracts were screened, 473 full texts assessed, and 31 papers included. Selenium exposure did not affect the risk of all/any congenital anomalies (n = 20,815), abdominal (n = 89,273) and limb anomalies (n = 551,547), chromosomal anomalies (n = 1242), or fetal alcohol syndrome (n = 41). Higher concentrations of Se were associated with increased risk for urinary tract anomalies (n = 2150), but decreased risk for congenital heart defects (n = 1807), neural tube defects (max n = 12,188), and orofacial clefts (max n = 1155). Conclusions: Available scientific evidence arises from observational studies and is prone to confounding mainly by gestational age, while only one randomized controlled trial has been identified. Given the major contribution of congenital anomalies to neonatal morbidity, mortality, and long-term impairment of quality of life, well-designed prospective studies are required to establish scientific consensus, define optimal maternal Se levels during pregnancy, and provide evidence-based recommendations for Se supplementation during pregnancy.

Background/Objectives: To construct and compare multivariable prediction models for the early prediction of large-for-gestational-age (LGA) neonates, using ultrasound biometry and maternal characteristics. Methods: This retrospective cohort study analyzed data from singleton pregnancies that underwent routine ultrasound examinations at 30+0-34+0 weeks of gestation. Ultrasound parameters included fetal abdominal circumference (AC), head circumference (HC), femur length (FL), HC-to-AC ratio, mean uterine artery pulsatility index (mUtA-PI), and presence of polyhydramnios. LGA neonates were defined as those having a birthweight > 90th percentile. Logistic regression was used to evaluate associations between ultrasound markers and LGA after adjusting for the following maternal and pregnancy-related covariates: maternal age, body mass index, parity, gestational diabetes mellitus (GDM), pre-existing diabetes, previous cesarean section (PCS), assisted reproductive technology (ART) use, smoking, hypothyroidism, and chronic hypertension. Associations were expressed as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Three prognostic models were developed utilizing the following predictors: (i) biometric ultrasound measurements including AC, HC-to-AC ratio, FL, UtA-PI, and polyhydramnios (Model 1), (ii) a combination of biometric ultrasound measurements and clinical-maternal data (Model 2), and (iii) only the estimated fetal weight (EFW) (Model 3). Results: In total, 3808 singleton pregnancies were included in the analyses. The multivariable analysis revealed that AC (aOR 1.07, 95% CI [1.06, 1.08]), HC to AC (aOR 1.01, 95% CI [1.006, 1.01]), FL (aOR 1.01, 95% CI [1.009, 1.01]), and the presence of polyhydramnios (aOR 4.97, 95% CI [0.7, 58.8]) were associated with an increased risk of LGA, while a higher mUtA-PI was associated with a reduced risk (aOR 0.98, 95% CI [0.98, 0.99]). Maternal parameters, such as GDM, pre-existing diabetes, elevated pre-pregnancy BMI, absence of uterine artery notching, mUtA-PI, and multiparity, were significantly higher in the LGA group. Both models 1 and 2 showed similar performance (AUCs: 84.7% and 85.3%, respectively) and outperformed model 3 (AUC: 77.5%). Bootstrap and temporal validation indicated minimal overfitting and stable model performance, while decision curve analysis supported potential clinical utility. Conclusions: Models using biometric and Doppler ultrasound at 30-34 weeks demonstrated good discriminative ability for predicting LGA neonates, with an AUC up to 84.7%. Adding maternal characteristics did not significantly improve performance, while the biometric model performed better than EFW alone. Sensitivity at conventional thresholds was low but increased substantially when lower probability cut-offs were applied, illustrating the model's threshold-dependent flexibility for early risk stratification in different clinical screening needs. Although decision curve analysis was performed to explore potential clinical utility, external validation and prospective assessment in clinical settings are still needed to confirm generalizability and to determine optimal decision thresholds for clinical application.

Background: Autonomy in decision making is a critical component of respectful, person-centered maternity care. The Mother's Autonomy in Decision Making (MADM) scale has been widely used internationally to evaluate women's perceptions of autonomy during perinatal period. Objectives: To assess the reliability and validity of the Greek translation of the MADM questionnaire among postpartum women who have given birth in hospitals and clinics in Greece. Methods: A cross-sectional study was conducted with 450 postpartum women who gave birth in public and private maternity facilities in Greece. Participants completed the Greek MADM scale, and statistical analyses included exploratory and confirmatory factor analysis (EFA/CFA), internal consistency (Cronbach's alpha), test-retest reliability (intraclass correlation coefficient, ICC), criterion validity (correlation with the Birth Satisfaction Scale (G-BSS), and Rasch analysis. Results: EFA revealed a one-factor structure explaining 77.6% of the variance (KMO = 0.913; Bartlett's p < 0.001). CFA supported good model fit (CFI = 0.924, RMSEA = 0.085). The Greek MADM showed excellent internal consistency (Cronbach's α = 0.951) and test-retest reliability (ICC = 0.995). Criterion validity was supported by moderate correlations with G-BSS subscales (r = 0.338-0.389, p < 0.005). Rasch analysis confirmed unidimensionality, high item reliability, and acceptable item fit. A cut-off score of 27.5 on the MADM scale was identified to distinguish between high and low-moderate birth satisfaction. Conclusions: The Greek version of the MADM scale demonstrates excellent psychometric properties and is a valid, reliable tool for assessing autonomy in maternity decision making. Its use can enhance quality assessment and promote respectful, autonomy-supportive perinatal care in Greek healthcare settings.

OBJECTIVES:The present study aimed to estimate macrosomia rates in Greece and investigate their temporal trends during the period 1980-2023. METHODS:This nationwide population-based study analyzed official birth registry data obtained from the Hellenic Statistical Authority. The dataset included 4,593,229 live births registered in Greece between 1980 and 2023. For each year, overall macrosomia rates (birth weight ≥4,000 g) and severe macrosomia rates (≥4,500 g) were calculated. Additional analyses were performed separately for grade 1 (4,000-4,499 g), grade 2 (4,500-4,999 g), and grade 3 (≥5,000 g) macrosomia, according to gestational age at delivery (37-39 vs. ≥40 weeks), and among singleton live births. Temporal trends were evaluated using Joinpoint regression analysis, and annual percent change (APC) and average annual percent change (AAPC) values with 95% confidence intervals (95% CI) were calculated. RESULTS:During 1980-2023, the overall macrosomia rate declined by 63%, from 7.66% in 1980 to a historic low of 2.85% in 2023 (AAPC = -2.3, 95% CI: -2.5 to -2.2). The decrease was moderate during 1980-1992 (APC = -1.5, 95% CI: -2.1 to -0.5) and became particularly pronounced between 1992 and 2001 (APC = -4.4, 95% CI: -7.8 to -3.6) and again during 2007-2010 (APC = -10.2, 95% CI: -12.2 to -6.5), following a period of stabilization between 2001 and 2007. After a modest increase during 2010-2020 (APC = 1.4, 95% CI: 0.8 to 2.9), rates declined again during 2020-2023 (APC = -6.9, 95% CI: -12.1 to -3.1). Severe macrosomia (≥ 4,500 g) decreased by 81%, from 10.17 to a record low of 1.95 per 1,000 live births between 1980 and 2023 (AAPC = -3.9, 95% CI: -4.2 to -3.6). Grade 1 macrosomia (4,000-4,499 g), grade 2 macrosomia (4,500-4,999 g), and grade 3 macrosomia (≥ 5,000 g) declined, with corresponding AAPC values of -2.2 (95% CI: -2.3 to -2.0), -3.4 (95% CI: -3.7 to -3.0), and -6.2 (95% CI: -6.8 to -5.7), respectively. Macrosomia rates decreased more markedly among births at 37-39 gestational weeks (AAPC = -2.8, 95% CI: -3.0 to -2.6) than among births at ≥ 40 weeks (AAPC = -1.0, 95% CI: -1.3 to -0.8). Similar declining trends were observed among singleton live births, with the overall macrosomia rate decreasing from 7.80% to 3.02% and severe macrosomia decreasing from 10.36 to 2.06 per 1,000 singleton live births. CONCLUSIONS:Since 1980, Greece has achieved substantial reductions in macrosomia rates, which reached historically low levels in 2023. The decline was more pronounced for the more severe categories of macrosomia. Continued surveillance and targeted interventions in high-risk populations may further improve fetal growth outcomes in the country.

A significant and persistent issue in assisted reproduction is recurrent implantation failure (RIF), which is often observed even after the transfer of embryos of high morphological and/or genetic quality. Accumulating data suggest that exposure to chemicals with endocrine-disrupting effects (EDCs) may be associated with adverse implantation outcomes. Many environmentally widespread substances have the potential to interfere with the regulation of the endocrine system, affecting critical mechanisms involved in implantation, such as endometrial receptivity, steroid hormone receptor signaling, immune tolerance at the maternal–fetal interface, and the epigenetic regulation of genes that are essential for successful implantation. Experimental studies have shown that exposure to EDCs can alter gene expression in the endometrium, inflammatory pathways, and the dynamics of early embryonic development, while clinical and epidemiological data have associated increased levels of EDCs in the body with lower implantation rates in assisted reproductive technology (ART) cycles. This narrative review examines the implications of these findings in reproductive medicine, summarizes recent experimental and clinical data, and highlights the molecular mechanisms linking exposure to endocrine disruptors with recurrent implantation failure. Recognizing environmental chemical exposure as a potentially modifiable risk factor may offer new perspectives for the prevention of RIF and the development of more personalized therapeutic strategies.