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Search Results (225)

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13 pages, 526 KB  
Review
The Role of Immunologic Factors in Endometrial Receptivity: An Embryo–Endometrium Dialogue
by Evangelia Panagodimou, Ianthi Terzopoulou, Olga Triantafyllidou, Georgios Markantes, Neoklis Georgopoulos, Nikolaos Vlahos, George Adonakis and Apostolos Kaponis
Int. J. Mol. Sci. 2026, 27(10), 4588; https://doi.org/10.3390/ijms27104588 - 20 May 2026
Abstract
Successful embryo implantation requires dynamic, bidirectional communication between a developmentally competent blastocyst and a receptive endometrium, integrating hormonal, molecular, and immunologic signals. Increasing evidence indicates that endometrial receptivity is critically dependent on a specialized immune microenvironment that supports trophoblast invasion while maintaining maternal [...] Read more.
Successful embryo implantation requires dynamic, bidirectional communication between a developmentally competent blastocyst and a receptive endometrium, integrating hormonal, molecular, and immunologic signals. Increasing evidence indicates that endometrial receptivity is critically dependent on a specialized immune microenvironment that supports trophoblast invasion while maintaining maternal tolerance. This review synthesizes current knowledge on the immunologic regulation of implantation, with emphasis on uterine natural killer (uNK) cells, regulatory T cells (Tregs), macrophages, dendritic cells, and cytokine networks. We further examine intracellular signaling pathways—including JAK/STAT, PI3K/AKT, NF-κB, and MAPK—that integrate immune and decidual responses. The bidirectional embryo–endometrium dialogue is explored through embryo-derived mediators such as human chorionic gonadotropin (hCG), cytokines, growth factors, and extracellular vesicles. The endometrium is increasingly recognized as a biosensor of embryo quality, selectively supporting viable embryos. Disruption of this complex communication network is implicated in recurrent implantation failure and early pregnancy loss. Despite substantial mechanistic advances, clinical translation remains limited. Emerging strategies, including immune profiling, microbiome modulation, and extracellular vesicle-based diagnostics, hold promise for precision reproductive medicine. Full article
(This article belongs to the Special Issue Molecular Pathways to Infertility)
9 pages, 240 KB  
Viewpoint
Autoimmune Disorders and Thrombophilia in Pathologic Pregnancies: Management Throughout the Full Gestation
by Rui Gao and Lang Qin
Biomedicines 2026, 14(5), 1143; https://doi.org/10.3390/biomedicines14051143 - 18 May 2026
Abstract
Pathologic pregnancies including recurrent pregnancy loss, stillbirth, early-onset pre-eclampsia and early-onset fetal growth restriction form a continuous spectrum throughout gestation and have attracted wide attention. Autoimmune disorders and associated acquired thrombophilia are key etiological factors. However, because of the complicated associations between various [...] Read more.
Pathologic pregnancies including recurrent pregnancy loss, stillbirth, early-onset pre-eclampsia and early-onset fetal growth restriction form a continuous spectrum throughout gestation and have attracted wide attention. Autoimmune disorders and associated acquired thrombophilia are key etiological factors. However, because of the complicated associations between various clinical manifestations, laboratory examinations and treatments, the management of pathologic pregnancies with autoimmune disorders and associated acquired thrombophilia are difficult. This viewpoint article presents a comprehensive full gestation management strategy emphasizing early identification and multidisciplinary management to improve pregnancy outcomes in these patients. Future research should focus on novel biomarkers, therapeutic methods and crosstalk mechanisms between autoimmune disorders and thrombophilia to optimize clinical strategies. Full article
(This article belongs to the Special Issue Immunology in Recurrent Pregnancy Loss, Preeclampsia and Infertility)
15 pages, 2269 KB  
Review
Redefining Endometrial Decidualization: The Central Role of the ER Stress–Immune–Metabolic Axis
by Özdem Karaoğlan, Özgül Tap and İbrahim Ferhat Ürünsak
Int. J. Mol. Sci. 2026, 27(10), 4382; https://doi.org/10.3390/ijms27104382 - 14 May 2026
Viewed by 89
Abstract
Decidualization in the human endometrium is not merely a hormone-dependent differentiation process; rather, it represents a multilayered adaptive program characterized by the tight integration of immune regulation, metabolic reprogramming, and cellular stress responses. In this review, endoplasmic reticulum (ER) stress and the associated [...] Read more.
Decidualization in the human endometrium is not merely a hormone-dependent differentiation process; rather, it represents a multilayered adaptive program characterized by the tight integration of immune regulation, metabolic reprogramming, and cellular stress responses. In this review, endoplasmic reticulum (ER) stress and the associated unfolded protein response (UPR) are proposed as central regulatory mechanisms governing this process. Triggered by increased protein synthesis and secretory demand, UPR activation under physiological conditions preserves proteostasis and supports the secretory capacity of stromal cells. In contrast, chronic or dysregulated activation leads to a maladaptive response characterized by apoptosis, inflammation, and metabolic dysfunction. UPR signaling pathways shape immune tolerance through their effects on macrophage polarization, uterine natural killer (uNK) cell function, and T cell balance. At the metabolic level, adenosine monophosphate-activated protein kinase (AMPK) regulates cellular adaptation through bidirectional interactions with mitochondrial function and redox homeostasis. Within this framework, the ER stress–immune–metabolic axis operates not as a linear pathway but as a dynamic network incorporating multiple feedback loops, thereby constituting a critical threshold mechanism that determines the success of decidualization. Disruption of this axis provides a shared mechanistic basis for pathologies such as recurrent implantation failure, pregnancy loss, and preeclampsia. From a therapeutic perspective, agents including chemical chaperones, UPR modulators, AMPK activators, and anti-inflammatory compounds hold translational potential by targeting these pathological feedback circuits. However, key knowledge gaps remain, particularly regarding the cell type-specific and temporal regulation of ER stress, the molecular boundaries defining the transition from adaptive to pathological states, and interspecies differences. Future studies employing single-cell omics approaches and functional in vivo models will be essential to elucidate the dynamic organization of this axis and to enable the development of targeted and personalized therapeutic strategies. Full article
(This article belongs to the Section Molecular Biology)
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11 pages, 517 KB  
Article
Asherman Syndrome in Mexican Women: Clinical Characteristics, Management, and Outcomes at a Tertiary Hospital
by Andrea Olguín-Ortega, Jessica Aidee Mora-Galván, Fernando Escobar-Ponce, Fernanda Villalobos-Mendoza, Alejandro Rendón-Molina, Oliver Cruz-Orozco and Enrique Reyes-Muñoz
J. Clin. Med. 2026, 15(10), 3672; https://doi.org/10.3390/jcm15103672 - 10 May 2026
Viewed by 215
Abstract
Background/Objective: Asherman syndrome is an acquired intrauterine adhesive disorder associated with menstrual abnormalities, infertility, recurrent pregnancy loss, and adverse reproductive outcomes. Data from Latin American tertiary referral centers remain limited. To characterize clinical history, classification, hysteroscopic management strategies, and anatomical and reproductive [...] Read more.
Background/Objective: Asherman syndrome is an acquired intrauterine adhesive disorder associated with menstrual abnormalities, infertility, recurrent pregnancy loss, and adverse reproductive outcomes. Data from Latin American tertiary referral centers remain limited. To characterize clinical history, classification, hysteroscopic management strategies, and anatomical and reproductive outcomes in a single cohort of Mexican women with Asherman syndrome. Methods: This retrospective cohort study included women identified through institutional electronic records between July 2016 and December 2023 with a diagnosis of Asherman syndrome and analyzable hysteroscopic records. Women were followed for twelve months. Recurrence was defined as hysteroscopic evidence of intrauterine adhesions during follow-up. Among women with follow-up hysteroscopy, two-sided Fisher’s exact tests were used to calculate odds ratios and 95% confidence intervals. Results: Fifty-four women were analyzed. A prior uterine procedure was documented in 44 women (81.5%), with sharp curettage in 35 (64.8%). The most common reasons for consultation were secondary infertility (29.6%), abnormal uterine bleeding (27.8%), primary infertility (20.4%), and recurrent pregnancy loss (13.0%). Disease severity was classified as mild in 30 women (55.6%), moderate in 11 (20.4%), and severe in 7 (13.0%). Hysteroscopic intervention was predominantly performed with cold knife adhesiolysis (83.3%). Twelve-month follow-up hysteroscopy was performed in 38 women (70.4%); recurrence was identified in 30 (55.6%). Among the 34 women with reproductive intent, 12 achieved a live birth, corresponding to a live birth rate of 35.3%. Conclusions: Prior uterine instrumentation, particularly sharp curettage, was the most frequent antecedent. Recurrence remained common despite surgical management, highlighting the need for standardized postoperative surveillance and preventive strategies. Full article
(This article belongs to the Special Issue Advanced Hysteroscopic Technology for Gynecological Disease)
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30 pages, 1231 KB  
Review
The Impact of Congenital Anomalies of the Male and Female Reproductive Organs on Infertility and Recurrent Pregnancy Loss: A Review
by Bojana Petrovic, Sanja Kostic, Ivana Milan Jovanovic, Milica Petronijevic, Milos Petronijevic, Igor Hudic and Svetlana Vrzic Petronijevic
Medicina 2026, 62(5), 812; https://doi.org/10.3390/medicina62050812 - 24 Apr 2026
Viewed by 788
Abstract
Congenital anomalies of the reproductive system represent a heterogeneous group of structural and functional abnormalities affecting both male and female genital organs. These anomalies typically arise during embryogenesis and may remain asymptomatic until they are incidentally identified during evaluation for infertility, recurrent pregnancy [...] Read more.
Congenital anomalies of the reproductive system represent a heterogeneous group of structural and functional abnormalities affecting both male and female genital organs. These anomalies typically arise during embryogenesis and may remain asymptomatic until they are incidentally identified during evaluation for infertility, recurrent pregnancy loss, or disorders of sexual development. In females, abnormalities include Müllerian duct anomalies and congenital malformations of the uterus, cervix, vagina, and ovaries, such as Mayer–Rokitansky–Küster–Hauser syndrome, septate, unicornuate, bicornuate, and didelphys uteri, and ovarian agenesis and undescended ovaries. In males, congenital conditions such as anorchia, cryptorchidism, hypospadias, ejaculatory duct obstruction, and ejaculatory dysfunction may be associated with impaired spermatogenesis and reduced fertility. Early recognition of these conditions may facilitate timely clinical evaluation and individualized management, which can include surgical correction, hormonal therapy, and reproductive counseling. When appropriate, early diagnosis may support multidisciplinary care, with the aim of optimizing sexual development, preserving reproductive potential, and reducing long-term morbidity associated with congenital anomalies. However, the clinical impact of early detection varies depending on the type and severity of the anomaly. A systematic and multidisciplinary approach may contribute to improved reproductive outcomes and better overall reproductive health in affected individuals. Further research is needed to better define the optimal timing and clinical utility of systematic evaluation strategies in this patient population. Full article
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17 pages, 827 KB  
Systematic Review
Diagnostic Accuracy of MUM1 (IRF4) Immunohistochemistry in Chronic Endometritis: A Systematic Review and Bayesian Meta-Analysis
by Ana Maria Mihoci, Demetra Socolov, Eduard Cristian Mihoci, Loredana Maria Toma, Andreea Ioana Pruteanu and Răzvan Vladimir Socolov
Diagnostics 2026, 16(8), 1167; https://doi.org/10.3390/diagnostics16081167 - 15 Apr 2026
Viewed by 508
Abstract
Background/Objectives: Chronic endometritis (CE) is an underrecognized inflammatory disorder associated with infertility, recurrent pregnancy loss, and implantation failure. CD138 immunohistochemistry is widely used to detect endometrial plasma cells; however, background epithelial staining and interobserver variability may limit diagnostic precision. MUM1 (IRF4), a nuclear [...] Read more.
Background/Objectives: Chronic endometritis (CE) is an underrecognized inflammatory disorder associated with infertility, recurrent pregnancy loss, and implantation failure. CD138 immunohistochemistry is widely used to detect endometrial plasma cells; however, background epithelial staining and interobserver variability may limit diagnostic precision. MUM1 (IRF4), a nuclear transcription factor expressed in plasma cells, has emerged as a potential complementary marker. We aimed to systematically evaluate the diagnostic performance of MUM1 immunohistochemistry relative to CD138-based histopathologic reference frameworks for chronic endometritis using a Bayesian meta-analytic framework. Methods: We conducted a systematic review and diagnostic test accuracy meta-analysis in accordance with PRISMA 2020 and PRISMA-DTA guidelines. MEDLINE, Embase, Scopus, and CENTRAL were searched from inception to 28 February 2026. Studies assessing MUM1 immunohistochemistry against predefined histopathologic reference frameworks for CE were eligible. Risk of bias was evaluated using QUADAS-2. A bivariate Bayesian random-effects model was applied to jointly estimate pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR). Results: Six studies (n = 1574 women) were included in the qualitative synthesis, and four provided sufficient 2 × 2 data for quantitative pooling. The pooled sensitivity of MUM1 was 0.876 (95% credible interval (CrI): 0.536–0.976), and the pooled specificity was 0.853 (95% CrI: 0.653–0.930). The pooled positive likelihood ratio was 5.83 (95% CrI: 2.18–12.04), and the negative likelihood ratio was 0.15 (95% CrI: 0.03–0.56), corresponding to a DOR of 40.27 (95% CrI: 5.04–254.59). Credible intervals were wide, reflecting statistical uncertainty related to the limited number of studies and heterogeneity in diagnostic thresholds. Conclusions: MUM1 (IRF4) immunohistochemistry demonstrates potentially favorable comparative diagnostic performance relative to CD138-based reference frameworks, although substantial uncertainty remains due to limited and heterogeneous evidence. As an adjunctive nuclear marker, MUM1 may support histopathologic assessment of chronic endometritis; however, prospective head-to-head studies using harmonized diagnostic criteria and predefined plasma cell thresholds are required before routine implementation can be firmly recommended. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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23 pages, 2284 KB  
Systematic Review
The Role of Endometrial Microbiota in the Pathogenesis of Chronic Endometritis: A Systematic Review and Meta-Analysis
by Angela Vidal, Anaïs Y. Kilian, Vithusha Vinayahalingam, Branislav Zagrapan, Janna Pape, Tanya Karrer and Michael von Wolff
Biomedicines 2026, 14(4), 871; https://doi.org/10.3390/biomedicines14040871 - 10 Apr 2026
Viewed by 684
Abstract
Background: Chronic endometritis (CE) is a subtle, often asymptomatic endometrial inflammation marked by CD138+ plasma cell infiltration and linked to recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), and unexplained infertility. Emerging evidence implicates endometrial microbiome dysbiosis in CE. Objective: To systematically [...] Read more.
Background: Chronic endometritis (CE) is a subtle, often asymptomatic endometrial inflammation marked by CD138+ plasma cell infiltration and linked to recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), and unexplained infertility. Emerging evidence implicates endometrial microbiome dysbiosis in CE. Objective: To systematically review and conduct meta-analysis on the association between CE and endometrial microbiome alterations and their reproductive implications. Methods: We searched MEDLINE, Embase, Web of Science, Scopus, Cochrane CENTRAL, and Google Scholar for studies diagnosing CE via CD138 immunostaining, assessing microbiota with molecular techniques. Data extraction, quality assessment, and meta-analysis were performed. Results: Twenty-two studies including 4022 women were analyzed. CE was associated with reduced prevalence of Lactobacillus-dominated microbiota and increased detection of non-Lactobacillus species, particularly Streptococcus spp., Enterococcus spp., Escherichia coli, Staphylococcus spp., Ureaplasma spp., and Gardnerella vaginalis. In the meta-analysis (2947 women), Enterococcus spp. and Ureaplasma spp. were significantly more prevalent in women with CE, whereas Streptococcus spp., E. coli, Staphylococcus spp. and G. vaginalis showed non-significant trends. Only E. coli and Streptococcus spp. showed significant heterogeneity between-studies. Conclusions: CE is linked to microbial dysbiosis with reduced Lactobacillus dominance and enrichment of potentially pathogenic taxa, notably Enterococcus and Ureaplasma spp. These findings suggest that the endometrial microbiome contributes to chronic inflammation and adverse reproductive outcomes, yet heterogeneity and limited evidence call for standardized diagnostics and robust trials before clinical implementation. Full article
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12 pages, 2349 KB  
Article
Retrospective Analysis of 1168 Cases of Ovular Decidual Tissue from First-Trimester Abortions: Proposal for a Histopathological Diagnostic Framework
by Eleonora Nardi and Vincenzo Arena
Diagnostics 2026, 16(8), 1128; https://doi.org/10.3390/diagnostics16081128 - 9 Apr 2026
Viewed by 478
Abstract
Background: Early pregnancy loss, defined as the spontaneous loss of a pregnancy before 20 weeks of gestation or when the fetus weighs less than 500 g, remains a common obstetric complication, affecting up to 15% of clinically recognized pregnancies. Chromosomal abnormalities, particularly [...] Read more.
Background: Early pregnancy loss, defined as the spontaneous loss of a pregnancy before 20 weeks of gestation or when the fetus weighs less than 500 g, remains a common obstetric complication, affecting up to 15% of clinically recognized pregnancies. Chromosomal abnormalities, particularly aneuploidies such as trisomies and monosomy X, account for 50–60% of first-trimester losses, with incidence increasing alongside maternal age. Additional risk factors include maternal medical conditions, uterine anomalies, infections, and modifiable lifestyle factors. Pregnancies conceived through assisted reproductive technologies also carry a slightly higher risk of miscarriage, often influenced by maternal age and embryo quality. Methods: Two pathologists, blinded to each other’s assessments, analyzed abortive material from patients who experienced spontaneous first-trimester abortion between January 2012 and January 2025 at Agostino Gemelli Hospital, Rome, Italy. Inclusion criteria were defined independently of patient demographics. No restrictions were applied regarding maternal age. With respect to gestational age, only first-trimester miscarriages (≤12 weeks of gestation) were considered. In cases of discordance, the case was reviewed and re-evaluated to reach a final diagnosis. Results: The findings of this study are presented as a proposed histopathological classification and diagnostic framework for first-trimester miscarriages. Specifically, a total of 1168 cases were categorized into eight distinct groups of miscarriage etiology based exclusively on the histomorphological features of chorionic villi and maternal decidua. Conclusions: Histopathological examination of products of conception is essential for confirming intrauterine pregnancy, identifying underlying maternal or fetal causes, and guiding future reproductive management, particularly in recurrent pregnancy loss. This study evaluates histopathological features of first-trimester losses, classifies findings by etiology, and proposes a practical diagnostic guide to support clinical decision-making and improve outcomes in subsequent pregnancies. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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18 pages, 1000 KB  
Article
A Pilot Study on Multigenic Thrombophilic Risk in Recurrent Pregnancy Loss: Interactions Between MTHFR Polymorphisms and Classical Thrombophilia-Associated SNPs
by Oana-Viola Badulescu, Monica Hancianu, Cornelia Mircea, Andrei Bojan, Dragos-Florin Tesoi, Maria Cristina Vladeanu, Manuela Ciocoiu, Otilia-Elena Frasinariu, Carmen Elena Plesoianu, Dan Iliescu-Halitchi and Iris Bararu Bojan
Int. J. Mol. Sci. 2026, 27(7), 3112; https://doi.org/10.3390/ijms27073112 - 29 Mar 2026
Viewed by 811
Abstract
Recurrent spontaneous miscarriages represent a significant reproductive challenge, often associated with inherited thrombophilia. Among the genetic factors involved, methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been increasingly studied. The two main variants, MTHFR C677T and MTHFR A1298C, have been suggested to contribute [...] Read more.
Recurrent spontaneous miscarriages represent a significant reproductive challenge, often associated with inherited thrombophilia. Among the genetic factors involved, methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been increasingly studied. The two main variants, MTHFR C677T and MTHFR A1298C, have been suggested to contribute to thrombotic events and adverse pregnancy outcomes. This study aims to evaluate the higher prevalence and potential role of MTHFR gene polymorphisms (C677T and A1298C) in the etiology of recurrent spontaneous miscarriages in pregnant women with inherited thrombophilia, in comparison with the classical thrombophilia-associated SNPs—F5 Leiden and the F2 G20210A gene mutation. In this single-center retrospective observational study, 64 women with recurrent pregnancy loss and confirmed inherited thrombophilia were evaluated. Genomic DNA extracted from peripheral blood samples was analyzed for thrombophilia-associated polymorphisms, including F5 Leiden (G1691A), F2 G20210A, MTHFR C677T, MTHFR A1298C, SERPINE1 4G/5G, and F13A1 V34L, using a real-time PCR-based Bosphore® Thrombophilia Panel. The presence of MTHFR C677T and A1298C polymorphisms was investigated and compared to the incidence of F5 Leiden and F2 G20210A gene SNPs. Associations between genotypes and clinical characteristics, including the number of pregnancy losses, were assessed using chi-square tests, Kruskal–Wallis analysis, and logistic regression models. The most frequently detected polymorphisms were heterozygous variants of the MTHFR gene, with prevalences of 57.8% for C677T and 53.1% for A1298C. Homozygous MTHFR C677T was significantly associated with a higher number of pregnancy losses (Kruskal–Wallis test, p = 0.001). Similarly, the homozygous MTHFR A1298C genotype showed a significant association with increased miscarriage frequency (p = 0.012). Classical thrombophilic mutations were less frequent, with F2 G20210A identified in only two patients, although its presence was associated with a higher number of pregnancy losses (p = 0.030). These findings suggest that combined thrombophilic polymorphisms may contribute to recurrent pregnancy loss, although larger studies are required to confirm these observations. Full article
(This article belongs to the Special Issue Role of Mutations and Polymorphisms in Various Diseases: 2nd Edition)
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13 pages, 860 KB  
Article
Impact of Cumulative Embryo Implantation Failures on Embryonic Ploidy Status and Post-PGT-A Clinical Outcomes: A Retrospective Cohort Analysis
by Jie Li, Wei Zhou, Tianxiang Ni, Yueting Zhu, Qian Zhang and Junhao Yan
Genes 2026, 17(4), 389; https://doi.org/10.3390/genes17040389 - 29 Mar 2026
Viewed by 649
Abstract
Objective: To investigate the relationship between the number of previous implantation failures (IFs) and embryo ploidy status, as well as subsequent clinical outcomes, in women with recurrent implantation failure (RIF) undergoing preimplantation genetic testing for aneuploidy (PGT-A). Methods: This retrospective cohort study included [...] Read more.
Objective: To investigate the relationship between the number of previous implantation failures (IFs) and embryo ploidy status, as well as subsequent clinical outcomes, in women with recurrent implantation failure (RIF) undergoing preimplantation genetic testing for aneuploidy (PGT-A). Methods: This retrospective cohort study included 422 women with RIF who underwent their first PGT-A cycle between 2017 and 2022. Participants were stratified by maternal age (<38 years, n = 292; ≥38 years, n = 130) and by the number of previous IFs, categorized as 3, 4, or ≥5. The primary outcomes were embryo ploidy rates (euploidy, aneuploidy, and mosaicism). Secondary outcomes included reproductive outcomes after single euploid blastocyst transfer (biochemical pregnancy, clinical pregnancy, ongoing pregnancy, live birth, and pregnancy loss) and neonatal birth weight. Results: Women aged ≥38 years had a significantly lower euploidy rate than those <38 years (24.8% vs. 47.3%, p < 0.001). Ploidy distribution did not differ significantly across IF categories. Among women aged <38 years with ≥5 IFs, a greater number of previous embryo transfer attempts was independently associated with higher odds of live birth after euploid embryo transfer (adjusted OR = 1.258, 95% CI: 1.051–1.505; p = 0.012). Neonatal weight did not differ significantly across IF categories. Conclusions: The number of previous IFs was not independently associated with embryo ploidy or clinical outcomes after euploid transfer, whereas advanced maternal age was strongly associated with a lower likelihood of obtaining euploid embryos. In younger women with ≥5 IFs, a greater number of previous embryo transfer attempts was associated with live birth after euploid transfer; however, this exploratory subgroup finding should be interpreted cautiously and requires prospective validation. Because this study did not directly evaluate therapeutic strategies, any potential role for individualized endometrial evaluation or optimization should be considered as hypothesis-generating rather than supported by the present data. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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15 pages, 761 KB  
Article
Diagnostic Yield of Phenotype-Guided Genetic Testing in Infertility: A Five-Year Retrospective Study from a Tertiary Referral Cohort
by Kristina Aleknavičienė, Marius Šukys, Živilė Žemeckienė, Birutė Žilaitienė and Rasa Ugenskienė
Diagnostics 2026, 16(6), 896; https://doi.org/10.3390/diagnostics16060896 - 18 Mar 2026
Viewed by 470
Abstract
Background/Objectives: To evaluate the diagnostic yield of phenotype-guided cytogenetic and targeted molecular genetic testing in patients referred for infertility and reproductive disorders within a tertiary medical genetics referral pathway. Methods: This retrospective study included 900 consecutive patients (473 males, 427 females) [...] Read more.
Background/Objectives: To evaluate the diagnostic yield of phenotype-guided cytogenetic and targeted molecular genetic testing in patients referred for infertility and reproductive disorders within a tertiary medical genetics referral pathway. Methods: This retrospective study included 900 consecutive patients (473 males, 427 females) referred to a tertiary medical genetics center between January 2020 and December 2024. Conventional karyotyping was performed in all patients. Additional targeted molecular tests were applied based on clinical indication: Y chromosome microdeletion analysis in azoospermia or oligospermia, CFTR sequencing in suspected congenital bilateral absence of the vas deferens, and F2/F5 genotyping in recurrent pregnancy loss (RPL). Diagnostic yield was analyzed in a predefined subgroup of 566 patients with RPL, unexplained infertility, azoospermia, or oligospermia; remaining referrals were included in descriptive cytogenetic analyses only. Results: Chromosomal abnormalities were identified in 3.22% (29/900) of the total cohort and in 5.12% (29/566) of the diagnostic-yield cohort. Targeted testing yields were 3.75% (6/160) for Y chromosome microdeletions, 9.38% (3/32) for CFTR variants, and 3.31% (4/121) for F2/F5 variants. Diagnostic yield varied markedly by phenotype, being highest in azoospermia (33.3%), followed by oligospermia (6.6%), RPL (5.3%), and unexplained infertility (3.1%). In unexplained infertility, all chromosomal abnormalities were detected in female patients. Conclusions: In a tertiary referral setting, phenotype-guided genetic testing provides the greatest diagnostic value in well-defined infertility phenotypes, particularly azoospermia. Lower yields in other referral groups support a targeted, indication-based approach to genetic evaluation and highlight the need for advanced genomic strategies in persistently unexplained cases. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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13 pages, 760 KB  
Article
Anti-β2GPI/HLA-DR Antibody, Chronic Endometritis, and Uterine Endometrial Microbiome in Women with Recurrent Pregnancy Loss: A Prospective Cohort Study
by Hideto Yamada, Yosuke Ono, Hajime Ota, Yuta Kobayashi, Yoshiyuki Fukushi, Shinichiro Wada and Hisashi Arase
Microorganisms 2026, 14(3), 544; https://doi.org/10.3390/microorganisms14030544 - 27 Feb 2026
Viewed by 775
Abstract
Anti-β2GPI/HLA-DR antibody, chronic endometritis (CE), and endometrial dysbiosis are likely to be associated with the etiologies of recurrent pregnancy loss (RPL). This prospective cohort study aimed to investigate these new risk factors together with conventional causes for RPL, and to evaluate pregnancy outcomes [...] Read more.
Anti-β2GPI/HLA-DR antibody, chronic endometritis (CE), and endometrial dysbiosis are likely to be associated with the etiologies of recurrent pregnancy loss (RPL). This prospective cohort study aimed to investigate these new risk factors together with conventional causes for RPL, and to evaluate pregnancy outcomes in women individually treated. A total of 87 women with RPL underwent conventional assessment together with anti-β2GPI/HLA-DR antibody measurements, CD138 immunohistochemistry for CE, and 16S rRNA sequence analysis for endometrial microbiome. Women with anti-β2GPI/HLA-DR antibody, CE, and endometrial dysbiosis received low-dose aspirin and heparin, antibiotics, and probiotics, respectively. Pregnancy outcomes of the participants were assessed. Anti-β2GPI/HLA-DR antibody, CE, non-Lactobacillus-dominant microbiome (NLDM)-1 (Lactobacillus + Bifidobacterium < 80%), and NLDM-2 (Lactobacillus without iners + Bifidobacterium < 80%) were detected in 16 (18.4%), 22 (25.3%), 27 (31.0%), and 46 (52.8%) women, respectively. Based on conventional assessment, 65.5% of women with RPL were classified as unexplained etiology; however, the percentage reduced to 16.1% when these new tests were assessed together. All 9 pregnancies with anti-β2GPI/HLA-DR antibody, 13 (92.9%) of 14 pregnancies with CE, and 24 (92.3%) of 26 pregnancies with NLDM-2 resulted in live birth. Assessment of these new tests may be clinically useful for reducing the proportion of unexplained RPL, and for providing high live birth rates if women receive relevant treatments. Full article
(This article belongs to the Collection Feature Papers in Medical Microbiology)
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33 pages, 2334 KB  
Review
Oxidative Stress, Sperm DNA Fragmentation, or Both? Optimizing Test Selection in Male Infertility Evaluation
by Aris Kaltsas, Stamatis Papaharitou, Pallav Sengupta, Ramadan Saleh and Ashok Agarwal
Antioxidants 2026, 15(3), 293; https://doi.org/10.3390/antiox15030293 - 26 Feb 2026
Viewed by 2257
Abstract
Oxidative stress (OS) and sperm DNA fragmentation (SDF) are complementary contributors to male infertility. OS characterizes a compromised seminal redox status, whereas SDF quantifies downstream genomic damage. Human sperm are highly susceptible to redox damage due to lipid-rich membranes and disrupted post-meiotic DNA-repair [...] Read more.
Oxidative stress (OS) and sperm DNA fragmentation (SDF) are complementary contributors to male infertility. OS characterizes a compromised seminal redox status, whereas SDF quantifies downstream genomic damage. Human sperm are highly susceptible to redox damage due to lipid-rich membranes and disrupted post-meiotic DNA-repair capacity. Excess reactive oxygen species (ROS) can cause lipid peroxidation, oxidative base lesions, and DNA strand breaks that impair fertilization, embryo development, and pregnancy outcomes. This review explains how OS promotes genomic instability and summarizes the main laboratory assays that assess redox status and SDF in semen. These include direct ROS chemiluminescence assay, oxidation–reduction potential, total antioxidant capacity/ferric reducing antioxidant power, and lipid peroxidation biomarkers, alongside SDF platforms (Sperm Chromatin Structure Assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling, alkaline/neutral Comet, and sperm chromatin dispersion). Additionally, guideline-aligned indications are highlighted to clarify the conditions for testing OS and SDF. OS testing is most relevant in men with leukocytospermia or suspected genital tract infection or inflammation, including dysbiosis; in cases of major modifiable exposures such as smoking or heat; and for early monitoring after treatment. SDF testing is particularly informative in couples with recurrent pregnancy loss and in unexplained infertility with normal semen parameters. Combined OS and SDF testing is recommended in clinical varicocele, repeated in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) failure, poor embryo development, and follow-up after targeted therapy. Management centers on treating infection and inflammation, improving lifestyle and environmental factors, considering varicocelectomy when indicated, using targeted antioxidant therapy in men with documented OS, and selectively applying sperm selection technologies or testicular sperm for ICSI when SDF remains high. Priorities include assay standardization, etiologic attribution of DNA damage, and trials testing OS/SDF-guided pathways with live birth as the primary endpoint. When used selectively and in the appropriate context, OS and SDF testing can help refine diagnosis, improve counseling, and help personalize care of infertile couples. Full article
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15 pages, 3022 KB  
Review
Acquired Uterine Arteriovenous Fistulas After First-Trimester Pregnancy Loss: A Narrative Review with Case-Based Insights into Minimally Invasive Management
by Răzvan-Grigoraș Căpitănescu, Elena-Iuliana-Anamaria Berbecaru, Anca-Maria Istrate-Ofițeru, Marian-Valentin Zorilă, Doru-Andrei Mitroi, Gabriela-Camelia Roșu, Dominic-Gabriel Iliescu, Roxana-Cristina Drăgușin, Laurențiu-Mihai Dîră, Maria-Cristina Comănescu and George-Lucian Zorilă
Medicina 2026, 62(2), 422; https://doi.org/10.3390/medicina62020422 - 23 Feb 2026
Viewed by 854
Abstract
Background and Objectives: Uterine arteriovenous fistulas (AVFs) and arteriovenous malformations (AVMs) are rare but potentially life-threatening vascular anomalies that most commonly develop after pregnancy-related uterine trauma, such as curettage or surgical evacuation. The widespread use of color Doppler ultrasonography has led to [...] Read more.
Background and Objectives: Uterine arteriovenous fistulas (AVFs) and arteriovenous malformations (AVMs) are rare but potentially life-threatening vascular anomalies that most commonly develop after pregnancy-related uterine trauma, such as curettage or surgical evacuation. The widespread use of color Doppler ultrasonography has led to increased recognition of these lesions and a shift from hysterectomy toward fertility-preserving, minimally invasive management. This narrative review summarizes current evidence on acquired uterine AVF/AVM after early pregnancy loss, with particular emphasis on diagnostic challenges and contemporary therapeutic approaches, illustrated by representative clinical experience. Materials and Methods: A narrative review of the literature was conducted focusing on the pathophysiology, ultrasound and Doppler diagnostic criteria, interventional radiologic techniques, hysteroscopic management, and fertility outcomes in acquired uterine AVF/AVM. Illustrative clinical insights from anonymized post-abortion cases managed at our institution were incorporated solely to contextualize diagnostic and therapeutic considerations. Results: Color and spectral Doppler ultrasonography emerged as the diagnostic cornerstone, typically demonstrating serpiginous myometrial vessels with high-velocity, low-resistance turbulent flow, allowing for differentiation from retained products of conception. Uterine artery embolization showed high efficacy in achieving hemorrhage control, while hysteroscopic coagulation or resection represented an effective complementary or, in selected focal lesions, definitive treatment. Clinical experience highlighted that AVF-related vascularity may be evident early or may evolve over time, underscoring the importance of repeat Doppler evaluation in patients with persistent or recurrent bleeding. Conclusions: Acquired uterine AVF should be considered in women presenting with ongoing or recurrent uterine bleeding following aspiration abortion or curettage, even when initial Doppler findings are inconclusive. Individualized, minimally invasive strategies—often combining uterine artery embolization and hysteroscopic techniques—offer effective, uterus-preserving alternatives to hysterectomy. Full article
(This article belongs to the Special Issue Recent Advances in Gynecological Surgery)
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Article
The Prevalence of Depression, Anxiety, and Stress in Women with Recurrent Pregnancy Loss and Infertility Compared to Normal Controls in Oman: A Prospective, Cross-Sectional Study
by Manal Al-Busaidi, Wadha Al-Ghafri, Maryam Al Shukri, Hamed Al-Sinawi, Rahma Al-Ghabshi and Vaidyanathan Gowri
Healthcare 2026, 14(4), 453; https://doi.org/10.3390/healthcare14040453 - 11 Feb 2026
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Abstract
Background: Recurrent pregnancy loss (RPL) and infertility are associated with significant psychological morbidity, including stress, anxiety, and depression. While these impacts are well-documented globally, their prevalence and severity in the Omani population remain unexplored. This study investigates the mental health outcomes of Omani [...] Read more.
Background: Recurrent pregnancy loss (RPL) and infertility are associated with significant psychological morbidity, including stress, anxiety, and depression. While these impacts are well-documented globally, their prevalence and severity in the Omani population remain unexplored. This study investigates the mental health outcomes of Omani women with RPL and infertility compared to fertile controls. Objectives: The objectives of this study are to assess the prevalence of stress, anxiety, and depression in women with recurrent pregnancy loss (RPL) and infertility and compare these rates to women with no fertility concerns in an Omani population. Design: This is a prospective, cross-sectional study. Setting: This study’s setting consisted of Sultan Qaboos University Hospital and Royal Hospital in Muscat, Oman. Participants: This study included 111 women with RPL, 131 women with infertility, and 210 antenatal controls with no fertility issues. Interventions: No clinical interventions were administered as this was an observational study. Participants completed validated psychological assessments (DASS-42 and BDI-II). Primary and secondary outcome measures: Primary outcomes were the prevalence rates of stress, anxiety, and depression assessed using DASS-42 and BDI-II. Secondary outcomes included sociodemographic correlates and risk factors Results: This study included 111 women in the RPL group, 131 in the infertility group, and 210 controls. Among RPL patients, 31% reported stress, ranging from mild to extremely severe, while 35.9% of infertility patients reported stress, compared to 17.1% in the control group (p = 0.003). Anxiety was present in 45% of RPL patients, 45.5% of infertility patients, and 28.1% of controls (p = 0.019). Depression, measured by DASS-42, was the most prevalent in the RPL group (34.2%), followed by the infertility group (33.6%) and controls (13.8%) (p < 0.001). Similar results were observed with BDI-II, with depression rates of 23.4% in the RPL group, 19.1% in the infertility group, and 7.6% in controls (p = 0.02). Conclusions: Women with RPL and infertility in Oman experience significantly higher levels of stress, anxiety, and depression compared to women without fertility concerns. This study did not assess the mental health of male partners, highlighting the need for further research on the psychological impact on both partners. Future studies should focus on developing psychological support interventions and evaluating their impact on patient outcomes. Full article
(This article belongs to the Section Mental Health and Psychosocial Well-being)
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