Search Results (3,762)

Background/Objectives: Endometriosis is frequently associated with infertility and may affect several aspects of reproductive competence. However, whether women with endometriosis exhibit different preimplantation genetic testing for aneuploidy (PGT-A) outcomes compared with women without endometriosis remains uncertain. This study aimed to compare the distribution of PGT-A chromosomal outcomes—including euploid, mosaic, aneuploid, and complex aneuploid results—between women with and without endometriosis undergoing IVF. Methods: This retrospective observational study included 160 women who underwent IVF treatment between January 2023 and January 2026, including 55 women with endometriosis and 105 controls without evidence of endometriosis. A total of 129 blastocysts underwent trophectoderm biopsy and PGT-A, of which 120 yielded conclusive chromosomal results. PGT-A outcomes were classified as euploid, mosaic, aneuploid, or complex aneuploid. The overall distribution of the four PGT-A outcome categories was compared between groups using an unadjusted chi-square test. Results: Among blastocysts with conclusive PGT-A results, the proportions of euploid, mosaic, aneuploid, and complex aneuploid embryos were 31.6%, 18.4%, 26.3%, and 23.7%, respectively, in the endometriosis group and 42.7%, 14.6%, 25.6%, and 17.1%, respectively, in the control group. The overall distribution of PGT-A chromosomal outcome categories did not differ significantly between groups (χ² = 1.65, df = 3, p = 0.648). Conclusions: In this retrospective cohort, no statistically significant difference was observed in the overall distribution of PGT-A chromosomal outcomes between women with endometriosis and controls. Although numerical differences were observed across individual outcome categories, the absence of statistical significance should not be interpreted as evidence of equivalence between the groups, particularly given the limited precision of the estimates. Larger patient-level studies accounting for within-patient clustering and relevant clinical and embryological confounders are needed to further clarify the relationship between endometriosis and PGT-A outcomes. Full article

Background/Objectives: Endometrial polyps (EPs) are common benign intrauterine lesions associated with abnormal uterine bleeding, infertility, recurrent implantation failure, and recurrent pregnancy loss. Although traditionally considered hormone-dependent lesions, increasing evidence suggests that chronic endometritis (CE) may contribute to their development and recurrence. This review summarizes current evidence regarding the relationship between CE and EPs, focusing on pathophysiological mechanisms, diagnostic approaches, and clinical implications. Methods: This narrative review was conducted according to the Scale for the Assessment of Narrative Review Articles (SANRA). A literature search was performed using PubMed/MEDLINE, Scopus, and Google Scholar to identify original studies, systematic reviews, meta-analyses, and consensus statements addressing CE, EPs, infertility, endometrial microbiota, and polyp recurrence. Results: Current evidence demonstrates a consistent association between CE and EPs, with approximately half of premenopausal women with EPs showing histological evidence of CE. Chronic inflammation may promote polyp formation through immune activation, inflammatory cytokine signaling, abnormal angiogenesis, extracellular matrix remodeling, dysregulated apoptosis, and alterations in the endometrial microbiome. CE has also been identified as an independent predictor of EP recurrence after hysteroscopic polypectomy and may impair endometrial receptivity. Histopathological examination with CD138 immunohistochemistry remains the diagnostic reference standard. Conclusions: Emerging evidence supports an inflammatory component in the pathogenesis of endometrial polyps and suggests that CE may represent a potentially modifiable risk factor for recurrence and reproductive failure. Incorporating assessment of CE into the evaluation of selected women with recurrent polyps or infertility may improve individualized management. However, prospective studies are needed before routine screening and treatment can be universally recommended. Full article

Obesity is one of the most pressing public health challenges of our time, with a growing impact on metabolic and reproductive dysfunction in women. The expansion of visceral adipose tissue drives a chronic, low-grade systemic inflammatory state that has been associated with functional changes in the ovary, the endometrium, and the placenta across different stages of the reproductive process. This structured narrative review, guided by a PICo-framed research question and literature searches across PubMed/MEDLINE, Scopus, Web of Science, Embase, and ScienceDirect, examined the main immunometabolic mechanisms underlying female obesity and their reported associations with ovarian dysfunction, implantation failure, placental dysfunction, infertility, and preeclampsia. The evidence indicates that chronic low-grade inflammation, insulin resistance (IR), and functional hyperandrogenemia may impair folliculogenesis, oocyte quality, and ovarian reserve, while cytokine and adhesion-molecule dysregulation in the endometrium has been linked to impaired decidualization and a narrower implantation window. At the maternal–fetal interface, this same inflammatory substrate has been associated with deficient trophoblast invasion, inadequate spiral artery remodeling, and angiogenic imbalance, mechanisms widely implicated in the pathophysiology of preeclampsia. Rather than demonstrating a proven longitudinal chain within the same individual, the evidence reviewed here, drawn from heterogeneous populations, study designs, and experimental models, supports a conceptual, hypothesis-generating model in which obesity-related systemic inflammation may contribute to dysfunction across the ovary, endometrium, and placenta. Clinically, these findings support further investigation of reproductive biomarkers and early screening strategies for women with obesity, particularly in the context of assisted reproduction, alongside emerging preconception therapeutic approaches that remain largely investigational. Female obesity should therefore be understood not merely as a metabolic disorder, but as an immunometabolic condition potentially associated with dysfunction across the ovary–endometrium–placenta axis, an integrative framework that may help guide future preventive and therapeutic strategies for reproductive health, pending confirmation in longitudinal studies. Full article

Background: Patient-centered care is particularly important in assisted reproductive technology, where treatment is clinically demanding and emotionally intensive. This study documented a preliminary cultural and linguistic adaptation of a fertility-care survey for Kazakhstan and evaluated patient–staff perception gaps, item-level priorities, preliminary reliability, and exploratory associations with global care ratings. Methods: A cross-sectional survey was conducted in two assisted-reproduction clinics in Almaty. The analytic workbook contained 273 patient and 74 staff records; 173 patient response patterns were unique and 100 records matched an earlier exact pattern. Group-level patient–staff comparisons between independent respondent samples used prespecified harmonized indices, Welch tests, false-discovery-rate correction, clinic-stratified analyses, and one-pattern-per-record sensitivity analyses. Importance–experience differences were calculated within respondents with both values available. Global-rating regressions used HC3 robust inference and were treated as exploratory. Results: Staff rated cost, attitude and communication, information and education, and participation more favorably, whereas patients rated privacy, emotional support, and continuity more favorably. Accessibility and competence showed little difference. Clinic-stratified and one-pattern-per-record analyses preserved the principal contrast directions, although the Physical Comfort proxy was not robust. Several indices showed weak or negative internal consistency. Global ratings had a marked ceiling, with 79.1% at 10/10, and the HC3 joint test for the added care-index block was not significant (p = 0.080). Conclusions: This exploratory survey identified substantial, bidirectional group-level patient–staff differences and concrete item-level priorities, but the scoring and psychometric evidence are insufficient to interpret the domain indices as established measurement scales. Source-codebook verification and broader structural validation are required. Full article

To investigate microRNA-369-5p (miR-369-5p) and miR-671-3p expression in maternal peripheral blood leukocytes, plasma, and placental tissue in women with intrahepatic cholestasis of pregnancy (ICP) undergoing intracytoplasmic sperm injection (ICSI), compared with spontaneous conception. In this exploratory cohort study, microRNA-369-5p (miR-369-5p) and microRNA-671-3p (miR-671-3p) expression levels were analyzed using real-time quantitative PCR in maternal peripheral blood leukocytes, plasma, and placental tissue in four groups: (1) women with uncomplicated pregnancies conceived via intracytoplasmic sperm injection (non-ICP-ICSI, n = 7), (2) women with intrahepatic cholestasis of pregnancy conceived via intracytoplasmic sperm injection (ICP-ICSI, n = 7), (3) women with intrahepatic cholestasis of pregnancy who conceived spontaneously (ICP-SC, n = 7), and (4) women with uncomplicated pregnancies conceived spontaneously (non-ICP-SC, n = 7). Relative expression levels were calculated using the RQ method. Leukocyte miR-369-5p expression was significantly upregulated in ICP-ICSI and non-ICP-ICSI groups compared with ICP-SC and non-ICP-SC groups (p = 0.0001). Plasma miR-671-3p expression levels were significantly decreased in ICSI groups compared with spontaneous conception groups (p = 0.029). No significant differences were observed in placental expression levels of miR-369-5p and miR-671-3p among the four groups (p > 0.05). In subgroup analysis, leukocyte miR-369-5p and miR-671-3p expression levels were significantly higher in the ICP-ICSI group compared with the ICP-SC group (p < 0.05). Serum fasting bile acid levels showed a significant positive correlation with placental miR-369-5p expression (r = 0.467; p = 0.012) and a negative correlation with plasma miR-369-5p expression (r = −0.413; p = 0.029). Our findings show compartment-specific differences in miR-369-5p and miR-671-3p expression across leukocytes and plasma in this exploratory cohort. These preliminary observations do not establish causality and require validation in larger, independent cohorts. Full article

Background: Alcohol consumption is common among women and men of reproductive age. The effects of alcohol use in the preconception and early-pregnancy periods on early reproductive outcomes are not well-known. Methods: In a population-based cohort study from preconception onwards among 3225 women and their partners, we examined the associations of preconception and early-pregnancy alcohol consumption, assessed by questionnaires, with fecundability (per-cycle probability of conceiving), infertility (time to pregnancy >12 months or use of assisted reproductive technology), and miscarriage (pregnancy loss before 22 weeks of gestation). Results: As compared to no alcohol consumption, preconception intake of <1 glass/week and ≥1 glass/week among women was associated with lower odds of infertility (odds ratio (OR) 0.61, 95% confidence interval (CI) 0.39, 0.94 and OR 0.54, 95% CI 0.35, 0.84, respectively). As compared to no alcohol consumption, early-pregnancy alcohol consumption among women of <1 glass/week and ≥1 glass/week was associated with increased odds of miscarriage (OR 1.99, 95% CI 1.36, 2.92 and OR 2.37, 95%CI 1.58, 3.57). Early-pregnancy binge drinking among women was also associated with increased odds of miscarriage (OR 1.52, 95%CI 1.04, 2.24). Alcohol consumption among men was not associated with infertility or miscarriage risk. Conclusions: The associations of low-to-moderate preconception alcohol consumption with lower odds of infertility might reflect healthier lifestyles, socioeconomic factors, and residual confounding by health-related abstinence from alcohol, all of which are associated with greater fertility. Therefore, preconception and early-pregnancy counseling should mainly focus on the risk of miscarriage and fetal health outcomes. Full article

Objective: To compare sleep quality, psychological resilience, and attachment dimensions between women with unexplained infertility and those with male factor infertility undergoing in vitro fertilization (IVF). Materials and Methods: In this single-center, cross-sectional study, 201 women undergoing IVF (101 with unexplained and 100 with male factor infertility) completed the Pittsburgh Sleep Quality Index (PSQI), the Brief Resilience Scale (BRS), and the Experiences in Close Relationships–Relationship Structures (ECR-RS) questionnaire. Poor sleep quality was defined as a global PSQI score greater than 5. The primary outcome was the global PSQI score. Between-group comparisons were supplemented by multivariable analyses adjusted for age, economic status, chronic disease, infertility duration, and number of previous IVF attempts. Results: No statistically significant differences were observed in most baseline characteristics, although low economic status was more frequent in the male factor group (34.0% vs. 15.8%; p = 0.008). The median global PSQI score did not differ significantly between the unexplained and male factor groups (6.0 vs. 5.0; p = 0.143). Poor sleep quality was observed in 51.5% and 42.0% of women, respectively (p = 0.178), with an overall prevalence of 46.8% (95% CI, 40.0–53.7%). Psychological resilience (3.33 vs. 3.17; p = 0.474), attachment avoidance (9.0 vs. 9.5; p = 0.336), and attachment anxiety (3.0 vs. 3.0; p = 0.648) did not differ significantly between the groups. After adjustment, unexplained infertility was not significantly associated with global PSQI score (β = 0.76, 95% CI −0.17 to 1.69; p = 0.110) or poor sleep quality (adjusted prevalence ratio = 1.24, 95% CI 0.92–1.67; p = 0.162). Conclusions: Women with unexplained and male factor infertility undergoing IVF showed similar patterns of sleep quality, psychological resilience, and attachment dimensions, with no statistically significant between-group differences detected. Poor sleep quality affected nearly half of the study population. These findings should not be interpreted as evidence of equivalence between infertility etiologies but highlight the potential relevance of sleep assessment in women undergoing IVF. Full article

Infertility affects approximately one in six individuals worldwide and is a highly heterogeneous disorder resulting from the complex interplay of genetic, epigenetic, endocrine, environmental and lifestyle factors. Although numerous genes and molecular pathways involved in female and male infertility have been identified, elucidating the functional consequences of disease-associated variants remains challenging due to the lack of relevant human experimental models. In recent years, reproductive organoids have emerged as powerful three-dimensional systems that recapitulate key structural, cellular and functional characteristics of the ovary, fallopian tube, endometrium, testis and early embryo. Here, we review the current landscape of reproductive organoid models based on a focused analysis of the literature, with particular emphasis on original studies describing their generation, characterization and applications. Beyond modeling tissue development and reproductive physiology, these models provide unique opportunities to investigate infertility-associated mechanisms, gene regulatory networks, cell–cell communication and tissue-specific responses to environmental and pharmacological stimuli. Single-cell and spatial transcriptomics, multi-omics, CRISPR/Cas9 genome editing, artificial intelligence and bioengineering technologies, including organ-on-chip systems, are expanding their potential as next-generation platforms for functional genomics, disease modeling, biomarker discovery and therapeutic screening. However, current reproductive organoids remain simplified representations of native tissues, with limitations in physiological maturity, reproducibility and standardization, while their clinical predictive value remains to be established. Overall, by linking genomic variation with molecular regulation, cellular phenotypes and tissue organization, reproductive organoids represent promising preclinical platforms for understanding human infertility and may ultimately contribute to the development of precision reproductive medicine. Full article

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. Full article

Spermatogenesis in Drosophila melanogaster is a classical model for studying cell polarity establishment, organelle remodeling, and extreme cellular morphogenesis. Spermatid elongation involves a series of highly coordinated dynamic events, including nuclear polarization, axonemal extension, mitochondrial remodeling, and individualization-mediated cytoplasmic clearance. Current studies have largely focused on individual structures, molecules, or pathways, resulting in a fragmented understanding of this process and a lack of an integrated framework that links mitochondrial function, cytoskeletal dynamics, and temporal translational regulation. Based on existing evidence, this review organizes current findings into three regulatory layers involving mitochondrial remodeling, cytoskeletal dynamics, and post-transcriptional translational control. Mitochondrial remodeling provides structural and metabolic support for sperm-tail formation, cytoskeletal processes execute axoneme organization and individualization, and post-transcriptional regulation controls the timing of protein production. Experimental evidence is strongest for mechanisms operating within each layer, whereas direct molecular coupling among the three layers remains incompletely established. We therefore present this model as a working framework rather than an established causal pathway. This framework helps organize current knowledge of extreme cellular differentiation and provides a basis for comparative studies of spermatogenesis and selected mechanisms associated with human male infertility. Full article

Background: Accumulating data suggest that human papillomavirus (HPV) infection may be associated with male infertility by impairing sperm quality. An induced anti-HPV humoral immune response could mediate the effective clearance of HPV infection. This systematic review aimed to assess reported differences in semen quality parameters and HPV presence in men with persistent HPV infection after adjuvant administration of a prophylactic HPV vaccine. Methods: Possibly eligible articles were retrieved from three electronic databases (PubMed, Scopus, and Web of Science) since 26 June 2026, with three ultimately included in both qualitative and quantitative analysis. Results: The estimated HPV DNA negativity was 74% (95% CI 59–86) and 98% (95% CI 78–100) at the end of vaccination and 6 months after complete vaccination. Conclusions: This study identified limited evidence suggesting a potential benefit of HPV vaccination in infertile HPV-positive men, particularly in terms of shift toward HPV negativity. Given the small number of available studies and their methodological limitations, further large, well-designed prospective trials are required to determine whether adjuvant administration of a prophylactic HPV vaccine provides clinically relevant benefits in this population. Full article

Non-coding RNAs (ncRNAs) are biologically plausible biomarkers in male infertility, but no assay is ready for routine use. This narrative review organizes human evidence by intended clinical decision and defines clinical actionability as a test’s ability to inform a specified decision through analytical reliability, clinical validity, incremental value, decision-level benefit, and feasible implementation. Evidence is most developed for obstructive versus non-obstructive azoospermia (NOA) classification and sperm-retrieval prognosis. Most reports, however, use selected case–control samples, single-center development cohorts, or same-program evaluations. Mixed biospecimens, incompletely specified RNA isoforms and normalization, uncertain cohort independence, imperfect diagnostic references, and protocol-dependent retrieval outcomes limit transportability. No independent geographic validation of a locked ncRNA assay or prospective evaluation of ncRNA-guided management was identified within the retrieved sources. Current guidelines do not recommend routine ncRNA testing. Progress requires prespecified intended uses, locked assays, representative multicenter validation, same-patient comparison with contemporary care, calibrated risk estimates, decision-curve analysis, and patient-important, couple-centered outcomes. Full article

Background/Objectives: Variability in the methylenetetrahydrofolate reductase (MTHFR) gene has been implicated in reproductive dysfunction and may influence ovarian physiology in women with thyroid autoimmunity (TAI). This prospective study aimed to investigate the association of the MTHFR C677T and A1298C polymorphisms with ovarian reserve and controlled ovarian hyperstimulation (COH) outcomes in infertile women with TAI. Methods: Genomic DNA was extracted from peripheral blood samples of 145 euthyroid infertile women with TAI undergoing assisted reproductive treatment and 100 fertile controls. The TAI cohort was divided into women with preserved ovarian reserve (TAI1) and diminished ovarian reserve (TAI2). MTHFR C677T and A1298C polymorphisms were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) analysis. Genotype and allele frequencies were compared between groups, and associations with COH outcomes were evaluated. Results: Significant differences in MTHFR C677T genotype and allele distributions were observed between the TAI1 and TAI2 subgroups. Genotype distributions also differed significantly between the overall TAI cohort and fertile controls, with significant differences observed between the TAI1 subgroup and controls, but not between the TAI2 subgroup and controls. No significant associations were found for the MTHFR A1298C polymorphism, while associations between MTHFR polymorphisms and COH outcomes were limited and inconsistent. Conclusions: The MTHFR C677T, but not A1298C, polymorphism is associated with ovarian reserve in infertile women with TAI. These findings suggest that genetic variation in MTHFR may contribute to the heterogeneity of ovarian reserve in this population, while its influence on ovarian response to stimulation appears limited. Full article

Cell-free DNA (cfDNA) fragments represent emerging biomarkers of major interest in the assessment of male fertility and the management of couples undergoing assisted reproductive technology (ART). Easy to quantify and present in most biological fluids, seminal cfDNA could reflect apoptosis and necrosis occurring within the male reproductive system. In this study, we compared cfDNA concentrations, measured by means of qPCR targeting the RNase P gene, in the seminal plasma of men with severe sperm quality abnormalities, including very severe asthenozoospermia (n = 25), total azoospermia (n = 25), very severe oligozoospermia (n = 25), and very severe teratozoospermia (n = 25), with those of normozoospermic controls (n = 25). Mean cfDNA concentrations were particularly elevated in men with azoospermia (5.47 ± 1.17 µg/mL) and very severe teratozoospermia (3.25 ± 1.21 µg/mL), compared with controls (1.96 ± 0.27 µg/mL). After adjustment for multiple testing, only azoospermia and very severe teratozoospermia remained significantly associated with increased cfDNA levels (Holm–Bonferroni adjusted p < 0.003), whereas the other phenotypes did not maintain statistical significance. These results suggest that seminal cfDNA is markedly increased in the most severe forms of spermatogenic impairment, potentially reflecting enhanced germ cell apoptosis or testicular cell involvement. Despite some limitations, including the modest sample size and single-center design, our observations support the value of cfDNA as a promising non-invasive biomarker of sperm quality. Larger multicenter and longitudinal studies are needed to validate its clinical relevance and determine standardized reference thresholds for clinical application. Full article

Intrauterine adhesion (IUA) is a fibrotic disorder resulting from aberrant repair following injury to the endometrial basal layer, leading to menstrual abnormalities, infertility, recurrent miscarriage, and pregnancy complications. Although hysteroscopic adhesiolysis remains the primary clinical treatment, the rate of postoperative re–adhesion is still high, especially in patients with moderate–to–severe IUA. Moreover, mechanical separation alone is often insufficient to restore intact endometrial architecture and reproductive function. Hydrogels, with their hydrated three–dimensional networks, extracellular matrix (ECM)–mimicking properties, injectability, biodegradability, tissue adhesion, and tunable delivery capacity, have evolved from passive barrier materials into multifunctional therapeutic platforms capable of regulating the pathological microenvironment and promoting tissue regeneration. Recent advances in responsive, self–healing, adhesive, antioxidant, and bioactive cargo–loaded hydrogels have expanded their applications from preventing adhesion formation toward functional endometrial reconstruction. In this review, we summarize recent progress in hydrogel–based IUA therapy, focusing on material composition, structural design, functional modification, therapeutic mechanisms, and translational considerations. Particular emphasis is placed on disease–informed hydrogel engineering strategies that integrate the unique anatomical characteristics of the uterine cavity, injury–associated microenvironment, and dynamic stages of endometrial repair. This perspective provides insights into the development of next–generation hydrogel systems for preventing re–adhesion and restoring reproductive function. Full article