Search Results (425)

Background/Objectives: Aberrant DNA methylation of imprinted genes and increased sperm DNA fragmentation (SDF) have been implicated in male infertility. However, their impact on assisted reproductive technology (ART) outcomes remains unclear. This pilot study aimed to investigate SDF and methylation status of H19, IGF2, and PEG1/MEST in relation to fertilisation and embryo development following intracytoplasmic sperm injection (ICSI). Methods: Twenty male partners of women undergoing ICSI were recruited and classified according to ART outcome into viable embryos (VEs, n = 7), non-viable embryos (NVEs, n = 7), and no fertilisation (NF, n = 6). Before sperm selection, an aliquot of each seminal sample was used for semen analysis according to WHO, 2021, SDF assessment (TUNEL assay), and sperm DNA methylation analysis of H19, IGF2, and PEG1/MEST (pyrosequencing). Results: Semen parameters were above the fifth percentile. SDF was significantly lower in the VE group compared with the other groups. H19 CpG1 methylation correlated positively with viable embryos (p = 0.016), while H19 CpG2 island showed a positive correlation with sperm concentration (p = 0.028). In male/couple infertility cases, total H19 methylation correlated negatively with SDF (p = 0.050). IGF2 CpG3 island methylation correlated positively with viable embryos (p = 0.027). Total PEG1/MEST methylation was positively correlated with fertilisation events (p = 0.002) and viable embryos (p = 0.011). PEG1/MEST CpG2 island also positively correlated with sperm motility (p = 0.034), while CpG3 and CpG4 showed significant correlations with fertilisation (p < 0.001; p = 0.004). Conclusions: This pilot study shows that SDF and sperm methylation levels of H19, IGF2, and PEG1/MEST are related to ICSI outcomes, supporting that sperm molecular and epigenetic features may influence fertilisation and embryo development. Full article

Background: There is growing evidence that uterine microbiota might be linked to endometrial receptivity (ER) and affect the outcome of assisted reproductive technology (ART) procedures. Owing to the invasive nature of endometrial sampling, the evaluation of microbiota in this biomaterial is only possible outside the embryo transfer (ET) cycle. However, menstrual blood might be the key to overcoming this challenge as it can be safely aspirated from the uterine cavity at the beginning of the target ET cycle. This study aimed to evaluate the association of the microbiological profiles of menstrual blood with ER in patients undergoing frozen ET. Methods: Menstrual blood was obtained from 98 individuals scheduled for frozen ET in a private ART clinic (ET success rate–50%). DNA was isolated from menstrual sediment and analyzed using a multiplex quantitative PCR assay designed to identify 28 relevant microbial taxa and 3 Herpesviridae viruses. Results: Bacterial DNA was detected in 75.5% of samples. There were no associations between the abundance of individual microbial taxa and the outcome of ET, and the same was true for Shannon’s α-diversity indices (p > 0.05). However, Candida spp. and Enterobacteriaceae were detected exclusively in patients with negative ET outcomes (p = 0.028). Individuals with recurrent implantation failure had a significantly lower abundance of Lactobacillus spp. than the rest (0.0 [0.0; 7.4] vs. 2.8 [0.0; 91.9] %, p = 0.024). Conclusions: Menstrual blood aspirated directly from the uterus is a promising biomaterial for endometrial microbiological profiling. Upon further investigation, its analysis might become a useful tool in managing infertile patients scheduled for ART treatment. Full article

Background and Objectives: Endometriosis is a chronic, estrogen-dependent disorder characterized by the presence of functional endometrial tissue, comprising both glandular and stromal components, located outside the uterine cavity, affecting approximately 6–10% of women of reproductive age and up to 30–50% of those with infertility. Increasing evidence indicates that endometriosis is not solely a localized gynecological condition but rather a systemic inflammatory and immune-mediated disease. Chronic inflammation and immune dysregulation contribute to disease progression and may impair reproductive function. This review aims to analyze the current evidence regarding the inflammatory and immunological mechanisms underlying endometriosis and to evaluate their impact on reproductive dysfunction and assisted reproductive technology (ART) outcomes. Materials and Methods: A comprehensive narrative review was conducted using major scientific databases, including PubMed, Scopus, and Web of Science. Relevant articles published in the last decade were selected using keywords such as “endometriosis”, “inflammation”, “immune response”, “cytokines”, and “ART outcomes”. Both clinical and experimental studies were included to assess the relationship between inflammatory markers, immune alterations, and reproductive performance. Results: Endometriosis is associated with elevated levels of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α), as well as increased oxidative stress and altered peritoneal microenvironment. Immune dysfunction is characterized by activated macrophages, decreased natural killer (NK) cell cytotoxicity, and an imbalance in T-cell populations. These alterations negatively affect oocyte quality, fertilization, embryo development, and endometrial receptivity. Emerging biomarkers such as IL-6, TNF-α, and CA-125 show potential in predicting disease severity and ART outcomes, although their clinical utility remains under investigation. Conclusions: Endometriosis should be regarded as a systemic immuno-inflammatory disorder with significant implications for reproductive health. The interaction between chronic inflammation and immune dysregulation plays a central role in infertility and suboptimal ART outcomes. Further research is required to validate reliable biomarkers and develop targeted therapeutic strategies to improve reproductive success in affected patients. Full article

Background/Objectives: Artificial intelligence (AI) models are increasingly applied across the assisted reproductive technology (ART) workflow, including male-factor assessment, ovarian stimulation, endometrial receptivity evaluation, embryo selection and prediction of pregnancy outcomes. However, many systems remain difficult to interpret, raising concerns regarding transparency, clinical integration and patient communication. Explainable artificial intelligence (XAI) aims to address these limitations by making model behavior more accessible to clinicians and embryologists. This review aimed to provide a narrative, concept-driven synthesis of how XAI has been implemented in ART, to critically examine methodological quality and clinical relevance and to outline priorities for responsible translation into practice. Methods: A structured narrative review was conducted using PubMed/MEDLINE as the primary database, supplemented by targeted reference-list screening of key primary studies and recent cross-disciplinary reviews relevant to AI in ART. Studies were curated and classified according to stage of the ART workflow, data modality, model family, explanation technique and validation strategy. Methodological features, performance reporting and implementation considerations were qualitatively appraised. Results: Most XAI applications in ART fall into two dominant categories: (i) feature-attribution methods such as SHAP and LIME applied to tabular clinical and laboratory data and (ii) saliency-based approaches, including Grad-CAM and related techniques, applied to embryo and ultrasound imaging. These methods can improve transparency and support counselling by clarifying which variables or image regions influence predictions. However, the majority of studies are retrospective and single centre, with limited external validation and heterogeneous outcome definitions, often prioritising clinical pregnancy over live birth. Calibration, decision-analytic evaluation and prospective assessment remain uncommon. XAI outputs are frequently interpreted as biologically causal despite being derived from observational data, highlighting the need for cautious clinical framing. Conclusions: XAI in ART has progressed from proof-of-concept demonstrations to early clinically oriented tools, but robust validation, standardised reporting and thoughtful workflow integration are still needed. Explanations can enhance auditability and communication, yet they do not compensate for methodological weakness. Future progress will depend on higher-quality multi-centre data, evaluation beyond discrimination metrics and governance frameworks that ensure transparency, fairness and sustained performance in real-world practice. Full article

Embryos being treated using assisted reproductive technology (ART) are unavoidably exposed to physical stressors, thus producing reactive oxygen species (ROS) which trigger mitophagy to support embryonic development. However, the mechanisms underlying the regulation of mitophagy in early embryonic development remain largely unexplored. Here, we found that Mucin 1 (MUC1) exhibited a uniform distribution in both mouse and human oocytes, and its expression peaked at the blastocyst stage. Further analysis revealed that Muc1 knockout impairs blastocyst formation in vitro. Correspondingly, Muc1 knockout led to the accumulation of mitochondrial reactive oxygen species (mtROS) and a reduction in phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)/Parkinson protein 2 (PARK2/Parkin)-dependent mitophagy. Stimulation of mitophagy via low-dose carbonyl cyanide 3-chlorophenylhydrazone (CCCP) treatment rescued the blastocyst formation defect in Muc1-null embryos. Vitamin C supplementation effectively scavenged mtROS and restored developmental competence. Together, our findings establish that MUC1 safeguards early embryonic development by promoting mitophagy to decrease mtROS levels in vitro. Moreover, vitamin C could compensate for Muc1 deficiency by eliminating mtROS. This study not only identified a new function of MUC1 in protecting early embryonic development in vitro, but also revealed a novel mechanism of mitophagy regulation in early embryos, which has potential applications for ART. Full article

Proteostasis, defined as the coordinated regulation of protein synthesis, folding, trafficking, and degradation, is essential for maintaining cellular integrity and supporting normal development. During reproduction and early life stages, efficient proteostasis is crucial for gamete quality, successful fertilization, embryonic development, and neurodevelopmental outcomes. Increasing evidence suggests that impaired proteostasis contributes to infertility and may be intertwined with biological vulnerabilities associated with assisted reproductive technologies [ARTs]. This review provides an integrative perspective on the role of disrupted proteostasis in infertility, ART procedures, and neurodevelopmental differences [NDD]. We review epidemiological and molecular findings indicating proteostasis failure in both male and female infertility, with particular emphasis on molecular chaperones. Among these, heat shock protein 60 [Hsp60] is discussed as a central mediator linking mitochondrial function, protein quality control, and reproductive competence. We further highlight that ART procedures coincide with sensitive periods of epigenetic reprogramming and proteostasis regulation during early embryogenesis, indicating that disturbances in proteostasis may affect epigenetic stability and subsequent neurodevelopmental outcomes. In addition, this review emphasizes the importance of proteoforms and proteome complexity as critical determinants of reproductive success and neurodevelopmental robustness in the context of ART. Finally, we discuss the potential of proteomic and chaperone-based biomarkers as emerging tools to optimize ART strategies, improve gamete and embryo selection, and enhance risk assessment and clinical outcomes. The current review underscores proteostasis as a fundamental yet underrecognized mechanism linking reproductive biology, ART outcomes, and long-term neurodevelopment while highlighting future directions for translational investigations. Full article

Sociotechnical imaginaries are collectively held and institutionally stabilised visions of desirable futures that link scientific and technological development with social and political order. Developed within Science and Technology Studies, the concept highlights the co-production of knowledge, technology, and governance, showing how ideas of progress are embedded in cultural values, moral assumptions, and political priorities. These imaginaries function as normative horizons that orient innovation, legitimise policy, shape regulation, and guide clinical practice. In health and biomedicine, sociotechnical imaginaries are particularly salient, as medical innovations directly affect life, death, and embodiment. Within medical sociology, the concept has been used to analyse how technologies such as assisted reproductive technologies (ARTs), genomics, regenerative medicine, and digital health are framed through narratives of hope, responsibility, risk, and transformation. These imaginaries shape what counts as legitimate knowledge, who accesses treatment, and how ethical debates are structured, from autonomy in ARTs to individualised care in precision medicine. Imaginaries are also shaped by national and institutional contexts. Comparative research shows that the United States, Europe, and East Asia produce distinct biomedical futures, reflecting different political traditions and governance models. As an analytical lens, sociotechnical imaginaries reveal health and biomedicine as domains where futures are imagined, contested, and enacted. Full article

Objective: This study aimed to identify distinct dyadic coping profiles among infertile couples undergoing assisted reproductive technologies (ARTs) and to examine the associations between these coping profiles, depressive symptoms, and fertility quality of life (FertiQOL). Methods: A total of 271 infertile couples undergoing ARTs were recruited from a reproductive medicine center in Zhengzhou, China, and completed standardized self-report measures. Latent profile analysis was conducted to identify distinct dyadic coping profiles at the couple level. Multinomial logistic regression was used to examine sociodemographic and infertility-related predictors of profile membership. Differences in depressive symptoms and FertiQoL across profiles were analyzed using the Bolck–Croon–Hagenaars method. Results: Four dyadic coping profiles were identified: high-coping wife and low-coping husband (15.4%), low dyadic coping (20.1%), medium dyadic coping (31.5%), and high dyadic coping (33.0%). Couples in the high dyadic coping profile reported the lowest levels of depression and the highest level of FertiQoL. Women in the low dyadic coping profile reported the highest depressive symptoms, while men in the high-coping wife and low-coping husband profile demonstrated the highest depression among male partners. Sociodemographic factors (household registration, family income) and infertility characteristics (type of infertility, infertility duration) were significant predictors of profile membership. Conclusions: Dyadic coping among infertile couples undergoing ARTs is heterogeneous and differentially associated with depression and FertiQoL. Low and asymmetric dyadic coping represent high-risk profiles linked to poorer outcomes in both partners. These findings suggest that dyadic coping may serve as a protective resource for infertile couples to improve their psychological well-being and quality of life, highlighting the importance of incorporating dyadic coping assessment into routine care and providing couple-centered psychosocial interventions in fertility care practice. Full article

Non-invasive assessment of oocyte quality remains a challenge in assisted reproductive technology (ART). Through their bidirectional communication with the gamete, cumulus cells (CCs) act as a functional mirror of oocyte competence; however, the specific angiogenic signature within this microenvironment is still poorly understood. In the present study, we performed RNA-seq on CCs from healthy oocyte donors and infertile patients, utilizing a multi-pipeline bioinformatic approach (STAR-Cufflinks, TopHat-HTSeq, and HISAT2-StringTie) to establish a high-confidence, exploratory transcriptomic profile. A set of 234 differentially expressed genes (DEGs) consistently identified across pipelines was obtained, with functional enrichment highlighting blood vessel morphogenesis and angiogenesis as primary drivers of transcriptomic divergence between groups. RT-qPCR validation in individual samples confirmed statistically significant differences for ANKRD22 (upregulated) and E2F7 (downregulated) in infertile patients, while other angiogenesis-related genes, including ANGPT1, ANGPT2 and THBS1, showed consistent but non-significant expression trends, suggesting alterations in angiogenesis-related processes within the follicular microenvironment. These findings support the presence of coordinated angiogenesis-related alterations in cumulus cells and provide a basis for future studies exploring their potential relevance in oocyte competence and ART outcomes. Full article

Background: Assisted reproductive technology has been linked to an increased risk of pregnancy-related cardiovascular complications, but the long-term cardiovascular outcome is poorly understood. This study aimed to assess whether women who use ART have an elevated long-term risk of adverse cardiovascular outcomes. Methods: We conducted a systematic review and meta-analysis to examine the association between ART and long-term cardiovascular outcomes after pregnancy. We systematically searched MEDLINE, Embase, and the Cochrane Library for studies published by January 2026. We evaluated the methodological quality of included studies using the Newcastle-Ottawa Scale. We used random effects models to calculate pooled adjusted risk ratios (aRR) with 95% confidence intervals (CI) for the association of ART with cardiovascular outcomes. Results: We included thirteen studies comprising 553,331 patients who used ART and 37,826,591 patients who conceived spontaneously. All women achieved a live birth. Mean duration of follow-up after delivery was 8.4 ± 8.3 years. In models adjusted for age, parity, and comorbidity, ART was associated with a small increase in the risk of cardiovascular disease compared with spontaneous conception (aRR 1.18, 95% CI 1.03–1.35), but the association was attenuated when studies that had only 42 days of follow-up were excluded (aRR 1.13, 95% CI 0.99–1.29). ART was not associated with cardiac complications (aRR 0.94, 95% CI 0.82–1.08), stroke (aRR 1.20; 95% CI 0.93–1.55), hypertension (aRR 1.02; 95% CI 0.72–1.44), or venous thrombosis (aRR 1.27, 95% CI 0.97–1.67). Conclusions: Our findings suggest that women who achieve a live birth following ART do not appear to have an increased long-term risk of adverse cardiovascular outcomes. These results provide reassuring evidence for patient counseling regarding the long-term cardiovascular safety of ART among women with successful pregnancies. Further research that includes women who do not achieve a live birth is warranted to more fully characterize the potential long-term cardiovascular effects of ART across the entire spectrum of treatment outcomes. Full article

Background and Objectives: Male infertility has emerged as a growing global health concern, contributing to 20–30% of all infertility cases. It is a multifactorial condition, arising from genetic, endocrine, structural, environmental and lifestyle factors. This narrative review synthesizes current evidence on epidemiology, diagnostic advances and therapeutic strategies while highlighting emerging trends and research priorities. Materials and Methods: This review adheres to SANRA guidelines. Literature was sourced from PubMed, Saudi Digital Library, Google Scholar, and PsycINFO using MeSH terms including “Male Infertility,” “Diagnosis,” “Treatment,” and “Epidemiology.” Results: Diagnostic evaluation of male infertility includes clinical assessment, advanced semen analysis, imaging techniques, hormonal assays and molecular testing. Despite significant advances in the evaluation of male infertility, idiopathic causes (30–40%) remain challenging. Management strategies include lifestyle modifications, medical therapies including hormones and drugs, surgical interventions, and assisted reproductive technologies (ARTs). However, outcomes remain suboptimal in idiopathic and severe cases, particularly regarding sperm DNA fragmentation and environmental exposures. Conclusions: Substantial knowledge gaps exist in male infertility, particularly in idiopathic cases, molecular mechanisms of environmental pollutants, and long-term ART offspring outcomes. Future research priorities include: (1) molecular and epigenetic biomarkers for improved diagnosis and prognosis; (2) environmental exposure assessment and mitigation strategies; (3) metabolomics-guided personalized therapies; (4) regenerative medicine approaches including spermatogonial stem cell therapy; and (5) multidisciplinary integrative care models. Addressing these gaps through coordinated research and clinical innovation is essential for improving male reproductive health globally. Full article

Reproductive efficiency in cattle is critically dependent on embryo quantity and quality, particularly in assisted reproductive technology (ART) programs such as superovulation, embryo transfer, and embryo production. Nutrition is a key determinant of embryo yield through its regulatory effects on metabolic signaling, ovarian function, oocyte competence, and early embryogenesis. This review synthesizes the current evidence describing mechanistic links between nutritional status and embryo production in dairy and beef cattle across both in vivo and in vitro systems. Energy balance, protein supply, micronutrients, and fatty acids influence metabolic hormones including insulin, insulin-like growth factor-1, and leptin, which regulate hypothalamic–pituitary–gonadal axis activity, follicular recruitment, and steroidogenesis. Negative energy balance disrupts endocrine signaling, elevates circulating non-esterified fatty acids, increases oxidative stress, and impairs oocyte mitochondrial function, resulting in reduced embryo yield, compromised blastocyst quality, and diminished cryotolerance. Targeted micronutrients such as selenium, zinc, vitamins A and E, B-complex vitamins, and omega-3 fatty acids enhance antioxidant capacity, membrane integrity, and epigenetic regulation, thereby supporting embryo viability and post-transfer survival. Furthermore, early-life nutrition programs long-term reproductive capacity by influencing ovarian reserve establishment and oocyte epigenetic competence. Strategic nutritional management is therefore essential to optimize ART outcomes and promote sustainable genetic progress in cattle production systems. Full article

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. Full article

The different Assisted Reproductive Technology techniques are offering hope to millions of couples struggling with infertility. However, the success of IVF/ICSI is related at least partially to the optimization of embryo culture conditions, which are influenced by myriad of physiological and environmental factors. This review reports the latest advancements in embryo culture techniques, with a particular focus on the roles of oxygen tension, pH regulation, temperature stability, air quality in enhancing embryo viability, competency and implantation rates. In addition, we explored the critical importance of quality assurance (QA) factors and key performance indicators (KPIs) to keep laboratory efficiency. We highlighted also some emerging technologies, such as dynamic culture systems, metabolomics, proteomics biomarkers potential, and artificial intelligence (AI) in embryo selection and monitoring, which hold promise for further improving embryo culture techniques. By providing a comprehensive overview of the current state of embryo culture optimization, this review aims to guide future research and clinical practices in the field of assisted reproductive technology (ART). Full article

Continuing advances in cancer diagnosis and treatment, particularly in reproductive-aged patients, has led to numerous national medical organizations, including the American Society for Reproductive Medicine (ASRM), the American College of Obstetrics and Gynecology (ACOG), and the American Society for Clinical Oncology (ASCO), recommending prompt discussion of the potential gonadotoxic effects of chemotherapy and referral to a fertility specialist for counseling regarding possible fertility preservation. Despite overall increased utilization of assisted reproductive technology (ART) in the United States (US), racial and ethnic disparities persist on a multisystem level, ranging from decreased access and utilization of ART to inconsistent and delayed counseling to worse outcomes. While innovations in ART and cancer treatment continue to evolve in parallel, the beneficial impacts have been disparate and more limited in minority populations. This review specifically highlights racial and ethnic disparities in fertility preservation for women with cancer in the United States, highlights the underdeveloped state of this literature, and identifies possible pathways for improvement using the Disparities in Assisted Reproductive Technology (DART) hypothesis as a template. We address three main bottlenecks resulting in delay from time of cancer diagnosis to utilization of fertility preservation services. Full article