Search Results (827)

Background: Data on assisted reproductive technology (ART) outcomes among Roma women are virtually absent from the literature, despite Roma being the largest and most socioeconomically marginalized ethnic minority in Europe. This study provides the first structured evaluation of IVF/ICSI outcomes among Roma women at a tertiary fertility center. Methods: A retrospective observational cohort study was conducted at the Clinic for Gynecology and Obstetrics, University Clinical Center Niš, Serbia (May 2010–September 2015). Roma (n = 88) and non-Roma women (n = 1197) undergoing IVF/ICSI were compared on baseline clinical, hormonal, and embryological parameters. Primary and secondary outcomes were clinical pregnancy and live birth, respectively. Multivariable logistic regression, propensity score matching (1:4, by age and AMH), first-cycle sensitivity analysis, and a machine learning pipeline (logistic regression, random forest, XGBoost) with SHAP interpretability analysis were applied. Results: Roma women were significantly younger (31.9 ± 4.0 vs. 34.5 ± 4.7 years; p < 0.001) and had a more favorable ovarian reserve profile (AMH 3.78 vs. 2.90 ng/mL; p = 0.004; FSH 6.87 vs. 8.23 IU/L; p < 0.001), yet had a markedly longer duration of infertility (9.3 vs. 6.3 years; p < 0.001). Clinical pregnancy rates (48.9% vs. 41.3%; p = 0.179) and live birth rates (28.4% vs. 30.9%; p = 0.720) were comparable between groups. In multivariable logistic regression and propensity score-matched analyses, Roma ethnicity was not an independent predictor of either outcome. XGBoost SHAP analysis ranked Roma ethnicity last (11th of 11) in feature importance for both clinical pregnancy (mean |SHAP| = 0.033) and live birth (mean |SHAP| = 0.009). The dominant predictors were the number of embryos transferred, AMH, and age. Only 88 Roma women accessed ART over the decade-long study period, indicating profound underutilization of fertility services. Conclusions: No independent association was detected between Roma ethnicity and IVF/ICSI outcomes within the statistical power afforded by the Roma subgroup (n = 88). An exploratory first-cycle live birth signal (adjusted OR = 0.478; 95% CI 0.249–0.920; p = 0.027), not replicated in primary or propensity-matched analyses, is interpreted as hypothesis-generating. The extreme underutilization of ART services among Roma women remains the most clinically salient observation and a priority for targeted public health intervention. Full article

Oxidative stress is a fundamental mechanism that impacts reproductive function by altering gamete quality, fertilisation, and the initial development of embryos. Excessive reactive oxygen species lead to the oxidation of polyunsaturated fatty acids in the cell membranes of sperm, oocytes, and adjacent somatic cells. F2-isoprostanes and isofurans are two of the most dependable indicators of oxidative lipid damage among the byproducts generated during free radical-mediated lipid oxidation. Both arise from the non-enzymatic peroxidation of arachidonic acid and provide a chemically stable depiction of in vivo oxidative processes. Reproductive studies indicate that elevated levels of F2-isoprostanes are associated with diminished sperm motility, compromised membrane stability, and an increased risk of DNA fragmentation in various forms of male infertility. Lipid peroxidation products have been detected in follicular fluid inside the female reproductive system, suggesting a relationship between oxidative imbalance, granulosa cell metabolism, and oocyte competency. Isofurans, which are more prevalent in the presence of elevated oxygen levels, may indicate oxidative stress in mitochondria and complications with cellular respiration. The current comprehension of lipid peroxidation indicators in infertility and assisted reproduction remains insufficient. This review aims to synthesise current information on isoprostanes and isofurans as reliable indicators of oxidative lipid damage in reproductive biology, highlighting their effects on gamete quality, mitochondrial dysfunction, and results in assisted reproduction. Our research seeks to clarify the biological importance of current experimental and clinical findings, highlighting their potential as clinically relevant biomarkers in reproductive medicine. Full article

Duolang sheep, an indigenous breed of southern Xinjiang, are significant for their agricultural systems due to their adaptation to arid and semi-arid environments. This review integrates recent advancements in Duolang’s reproductive biology, genomic studies, and management strategies to address the breed’s reproductive efficiency under challenging ecological conditions. Reproductive traits such as puberty onset, estrous cycle characteristics, and seasonal breeding are influenced by complex genetic and several environmental factors. Numerous remarkable genomic findings highlight key loci related to fecundity, including the Booroola FecB mutation, as well as genes involved in steroidogenesis, folliculogenesis, and HPG axis regulation. Despite the genetic potential for increased prolificacy, Duolang sheep often exhibit low litter sizes, largely constrained by detrimental environmental factors and management practices. This review emphasizes the significance of integrating genetics, nutrition, and reproductive management to optimize productivity. Strategies such as nutritional flushing, hormone-based estrous synchronization, and selective breeding for increased litter size are discussed, with a focus on minimizing the risks associated with early puberty and lamb survival. Furthermore, the review explores the potential of genomic selection, marker-assisted breeding, and advanced reproductive technologies to enhance the breed’s performance. Finally, the review outlines future research directions, necessitating the development of genomic resources, precise breeding programs, and field trials on reproductive interventions to accelerate genetic gains in Duolang sheep. This integrated approach promises to improve reproductive outcomes, with implications for sustainable sheep production in Xinjiang and similar environments across the globe. Full article

Male infertility, implicated in nearly 50% of couples’ infertility cases, represents a major medical and sociocultural challenge in Morocco. This narrative review synthesizes available epidemiological, etiological, and genetic data within national and international contexts. In Morocco, male infertility is characterized by the frequent involvement of modifiable factors, notably varicocele, smoking, and occupational exposures. From a genetic standpoint, chromosomal abnormalities, particularly Klinefelter syndrome, together with Y chromosome microdeletions, especially within the AZFc region, represent the main identified etiologies. Emerging technologies, such as next-generation sequencing, offer promising diagnostic perspectives, although their clinical application remains limited and mainly confined to research. Despite advances in medically assisted reproduction, the management of male infertility in Morocco continues to face psychosocial and economic barriers, as well as inequalities in access to care. These findings underscore the need to establish national registries, conduct multicenter studies, and facilitate the translation of innovations (particularly multi-omics approaches) into clinical practice to improve male infertility management in the Moroccan context. Full article

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

Cryopreserved bovine semen represents an accessible source of genetic material due to its widespread use in assisted reproductive technologies and the conservation of genetically valuable animals. However, DNA extraction from spermatozoa within this type of sample remains challenging due to the high protein content and the complex structure of the ejaculate, which can affect DNA yield and quality. The aim of this study was to identify and validate an efficient method for obtaining high-quality DNA from spermatozoa present in cryopreserved bovine semen for molecular diagnostic applications. Five DNA extraction protocols were evaluated: TRIzol™, MagMax™ Nucleic Acid Purification Kit, Rapid DNA™ Fecal/Soil Microbe Kit, a conventional phenol–chloroform protocol, and a modified phenol–chloroform–isoamyl alcohol protocol. All extracted genetic material was assessed by spectrophotometry (concentration and purity), and DNA integrity was evaluated by agarose gel electrophoresis. Statistical analysis revealed significant differences in DNA concentration among extraction methods (Friedman test, χ² = 22.0, df = 4, p = 0.0002). Post hoc comparisons indicated that the modified phenol–chloroform–isoamyl alcohol protocol yielded significantly higher DNA concentrations compared to selected methods. This protocol showed the highest DNA concentration (1006.2 ± 829.4 ng/μL) and favorable purity values, and enabled consistent amplification in both conventional PCR and qPCR assays targeting the β-actin gene and Tritrichomonas foetus, respectively. These findings suggest that the modified protocol represents a suitable and promising approach for extracting genomic DNA from spermatozoa in cryopreserved bovine semen, with potential applications in molecular diagnostics and reproductive biotechnology. 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

Age-related decline in oocyte quality is closely associated with mitochondrial dysfunction and oxidative imbalance, which disrupt redox-sensitive meiotic signaling and compromise embryo developmental competence. Rescue in vitro maturation (r-IVM) enables the utilization of immature oocytes retrieved during conventional in vitro fertilization (IVF) cycles. However, the developmental potential of r-IVM oocytes remains limited, particularly in women of advanced maternal age. This study evaluated whether transient caffeine supplementation during r-IVM improves the developmental competence of immature human oocytes in clinical assisted reproduction technology cycles. Immature oocytes obtained during conventional IVF were cultured with or without short-term caffeine exposure during r-IVM prior to standard culture conditions. After maturation, metaphase II oocytes underwent intracytoplasmic sperm injection, and embryonic development was assessed by fertilization rate, day 3 good-quality embryo formation, and blastocyst development. Although caffeine supplementation did not significantly affect nuclear maturation rates, it significantly increased fertilization efficiency and the proportion of good-quality embryos compared with controls. These effects were most pronounced in women aged ≥37 years. Time-lapse morphokinetic analysis further revealed more synchronized developmental kinetics in embryos derived from caffeine-treated oocytes, resembling those derived from in vivo-matured oocytes. Collectively, these findings suggest that transient caffeine exposure during r-IVM enhances post-fertilization developmental competence. The underlying mechanisms remain to be elucidated, and future studies are required to determine whether redox-sensitive meiotic pathways and mitochondrial function are involved. Full article

Background/Objectives: Infertility affects about 17.5% of people globally, with higher rates in women. Despite advances in assisted reproductive technologies, success remains limited. Endometrial scratching (ES) is proposed to enhance implantation by altering cytokines and gene expression, but evidence is conflicting. Methods: A systematic search of the PubMed, Cochrane Library, and Scopus databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eight randomized controlled trials (RCTs) involving women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), with ES performed in the luteal phase of the cycle preceding IVF or ICSI, were included. Results: The meta-analysis included 3210 patients and 1445 clinical pregnancies (754 in the ES group and 691 in the control group). In the ES group, a significantly higher clinical pregnancy rate (CPR) (RR 1.09, 95% CI 1.01–1.18, p = 0.02) was revealed. Pooled data from six studies reporting live birth rates (1268 births) showed a significant increase in the LBR after ES (RR 1.12, 95% CI 1.03–1.22, p = 0.01). The ongoing pregnancy rate (OPR) was also statistically significant in the ES group (RR 1.13, 95% CI 1.01–1.26, p = 0.03). Conclusions: This meta-analysis shows a small but statistically significant and consistent positive effect of ES on the LBR, CPR, and OPR in women undergoing IVF or ICSI, with a modest but measurable absolute benefit of approximately 4–5 additional events per 100 individuals. This procedure may particularly benefit patients with impaired endometrial receptivity, potentially enhancing reproductive outcomes while reducing the time and cost required to achieve a successful pregnancy. Further research is warranted to optimize its use and identify patients most likely to benefit. 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

Ovarian function relies on a network of well-coordinated molecular mechanisms that regulate follicular development, oocyte maturation, ovulation, and corpus luteum function. When these processes are disrupted, infertility can result. Extracellular matrix (ECM) remodeling represents a central regulatory component in these processes and is essential for follicle rupture and oocyte release. This mechanism involves metalloproteinases (MMPs), mainly MMP-2 and MMP-9, which degrade the ECM and allow the necessary structural changes. Other ECM-modulating proteases, such as ADAM and ADAMTS families, also contribute to this process. Their activity is tightly regulated by tissue inhibitors of metalloproteinases (TIMPs), ensuring that tissue remodeling occurs in a controlled manner. Disruption of the balance between MMPs and TIMPs increases the risk of infertility-related conditions such as polycystic ovary syndrome (PCOS), endometriosis, luteinizing hormone (LH) deficiency syndrome, and ovarian aging. In addition to the ECM, other factors, including intracellular signaling pathways, oxidative stress (OS), and mitochondrial function, contribute to ovarian physiology and directly affect oocyte quality and viability. This narrative review focuses on the molecular mechanisms governing ovarian function, with particular emphasis on the remodeling of the ECM by MMPs during ovulation, and examines how their disorders contribute to infertility. A deeper understanding of these mechanisms may lead to the identification of new therapeutic targets and the improvement of assisted reproduction outcomes. 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