Search Results (766)

Objective: This retrospective observational study evaluated the efficacy and safety of an ovarian stimulation protocol for embryo banking that involves continuous administration of clomiphene citrate (CC) in combination with gonadotropins, without the use of GnRH antagonists. Methods: Conducted at the Serum IVF Clinic in Athens, Greece, the study included 250 women aged 25–45 who underwent IVF for embryo banking. The protocol involved administering 150 mg of CC daily from day 2 of the menstrual cycle until the day before hCG trigger, alongside 150 IU/day of Meriofert. Outcomes assessed included oocyte yield, fertilization rates, incidence of ovarian hyperstimulation syndrome (OHSS), and hormonal correlations. Comparative and regression analyses explored differences between age groups and predictors of success. Results: The protocol demonstrated a favorable safety profile with no cases of OHSS and yielded a mean of 10.25 oocytes per patient. Group analysis showed significantly more oocytes retrieved in women under 40 (mean: 12.5) versus those over 40 (mean: 8.43), while fertilization rates were paradoxically higher in the older cohort (59.16% vs. 30.68%, p < 0.0001). Regression models revealed basal FSH to be a significant inverse predictor of oocyte yield, but it was positively associated with fertilization rate. Continuous CC use effectively suppressed premature LH surges without compromising oocyte or embryo quality, allowing flexible and cost-effective stimulation with minimal monitoring. Conclusions: Continuous administration of clomiphene citrate in combination with gonadotropins presents a promising, antagonist-free ovarian stimulation protocol for embryo banking. The approach is economically efficient, reduces monitoring requirements, and maintains safety and effectiveness and is particularly notable in women over 40. Further studies are warranted to validate these findings and refine protocol mechanisms. Full article

Objectives: To investigate how the FLASH effect modulates radiation response on multiple developmental endpoints of zebrafish embryos under normoxic and hypoxic conditions, after irradiation with proton beams at a conventional and an ultra-high dose rate (UHDR). Methods: Embryos were obtained from adult zebrafish and irradiated with a 228 MeV proton beam 24 h post-fertilization (hpf) at a dose rate of 0.6 and 317 Gy/s. For the hypoxic group, samples were kept inside a hypoxic chamber prior to irradiation, while standard incubation was adopted for the normoxic group. After irradiation, images of single embryos were acquired, and radiation effects on larval length, yolk absorption, pericardial edema, head size, eye size, and spinal curvature were assessed at specific time points. Results: Data indicate a general trend of significantly reduced toxicity after exposure to a UHDR compared to conventional regimes, which is maintained under both normoxic and hypoxic conditions. Differences are significant for the levels of pericardial edema induced by a UHDR versus conventional irradiation in normoxic conditions, and for eye and head size in hypoxic conditions. The toxicity scoring analysis shows a tendency toward a protective effect of the UHDR, which appears to be associated with a lower percentage of embryos in the high score categories. Conclusions: A radioprotective effect at a UHDR is observed both for normoxic (pericardial edema) and hypoxic (head and eye size) conditions. These results suggest that while the UHDR may preserve a potential to reduce radiation-induced damage, its protective effects are endpoint-dependent; the role of oxygenation might also be dependent on the tissue involved. Full article

Background: Toxoplasma gondii is a globally widespread parasite responsible for toxoplasmosis, a zoonotic disease with significant impact on both human and animal health. The current lack of safe and effective treatments underscores the need for new drugs. Earlier, thiosemicarbazones (TSCs) and their metal complexes have shown promising activities against T. gondii. This study evaluated a gold (III) complex C3 and its TSC ligand C4 for safety in host immune cells and zebrafish embryos, followed by efficacy assessment in a murine model for chronic toxoplasmosis. Methods: The effects on viability and proliferation of murine splenocytes were determined using Alamar Blue assay and BrdU ELISA, and potential effects of the drugs on zebrafish (Danio rerio) embryos were detected through daily light microscopical inspection within the first 96 h of embryo development. The parasite burden in treated versus non-treated mice was measured by quantitative real-time PCR in the brain, eyes and the heart. Results: Neither compound showed immunosuppressive effects on the host immune cells but displayed dose-dependent toxicity on early zebrafish embryo development, suggesting that these compounds should not be applied in pregnant animals. In the murine model of chronic toxoplasmosis, C4 treatment significantly reduced the parasite load in the heart but not in the brain or eyes, while C3 did not have any impact on the parasite load. Conclusions: These results highlight the potential of C4 for further exploration but also the limitations of current approaches in effectively reducing parasite burden in vivo. Full article

Triphenyl phosphate (TPhP) is a widely used organophosphate flame retardant and plasticizer, raising concerns over its health impacts. This study examined the effects of embryonic TPhP exposure on axial skeletal development and metabolism in medaka (Oryzias latipes), a vertebrate fish model relevant to human bone biology. Medaka embryos were exposed to 1 µM TPhP and assessed through early larval stages. TPhP impaired vertebral ossification, causing shortened centra and reduced cartilage in the caudal complex, alongside disrupted distribution of osteoblast-lineage cells. Key osteogenic genes were significantly downregulated at 14 days post fertilization, and transcriptomic analysis revealed altered mitochondrial pathways linked to skeletal disorders. Functionally, TPhP-exposed larvae showed reduced caudal fin regeneration and decreased metabolic rate and oxygen consumption, consistent with mitochondrial dysfunction. These findings indicate that TPhP disrupts bone development and metabolism by affecting osteoblast differentiation and mitochondrial regulation, highlighting the value of small fish models for studying environmental toxicants and bone metabolic disease risk. Full article

Background: Artificial intelligence (AI) and machine learning (ML) have been reshaping maternal, fetal, neonatal, and reproductive healthcare by enhancing risk prediction, diagnostic accuracy, and operational efficiency across the perinatal continuum. However, no comprehensive synthesis has yet been published. Objective: To conduct a scoping review of reviews of AI/ML applications spanning reproductive, prenatal, postpartum, neonatal, and early child-development care. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus through April 2025. Two reviewers independently screened records, extracted data, and assessed methodological quality using AMSTAR 2 for systematic reviews, ROBIS for bias assessment, SANRA for narrative reviews, and JBI guidance for scoping reviews. Results: Thirty-nine reviews met our inclusion criteria. In preconception and fertility treatment, convolutional neural network-based platforms can identify viable embryos and key sperm parameters with over 90 percent accuracy, and machine-learning models can personalize follicle-stimulating hormone regimens to boost mature oocyte yield while reducing overall medication use. Digital sexual-health chatbots have enhanced patient education, pre-exposure prophylaxis adherence, and safer sexual behaviors, although data-privacy safeguards and bias mitigation remain priorities. During pregnancy, advanced deep-learning models can segment fetal anatomy on ultrasound images with more than 90 percent overlap compared to expert annotations and can detect anomalies with sensitivity exceeding 93 percent. Predictive biometric tools can estimate gestational age within one week with accuracy and fetal weight within approximately 190 g. In the postpartum period, AI-driven decision-support systems and conversational agents can facilitate early screening for depression and can guide follow-up care. Wearable sensors enable remote monitoring of maternal blood pressure and heart rate to support timely clinical intervention. Within neonatal care, the Heart Rate Observation (HeRO) system has reduced mortality among very low-birth-weight infants by roughly 20 percent, and additional AI models can predict neonatal sepsis, retinopathy of prematurity, and necrotizing enterocolitis with area-under-the-curve values above 0.80. From an operational standpoint, automated ultrasound workflows deliver biometric measurements at about 14 milliseconds per frame, and dynamic scheduling in IVF laboratories lowers staff workload and per-cycle costs. Home-monitoring platforms for pregnant women are associated with 7–11 percent reductions in maternal mortality and preeclampsia incidence. Despite these advances, most evidence derives from retrospective, single-center studies with limited external validation. Low-resource settings, especially in Sub-Saharan Africa, remain under-represented, and few AI solutions are fully embedded in electronic health records. Conclusions: AI holds transformative promise for perinatal care but will require prospective multicenter validation, equity-centered design, robust governance, transparent fairness audits, and seamless electronic health record integration to translate these innovations into routine practice and improve maternal and neonatal outcomes. Full article

Recurrent implantation failure (RIF) remains a challenging clinical problem. Growth hormone (GH) co-treatment has been explored as an adjunct in poor responders and RIF patients, with inconsistent evidence of benefit. This prospective cohort study assessed the impact of GH supplementation in 91 RIF patients undergoing in vitro fertilization, stratified by FSHR (follicular stimulating hormone receptor) genotype Asn680Ser with or without GH supplementation. Patients were stratified by FSHR genotype into homozygous Ser/Ser versus Ser/Asn or Asn/Asn groups. Overall, GH co-treatment conferred modest benefits in the unselected RIF cohort, limited to a higher cumulative live birth rate compared to controls and elevated leukemia inhibitory factor (LIF) levels (p < 0.05 both). When stratified by FSHR genotype, the Ser/Ser subgroup exhibited markedly better outcomes with GH. These patients showed a higher (0.5 vs. 0.33, p = 0.003), produced more embryos (2.88 vs. 1.53, p = 0.02), and had a markedly improved cumulative live birth rate—50% with GH versus 13% without—highlighting a clinically meaningful benefit of GH in the Ser/Ser subgroup. No significant benefit was observed in Asn allele carriers. These findings suggest that FSHR genotyping may help optimize treatment selection in RIF patients by identifying those most likely to benefit from GH supplementation. Full article

Strobilurins are a prominent class of fungicides capable of entering aquatic environments via runoff and leaching from the soil. Findings from previous studies suggest that strobilurins are highly toxic in aquatic environments, and evidence of acute developmental toxicity and altered behavioral responses have been emphasized. The objective here was to determine the effects of a new strobilurin, metyltetraprole (MTP), on zebrafish using developmental endpoints, gene expression, and behavioral locomotor assays. We hypothesized that MTP would cause developmental toxicity and induce hyperactivity in zebrafish (Danio rerio). To test this, developing zebrafish embryos/larvae were exposed to environmentally relevant levels of MTP (0.1, 1, 10, and 100 µg/L) until 7 days post-fertilization. Survival percentages did not differ among the treatment groups. No change in reactive oxygen species production was detected, but two genes involved in the mitochondrial electron transport chain (mt-nd3 and uqcrc2) were altered in abundance following MTP exposure. Moreover, the highest concentration (100 µg/L) of MTP caused notable hyperactivity in the zebrafish in the visual motor response test. Overall, results from this study increase our knowledge regarding sub-lethal effects of MTP, helping inform risk assessment for aquatic environments. Full article

This study assesses sediment toxicity in the historically contaminated Orbetello Lagoon (southern Tuscany) using Paracentrotus lividus embryo development bioassays. Elutriates from 15 sites were analysed for trace metals, organic matter, and ammonium. Despite elevated mercury concentrations, toxicity did not consistently correlate with metal levels. Instead, Principal Component Analysis (PCA) identified ammonium as a key driver of developmental toxicity, suggesting that it significantly influences both biological effects and metal bioavailability. These results demonstrate that ammonium, often overlooked, can confound sediment toxicity assessments and should be integrated into risk evaluation frameworks for coastal systems affected by legacy pollution. Full article

In this study, we demonstrated that lrp6a, a co-receptor in the Wnt signaling pathway, is essential for proper median fin formation and somitogenesis in goldfish. We analyzed the gene’s sequence features and expression patterns in both wen-type and egg-type goldfish, uncovering distinct tissue-specific expression differences between the two varieties. To explore the functional role of lrp6a, we performed CRISPR/Cas9-mediated gene knockout using eight designed single-guide RNAs (sgRNAs), of which four showed effective targeting. Three high-efficiency sgRNAs were selected and co-injected into embryos to achieve complete gene disruption. Morphological assessments and X-ray microtomography (μCT) imaging of the resulting mutants revealed various abnormalities, including defects in the dorsal, caudal, and anal fins, as well as skeletal deformities near the caudal peduncle. These results confirm that lrp6a plays a key role in median fin development and axial patterning, offering new insights into the genetic regulation of fin formation in teleost fish. Full article

Background/Objectives: Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women of advanced maternal age remains unclear due to limited randomized data. This pilot trial assessed the feasibility of a full-scale RCT comparing PGT-A to morphology-based selection in women aged 35–42. Methods: This single-centre, two-arm parallel RCT (NCT05009745) enrolled women aged 35–42 undergoing IVF/ICSI with ≥3 good-quality day-3 embryos. Participants were randomized (1:1) to either embryo selection by morphology with fresh transfer or PGT-A with frozen transfer of a single euploid embryo. Allocation concealment was achieved via a secure web-based randomization platform; patients and clinicians were unblinded, but the biostatistician remained blinded. The primary outcome was feasibility of recruitment, randomization, and adherence. Results: Between June 2021 and January 2023, 138 women consented (recruitment rate: 55.8%, 95% CI: 49.7–62.0%) and 100 were randomized. Protocol adherence was 94%. Barriers to recruitment included preference for private PGT-A (19%) or fresh transfer (6%). Among biopsied embryos, 51.4% were euploid and 6.6% low-level mosaic. Intention-to-treat analysis showed no significant differences between PGT-A and control groups in clinical pregnancy rate (50% vs. 40%), live birth rate (50% vs. 38%), or miscarriage rate (12% vs. 8%). Cumulative live birth rate after up to three SETs was 72% vs. 52%, respectively (p > 0.05). No multiple pregnancies occurred. Conclusions: RCTs of PGT-A in older women are feasible. A multicentre design with broader inclusion criteria could improve recruitment and allow better assessment of clinical benefit. Full article

Immunological factors have gained growing recognition as key contributors to recurrent pregnancy loss (RPL) after in vitro fertilization (IVF), representing a major challenge in reproductive medicine. RPL affects approximately 1–2% of women trying to conceive naturally and up to 10–15% of those undergoing IVF, where overall success rates remain around 30–40% per cycle. An imbalance in maternal immunological tolerance toward the semi-allogeneic fetus during pregnancy may lead to miscarriage and implantation failure. IVF-related ovarian stimulation and embryo modification offer additional immunological complications that can exacerbate existing immune dysregulation. Recent advances in reproductive immunology have significantly deepened our understanding of the immune mechanisms underlying RPL following IVF, particularly highlighting the roles of regulatory T cells (T regs), natural killer cells, cytokine dysregulation, and disruptions in maternal–fetal immune tolerance. In order to better customize therapies, this evaluation incorporates recently discovered immunological biomarkers and groups patients according to unique immune profiles. Beyond conventional treatments like intralipid therapy and intravenous immunoglobulin, it also examines new immunomodulatory medications that target certain immune pathways, such as precision immunotherapies and novel cytokine modulators. We also discuss the debates over immunological diagnostics and therapies, such as intralipid therapy, intravenous immunoglobulin, corticosteroids, and anticoagulants. The heterogeneity of patient immune profiles combined with a lack of strong evidence highlights the imperative for precision medicine to improve therapeutic consistency. Novel indicators for tailored immunotherapy and emerging treatments that target particular immune pathways have encouraging opportunities to increase pregnancy success rates. Improving management approaches requires that future research prioritize large-scale clinical trials and the development of standardized immunological assessments. This review addresses the immunological factors in RPL during IVF, emphasizing underlying mechanisms, ongoing controversies, and novel therapeutic approaches to inform researchers and clinicians. Full article

Background: Astrocytes are not only structural cells but also play a pivotal role in neurogenesis and neuroprotection by secreting a variety of neurotrophic factors that support neuronal survival, growth, and repair. This study investigates the time-dependent responses of primary rat cortical astrocytes to oxygen–glucose deprivation (OGD) and evaluates the neuroprotective potential of astrocyte-conditioned medium (ACM). Methods: Primary rat cortical astrocytes and neurons were obtained from postnatal Sprague Dawley rat pups (P1–3) and embryos (E17–18), respectively. Astrocytes exposed to 6, 24, and 48 h of OGD (0.3% O₂) were assessed for viability, metabolic function, hypoxia-inducible factor 1 and its downstream genes expression. Results: While 6 h OGD upregulated protective genes such as Vegf, Glut1, and Pfkfb3 without cell loss, prolonged OGD, e.g., 24 or 48 h, led to significant astrocyte death and stress responses, including elevated LDH release, reduced mitochondrial activity, and increased expression of pro-apoptotic marker Bnip3. ACM from 6 h OGD-treated astrocytes significantly enhanced neuronal survival following 6 h OGD and 24 h reperfusion, preserving dendritic architecture, improving mitochondrial function, and reducing cell death. This protective effect was not observed with ACM from 24 h OGD astrocytes. Furthermore, 6 h OGD-ACM induced autophagy in neurons, as indicated by elevated LC3b-II and decreased p62 levels, suggesting autophagy as a key mechanism in ACM-mediated neuroprotection. Conclusions: These findings demonstrate that astrocytes exhibit adaptive, time-sensitive responses to ischemic stress and secrete soluble factors that can confer neuroprotection. This study highlights the therapeutic potential of targeting astrocyte-mediated signalling pathways to enhance neuronal survival following ischemic stroke. Full article

To date, there is no effective treatment for glioblastoma (GBM). This study aimed to compare the effectiveness of sodium dichloroacetate (NaDCA), a valproic acid and NaDCA combination (VPA–NaDCA), or temozolomide (TMZ) on U87 and T98G cell tumors on the chick embryo chorioallantoic membrane (CAM), and on the expression of proliferating cell nuclear antigen (PCNA), polycomb inhibitory complex catalytic subunit 2 (EZH2), and TP53 gene-encoded p53 protein (p53) in tumors on the CAM, and SLC12A2 (gene encoding Na⁺-K⁺-2Cl⁻ (NKCC1) co-tarnsporter), SLC12A5 (gene encoding K⁺-Cl⁻ (KCC2) co-transporter), SLC5A8 (gene encoding Na⁺-dependent monocarboxylate transporter) and CDH1 (gene encoding the E-cadherin protein) and CDH2 (gene encoding the N-cadherin protein) in cells. VPA–NaDCA and TMZ reduced the invasion of U87 and T98G tumors, as well as the expression of PCNA and EZH2 in the tumor. TMZ reduced p53 expression in tumors from both cell lines, whereas VPA–NaDCA did not affect the expression of this marker. VPA–NaDCA, but not TMZ, reduced SLC12A2 expression in T98G cells. However, VPA–NaDCA and TMZ did not affect SLC12A2 expression in U87 cells. VPA–NaDCA increased SLC5A8 expression only in U87 cells, and TMZ did not affect gene expression in either cell line. Only VPA–NaDCA increased CDH1 expression and decreased CDH2 expression in T98G cells, whereas TMZ had no effect on gene expression in the study cells. This study demonstrated that VPA–NaDCA exhibits a more effective anticancer effect than NaDCA. The data suggest that VPA–NaDCA has a more effective impact than TMZ; however, the effect of investigational medicines on carcinogenesis varies depending on the cell line. The study of the efficacy of drugs used to treat tumors on the CAM and cells demonstrates that it is essential to assess the effectiveness of treatment, which should be personalized, before administering chemotherapy. Full article

Avian infectious bronchitis virus (IBV) infection has caused significant economic losses to the poultry industry. Unfortunately, there is currently no effective cure for this disease. Understanding the pathogenic mechanism is crucial for the treatment of the disease. Studying the pathogenic mechanism of IBV based on metabolomics analysis is helpful for identifying antiviral drugs. However, studies on metabolomics analysis of IBV infection have been relatively limited, particularly without metabolomics analysis in sera after IBV infection. In this study, 17-day-old SPF chicks were infected with the IBV GX-YL5 strain, and serum samples were collected 7 days post-infection (DPI) for metabolomics analysis using ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). A total of 143 differential metabolites were identified across 20 metabolic pathways, with the phenylalanine pathway showing the most significant changes. The level of cinnamic acid (CA), an upstream metabolite in the phenylalanine pathway, was notably increased following IBV infection. To investigate the antiviral effects of CA, chicken embryo kidney (CEK) cells and SPF chicks infected with IBV were treated with different concentrations of CA to assess its effect on viral replication. The results demonstrated that CA at 25 μg/mL effectively inhibited IBV replication in vitro; meanwhile, CA at 50 μg/mL and 25 μg/mL effectively inhibited IBV replication in vivo. Molecular docking and molecular dynamics simulation studies showed that CA interacts with the N domains of the IBV nucleocapsid (N) protein. In conclusion, the serum metabolite CA is significantly elevated following IBV infection and demonstrates remarkable antiviral effects both in vitro and in vivo, providing a promising avenue for the development of antiviral therapies to combat IBV infection. Full article

Body stalk anomaly (BSA) is a rare and usually fatal congenital disorder involving severe malformations of the body wall, limbs, spine, and internal organs. This study presents the first documented cases of BSA in seven dogs, offering new insights into how the disorder manifests in animals. The affected fetuses consistently exhibited major anomalies, including large abdominal wall defects, structural spinal abnormalities, and a variety of limb malformations ranging from partial agenesis and meromelia to phocomelia and complete amelia. Structural urogenital anomalies and orofacial clefts were also observed, aligning with similar findings in BSA cases reported in pigs and cats. These findings support the hypothesis of a multifactorial etiology involving early embryonic disruptions, such as abnormal folding of the embryo, rupture of the amniotic membrane, and vascular compromise. The frequent occurrence of abdominal wall defects alongside umbilical cord abnormalities further suggests a shared developmental pathway. This study also highlights the value of veterinary cases in comparative embryology and the need to assess congenital anomalies as part of a broader malformation complex. By expanding the phenotypic spectrum of BSA in domestic animals, this work contributes to a deeper understanding of its pathogenesis and emphasizes the importance of further research into the genetic and environmental factors involved. Such efforts could lead to improved classification and diagnosis of complex congenital malformations, as well as facilitate cross-species comparisons. Full article