Search Results (3,269)

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

Ovarian cancer is the most lethal gynaecological cancer, largely because it is often diagnosed late and shows strong tumour heterogeneity, therapy resistance, and rapid metastatic spread. A key driver of this aggressive behaviour is the tumour’s ability to reshape its surrounding microenvironment to support invasion, angiogenesis, and escape from treatment. Cathepsin L (CTSL), a lysosomal cysteine protease, has emerged as an important mediator of these processes and is gaining attention as both a prognostic marker and a potential therapeutic target. This review examines the diverse roles of CTSL in ovarian cancer progression, focusing on how its expression, localisation, and extracellular release are altered within the hypoxic and acidic conditions typical of the tumour microenvironment. It also outlines emerging therapeutic strategies aimed at targeting CTSL, including selective inhibitors, multi-cathepsin approaches, CTSL-activated prodrugs and antibody-drug conjugate linkers, and nanomedicine systems designed for tumour-specific delivery. Overall, the evidence highlights CTSL as a central regulator of invasion, angiogenesis, and relapse in ovarian cancer, underscoring its potential as a target for new therapies in aggressive disease. Full article

Background/Objectives: Accurate evaluation of fallopian tube patency is an essential step in infertility assessment. This study investigated the diagnostic capability of saline infusion sonography combined with color Doppler flow (SIS-CF), using laparoscopic chromopertubation as the comparator method. Methods: A prospective diagnostic accuracy study was conducted between January and November 2025 at the Infertility Unit, Chiang Mai University Hospital, Thailand. Women requiring laparoscopic assessment for infertility evaluation or preconception investigation were consecutively enrolled. Each participant underwent SIS-CF immediately before laparoscopic chromopertubation within the same operative session. Primary outcomes included diagnostic indices for tubal patency. Secondary outcomes included procedural duration and perioperative safety. Results: Forty-four women (88 fallopian tubes) were included. SIS-CF demonstrated sensitivity of 89.4% (95% CI 78.1–95.9) and specificity of 95.5% (95% CI 77.2–99.9). Positive and negative predictive values were 98.3% and 75.0%, respectively. Likelihood ratios were 19.65 (positive) and 0.11 (negative), with overall accuracy of 90.9% (95% CI 82.9–95.8). Median procedure duration was 5.7 min for SIS-CF and 3.0 min for laparoscopic chromopertubation. No adverse events were recorded. Conclusions: SIS-CF demonstrated favorable diagnostic characteristics for evaluation of tubal patency. The technique provided functional information regarding tubal status while maintaining a minimally invasive profile. Further investigation is warranted to determine its role within routine infertility workups. Full article

Premature ovarian insufficiency (POI) is a clinical condition characterized by loss of ovarian function indicated by amenorrhea or irregular menstrual cycles for at least 4 months and elevated gonadotrophins (FSH > 25 IU/L, measured on one occasion) and low estrogen serum levels in women under the age of 40. Premature ovarian insufficiency can be non-iatrogenic or spontaneous (idiopathic or due to genetic, autoimmune, or metabolic reasons, or infections) and iatrogenic (a consequence of oophorectomy, chemotherapy, radiotherapy, or uterine artery embolization). Women with POI are faced not only with estrogen deficiency but also with infertility and psychological implications. Hormonal replacement therapy is effective in treating the symptoms of premature ovarian insufficiency as well as in lowering the health risk of long-term consequences of premature ovarian insufficiency. Currently, oocyte donation is the standard treatment for patients with POI desiring pregnancy. Recently developed methods for the regeneration of ovarian tissue, such as stem cell therapy, platelet-reach plasma therapy and in vitro activation of ovarian tissue, are still under research and further adequate multicentric clinical studies are needed to develop standardized effective and safe protocols for the infertility treatment of patients with premature ovarian insufficiency. Full article

Formalin-fixed paraffin-embedded (FFPE) tissues represent an invaluable resource for both basic and clinical research due to their stable preservation of tissue architecture and molecular integrity. Multiplex immunofluorescence (mIF) using tyramide signal amplification (TSA) enables the simultaneous detection of multiple antigens within a single FFPE section. Here, we describe a kit-independent and customizable TSA-based mIF protocol that utilizes commercially available horseradish peroxidase (HRP)-conjugated secondary antibodies and tyramide–fluorophore reagents. The method was applied using FFPE endometriosis tissue, targeting estrogen receptor alpha (ERα), progesterone receptor (PR), α-smooth muscle actin (αSMA), CD20 and CD31. Each staining round was followed by heat-induced epitope removal (HIER) of the bound antibodies while preserving covalently deposited signals. Fluorescence imaging was performed using a multi-channel slide scanner with carefully selected fluorophores to enable optical separation between detection channels. Under the conditions described, the protocol enabled clear visualization of maker-specific staining patterns with preserved tissue morphology. This study provides a practical and flexible TSA-based mIF protocol as a qualitative proof of concept, offering an accessible alternative to commercial kit-based approaches. Further studies will be required to establish quantitative performance and a broader applicability across tissue types. Full article

Achromobacter spp. are opportunistic pathogens in people with cystic fibrosis (PwCF), yet the role of the upper airways in their persistence and adaptation remains poorly understood. We investigated whether the sinonasal compartment may act as reservoir and evolutionary niche for Achromobacter spp. during airway infection. Twenty-two isolates obtained from paired nasal lavage and sputum samples of seven PwCF were analysed by whole-genome sequencing. Within each PwCF, identical clone types were detected in both airway compartments, supporting bacterial exchange between upper and lower airways. Despite clonal relatedness, substantial genomic diversification was observed between paired isolates. Genomic signatures indicative of elevated mutation rates were detected in a high number of isolates (73%) and in both airway compartments, highlighting widespread genomic diversification across the respiratory tract. Mobilome analysis revealed compartment-specific variations in insertion sequences, prophages, and integrative elements, suggesting genome plasticity. Additionally, mutation in an aspartate kinase gene was consistently associated with loss of biofilm formation in vitro, highlighting a potential link between this pathway and biofilm phenotype. Overall, our findings indicate that upper and lower airways represent interconnected but partially independent ecological niches where Achromobacter populations can diverge during colonization, supporting the view that both compartments contribute to their persistence and evolution in CF airways. Full article

Background/Objectives: Older adults with an LGBT+ identity represent an under-researched population within healthcare systems. Existing evidence suggests that they experience distinct health challenges compared to their heterosexual counterparts, partly shaped by lifelong experiences of stigma and discrimination. Such experiences may contribute to minority stress, which is associated with adverse mental health outcomes and lifestyle-related health issues. This review aims to synthesise the existing literature on how older adults with an LGBT+ identity experience encounters with healthcare. Methods: An integrative literature review was conducted following PRISMA guidelines. A systematic search of multiple databases was performed, and studies were screened using predefined inclusion and exclusion criteria. Data were analysed using systematic text condensation. Results: A total of 18 studies were included, comprising approximately 450 participants. All studies contained a qualitative component. Three overarching themes were identified: (1) double-edged discrimination—experiences of stigma and anticipated fear in healthcare; (2) relational networks as essential yet fragile sources of support in later life; and (3) healthcare practices as shaping inclusion or invisibility—the need for competence and recognition. Conclusions: The findings highlight significant barriers faced by older adults with an LGBT+ identity in healthcare, including fear of discrimination and challenges related to disclosure. Social networks play a crucial role as sources of support, while healthcare professionals’ competencies and practices are central to ensuring inclusive and equitable care. 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

A novel graphene-based nanomaterial, trade registered Hastalex^®, has been synthesised and investigated for its application as a 3D scaffold in surgical implantation. Hastalex is developed through the covalent bonding of amine-group-functionalised graphene oxide to the base chemical, poly(carbonate-urea)urethane. The material is under development for medical application including tendon, heart valve, and pelvic implant for prolapse surgery. For successful clinical translation, long-term rheological and chemical stability must be demonstrated and until now no systematic multi-year evaluation has been reported for graphene-poly(carbonate-urea)urethane nanocomposites. The material was synthesised in accordance with the patented formulation and evaluated at 0, 6, 12, and 24 months post-synthesis. Physicochemical properties were assessed using attenuated total reflectance Fourier-transform infrared spectroscopy, scanning electron microscope, contact angle measurements, thermogravimetric analysis, and mechanical analysis with tensile tests. Flow behaviour of Hastalex was evaluated using a rheometer to determine viscosity, shear stress response and impact of temperature changes and ageing on these factors. Hastalex exhibited non-Newtonian, shear-thinning behaviour consistent across all timepoints. Viscosity was found to increase progressively with ageing, attributed not to chemical degradation, but likely due to gradual solvent evaporation and densification of the polymer matrix during storage under ambient conditions. Rheological measurements across increasing temperature regimes revealed a heat-sensitive decrease in viscosity, followed by a reversal of changes beyond ~80 °C—likely due to enhanced solvent evaporation and chain reorganisation. This comprehensive material characterisation supports Hastalex as a promising candidate for bioengineering applications. Full article

Persistent post-endometrial ablation uterine bleeding indicates that no method of EA eliminates the entire endometrium, and post-EA hysteroscopy shows a distorted and scarred uterine cavity in the majority of patients. These observations raise concerns regarding presentation, assessment and stage of potential post-ablation endometrial cancer (PAEC), developing in residual endometrium pockets. To better understand these concerns, a literature search was conducted, from the introduction of EA in the 1980s through 2025, to capture reports of endometrial cancer (EC) associated with or following EA using multiple data bases, imputing search terms of EC following EA and possible combinations of first- and second-generation EA techniques associated with EC. Upon review of all publications, we identified 86 ECs associated with EA, described in 20 case reports (N = 20), four case series (N = 18), eleven cohort studies (N = 21), one registry (N = 27) and five reviews. Based on 12 relevant studies at a median follow-up of 8.5 years (range 1.9–25), 43 EC were identified in 39,795 women with a history of EA, with a summary incidence of 0.11% (range 0.0–1.59%). Although the studies and data are very heterogeneous, it appears that EA may afford a protective effect in reducing the risk of EC in the short term. The mechanistic effect is likely due to a quantitative reduction in the endometrium that can potentially become malignant, and/or due to the elimination of occult pre- or malignant endometrial elements which are vulnerable to EA. Moreover, based on 25 evaluable cases, the mode and time to presentation, the diagnostic work-up (including endometrial biopsy and hysteroscopy), and the stage of PAEC appear not to be altered by EA. Full article

Adenomyosis is a benign gynaecological disorder in which endometrial glands and stroma enter the uterine myometrium with varying degrees of spreading. To analyse the presence of developmentally displaced endometrial glands and stroma in the foetal myometrium, a retrospective cohort of 420 foetal uteri, including one monozygotic twin pair, was histopathologically evaluated. The gestational age ranged between 18 and 37 weeks; the clinical characteristics included various foetal malformations with a predominantly normal karyotype, except in one case with trisomy 18. Ectopic endometrial tissue enclosed in the myometrium was discovered in twelve individual foetuses from the cohort (12/420). The investigation of the histogenetic attributes of the misplaced endometrial tissue in both monozygotic twins’ (MZ) foetal uteri revealed isolated glands and thin channels containing cords of endometrial-type glands penetrating the myometrium. Through immunohistochemistry, low levels of oestrogen receptors (ERs) were detected, whereas a moderate level of progesterone receptor (PR) expression was observed in the ectopic glandular and stromal cell nuclei in all cases. Additionally, the surrounding periglandular component consistently expressed the vimentin and CD10 stromal cell markers, while the myometrial smooth muscle cells revealed the strong expression of both alpha-Smooth Muscle Actin (α-SMA) and desmin marker proteins. Full article

Background: While combined diet and physical activity interventions are recommended, evidence specific to low-risk pregnant women remains limited. As responses to combined interventions may vary by pre-pregnancy BMI, maternal health status and pregnancy outcomes, targeted evaluation in low-risk pregnant women is needed. Inconsistencies across studies, along with the lack of a comprehensive synthesis of both effects and intervention components, further limit their implementation. Objective: Our aims were to assess the effects of combined diet and physical activity interventions on gestational weight gain among low-risk women and to systematically characterize the intervention components. Design: We conducted a systematic review and meta-analysis following the Cochrane Handbook guidelines and PRISMA 2020. Methods: Eight databases and trial registries were searched from inception to 16 March 2026. Two reviewers independently conducted study selection, data extraction and risk of bias assessment. Intervention components were coded using the TIDieR checklist. The quality of included studies was assessed using the updated Cochrane risk of bias 2.0 tool. Meta-analyses were performed using Review Manager 5.4, and certainty of evidence was assessed using the GRADEpro online tool. Results: A total of 10 studies involving 3977 pregnant women were included. Combined diet and physical activity interventions significantly reduced total gestational weight gain (GWG) (MD = −0.78 kg, 95% CI: −1.12 to −0.44, p < 0.00001) and the risk of excessive gestational weight gain (EGWG) (OR = 0.63, 95% CI: 0.49–0.81, p = 0.0003). Additionally, individually delivered physical activity components and those implemented in healthcare facilities appeared to be associated with lower total GWG (MD = −0.76 kg, 95% CI: −0.98 to −0.53, p < 0.00001). For EGWG, lower risk was observed in interventions using combined face-to-face and remote formats (OR = 0.54, 95% CI: 0.41–0.72, p < 0.0001) and moderate frequency (diet: OR = 0.64, 95% CI: 0.51–0.81, p = 0.0002, physical activity: OR = 0.65, 95% CI: 0.52–0.83, p = 0.0004). Conclusions: Combined diet and physical activity interventions were associated with reduced total GWG and lower EGWG risk in low-risk pregnant women. Intervention characteristics, such as individual delivery formats, combined face-to-face and remote formats, moderate frequency and implementation in healthcare facilities, may be related to intervention effectiveness. Registration number: CRD420251013116 (PROSPERO). Full article

Background: Pregnancy in women with liver cirrhosis is considered a rare clinical condition due to the decreased fertility commonly associated with chronic liver disease. Hormonal disturbances, anovulation and impaired hepatic function contribute to the lower conception rates observed in this population. However, when pregnancy occurs, it is associated with a significantly increased risk of maternal and fetal complications. Maternal risks include hepatic decompensation, variceal bleeding, ascites, coagulopathy and a higher rate of hypertensive disorders during pregnancy and related complications. Fetal complications involve prematurity, intrauterine growth restriction, and increased perinatal mortality. Methods: We present the clinical case of a woman with idiopathic liver cirrhosis who experienced four consecutive pregnancies with different clinical courses and outcomes. Results: The case highlights the complexity of managing pregnancy in patients with chronic liver disease and underscores the importance of individualized clinical assessment and multidisciplinary management. This report also reviews current management strategies and discusses key considerations for optimizing care in pregnant women with liver cirrhosis. Conclusions: Advances in multidisciplinary care and improved management strategies have contributed to better pregnancy outcomes in recent years. Careful monitoring during pregnancy, appropriate management of portal hypertension, and coordinated care between obstetricians, hepatologists, and neonatologists are essential to minimizing potential complications, ensuring favorable maternal and fetal outcomes. Full article

Endometriosis is a chronic estrogen-dependent disorder affecting approximately 10% of women of reproductive age. Increasing epidemiological and molecular evidence indicates that it may represent a precursor condition for a subset of ovarian malignancies collectively defined as endometriosis-associated ovarian cancer (EAOC), predominantly endometrioid and clear cell carcinomas. Malignant transformation is driven by the interplay between chronic inflammation, oxidative stress, and local hyperestrogenism within the endometriotic microenvironment. Recurrent hemorrhage and persistent immune activation further promote genomic instability and clonal expansion. Shared somatic mutations have been identified in both atypical endometriosis and adjacent carcinomas, supporting a model of stepwise tumorigenesis. Dysregulation of signaling pathways and epigenetic mechanisms, including microRNA alterations, further contribute to tumor development. Although the absolute risk of malignant transformation remains low, women with ovarian endometriosis and deep infiltrating disease show an increased risk of ovarian cancer. EAOC is frequently diagnosed at earlier stages and generally demonstrates a more favorable prognosis than high-grade serous carcinoma, although clear cell histotypes may exhibit chemoresistance and distinct molecular vulnerabilities. This review summarizes current evidence on the pathogenesis, molecular mechanisms, and clinical implications of EAOC, highlighting future strategies for risk stratification and personalized surveillance. Full article