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This study aimed to investigate the effect of diagnosis and treatment of chronic endometritis (CE) on the outcome of assisted reproductive technology (ART) with or without repeated implantation failure (RIF). This retrospective analysis included patients who underwent pathological examination for diagnosis of CE at Yamagata University Hospital. The examination was performed for all patients planned for ART with or without RIF. Patients who were examined within 6 months of the first oocyte retrieval or embryo transfer were included. We counted the number of CD138-positive cells within the endometrial stroma in patients’ specimens and analyzed the patients’ clinical information. Clinical rates of pregnancy and implantation were determined. A total of 80 women met the inclusion criteria: 13 CE-negative patients (17.3%) and 67 CE-positive patients (83.7%). A significant decrease was noted in the CD138-positive cell count between the first biopsy and second biopsy after CE treatment ( p  < 0.001). In addition, no significant differences were noted in ongoing pregnancy rates between the CE-negative patients and those who underwent CE treatment. The CD138-positive cell counts at first biopsy tended to be lower in each pregnancy group than in the non-pregnancy group. For patients planned to undergo ART, examination for diagnosis of CE with or without RIF could be considered. Pathological CD138-positive cell counts were considered useful for CE diagnosis and treatment decision-making. The study findings suggest the efficacy of antimicrobial agents in CE treatment, contributing to improved pregnancy outcomes.

Recurrent implantation failure (RIF) refers to cases in which women have had three failed in vitro fertilization (IVF) attempts with good quality embryos. The definition should also take advanced maternal age and embryo stage into consideration. The failure of embryo implantation can be a consequence of uterine, male, or embryo factors, or the specific type of IVF protocol. These cases should be investigated to determine the most likely etiologies of the condition, as this is a complex problem with several variables. There are multiple risk factors for recurrent implantation failure including advanced maternal age, smoking status of both parents, elevated body mass index, and stress levels. Immunological factors such as cytokine levels and presence of specific autoantibodies should be examined, as well as any infectious organisms in the uterus leading to chronic endometritis. Uterine pathologies such as polyps and myomas as well as congenital anatomical anomalies should be ruled out. Sperm analysis, pre-implantation genetic screening and endometrial receptivity should be considered and evaluated, and IVF protocols should be tailored to specific patients or patient populations. Treatment approaches should be directed toward individual patient cases. In addition, we suggest considering a new initial step in approach to patients with RIF, individualized planned activities to activate the brain's reward system in attempt to improve immunological balance in the body.

Post-breeding endometritis (i.e., inflammation/infection of the endometrium), is a physiological reaction taking place in the endometrium of mares within 48 h post-breeding, aimed to clear seminal plasma, excess sperm, microorganisms, and debris from the uterine lumen in preparation for the arrival of an embryo. Mares are classified as susceptible or resistant to persistent breeding-induced endometritis (PBIE) based on their ability to clear this inflammation/infection by 48 h post-breeding. Mares susceptible to PBIE, or those with difficulty clearing infection/inflammation, have a deficient immune response and compromised physical mechanisms of defense against infection. Molecular pathways of the innate immune response known to be involved in PBIE are discussed herein. The role of the adaptive uterine immune response on PBIE remains to be elucidated in horses. Advances in the pathobiology of microbes involved in PBIE are also revised here. Traditional and non-traditional therapeutic modalities for endometritis are contrasted and described in the context of clinical and molecular aspects. In recent years, the lack of efficacy of traditional therapeutic modalities, alongside the ever-increasing incidence of antibiotic-resistant microorganisms, has enforced the development of non-traditional therapies. Novel biological products capable of modulating the endometrial inflammatory response are also discussed here as part of the non-traditional therapies for endometritis.

Endometritis is defined as an infection or inflammation of the endometrium. Endometritis is of two types: acute and chronic. Acute endometritis is the symptomatic acute inflammation of the endometrium, which upon examination with a microscope shows micro-abscess and neutrophil invasion in the superficial endometrium. One of its most common manifestations is postpartum endometritis. Chronic endometritis is a silent disease usually diagnosed on the workup of secondary amenorrhoea and infertility. An important cause of chronic endometritis is tuberculosis, especially in developing nations. Chronic and acute endometritis have been associated with poor reproductive outcomes. Worse outcomes have been reported for individuals with chronic endometritis. This is a scoping review of endometritis and its impact on fertility.

Chronic endometritis (CE) is a persistent inflammatory disorder of the endometrium, associated with infertility, recurrent pregnancy loss, and implantation failure. Diagnosis primarily depends on hysteroscopy and immunohistochemistry, while microbial dysbiosis and antibiotic resistance pose significant challenges to effective management. The pathogenesis of CE involves microbial infections that induce immune dysregulation through TLR/NLR signaling pathways, metabolic reprogramming of immune cells, miRNA-mediated inflammatory responses, and DNA methylation alterations. The activation of pro-inflammatory mediators and the NLRP3 inflammasome further aggravates endometrial dysfunction. Treatment typically includes oral antibiotics and intrauterine therapies, although their efficacy is variable. Probiotics have demonstrated potential in restoring microbial balance. This review outlines the inflammatory mechanisms underlying CE and recent therapeutic advancements, highlighting potential targets for improving treatment outcomes.

Endometritis impairs uterine function and reduces reproductive performance in dairy cows. Conventional treatment involves intrauterine antibiotics; however, antimicrobial resistance has become an increasing concern worldwide. Biofactors secreted by mesenchymal stem/stromal cells (MSCs), collectively known as the secretome possess immunomodulatory, anti-apoptotic, angiogenic, and antimicrobial properties and may represent a novel alternative for treating bovine endometritis. This study evaluated the in vitro antimicrobial potential of bovine fetal MSC-derived secretome (sMSC) against Escherichia Coli and assessed the safety and efficacy of sMSC-based therapy in dairy cows. Conditioned media (CM) derived from fetal bone marrow (BM) and adipose tissue (AT) MSCs reduced E. Coli survival by up to 98%. Intrauterine administration of sMSC produced no significant clinical or hematological alterations, demonstrating that the treatment is safe. Cows with clinical endometritis receiving two intrauterine doses of lyophilized sMSC, separated by 14 days, showed lower ( P  < 0.05) endometrial polymorphonuclear (PMN) counts (~ 47%) and postpartum endometritis grade (EG) (~ 78%) than placebo-treated animals (PCB). Proteomic analysis of lyophilized sMSC revealed that 11% of the total protein content corresponded to secreted protein acidic and cysteine rich (SPARC), a molecule with known roles in tissue repair and immune regulation, which may underlie the observed therapeutic effects. Together, these results indicate that bovine sMSC-derived secretome is a safe and effective therapy for treating bovine endometritis, potentially contributing to a reduction in antibiotics use in dairy cows.

Background Endometritis reduces fertility and is responsible for major economic losses in beef and dairy industries. The aim of this study was to evaluate an alternative therapy using platelet-rich plasma (PRP). PRP was tested in vivo , after bovine intrauterine administration, and in vitro on endometrial cells. Methods Bovine endometrial cells were cultured until passage (P) 10 with 5 % or 10 % PRP. Effect of PRP on endometrial cell proliferation and on the expression of genes [prostaglandin-endoperoxide synthase 2 ( COX2 ), tumor protein p53 ( TP53 ), oestrogen receptors ( ER-α and ER-β ), progesterone receptor ( PR ) and c-Myc ] involved in the regulation of oestrus cycle and fetal-maternal interaction were evaluated. Moreover, to evaluate the ability of PRP to counteract inflammation, 10 and 100 ng/ml of bacterial endotoxin lipopolysaccharide (LPS) were used to inflame endometrial cells in vitro for 1, 6, 12, 24 and 48 h. The expression of genes such as interleukin 1β ( IL-1β ), interleukin-8 ( IL-8 ), inducible nitric oxide synthase ( iNOS ), prostaglandin-endoperoxide synthase 2 ( COX2/PTGS2 ), and the release of PGE-2, IL-1β and IL-8 were evaluated. Results In vivo treatment with PRP increased the detection of PR. In vitro , 5 % PRP at passage 5 increased proliferation rate and induced a significant increase in the expression of all studied genes. Furthermore, the results revealed that 10 ng/ml of LPS is the most effective dose to obtain an inflammatory response, and that PRP treatment significantly down regulated the expression of pro-inflammatory genes. Conclusion This study lays the foundations for the potential treatment of endometritis with PRP in vivo .

Chronic endometritis (CE) is closely linked to the reproductive failure. Exosome (Exo)-based therapy is proposed as an encouraging strategy in inflammation-related disorders; however, little work has been devoted to its usage in CE therapy. An in vitro CE was established by administration of lipopolysaccharide (LPS) in human endometrial stromal cells (HESCs). The cell proliferation, cell apoptosis, and inflammatory cytokine assays were performed in vitro, and the efficacy of Exos derived from adipose tissue–derived stem cells (ADSCs) was evaluated in a mouse model of CE. We found that Exos isolated from ADSCs could be taken up by HESCs. Exos elevated the proliferation and inhibited apoptosis in LPS-treated HESCs. Administration of Exos to HESCs suppressed the content of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Moreover, Exos exposure repressed the inflammation stimulated by LPS in vivo. Mechanistically, we demonstrated that Exos exerted their ant-inflammatory effect via miR-21/TLR4/NF-kB signaling pathway in endometrial cells. Our findings suggest that ADSC-Exo-based therapy might serve as an attractive strategy for the treatment of CE.

Chronic endometritis (CE) has been widely recognized as a potential cause of infertility, however, access to effective treatment is a formidable challenge due to the rudimentary understanding of the pathogenesis of persistent CE. Here, we aimed to analyze the impact of platelet-rich plasma (PRP) treatment on pregnancy outcomes and the endometrial microenvironment in patients with persistent CE. A total of 89 infertility patients were selected, including 56 non-CE (as the control group) and 33 persistent CE. The persistent CE patients received an intrauterine infusion of PRP four times before embryo transfer. Immunohistochemistry staining and transcriptomic sequencing were used to investigate the uterine-specific role of PRP in patients with persistent CE. The implantation rate and clinical pregnancy rate were significantly increased in the cured CE group compared to the non-cured CE group. After PRP treatment, the proportions of endometrial CD8 T cells, CD56 NK cells, Foxp3 Treg cells, and T-bet Th1 cells were significantly decreased in patients with persistent CE. Specifically, DEG analysis showed that genes implicated in endometrial receptivity-related and antimicrobial were upregulated and genes involved in the immune response processes were downregulated in cured CE patients after PRP treatment. Functional enrichment analysis suggested that the effects of changes in leukocyte chemotaxis-related genes played a critical role in the endometrial immune environment. Autologous PRP treatment has been shown as a potentially successful therapy for improving pregnancy outcomes by reconstructing the uterine local immune microenvironment to improve endometrial receptivity in patients with persistent CE.

AbstractEndometritis in dairy cows is a major economic problem worldwide; without advances in lifestyle management and drug treatment, it causes high morbidity and death. Micro ribonucleic acid (miRNAs) these days is seen as an important part of gene control networks. It is a class of small nucleotides 20–25, single-stranded RNA molecules. In endometritis, the inflammatory response caused by the gram-negative bacteria Escherichia coli (E. coli) alters the expression of miRNA which can regulate the innate immune system. This manuscript reviews (1) the interaction of miRNAs with the signaling of NF-κB and dysregulation of miRNAs and NF-κB activity in endometritis and (2) the activity of miR-let-7c, miR-148a, and miR-488 in NF-κB activation and their effect on endometritis. Cows with reduced immunity are more vulnerable to transition diseases, such as endometritis. During post-partum, cows undergo stress, metabolic disorders, hormonal imbalance, negative energy balance, and changes in diet. One of the many categories of regulatory molecules, which explain its natural function and pathological impact on NF-κB dysregulation, is important to inform the complexity of the immune system and to develop treatments for endometritis. It shows that miRNAs could have multiple applications in veterinary medicine. Nevertheless, a comprehensive study of is essential which should be aimed at exploring the role of microRNA at physiological level and its effect due to dysfunction and dysregulation.