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Genital tract infections can cause a variety of harmful health outcomes, including endometritis, bacterial vaginosis, and pelvic inflammatory disease, in addition to infertility. Anaerobic bacteria, such as Gardnerella vaginalis, Megasphaera spp., and Atopobium vaginae, are more commonly identified in cases of bacterial vaginosis than lactobacilli. It is unknown how the microorganisms that cause pelvic inflammatory diseases and endometritis enter the uterus. Both prospective and retrospective research have connected pelvic inflammatory disorders, chronic endometritis, and bacterial vaginosis to infertility. Similar to bacterial vaginosis, endometritis-related infertility is probably caused by a variety of factors, such as inflammation, immune system recognition of sperm antigens, bacterial toxins, and a higher risk of STDs. Preconception care for symptomatic women may include diagnosing and treating pelvic inflammatory disease, chronic endometritis, and bacterial vaginosis before conception to optimize the results of both natural and assisted reproduction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The aim was to develop a predictive tool for anticipating postpartum endometritis occurrences and to devise strategies for prevention and control., Methods: Employing a retrospective approach, the baseline data of 200 women diagnosed with postpartum endometritis in a tertiary maternity hospital in Zhejiang Province, spanning from February 2020 to September 2022, was examined. Simultaneously, the baseline data of 1,000 women without endometritis during the same period were explored with a 1:5 ratio. Subsequently, 1,200 women were randomly allocated into a training group dataset and a test group dataset, adhering to a 7:3 split. The selection of risk factors for postpartum endometritis involved employing random forests, lasso regression, and traditional univariate and multifactor logistic regression on the training group dataset. A nomogram was then constructed based on these factors. The model's performance was assessed using the area under the curve (AUC), calculated through plotting the receiver operating characteristic (ROC) curve. Additionally, the Brier score was employed to evaluate the model with a calibration curve. To gauge the utility of the nomogram, a clinical impact curve (CIC) analysis was conducted. This comprehensive approach not only involved identifying risk factors but also included a visual representation (nomogram) and thorough evaluation metrics, ensuring a robust tool for predicting, preventing, and controlling postpartum endometritis., Results: In the multivariate analysis, six factors were identified as being associated with the occurrence of maternal endometritis in the postpartum period. These factors include the number of negative finger tests (OR: 1.159; 95%CI: 1.091-1.233; P < 0.05), postpartum hemorrhage (1.003; 1.002-1.005; P < 0.05), pre-eclampsia (9.769; 4.64-21.155; P < 0.05), maternity methods (2.083; 1.187-3.7; P < 0.001), prenatal reproductive tract culture (2.219; 1.411-3.47; P < 0.05), and uterine exploration (0.441; 0.233-0.803; P < 0.001).A nomogram was then constructed based on these factors, and its predictive performance was assessed using the area under the curve (AUC). The results in both the training group data (AUC: 0.803) and the test group data (AUC: 0.788) demonstrated a good predictive value. The clinical impact curve (CIC) further highlighted the clinical utility of the nomogram., Conclusion: The development of an individualized nomogram for postpartum endometritis infection holds promise for doctors in screening high-risk women, enabling early intervention and ultimately reducing the rate of postpartum endometritis infection. This comprehensive approach, integrating key risk factors and predictive tools, enhances the potential for timely and targeted medical intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: To explore the incidence of chronic endometritis (CE) in patients with infertility and different forms of adenomyosis and analyze potential high-risk factors for infection., Methods: This retrospective cohort study included 154 patients with infertility in the Liuzhou Maternity and Child Healthcare Hospital. Among them, 77 patients with adenomyosis were divided into four subgroups based on magnetic resonance imaging (MRI): internal, exterior, intramural, and full-thickness. Meanwhile, 77 patients did not have adenomyosis. Hysteroscopy and endometrial biopsy were performed in the proliferative phase. The main outcome measures were the morphology of the endometrium, syndecan-1 (CD138) immunohistochemical staining, clinical characteristics, and prevalence of CE in the adenomyosis subgroups., Results: In comparison to the non-adenomyosis group, the adenomyosis group had significantly higher body mass index (BMI) and CA125 levels. The menstrual cycle in the adenomyosis group was significantly shorter, and menarche was significantly earlier. In comparison to the non-adenomyosis group, the adenomyosis group had a significantly higher diagnostic rate of CE (75.3% vs. 46.8% according to hysteroscopy and 74.0% vs. 33.8% according to histopathology, both with p < .050). The incidence of CE was significantly lower in patients with internal adenomyosis when compared with the other three subgroups. Increased BMI contributed to a higher risk of CE., Conclusions: The prevalence of CE was significantly higher in patients with adenomyosis and infertility. The differences in the incidence of CE are closely associated with the classification of adenomyosis. When patients with infertility are diagnosed with adenomyosis, it is recommended to identify the subtype and screen for endometritis., (© 2024. The Author(s).)

The Metrisor device has been developed using gas sensors for rapid, highly accurate and effective diagnosis of metritis. 513 cattle uteri were collected from abattoirs and swabs were taken for microbiological testing. The Metrisor device was used to measure intrauterine gases. The results showed a bacterial growth rate of 75.75 % in uteri with clinical metritis. In uteri positive for clinical metritis, the most commonly isolated and identified bacteria were Trueperella pyogenes, Fusobacterium necrophorum and Escherichia coli. Measurements taken with Metrisor to determine the presence of metritis in the uterus yielded the most successful results in evaluations of relevant machine learning algorithms. The ICO (Iterative Classifier Optimizer) algorithm achieved 71.22 % accuracy, 64.40 % precision and 71.20 % recall. Experiments were conducted to examine bacterial growth in the uterus and the random forest algorithm produced the most successful results with accuracy, precision and recall values of 78.16 %, 75.30 % and 78.20 % respectively. ICO also showed high performance in experiments to determine bacterial growth in metritis-positive uteri, with accuracy, precision and recall values of 78.97 %, 77.20 % and 79.00 %, respectively. In conclusion, the Metrisor device demonstrated high accuracy in detecting metritis and bacterial growth in uteri and could identify bacteria such as E. coli, S. aureus, coagulase-negative staphylococci, T. pyogenes, Bacillus spp., Clostridium spp. and F. necrophorum with rates up to 80 %. It provides a reliable, rapid and effective means of detecting metritis in animals in the field without the need for laboratory facilities., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Endometritis is a common condition in mares that causes significant economic loss. Lacking obvious clinical signs, the clinical diagnosis of endometritis in mares relies on case-by-case clinical examinations, which can be particularly inefficient in large-scale farms. Therefore, the identification of potential biomarkers can serve as a non-invasive and efficient screening technique for endometritis in mares., Objectives: To compare the blood proteome between fertile mares and mares with endometritis to identify biomarkers potentially associated with the development of endometritis and validate their predictive potential., Study Design: Observational and experimental study., Methods: Differentially expressed proteins were identified via Data Independent Acquisition (DIA) proteomic profiling in a screening cohort composed of eight healthy mares and eight mares with endometritis. Subsequently, enzyme-linked immunosorbent assay was employed that included a validation cohort of 40 healthy mares and 40 mares with endometritis to verify the accuracy and sensitivity of the identified proteins, thereby establishing a diagnostic threshold., Results: In the screening cohort, 12 proteins were significantly differentially expressed between endometritis mares and healthy controls (p < 0.05, outside the 1/1.2 to 1.2-fold). In the validation experiment, all six screened proteins were assessed with area under the curve (AUC) >0.8., Main Limitations: The samples displayed certain levels of individual heterogeneity, and the number of samples analysed was limited. Additionally, the identified biomarkers were primarily associated with generalised inflammation, which potentially limited their specificity for endometritis., Conclusion: Levels of plasma proteins are sensitive indicators of equine endometritis and potential tools for endometritis screening. In plasma, fetuin B, von Willebrand factor, vitamin K-dependent protein C, insulin-like growth factor binding protein 3, interleukin 1 receptor accessory protein, and type II cell cytoskeleton showed great predictive ability, with fetuin B being the best predictor (AUC = 0.93, 95% CI: 0.89-0.98), which performs better when combined with all six detected proteins (AUC = 1, 95% CI: 0.99-1.00)., (© 2024 EVJ Ltd.)

Our objective was to evaluate the accuracy of predictive models for metritis spontaneous cure (SC) and cure among ceftiofur-treated cows using farm-collected data only, and with the addition of hemogram variables and circulating concentration of metabolites, minerals, and biomarkers (BM) of inflammation measured at time of diagnosis. Data related to parity, calving-related issues, BCS, rectal temperature, and DIM at metritis diagnosis were collected from a randomized clinical trial that included 422 metritic cows from 4 herds in Texas, California, and Florida. Metritis was defined as the presence of red-brownish, watery, and fetid vaginal discharge, and cure was defined as the absence of metritis 14 d after initial diagnosis. Cows were randomly allocated to receive systemic ceftiofur therapy (2 subcutaneous doses of 6.6 mg/kg of ceftiofur crystalline-free acid on the day of diagnosis and 3 d later; CEF) or to remain untreated (control). At enrollment (day of metritis diagnosis), blood samples were collected and submitted to complete blood count (CBC) and processed for the measurement of 13 minerals and BM of metabolism and inflammation. Univariable analysis to evaluate the association of farm-collected data and blood-assessed variables with metritis cure were performed, and variables with P ≤ 0.20 were offered to multivariable logistic regression models and retained if P ≤ 0.15. The areas under the curve for models predicting SC using farm data only and farm + BM were 0.70 and 0.76, respectively. Complete blood count variables were not retained in the models for SC. For models predicting cure among CEF cows, the area under the curve was 0.75, 0.77, 0.80, and 0.80 for models using farm data only, farm + CBC, farm + BM, and farm + CBC + BM, respectively. Predictive models of metritis cure had fair accuracy, with SC models being less accurate than models predictive of cure among CEF cows. Additionally, adding BM variables marginally improved the accuracy of models using farm collected data, and CBC data did not improve the accuracy of predictive models., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Endometrial biopsy is required to diagnose mares with chronic endometritis and endometrial degenerative fibrosis. An increase in understanding of equine reproductive immunology could be utilised to create less-invasive, time-efficient diagnostic tools especially when evaluating mares for chronic endometritis., Objectives: To evaluate inflammatory cytokine and chemokine concentrations in uterine fluid samples collected by low-volume lavage (LVL) as a potential screening diagnostic biomarker for endometritis., Study Design: Prospective cross-sectional clinical study., Methods: Forty-six mares underwent a LVL and subsequently endometrial biopsy. Mares were split in three groups: healthy, acute endometritis, and chronic endometrial fibrosis (CEF) based on cytological and histological evaluation. A fluorescent bead-based multiplex assay for IFN-γ, IFN-α, IL-1β, IL-4, IL-10, IL-17, sCD14, TNF-α, CCL2, CCL3, CCL5 and CCL11 were carried out on the LVL fluid. The endometrial biopsy was utilised for histology and qPCR of IFN-γ, IL-1β, IL-6, IL-8, IL-17, TNF-α, CCL2 and CCL3 genes. Statistical analyses examined differences in inflammatory markers and predictive modelling for diseased endometrium., Results: Secreted concentrations of IFN-γ were lower in LVL fluid from reproductively healthy mares compared with acute endometritis (p = 0.04) and CEF (p = 0.006). Additionally, IL-17, IL-10, IL-1β, TNF-α, CCL2, CCL3, CCL5 and CCL11 were significantly increased (p ≤ 0.04) in LVL from CEF mares compared with healthy mares. Mares with CCL2 concentrations ≥550 pg/mL (14/14) had 100% probability of having CEF and/or acute endometritis. Healthy mares had lower relative abundance of IL-17 mRNA compared with mares in CEF group [median (interquartile rage) = 14.76 (13.3, 15.3) and 12.4 (10.54, 13.81)], respectively (p = 0.02)., Main Limitations: Limited sample size: larger numbers of mares with and without endometritis are required and reference intervals in LVL samples have to be established., Conclusions: Inflammatory chemokines and cytokines concentrations differed between healthy mares and mares with acute endometritis or CEF in LVL., (© 2024 EVJ Ltd.)

Purpose: To evaluate the utility of cervical cultures in the diagnosis and management of postpartum endometritis., Methods: A retrospective study was conducted on 1069 cervical cultures collected from postpartum women with suspected endometritis between 2011 and 2021. Patient demographics, obstetric history, clinical parameters, and culture results were analyzed. Microorganisms were categorized into five groups based on species and virulence. Statistical analysis was performed to identify associations between risk factors, pathogens, and disease severity., Results: The positivity rate for distinct microorganisms in cervical cultures was 33.1%. Escherichia coli (10.8%) and Group B Streptococcus (7.5%) were the most common isolates. Prolonged labor duration and prolonged rupture of membranes were associated with Enterobacterales infections. Elevated white blood cell count was linked to Enterobacterales and beta-hemolytic Streptococci, while the former were also associated with higher rate of postpartum clinic visit. No significant differences in disease severity were found between other microorganism groups., Conclusion: The study suggests that while cervical cultures can identify potential pathogens in postpartum endometritis, their clinical utility is questionable due to the polymicrobial nature of the disease and the isolation of commensal microorganisms. The lack of significant differences in disease severity across various microorganism groups raises questions regarding the contribution of distinct bacterial identification in endometritis management., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic endometritis (CE), an inflammatory condition characterized by plasma cell infiltration within the endometrial stroma, is prevalent among women experiencing unexplained infertility or recurrent miscarriages. CE is traditionally diagnosed by endometrial biopsy using CD138 immunohistochemistry staining. Despite some studies suggesting hysteroscopy as an alternative diagnostic tool, its reliability compared with biopsy remains controversial. This study evaluated the diagnostic accuracy of hysteroscopy for CE by examining endometrial features, such as congestion, micropolyps, edema, and polyps, and comparing these with biopsy-confirmed cases of CE. This retrospective observational study was conducted at Toho University Omori Medical Center between June 2017 and November 2019 and included patients undergoing both hysteroscopy and histopathological examination. Endometrial congestion was identified as the only hysteroscopic finding significantly associated with CE, showing a moderate diagnostic agreement with biopsy results. These findings highlight the importance of further investigating hysteroscopic features of CE and their diagnostic implications and identify endometrial congestion as a potential predictive marker for CE., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Furui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Underdiagnosis of female genital tuberculosis (FGTB) often leads to infertility. In this study, we aimed to determine the site and histopathologic patterns of FGTB and its correlation with clinical presentation and acid-fast bacilli (AFB) status., Methods: A retrospective cross-sectional study was conducted on 122 patients with a histopathological diagnosis of FGTB at the Department of Pathology, College of Health Sciences (CHS), Tikur Anbessa Specialized Hospital (TASH), Addis Ababa University (AAU), from January 1, 2013, to August 30, 2022., Results: Female genital tuberculosis was found in 0.94% of the gynecology specimens examined. The most common presentations were menstrual disturbance, abdominopelvic pain, and infertility. Among patients with FGTB, 4.6% exhibited misleading clinical and radiologic findings, leading to suspicion of malignancy and subsequent aggressive surgical management. The endometrium was the most frequently affected organ, followed by the fallopian tube, ovary, cervix, and vulva. In the majority of tuberculous endometritis cases (53.3%), histopathology revealed early-stage granulomas. Acid-fast bacilli were found in a significant proportion (42.6%) of FGTB tissues with TB histopathology. The ovary had the highest rate of AFB detection, followed by the fallopian tube, endometrium, and cervix., Conclusion: Female genital tuberculosis should be considered in reproductive-age women presenting with menstrual irregularities, abdominopelvic pain, infertility, or an abdominopelvic mass. The endometrium is commonly affected, displaying early granulomas with low AFB positivity., (© 2024. The Author(s).)

Chronic endometritis (CE) is an inflammatory pathologic condition of the uterine mucosa characterized by unusual infiltration of CD138(+) endometrial stromal plasmacytes (ESPCs). CE is often identified in infertile women with unexplained etiology, tubal factors, endometriosis, repeated implantation failure, and recurrent pregnancy loss. Diagnosis of CE has traditionally relied on endometrial biopsy and histopathologic/immunohistochemistrical detection of ESPCs. Endometrial biopsy, however, is a somewhat painful procedure for the subjects and does not allow us to grasp the whole picture of this mucosal tissue. Meanwhile, fluid hysteroscopy has been recently adopted as a less-invasive diagnostic modality for CE. We launched the ARCHIPELAGO (ARChival Hysteroscopic Image-based Prediction for histopathologic chronic Endometritis in infertile women using deep LeArninG mOdel) study to construct the hysteroscopic CE finding-based prediction tools for histopathologic CE. The development of these deep learning-based novel models and computer-aided detection/diagnosis systems potentially benefits infertile women suffering from this elusive disease.

Competing Interests: Declaration of Interests E.C. has nothing to disclose. D.d.Z. has nothing to disclose. A.V. has nothing to disclose.

Objective(s): Chronic endometritis (CE) is a localized mucosal inflammatory disorder associated with female infertility of unknown etiology, endometriosis, tubal factors, repeated implantation failure, and recurrent pregnancy loss, along with atypical uterine bleeding and iron deficiency anemia. Diagnosis of CE has traditionally relied on endometrial biopsy and detection of CD138(+) endometrial stromal plasmacytes. To develop a less invasive diagnostic system for CE, we aimed to construct a deep learning-based convolutional neural network (CNN) model for the automatic detection of endometrial micropolyps (EMiP), a fluid hysteroscopy (F-HSC) finding recognized as tiny protrusive lesions that are closely related to this disease., Study Design: This is an in silico study using archival images of F-HSC performed at an infertility center in a private clinic. A total of 244 infertile women undergoing F-HSC on the days 6-12 of the menstrual cycle between April 2019 and December 2021 with histopathologically-confirmed CE with the aid of immunohistochemistry for CD138 were utilized., Results: The archival F-HSC images of 208 women (78 with EMiP and 130 without EMiP) who met the inclusion criteria were finally subjected to analysis. Following preprocessing of the images, half a set was input into a CNN architecture for training, whereas the remaining images were utilized as the test set to evaluate the performance of the model, which was compared with that of the experienced gynecologists. The sensitivity, specificity, accuracy, precision, and F1-score of the CNN model-aided diagnosis were 93.6 %, 92.3 %, 92.8 %, 88.0 %, and 0.907, respectively. The area under the receiver operating characteristic curves of the CNN model-aided diagnosis (0.930) was at a similar level (p > .05) to the value of conventional diagnosis by three experienced gynecologists (0.927, 0.948, and 0.906)., Conclusion: These findings indicate that our deep learning-based CNN is capable of recognizing EMiP in F-HSC images and holds promise for further development of the computer-aided diagnostic system for CE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cow uterine infections pose a challenge in dairy farming, resulting in reproductive disorders. Uterine fluid extracellular vesicles (UF-EVs) play a key role in cell-to-cell communication in the uterus, potentially holding the signs of aetiology for endometritis. We used mass spectrometry-based quantitative shotgun proteomics to compare UF-EV proteomic profiles in healthy cows (H), cows with subclinical (SE) or clinical endometritis (CLE) sampled at 28-35 days postpartum. Functional analysis was performed on embryo cultures with the exposure to different EV types. A total of 248 UF-EV proteins exhibited differential enrichment between the groups. Interestingly, in SE, EV protein signature suggests a slight suppression of inflammatory response compared to CLE-UF-EVs, clustering closer with healthy cows' profile. Furthermore, CLE-UF-EVs proteomic profile highlighted pathways associated with cell apoptosis and active inflammation aimed at pathogen elimination. In SE-UF-EVs, the regulation of normal physiological status was aberrant, showing cell damage and endometrial repair at the same time. Serine peptidase HtrA1 (HTRA1) emerged as a potential biomarker for SE. Supplementation of CLE- and SE-derived UF-EVs reduced the embryo developmental rates and quality. Therefore, further research is warranted to elucidate the precise aetiology of SE in cattle, and HTRA1 should be further explored as a potential diagnostic biomarker.

Up to 50 % of dairy cows fail to resolve uterine involution and develop chronic clinical (CE) or subclinical endometritis (SE) 21 days after calving. Clinical endometritis is associated with purulent discharge, while SE is not associated with overt clinical signs. Along with numerous knowledge gaps related to its pathogenesis, SE does not allow for a straightforward and effective therapy. Therefore, it is crucial to unravel differences in the expression of genes among healthy, CE, and SE cows. This might contribute to the discovery of new drug candidates and, in consequence, a potentially effective treatment. In the present study, cows between 21 and 28 days postpartum (PP) were examined using vaginoscopy for the presence of vaginal discharge and endometrial cytology for the determination of the endometrial polymorphonuclear cell (PMN) percentage. Next, an endometrial biopsy sample was taken to investigate the expression of 13 selected candidate genes by qPCR. Uterine health status was assigned to healthy (absence of abnormal vaginal discharge and ≤5 % PMN, n = 13), SE (absence of abnormal vaginal discharge and >5 % PMN, n = 30), and CE (mucopurulent or purulent vaginal discharge and >5 % PMN, n = 9). At the same time, a blood sample was collected to assess serum progesterone concentration and to categorize cows as low (≤1 ng/mL) or high (>1 ng/mL) in progesterone. High expression of IL1B, IL6, IL17A, CXCL8, PTGES, PTGS1, PTGS2, and INHBA genes and low expression of FST was noted in the endometrium of CE compared to healthy cows. Increased endometrial INHBA expression was observed in both SE and CE compared to healthy cows. Interestingly, greater expression of PTGES and PRXL2B genes and lower expression of PTGS2 were characteristic of SE versus CE or healthy. Among cows with no overt clinical symptoms of uterine disease (healthy and SE), the endometrial expression of IL1 B, CXCL8, and PTGES was greater in cows with high versus low serum progesterone. Several genes were differentially expressed among healthy, SE, and CE cows indicating different pathways for the development of different uterine diseases. In conclusion, we found progesterone-independent SE markers, which suggests that low endometrial PTGS2 expression may be indicative of an inadequate immune response and thus contribute to the pathogenesis of SE., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

Universal diagnostic criteria for chronic endometritis (CE) have not been established due to differences in study design among researchers and a lack of typical clinical cases. Lipopolysaccharides (LPSs) have been reported to cause inflammation in the reproductive systems of several animals. This study aimed to elucidate the influence of LPS in the pathogenesis of CE in humans. We investigated whether LPS affected cytokine production and cell proliferation in the endometrium using in vivo and in vitro experiments. LPS concentrations were analyzed between control and CE patients using endometrial tissues. LPS administration stimulated the proliferation of EM-E6/E7 cells derived from human endometrial cells. High LPS concentrations were detected in CE patients. LPS concentration was found to correlate with IL-6 gene expression in the endometrium. Inflammation signaling evoked by LPS led to the onset of CE, since LPS stimulates inflammatory responses and cell cycles in the endometrium. We identified LPS and IL-6 as suitable candidate markers for the diagnosis of CE.

Objective: A review of current knowledge on the pathophysiology, diagnostic and treatment options for chronic endometritis in infertile women., Methods and Results: One of the major causes of failed in vitro fertilization (IVF) is undiagnosed intrauterine pathologies, including chronic inflammation of the uterine mucosa - chronic endometritis. However, some authors relativize the negative impact of chronic endometritis on reproductive outcomes. The etiopathogenesis of chronic endometritis is due to qualitative and quantitative changes in the endometrial microbiome with abnormal multiplication of microorganisms naturally occurring in the uterine cavity or vagina. There is no uniform consensus on the most common pathogen causing chronic endometritis. It is characterized by infiltration of plasma cells into the endometrial stroma outside the menstrual cycle, accompanied by hyperaemia and endometrial oedema. Clinical symptoms are very mild or absent. The diagnosis of chronic endometritis is often difficult because there is no specific clinical or laboratory diagnostic method. The following investigative options are commonly used for the diagnosis of chronic endometritis: diagnostic hysteroscopy, histopathological examination of the endometrium including CD 138 immunohistochemistry and culture from the uterine cavity. However, standardised international hysteroscopic and histopathological criteria for accurate diagnosis of chronic endometritis are still lacking. Empirically administered antibiotic therapy improves the success rate of pregnancy and delivery of a viable foetus in infertile patients with proven chronic endometritis. In addition to reviewing the current knowledge of chronic endometritis, this article discusses the importance of hysteroscopy in the diagnostic process., Conclusion: Chronic endometritis is often a clinically silent disease with negative impact on reproduction in infertile women. Although there are still many unresolved issues, the introduction of hysteroscopy into the diagnostic process is important for clinical practice; however, hysteroscopy even in combination with histological examination of the endometrium, often does not allow an unequivocal diagnosis of chronic endometritis. Further prospective randomised studies in a selected group of women with proven chronic endometritis and repeated failure to implant proven euploid embryos should refine this knowledge.

The most reliable chronic endometritis diagnosis is based on immunohistochemistry plasma cell identification in endometrial samples. Our study aimed to compare multiple myeloma oncogene 1 (MUM1) and syndecan-1/CD138 immunohistochemistry staining for chronic endometritis diagnosis among patients with recurrent pregnancy loss. We evaluated the presence of endometrial stromal changes. Fifty-four patients with a history of at least two intrauterine pregnancy losses underwent diagnostic hysteroscopy in the follicular phase of the cycle with endometrial aspiration biopsy. In all 54 cases, three successive sections were cut from each paraffin-embedded tissue block for hematoxylin and eosin (H&E), CD138 and MUM1 staining. The goal was to evaluate the level of agreement between the MUM1 and CD138 results and plasma cell detection rate in assessing the endometrial stromal changes. The concordance analysis between CD138 and MUM1 immunohistochemistry staining showed consistent results in 43 of 54 (79.6%) cases. The level of agreement was moderate, based on a Kappa value of 0.60. MUM1 immunostaining was positive for CE in more cases than CD138 staining, and this difference was statistically significant, showing a higher sensitivity of MUM1 in plasma cell detection (p=0.01). Endometrial stromal changes were observed in the majority of cases - 49/54 (90%). Samples without stromal changes were consistently negative for plasma cells using both CD138 and MUM1 staining. We demonstrated that MUM1 staining, used in conjunction with assessing endometrial stromal changes, contributes to a more accurate and comprehensive diagnosis of chronic endometritis.

Purpose: To evaluate the agreement rate between hysteroscopy and pathological examination in case of chronic endometritis., Methods: A retrospective observational study carried out at Gynecology and Obstetrics Department, Puerta de Hierro Hospital, Autónoma University of Madrid, Spain, from January 2021 to June 2022 was performed by obtaining data from 115 medical records of women who underwent office hysteroscopies that was compared with the findings of final histological examination of endometrial biopsy. Cohen's kappa index was used to evaluate this agreement rate. In addition, sensitivity, specificity, positive and negative predictive value and diagnostic accuracy were obtained., Results: The agreement between hysteroscopic findings and histological examination showed a modest result with a Cohen's kappa index of 34%. In addition, we obtained a specificity of 70% and a sensitivity of 64%. The positive and negative predictive value were 60.8% and 73.4%, respectively. An excellent agreement rate (100%) between histological and hysteroscopic results was observed in presence of hyperemia and micropolyps., Conclusion: Although the sample size is not as large as that of other studies published so far, the first glance of our experience is that hysteroscopic signs are not yet sufficient to make an accurate diagnosis of chronic endometritis, thus requiring a histopathological confirmation to make it., (© 2023. The Author(s).)

The purpose of this systematic review is to identify common hysteroscopic findings suggestive of endometritis, chronic or subclinical, based on current scientific evidence. Data sources were MEDLINE, Embase, PubMed and other sources of grey literature. Four (4) authors independently selected studies addressing hysteroscopic detection of CE based on specific and clearly stated hysteroscopic criteria. The diagnosis was confirmed by histologic assessment, as stated in the materials and methods of these studies included. The initial search identified 599 studies, of which 21 met the inclusion criteria. Significant heterogeneity among published studies on Chronic endometritis (CE) remains the main limitation in performing a metanalysis and further analysis of diagnostic accuracy on the subject. Hysteroscopy is an important diagnostic tool in cases of chronic endometritis when accompanied by endometrial biopsies. Clinicians relate hyperaemia and endometrial oedema with chronic endometritis while more than half include micropolyposis as a pathognomonic feature of this subclinical condition. Micropolyps, stromal oedema, haemorrhagic spots, strawberry aspect, and hyperaemia are proposed as adequate indicators of hysteroscopic evidence of CE according to the literature. The impact of CE in long-term reproductive outcomes remain unclear, thus clinicians ought to communicate this to the patients and provide treatment where clinically appropriate. In addition, we present hysteroscopic images of histologically confirmed CE cases that could play the role of a hysteroscopic atlas.

Group A Streptococcus (GAS) in the setting of postpartum endometritis can have severe and life-threatening complications. We report a rare case of septic pulmonary emboli that we surmised to have originated from septic pelvic thrombosis in the setting of GAS toxic shock syndrome (TSS) secondary to postpartum endometritis and intrauterine demise. Although the patient had source control with hysterectomy, she continued to have new septic emboli to the lungs seen on CT scans. CT scan of the pelvis demonstrated several filling defects in the renal and pelvic veins. The patient eventually responded well to anticoagulation in addition to antibiotics, which is similar to cases of Lemierre's syndrome. Additionally, we would like to bring attention to how important radiological findings can be missed if there is lack of interspecialty communication about the patient's clinical situation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Endometritis plays an important role in mare infertility. Certain infectious agents interfere with the innate immune system of endometrium, causing a systemic inflammatory response that lasts for a long time and circulates via the blood or cellular degeneration, leading to endometritis due to bacterial endotoxins. Different small, non-coding RNA molecules are involved in many biological functions. For instance, microRNAs (miRNAs) are involved in the post-transcriptional regulation of gene expression. These miRNAs are important regulators of gene expression, primarily via inhibiting transcription and translation processes. This manuscript reviews: (1) pathomorphological findings in equine endometritis, (2) the expression and effects of eca-miR-17, eca-miR-223, eca-miR-200a, eca-miR-155, and eca-miR-205 in endometritis and (3) the therapeutic role of miRNA in equine endometritis. The miRNAs have a vital regulatory role in a wide range of inflammatory diseases by regulating the molecular mechanism of cytokines that cause inflammation through signal pathways. This review emphasizes the demand for cutting-edge genetic technologies and the development of novel pharmaceutical preparations to improve our understanding of the genes encoding by these miRNAs. It also focuses on the efficacy of miRNAs for control, early diagnosis, and prevention of endometritis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To identify the prevalence of chronic endometritis (CE), compare the efficacy of antibiotic regimens for CE, and examine pregnancy outcomes after treatment for CE among patients in an academic fertility clinic., Methods: In this retrospective cohort study, data from patients who underwent endometrial sampling (ES) for CE evaluation at a single academic institution from 2014 to 2020 were collected and analyzed. Rates of CE were compared by indication for ES including recurrent pregnancy loss (RPL), implantation failure (IF), and recent first-trimester pregnancy loss. Treatment and pregnancy outcomes were also evaluated., Results: Six hundred fifty-three individuals underwent ES to evaluate for CE. The overall prevalence of CE was 28.5%; when stratified by indication, the prevalence of CE was 66.2% for recent first-trimester loss, 27.9% for RPL, and 13.1% for IF (p < .001). Of those with CE, 91.9% received antibiotics, most commonly doxycycline (76.0%). CE clearance was not significantly different when doxycycline was compared to all other regimens (71.3% vs. 58.8%, p = .17), and 68.5% of patients cleared CE after one course of antibiotics. Following two antibiotic courses, CE was cleared in 88.3% of patients. Live birth rates (LBRs) were higher for those with cleared CE compared to patients with untreated CE (34.1% vs. 5.6%, p = .014) and similar for those with cleared CE versus those without CE (34.1% vs. 29.3%, p = .297)., Conclusion: CE is common among patients with infertility, particularly those with a recent first-trimester loss. Treatment and clearance of CE were associated with higher LBRs; however, persistent CE was common despite treatment with antibiotics., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Our objective was to determine the effects of intrauterine infusion of proteolytic enzymes in buffaloes with subclinical endometritis (SCE) at estrus on the resolution of endometrial inflammation and reproductive performance. Buffaloes at spontaneous estrus (E1) were screened for SCE by endometrial cytology to identify SCE (≥5% PMN, n = 22) and non-SCE (<5% PMNs, n = 14) animals. All buffaloes underwent uterine ultrasonographic examination, low volume uterine lavage (cytokines and acute phase proteins) and blood sampling (cytokines and acute-phase proteins) at E1. On the same day (E1), SCE buffaloes were randomly selected either for intrauterine infusion of proteolytic enzymes (ENY, n = 11) or saline (PC, n = 11). Buffaloes without SCE were kept as untreated control (NC; n = 14). All buffaloes were re-examined and re-sampled during subsequent estrus (E2), inseminated during the following estrus (E3), and assessed for fertility related outcomes. Proteolytic infusion resulted a reduction in uterine PMN (P < 0.01) in SCE buffaloes. The concentrations of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in uterus, and TNF-α and IL-10 in serum were higher (P < 0.01) at E1 in buffaloes with SCE (PC and ENY) compared to NC. After treatment, uterine IL-1β and TNF-α (P = 0.02), and serum TNF-α and IL-10 were lower within the animals of ENY group (P < 0.01). Before treatment, buffaloes with SCE had higher concentrations (P < 0.01) of serum and uterine amyloid-A and haptoglobin, which decreased (P < 0.01) after treatment in the ENY group. None of the fertility outcomes differ between the treatment groups. In conclusion, intrauterine infusion of proteolytic enzymes reduced endometrial inflammation; however, did not improve reproductive outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The inflammatory system activated by uterine infection is associated with decreased fertility. Diseases can be detected in advance by identifying biomarkers of several uterine diseases. Escherichia coli is one of the most frequent bacteria that is involved in pathogenic processes in dairy goats. The purpose of this study was to investigate the effect of endotoxin on protein expression in goat endometrial epithelial cells. In this study, the LC-MS/MS approach was employed to investigate the proteome profile of goat endometrial epithelial cells. A total of 1180 proteins were identified in the goat Endometrial Epithelial Cells and LPS-treated goat Endometrial Epithelial Cell groups, of which, 313 differentially expressed proteins were accurately screened. The proteomic results were independently verified by WB, TEM and IF techniques, and the same conclusion was obtained. To conclude, this model is suitable for the further study of infertility caused by endometrial damage caused by endotoxin. These findings may provide useful information for the prevention and treatment of endometritis.

Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) is one of the causative agents of equine endometritis. In this study, a panel of different bacterial species, and colonies derived from bacteriological cultures of 38 clinical samples, were subjected to Loop-Mediated Isothermal Amplification (LAMP) assay and PCR, followed by high-resolution melt (HRM) curve analysis. All clinical samples were genotyped into three distinct groups based on HRM curve analysis. Differences in melting curve profiles were a reflection of DNA variation in sorD gene which was confirmed by DNA sequencing. A mathematical model based on Genetic Confidence Percentage (GCP) was used in HRM curve analysis and a cut-off point value was established which differentiated S. zooepidemicus isolates without requiring visual interpretation of curve profiles. The accuracy of PCR-HRM and bacterial culture in detection of S. zooepidemicus were identical with 100% sensitivity and specificity, while LAMP assay had similar specificity but a lower sensitivity (89.5%). PCR-HRM and LAMP assay provided an effective detection method with a turn-around time of six hours for PCR-HRM and 120 min for LAMP assay, compared to a minimum three days that was required when routine bacteriological culture method was used. In summary, results indicate that LAMP had the quickest turnaround, and HRM curve analysis could potentially be used for genotyping without DNA sequencing. Any mare suspected of endometritis will benefit from developed rapid diagnostic tests for detection of S. zooepidemicus and proper treatment prior to being bred and will mitigate unnecessary treatment and antibiotic resistance., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives were to evaluate differences in the uterine and serum metabolomes associated with metritis in dairy cows. Vaginal discharge was evaluated using a Metricheck device (Simcro) at 5, 7, and 11 d in milk (DIM; herd 1) or 4, 6, 8, 10, and 12 DIM (herd 2). Cows with reddish or brownish, watery, and fetid discharge were diagnosed with metritis (n = 24). Cows with metritis were paired with herdmates without metritis (i.e., clear mucous vaginal discharge or clear lochia with ≤50% of pus) based on DIM and parity (n = 24). Day of metritis diagnosis was considered study d 0. All cows diagnosed with metritis received antimicrobial therapy. The metabolome of uterine lavage collected on d 0 and 5, and serum samples collected on d 0 were evaluated using untargeted gas chromatography time-of-flight mass spectrometry. Normalized data were subjected to multivariate canonical analysis of population using the MultBiplotR and MixOmics packages in R Studio. Univariate analyses including t-test, principal component analyses, partial least squares discriminant analyses, and pathway analyses were conducted using Metaboanalyst. The uterine metabolome differed between cows with and without metritis on d 0. Differences in the uterine metabolome associated with metritis on d 0 were related to the metabolism of butanoate, amino acids (i.e., glycine, serine, threonine, alanine, aspartate, and glutamate), glycolysis and gluconeogenesis, and the tricarboxylic acid cycle. No differences in the serum metabolome were observed between cows diagnosed with metritis and counterparts without metritis on d 0. Similarly, no differences in uterine metabolome were observed between cows with metritis and counterparts not diagnosed with metritis on d 5. These results indicate that the establishment of metritis in dairy cows is associated with local disturbances in amino acid, lipid, and carbohydrate metabolism in the uterus. The lack of differences in the uterine metabolome on d 5 indicates that processes implicated with the disease are reestablished by d 5 after diagnosis and treatment., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

This paper reviews recent data and concepts on metritis, purulent vaginal discharge (PVD), and endometritis in dairy cows and the ways in which these diseases affect reproductive performance. Metritis is characterized by fetid discharge from the uterus, with or without fever. Purulent vaginal discharge describes exudate that is >50% pus that may be attributable to uterine infection or cervicitis. Endometritis is inflammation of the uterus diagnosed by endometrial cytology with a proportion of neutrophils (typically ≥5%) that is associated with impaired fertility. Metritis and PVD are associated with uterine bacterial dysbiosis: changes in the microbiota to lesser diversity and greater abundance of pathogens, especially Gram-negative anaerobic bacteria, and Trueperella pyogenes in the case of PVD. Metritis is justifiably treated with approved antibiotics but criteria for more selective treatment without loss of performance are emerging. Purulent vaginal discharge is not synonymous with clinical endometritis, and greater precision in terminology is warranted. PVD is likely under-diagnosed and represents an opportunity for improved management in many herds. Endometritis seems in many cases to reflect persistent, dysregulated inflammation, for which the inciting cause is unclear. Postpartum uterine infection and inflammation have harmful effects on oocytes, embryo development, and the endometrium for at least three months, even if the disease is apparently resolved. Emerging concepts of the resolution and regulation of inflammation are promising for the improvement of prevention and therapy of endometritis., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To investigate the reproductive outcomes by comparing two kinds of antibiotic schemes for chronic endometritis (CE) in infertile women's fresh embryo transfer (FET) cycles and identify subgroups of patients with CE who need long-term antibiotics treatment., Design: A retrospective cohort study., Setting: University-based reproductive medical center., Patient(s): A total of 492 women with CD138-positive plasmacytes per 10 high-power fields (CD138+/10HPF)., Intervention(s): Hysteroscopy was performed and endometrial biopsy samples were collected in the proliferative phase. Long-term or short-term antibiotics were administrated. After antibiotics treatment, patients underwent in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) and received ET., Main Outcome Measure(s): Ongoing pregnancy rate, clinical pregnancy rate, clinical miscarriage rate., Result (s): There were no significant differences in pregnancy outcomes between patients with CD138+/10HPF 1-4 (low-grade CE) who received long-term antibiotic therapy and short-term antibiotics groups. Among women with CD138+/10HPF ≥5 (high-grade CE), live birth rate (48.4% vs. 14.7%, p = .001), clinical pregnancy rate (66.7% vs. 35.3%, p = .002) and ongoing pregnancy rate (59.1% vs. 20.6%, p < .001) in the long-term arm were significantly higher than that in the short-term arm. The clinical miscarriage rate (21.0% vs. 58.3%, p = .013) was statistically lower in the long-term antibiotics group, but no statistical differences were found between the two groups in preterm delivery rate., Conclusion: Long-term antibiotics treatment was a sensible choice to improve pregnancy outcomes in women with CD138+/10HPF ≥5 (high-grade CE). The pregnancy outcomes of women with low-grade CE only defined by histological diagnosis were not greatly improved after antibiotic therapy. Therefore, we recommended the proper diagnosis criteria were CD138+/10HPF ≥5 pathologically., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To establish and verify a hysteroscopic scoring system for the diagnosis of chronic endometritis (CE) in infertile patients., Methods: A total of 238 infertile patients who underwent hysteroscopy and endometrial biopsy in the Reproductive Medicine Center, Shijiazhuang Obstetrics and Gynecology Hospital Affiliated to Hebei Medical University from October 1 to December 31, 2019 were enrolled in the study. According to the results of CD138 immunohistochemistry, the patients were divided into CE group ( n =73) and non-CE group ( n =165). Univariate and binary logistic regression analyses were used to screen the risk factors of CE and a nomogram was establish for hysteroscopic scoring. Receiver operating characteristic (ROC) curve, calibration curve and Bootstrap resampling method were used to evaluate and verify the system., Results: Univariate and binary logistic regression analyses showed that hyperemia area (HA) degree ≥2, micropolyps, polypoid hyperplasia of endometrium and history of ectopic pregnancy were independent risk factors for CE (all P <0.05). A nomogram was generated to establish a hysteroscopy scoring system based on the above four factors. The area under ROC curve of the hysteroscopy scoring system for predicting CE was 0.801 (95% CI :0.742-0.861), the sensitivity was 74.0% and the specificity was 73.9%. The calibration curve showed that the predicting value of the scoring system was highly consistent with the actual value. In the internal verification, the C-index was 0.7811. The predicting value of the verification group in the calibration curve was basically consistent with the actual value, indicating that the scoring system had good stability., Conclusions: The hysteroscopic scoring system composed of HA, micropolyp, polypoid hyperplasia of endometrium and history of ectopic pregnancy can effectively and intuitively predict CE, which is conducive to improving the diagnosis of CE.

Objective: A significant cause of infertility is the inability of the embryo to implant. Endometritis is one of the major causes affecting embryo implantation. The present study addressed the diagnosis and effects of chronic endometritis (CE) treatment on pregnancy rates after in vitro fertilization (IVF)., Patients and Methods: We conducted this retrospective study on 578 infertile couples treated with IVF. In 446 couples, we performed a control hysteroscopy with biopsy before IVF. In addition, we examined the visual aspects of the hysteroscopy and the results of the endometrial biopsies, followed by antibiotic therapy if necessary. Finally, the results of IVF were compared., Results: Of the 446 cases studied, we diagnosed 192 (43%) with chronic endometritis, either by direct observation or based on the histopathological result. In addition, the cases diagnosed with CE we treated with a combination of antibiotics. The group diagnosed at CE and subsequently treated with antibiotic therapy had a significantly higher pregnancy rate after IVF (43.2%) than the group without treatment (27.3%)., Conclusions: Hysteroscopic examination of the uterine cavity was particularly important for the success of IVF. The initial CE diagnosis and treatment were an advantage for the cases in which we performed the IVF procedures.

Xanthogranulomatous endometritis (XGE) is a rare pathological entity which is characterised by sheets of foamy histiocytes and lymphoplasmacytic infiltrates. This condition can mimic endometrial carcinoma. We report a case, clinically suspected as carcinoma of the endometrium/ovary, which was diagnosed as XGE with left salpingo-oophoritis on histopathology., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Chronic endometritis is a persistent, low-intensity inflammation of endometrial mucosa, characterized by the infiltration of plasma cells into the endometrial stroma This immunological alteration is thought to be a consequence of a bacterial infection. For a long time, chronic endometritis was poorly investigated and rarely considered in clinical practice because it is either asymptomatic or presents with no specific symptoms. Its association with adverse effects on fertility and retrospectively reported effectiveness of antibiotic treatment were the main reasons for a growing interest in this endometrial pathology. Chronic endometritis is now a hot topic in recurrent pregnancy loss and recurrent implantation failure research. Nevertheless, there are still no recommendations to include chronic endometritis investigation in a clinical evaluation of infertile patients. The uncertain role of this condition is an effect of significant differences in study results presented by different research groups. One important reason for these inconsistent findings is a lack of standardised chronic endometritis diagnostic methods. We present a review of the literature, focusing on the currently available chronic endometritis diagnostic techniques. The review is subdivided into three parts concerning the diagnostic accuracy of three main diagnostic modalities. Histopathological examination of endometrial tissue, hysteroscopic evaluation of uterine cavity and identification of the bacterial factor. In conclusion, it is of great importance to establish a consensus on the diagnostic criteria for chronic endometritis. This is the only way to enhance international cooperation and create well-design multicenter studies to evidence the role of this endometrial pathology in infertility.

Objectives: The objective of this study was to examine the prevalence of chronic endometritis (CE) in infertile women, its impact on reproductive outcomes, and the accuracy of hysteroscopy as a screening tool for CE., Design: This was a prospective observational study., Participants: Participants involved in this study were 514 asymptomatic patients with infertility., Setting: The review was conducted in a tertiary care center., Methods: The participants underwent a hysteroscopy and endometrial biopsy (EMB). Antibiotics were given for cases of CE. We investigated the prevalence of CE in patients starting assisted reproductive technologies (ART) as a primary outcome. Secondary outcomes were the clinical pregnancy rate (CPR) in the ART cycle after hysteroscopy, EMB, and antibiotic treatment in cases of CE; the cumulative CPR in the subsequent 2 years after hysteroscopy and EMB; the sensitivity and specificity of hysteroscopy as a screening tool compared to EMB as the "gold standard" for diagnosing CE., Results: CE was identified in 2.8% of patients starting ART (11/393). CPRs did not differ significantly between patients with CE and the entire cohort of patients without CE in the subsequent ART cycle (OR: 0.43; 95% CI: 0.09-2.02) or in the 2 years after EMB (OR: 0.56; 95% CI: 0.16-1.97). In a matched control comparison (with matching for age, basal FSH, and cause of infertility), CPR in patients with CE did not differ in the subsequent ART cycle (OR: 0.39; 95% CI: 0.09-1.61); however, their CPR in the 2 years after EMB was significantly lower (OR: 0.22; 95% CI: 0.13-0.38). The sensitivity and specificity of hysteroscopy as a screening tool for diagnosing CE were 8.3% and 90.1%, respectively., Limitations: Due to our cohort's low CE prevalence, we could not detect significant differences in CPRs., Conclusion: CE is rare in our studied population of asymptomatic patients starting ART. Hysteroscopy cannot replace EMB for diagnosing CE., (© 2023 S. Karger AG, Basel.)

Chronic endometritis is a poorly understood infectious or inflammatory process, potentially disrupting the correct implantation of a human embryo (Puente et al., 2020). The exact prevalence is a subject of discussion and ranges across the available literature from 2% to almost 60%, with a higher suspicion of the condition being present in women with recurrent early pregnancy loss and recurrent implantation failure (Puente et al., 2020). The impact of chronic endometritis on reproductive outcomes following IVF remains questionable given the lack of proper data convincingly showing an improvement after diagnosis and treatment. This article aims to provide the reader with a critical appraisal of current diagnostic methods, treatments and patient populations to be tested for chronic endometritis., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Chronic Endometritis (CE) is a subtle pathology, likely infectious in most cases, with a negative impact on the female fertility, but often overlooked even among fertility specialists. The purpose of the study is to demonstrate the predominant infectious nature of CE and to find the best therapeutic option by comparing the results of oral antibiotic therapy versus intrauterine antibiotic infusion in patients with CE undergoing IVF procedures. The objective was to compare the cure rate of CE-defined as the percentage of patients without CE at the test of cure, between the two groups and, the hysteroscopic aspect with the positive CD 138 staining., Methods: This was a prospective, case-control study that took place in a single university fertility clinic, in Oradea, Romania and included 57 patients with CE divided into 2 groups: orally administered antibiotics group who received a combination of antibiotics compared to intrauterine infusion group who received intrauterine infusion of antibiotic. Chronic Endometritis was diagnosed through hysteroscopy and immunohistochemistry for CD 138. Patients in both groups were tested for CE twice to evaluate the cure rate after oral combination antibiotic therapy versus intrauterine infusion of antibiotic., Results: Out of 115 patients with endometrial biopsies 57 tested positive for CE, with a 49.6% chronic endometritis prevalence. Among the group that was administered oral antibiotics, 11 patients (45.83%) experienced CE resolution after triple antibiotic therapy. Of the intrauterine infusion group, 25 patients (89.29%) presented negative results (p 0.0020). The normal hysteroscopic aspect had a similar prevalence in the patients with immunohistochemical positive and negative CD 138., Conclusions: Our study demonstrated the effectiveness and superiority of intrauterine antibiotic infusion over the use of oral combination antibiotic therapy for CE cure., Trial Registration: ISRCTN17542620/14.09.2022., (© 2022. The Author(s).)

Background: Endometrial receptivity array (ERA) is used to determine the timing of embryo transfer (ET) synchronized with the window of implantation (WOI). The effectiveness and evaluation of ERAs in women with recurrent implantation failure remain controversial. We report the case of a patient with recurrent implantation failure that raises the issue of reproducibility of ERA tests., Case Report: A 36-year-old Japanese woman with secondary infertility who had previously given birth failed to conceive after three frozen-thawed embryo transfer (FET) cycles. An ERA test was conducted to confirm the WOI. The first ERA test was performed 125 h after progesterone exposure. The laboratory reported that the endometrium was in a non-receptive (post-receptive) phase, and recommended retesting 101 h after progesterone exposure. A simultaneous chronic endometritis (CE) test showed a score of 3. After the antibiotics administration to treat CE, the second ERA test was performed after 101 h of progesterone exposure. The laboratory reported that the endometrium had not reached the WOI and estimated the WOI to be 113 ± 3 h after progesterone exposure. The third ERA test was performed 113 h after progesterone exposure. The laboratory reported that the endometrium was in a non-receptive (pre-receptive) phase and estimated the WOI to be 137 ± 3 h after progesterone exposure. A CE test performed at the same time as the second and third ERA tests showed a score of 1 for the collected endometrium. According to the third ERA test results, the vitrified-warmed blastocyst was transferred at 137 h of progesterone exposure. Pregnancy was achieved and the patient had an uncomplicated vaginal delivery at 39 weeks. One year later, another pregnancy was achieved after FET at 137 h of progesterone exposure, and the patient delivered at 33 weeks due to an unexpected membrane rupture., Conclusion: Because the results of the ERA test may vary in the presence of CE, CE should be diagnosed simultaneously with or before conducting ERA tests. If CE is diagnosed, ERA testing should be performed after treatment with antimicrobials or other drugs., (© 2022. The Author(s).)

Endometritis is a relevant cause of subfertility in mares. However, the accurate diagnosis, essential for effective treatment, can be difficult due to the variability of results and interpretations resulting from different examination methods and sample collection techniques. The present work compared gynecological evaluation methods and sample collection techniques to diagnose endometritis in subfertile mares. Forty animals with a history of subfertility were selected for gynecological evaluation using clinical methodologies, such as perineal conformation, transrectal palpation and ultrasonography, vaginoscopy, and digital examination of the cervix. In addition, we performed laboratory analyses, including uterine microbiological culture and endometrial cytology and histology, of which the latter is the gold standard for the diagnosis of endometritis. Samples were collected for microbiological culture and endometrial cytological evaluations using three different techniques: a commercial cytobrush/swab collector, low-volume uterine flush, and a new tested technique, by flush the fragment resulting from the endometrial biopsy. Transrectal palpation and ultrasound showed the best results among clinical examinations. However, they were less efficient in laboratory tests of endometrial cytology and uterine microbiological culture, in which the latter showed the highest sensitivity and specificity for endometritis compared with endometrial histology. The use of multiple results from different methods has also proved to be an effective alternative for diagnosis. Among the techniques used to collect endometrial material for cytology and microbiological culture, the most effective and practical in this study was the commercial cytobrush/swab collector., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The overall aim of this work was to identify the potential impact of misclassification errors associated with routine screening and diagnostic testing for endometritis in mares. Using Bayesian latent class models (BLCM), specific objectives were to: 1) estimate the diagnostic accuracy of cytology and culture of endometrial swab samples to detect endometritis in mares; 2) assess the impact of different cytology thresholds on test accuracy and misclassification costs; and 3) assess the sensitivity (Se) and specificity (Sp) of a diagnostic strategy including both tests interpreted in series and parallel. Diagnostic and pre-breeding endometrial swab samples collected from 3448 mares based at breeding premises located in the South East of England between 2014 and 2020 were retrospectively analysed. Culture results were classified as positive according to three different case definitions: (A) > 90% of the growth colonies were a monoculture; (B) pathogenic or pathogenic and non-pathogenic bacteria were identified; and (C) any growth was observed. Endometrial smears were graded based on the percent of polymorphonuclear cells (PMN) per high power field (HPF). A hierarchical BLCM was fitted using the cross-tabulated results of the three culture case definitions with a cytology threshold fixed at > 0.5% PMN. Fit for purpose cytology thresholds were proposed using a misclassification cost analysis in the context of good antimicrobial stewardship and for varying endometritis prevalence estimates. Median [95% Bayesian credible intervals (BCI)] cytology Se estimates were 6.5% (2.2-11.6), 6.4% (2.2-10.8) and 6.3% (2.2-10.8) for scenario A, B and C, respectively. Median (95% BCI) cytology Sp estimates were 88.8% (83.1-94.8), 88.9% (83.9-93.8) and 88.8% (84.0-93.8) for scenarios A, B and C, respectively. Median (95% BCI) culture Se estimates were 37.5% (29.9-46.0), 42.3% (33.8-51.1) and 46.4% (35.7-55.9) for scenarios A, B and C, respectively. Median (95% BCI) culture Sp estimates were 92.8% (84.3-99.0), 91.5% (82.5-98.0) and 90.8% (80.1-97.4) for scenarios A, B and C, respectively. Regardless of the culture case definition, Se and Sp of cytology (> 0.5% PMN) was lower than previously reported for swab samples in studies using histology as the reference standard test. The misclassification cost term decreased as the cytology threshold increased for all scenarios and all prevalence contexts, suggesting that, regardless of the endometritis prevalence in the population, increasing the cytology threshold would reduce the misclassification costs associated with false positive mares contributing to good antimicrobial stewardship., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: To assess the efficacy of dysdrogesterone in the treatment of chronic endometritis (CE) treated with antibiotic in premenopausal women with endometrial polyps (EPs)., Methods: Routine detection of endometrium was simultaneously conducted to determine whether there was CE by syndecan-1 (CD138), while women underwent hysteroscopic polypectomy in our hospital. Antibiotic was given for the treatment of CE. A total of 235 premenopausal women with CE who underwent hysteroscopic polypectomy were enrolled in the retrospective observational study. In the control group, single antibiotic was given for the treatment of CE form January 2016 to December 2018, and in the treatment group additional dydrogesterone was used from January 2019 to November 2020. Comparison of cure rates of CE with different treatment regimens was performed., Results: The cure rates of CE in dydrogesterone and antibiotic combination group and the single antibiotic group were 85.2% and 74.3%, respectively, with overall cure rate of 80.0% (188/235). The combination group showed better effects regarding the cure rate of CE (P &lt; .05). Multivariate analysis confirmed that the cure rate of CE was not affected by age, body mass index, number of EPs, the status of estrogen receptor and the status of progesterone receptor. Conversely, dydrogesterone and endometrial scratching were beneficial factors for cure rate increase with antibiotic treatment., Conclusion: Combination of dydrogesterone and antibiotic was more effective for cure rate of CE than antibiotic alone in premenopausal women after hysteroscopic polypectomy. Endometrial scratching also contributed to the cure rate increase with antibiotic treatment., (© 2022. The Author(s).)

Background: Postpartum endometritis can cause subfertility in cows and reduce the reproductive performance of dairy herds. Thus, there is a critical need to improve the accuracy of the diagnosis of this disease, particularly in dairy cows., Objectives: This study confirmed the effects of the combined use of two non-laboratory methods: Metricheck device (MT) and ultrasonography (UT) to detect signs of endometritis and therefore predict the likelihood of pregnancy., Methods: The reproductive tract of 67 lactating Holstein cows (25 primiparous and 42 multiparous) was observed at 4 and 6 weeks postpartum using the MT and UT. The cows with flecks and more purulent material in the vaginal discharge were defined as MT-positive, and the cows with uterine echogenic contents were defined as UT-positive. The combined definition was also used; both the UT and MT results or either the UT or MT result had to be positive for the final decision to be positive. The true-negative cows were determined as both MT-UT-negative., Results and Discussion: When comparing the diagnostic results obtained by MT and UT, 37.3% and 32.8% of the total cows showed conflicting results at 4 and 6 weeks postpartum. The proportion of non-pregnant cows until 200 days postpartum was significantly greater in both MT-UT-positive cows than in the true negative cows. The hazard ratios of pregnancy rate were 0.37 for both MT-UT-positives relative to the true negatives at 4 weeks postpartum. Similar significant differences were not detected using the MT or UT alone. These results indicate that a more severe effect on the chance of pregnancy could be detected in cows that are both MT-UT-positive compared with those positive for MT or UT alone., Conclusions: The combined use of MT and UT could support veterinary practitioners in diagnosing endometritis, potentially improving the accuracy of predicting subsequent reproductive performance., (© 2022 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Objective: To assess the impact of menstrual cycle phase on the detection of plasma cells., Design: A retrospective cohort study., Setting: Fertility clinic., Patient(s): Biopsies from 157 patients met criteria for inclusion, 91 in the follicular phase and 60 in the luteal phase. Patient groups were similar in body mass index and number of previous live births; however, differed in terms of age, infertility history, and biopsy indication., Interventions: Endometrial biopsies from patients at a fertility clinic from 2018-2020 were retrospectively reviewed. Biopsies were excluded if patients had a previous chronic endometritis diagnosis, abnormal uterine cavity or were on hormone therapy. Each case was reviewed by a gynecologic pathologist for plasma cells by hematoxylin and eosin and CD138 staining. Demographic and clinical data were collected. Continuous variables were compared using Welch t test and Wilcoxon's rank sum test, and categorical variables using Pearson's χ 2 test. Logistic regression was used to calculate odds ratio and 95% confidence intervals for the association between the presence of plasma cells and cycle phase. Multinomial logistic regression was used to estimate the odds ratios for nominal outcomes. Pathology reports were reviewed. Plasma cell enumeration using hematoxylin and eosin-stained sections and CD138 immunohistochemical stains (performed at the time of biopsy by a gynecologic pathologist) was recorded., Main Outcome Measure(s): Presence and density of plasma cells., Result(s): We found a higher likelihood of finding plasma cells in the follicular than in luteal phase (59.3% vs. 19.7%). There was a higher likelihood of finding plasma cells in the early (cycle days 5-8, 29 cases or 76.3% of cases with plasma cells) than in the late follicular phase (cycle days 9-14, 25 cases or 47.2%). There was a higher density of plasma cells in the follicular phase group than in the luteal phase group (25.3% vs. 1.5% scattered and 13.2% vs. 0 clusters)., Conclusion(s): Plasma cells are more likely to be present during the follicular phase compared with the luteal phase and in the early compared with the late follicular phase. Further studies are needed to identify the optimal timing of biopsy to standardize the diagnosis., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To identify the prevalence of and risk factors for chronic endometritis (CE) in patients with intrauterine disorders and the therapeutic efficacy of hysteroscopic surgery in the treatment of CE without antibiotic therapy., Design: Prospective cohort study., Setting: Hospital specializing in reproductive medicine., Patient(s): The study population consisted of 350 women with infertility, of whom 337 were recruited, who underwent hysteroscopic surgery between November 2018 and June 2021. Eighty-nine consecutive patients without intrauterine disorders were also recruited as controls., Intervention(s): Endometrial samples were collected during the surgery for CD138 immunostaining for the diagnosis of CE. In women diagnosed with CE, endometrial biopsy was performed without antibiotic use in the subsequent menstrual cycle., Main Outcome Measure(s): Prevalence of and risk factors for CE in intrauterine disorders and therapeutic effects of hysteroscopic surgery on CE., Result(s): The prevalence of CE with ≥5 CD138-positive cells in women with no intrauterine disorder and with endometrial polyps, myomas, intrauterine adhesions (IUAs), and septate uterus was 15.7%, 85.7%, 69.0%, 78.9%, and 46.2%, respectively. A multivariate analysis revealed that CE was diagnosed significantly more often in the endometrial polyp (odds ratio, 27.69; 95% confidence interval, 15.01-51.08) and IUA groups (odds ratio, 8.85; 95% confidence interval, 3.26-24.05). The rate of recovery from CE with surgery in women with endometrial polyps, myomas, IUA, and septate uterus was 89.7%, 100%, 92.8%, and 83.3%, respectively., Conclusion(s): Endometrial polyp and IUA were risk factors for CE. Most CE cases with intrauterine disorders were cured with hysteroscopic surgery without antibiotic therapy, regardless of the type of intrauterine abnormalities., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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.

Objective: To investigate whether cured chronic endometritis (CE) from antibiotic treatment would be associated with a higher risk of spontaneous abortion in the following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment., Design: Prospective cohort study., Setting: Tertiary reproductive medicine center., Patient(s): Patients with infertility who underwent a routine hysteroscopy underwent an IVF/ICSI stimulation between January 1, 2019, and December 31, 2020. Women with CE (N = 338) underwent antibiotic therapy, and the assisted reproductive outcomes were then compared with women without CE (N = 7,962)., Intervention(s): Chronic endometritis was diagnosed through hysteroscopy and confirmed by histology and immunohistochemistry for CD138., Main Outcome Measure(s): Spontaneous abortion rate after the initial embryo transfer., Result(s): A total of 7,218 patients underwent embryo transfer, with 330 in the cured CE group and 6,888 in the non-CE group. Women with cured CE had a higher rate of spontaneous abortion than did those without CE (11.8% vs. 9.2%; crude odds ratio [OR], 1.32 [0.94, 1.86]), and this difference was statistically significant after adjusting for confounding variables (adjusted OR, 1.49 [1.01, 2.19]). The live birth rate was 43.9% in the cured CE group and 50.5% in the non-CE group (crude OR, 0.77 [0.62, 0.96]; adjusted OR, 0.73 [0.59, 0.92]). The incidence of clinical pregnancy did not differ significantly between the 2 groups (56.1% vs. 60.0%; crude OR, 0.85 [0.68, 1.06]; adjusted OR, 0.83 [0.66, 1.03]). Sensitivity analyses stratified by initial fresh- or frozen-thawed embryo transfer cycles resulted in similar results., Conclusion(s): Chronic endometritis cured with antibiotic therapy was associated with an increased risk of spontaneous abortion among women undergoing IVF/ICSI treatment. The interpretation of the findings is limited by a potential confounding bias., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Chronic endometritis (CE) is a persistent and subtle local inflammatory disease characterized by abnormal plasma cell infiltration in the endometrial stroma.The incidence of chronic endometritis is as high as 15-57.5% in women suffering from infertility, implantation failure of in vitro fertilization (IVF) and unexplained recurrent abortion. Many studies both at home and abroad have shown that CE can reduce the receptivity of endometrium and affect embryo implantation. According to the existing reproductive immunity research, the abnormality of immune cell subsets in endometrium is an important factors leading to pregnancy failure. The immune microenvironment in endometrium consists of immune cells and immune molecules, and their influence on embryo implantation can not be ignored. This review paper discusses the controversy of pathogenesis, diagnosis and treatment of CE from the perspective of immune microenvironment by referring to related literature at home and abroad, and investigates the possible ways to improve the diagnosis and treatment of CE., (Copyright © 2022 Elsevier B.V. All rights reserved.)