Chronic endometritis - a constantly discussed issue in infertile women.

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.

Prevalence and risk factors for chronic endometritis in patients with adenomyosis and infertility: a retrospective cohort study.

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.

Endometrial congestion is the only hysteroscopic finding indicative of chronic endometritis.

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.

Bridging the Diagnostic Gap between Histopathologic and Hysteroscopic Chronic Endometritis with Deep Learning Models.

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.

Histopathologic patterns of female genital tuberculosis with clinical correlation: a 10-year (2013-2022) retrospective cross-sectional study.

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.

Investigation of Uterine Fluid Extracellular Vesicles' Proteomic Profiles Provides Novel Diagnostic Biomarkers of Bovine Endometritis.

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.

Construction of deep learning-based convolutional neural network model for automatic detection of fluid hysteroscopic endometrial micropolyps in infertile women with chronic endometritis.

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.

Metrisor: A novel diagnostic method for metritis detection in cattle based on machine learning and sensors.

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.

Selecting potential biomarkers of plasma proteins in mares with endometritis.

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).

Predictive models for metritis cure using farm-collected data, metabolic and inflammation biomarkers, and hemogram variables measured at diagnosis.

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.

Evaluation of Lipopolysaccharide and Interleukin-6 as Useful Screening Tool for Chronic Endometritis.

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.

Inflammatory markers for differentiation of endometritis in the mare.

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-1ß, 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-1ß, 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-1ß, 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.

Progesterone-independent endometrial mRNA expression in dairy cows with clinical or subclinical endometritis.

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.

Group A Streptococcal Endometritis and Toxic Shock causing Septic Pelvic Thrombophlebitis and Septic Pulmonary Emboli.

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.

Hysteroscopic features suggestive of chronic endometritis: a systematic review.

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.

Hysteroscopic versus histopathological agreement in the diagnosis of chronic endometritis: results from a retrospective observational study.

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.

MicroRNAs in equine Endometritis: A review of pathophysiology and molecular insights for diagnostic and therapeutic strategies.

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.

Review: Postpartum reproductive disease and fertility in dairy cows.

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.

Chronic endometritis: screening, treatment, and pregnancy outcomes in an academic fertility center.

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.