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.

Microbial responses and changes in metabolic products in bovine uteri infected with Staphylococcus aureus.

There is mounting evidence that the uterine microbiota has an important role in the pathogenesis of endometritis, with invasion of pathogenic bacteria being a main cause of uterine microbial imbalance. However, mechanisms of uterine microbiota resistance to pathogen invasion remain unclear. In this study, an intrauterine infusion of Staphylococcus aureus was used as a bovine endometritis model; it significantly increased abundance of pathogenic bacteria (Streptococcus, Helccoccus, Fusobacterium, and Escherichia-Shigella) and significantly decreased abundance of probiotics (Allstipes, Bacteroides, Phascolarctobacterium, Romboutsia, and Prevotella). In addition, the metabolite aloe-emodin was positively correlated with Prevotella and based on combined analyses of omics and probiotics, the presence of its metabolite aloe-emodin in the uterus at least partially resisted Staphylococcus aureus invasion. Therefore, Aloe-emodin has potential for regulating microbial structure and preventing endometritis.

Luteolin attenuates Staphylococcus aureus-induced endometritis through inhibiting ferroptosis and inflammation via activating the Nrf2/GPX4 signaling pathway.

Endometritis, a local inflammatory disease, has been known as the most common cause of infertility in mares. In this study, we investigated the protective effects of luteolin on endometritis induced by Staphylococcus aureus (S. aureus) and further clarified the possible molecular mechanisms. An S. aureus-induced endometritis model was established by the infusion of S. aureus into the uterus. Luteolin was intraperitoneally administered to mice 1 h before S. aureus treatment. The results showed that the mice of the S. aureus group showed severe histological changes of uterine tissues, increased myeloperoxidase (MPO) activity, and elevated TNF-α, IL-1ß, and IL-6 levels. These changes induced by S. aureus were dose-dependently inhibited by luteolin. Furthermore, luteolin inhibited MDA and Fe2+ production and increased the production of GSH decreased by S. aureus. Luteolin prevented S. aureus-induced endometrial barrier disruption through up-regulating ZO-1 and occludin expression. Luteolin dramatically inhibited S. aureus-induced NF-κB activation. The expression of Nrf2 and HO-1 was increased by luteolin. In addition, the inhibitory effects of luteolin on S. aureus-induced endometritis were reversed in Nrf2 knockdown mice. In conclusion, these data indicated that luteolin protected mice against S. aureus-induced endometritis through inhibiting inflammation and ferroptosis via regulating the Nrf2 signaling pathway.IMPORTANCEEndometritis is an inflammatory disease of the endometrium, which is a common gynecological disease. Up to now, there is no evidence for the protective effects of luteolin on endometritis. The purpose of this study was to investigate whether luteolin has protective effects against S. aureus-induced endometritis and attempts to clarify the mechanism.

The association between endometrial polyps, chronic endometritis, and IVF outcomes.

OBJECTIVE: Endometrial polyps (EPs) are one of the most common pathologies detected during the examination of the uterine cavity of infertile women. We aimed to demonstrate the relationship between EPs, chronic endometritis (CE) and in vitro fertilization (IVF) outcomes. PATIENTS AND METHODS: This retrospective study was performed on 394 hysteroscopically examined infertility cases. We performed polyp resections (PR) and extensive biopsies of the endometrium to demonstrate the association with clinical pregnancy (CP) by IVF. We performed statistical analysis to compare these associations. RESULTS: The incidence of CE was twice as high in the presence of EPs as in the absence of EPs. The associations between EPs and PR were found to be significant for positive CP outcomes. A significant difference in IVF outcome was found between the group with EPs and the group without EPs. All these associations were statistically significant (p < 0.05). CONCLUSIONS: We found a frequent association between EPs and CE. The pregnancy rate obtained after IVF was negatively affected by the presence of EPs. Treatment of these pathologies improved IVF outcomes.

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.

Establishment and verification of hysteroscopic scoring system for chronic endometritis in infertile patients. / ä¸å­•æ‚£è€ æ ¢æ€§å­å®«å† è†œç‚Žå®«è ”é•œè¯„åˆ†ç³»ç»Ÿçš„æž„å»ºåŠéªŒè¯.

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.

The microbiota of uterine biopsies, cytobrush and vaginal swabs at artificial insemination in Norwegian red cows.

The individual resistance or tolerance against uterine disease in dairy cattle might be related to variations in the uterine tract microbiota. The uterine tract microbiota in dairy cattle is a field of increasing interest. However, its specific taxonomy and functional aspects is under-explored, and information about the microbiota in the endometrium at artificial insemination (AI) is still missing. Although uterine bacteria are likely to be introduced via the vaginal route, it has also been suggested that pathogens can be transferred to the uterus via a hematogenous route. Thus, the microbiota in different layers of the uterine wall may differ. Norwegian Red (NR) is a high fertility breed that also has a high prevalence of subclinical endometritis (SCE), an inflammation of the uterus that has a negative effect on dairy cattle fertility. However, in this breed the negative effect is only moderate, raising the question of whether this may be due to a favorable microbiota. In the present study we investigated the endometrial microbiota in NR at AI by biopsy and cytobrush samples, and comparing this to the vaginal microflora. The second objective was to describe potential differences at both distinct depths of the endometrium, in healthy vs SCE positive NR cows. We sampled 24 lactating and clinically healthy Norwegian red cows in their second heat or more after calving, presented for first AI. First, we obtained a vaginal swab and a cytobrush sample, in addition to a cytotape to investigate the animal's uterine health status with respect to SCE. Secondly, we acquired a biopsy sample from the uterine endometrium. Bacterial DNA from the 16S rRNA gene was extracted and sequenced with Illumina sequencing of the V3-V4 region. Alpha and beta diversity and taxonomic composition was investigated. Our results showed that the microbiota of endometrial biopsies was qualitatively different and more even than that of cytobrush and vaginal swab samples. The cytobrush samples and the vaginal swabs shared a similar taxonomic composition, suggesting that vaginal swabs may suffice to sample the surface-layer uterine microbiota at estrus. The current study gave a description of the microbiota in the healthy and SCE positive NR cows at AI. Our results are valuable as we continue to explore the mechanisms for high fertility in NR, and possible further improvements.

Deoxycholic acid inhibits Staphylococcus aureus-induced endometritis through regulating TGR5/PKA/NF-κB signaling pathway.

Endometritis, a common gynecological disease, is the most common cause of infertility. As a natural metabolite of gut microbiota, deoxycholic acid (DCA) has been reported to have anti-inflammatory function. In the current study, the protective role of DCA on Staphylococcus aureus (S.aureus)-induced endometritis was tested. In vivo, DCA inhibited uterine histological change, MPO activity, endometrial barrier disruption, and inflammatory cytokine production induced by S.aureus. In vitro, DCA suppressed S.aureus-induced TNF-α and IL-1ß production in mouse endometrial epithelial cells (mEECs). Also, DCA markedly suppressed S.aureus-induced NF-κB activation. Takeda G protein-coupled receptor 5 (TGR5)is a critical bile acid membranereceptor that mainly regulated the cyclic AMP (cAMP)/protein kinase A (PKA)signaling pathway to inhibit NF-κB activation. We found DCA significantly increased TGR5 and PKA expression and S.aureus-induced inflammatory cytokine production and NF-κB activation were prevented by TGR5 inhibitor and PKA inhibitor. In conclusion, DCA protected S.aureus-induced endometritis by regulating TGR5/PKA/NF-κB signaling pathway.

Results of in vitro fertilization after diagnosis and treatment of chronic endometritis.

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.

The Impact of Chronic Endometritis on Infertility: Prevalence, Reproductive Outcomes, and the Role of Hysteroscopy as a Screening Tool.

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.

Commonalities and Disparities between Endometriosis and Chronic Endometritis: Therapeutic Potential of Novel Antibiotic Treatment Strategy against Ectopic Endometrium.

Chronic endometritis (CE) is a local mucosal inflammatory disorder of the uterine lining, which is histopathologically recognized as the unusual infiltration of CD138(+) plasmacytes into the endometrial stromal compartment. Accumulating body of research documented that CE is associated with female infertility and several obstetric/neonatal complications. The major cause of CE is thought to be intrauterine infection represented by common bacteria (Escherichia coli, Enterococcus faecalis, Streptococcus, and Staphylococcus), Mycoplasma/Ureaplasma, and Mycobacterium. Additionally, local dysbiosis in the female reproductive tract may be involved in the onset and development of CE. Antibiotic treatments against these microorganisms are effective in the elimination of endometrial stromal plasmacytes in the affected patients. Meanwhile, endometriosis is a common female reproductive tract disease characterized by endometriotic tissues (ectopic endometrium) growing outside the uterus and potentially causes chronic pelvic symptoms (dysmenorrhea, dyspareunia, dyschezia, and dysuria), infertility, and ovarian cancers. Endometriosis involves endocrinological, genetic, and epigenetic factors in its etiology and pathogenesis. Recent studies focus on immunological, inflammatory, and infectious aspects of endometriosis and demonstrate several common characteristics between endometriosis and CE. This review aimed to better understand the immunological and microbial backgrounds underlying endometriosis and CE and look into the therapeutic potential of the novel antibiotic treatment strategy against endometriosis in light of endometrial infectious disease.

The Role of NF-κB in Endometrial Diseases in Humans and Animals: A Review.

The expression of genes of various proinflammatory chemokines and cytokines is controlled, among others, by the signaling pathway of the nuclear factor kappaB (NF-κB) superfamily of proteins, providing an impact on immune system functioning. The present review addresses the influence and role of the NF-κB pathway in the development and progression of most vital endometrial diseases in human and animal species. Immune modulation by NF-κB in endometritis, endometrosis, endometriosis, and carcinoma results in changes in cell migration, proliferation, and inflammation intensity in both the stroma and epithelium. In endometrial cells, the NF-κB signaling pathway may be activated by multiple stimuli, such as bacterial parts, cytokines, or hormones binding to specific receptors. The dysregulation of the immune system in response to NF-κB involves aberrant production of chemokines and cytokines, which plays a role in endometritis, endometriosis, endometrosis, and endometrial carcinoma. However, estrogen and progesterone influence on the reproductive tract always plays a major role in its regulation. Thus, sex hormones cannot be overlooked in endometrial disease physiopathology. While immune system dysregulation seems to be NF-κB-dependent, the hormone-independent and hormone-dependent regulation of NF-κB signaling in the endometrium should be considered in future studies. Future goals in this research should be a step up into clinical trials with compounds affecting NF-κB as treatment for endometrial diseases.

Chronic endometritis increases the recurrence of endometrial polyps in premenopausal women after hysteroscopic polypectomy.

BACKGROUND: The reported recurrence rate of endometrial polyps (EPs) after hysteroscopic polypectomy varied widely, and the factors influencing the recurrence of EPs are still controversial. Furthermore, the known definite independent risk factors are almost unchangeable, such as the number of EPs and previous polypectomy history. The aim of this study was to evaluate the impact of chronic endometritis (CE) on the recurrence of EPs in premenopausal women who underwent hysteroscopic polypectomy. METHODS: A retrospective study was conducted at a university-affiliated hospital. Premenopausal women who underwent hysteroscopic polypectomy were enrolled, and those with definite confounding factors for polyp recurrence were excluded, including endometriosis and previous polypectomy history. A total of 233 women were enrolled in this study, including 64 (27.5%) cases with CE and 169 (72.5%) cases without CE. CE was diagnosed via immunohistochemical detection of CD138 on the endometrial specimen. Comparison of the recurrence rate of EPs was performed in women with or without CE at each monitoring stage (i.e., at 3, 6, 9 and 12 months) after hysteroscopic polypectomy. RESULTS: The recurrence rates of EPs at one year in patients with and without CE were 26.6% (95% confidence interval [CI] 15.8-37.4%) and 9.5% (95% CI 5.0-14.0%), respectively, with an overall recurrence rate of 14.2% (95% CI 9.7-18.7%). The hazard ratio (HR) for EPs recurrence in the EPs with CE cohort versus the EPs without CE cohort was 3.08 (95% CI 1.56-6.09) (P = 0.001). Similarly, the recurrence rate of EPs was significantly higher in women with CE than in those without CE at each monitoring stage (i.e., 3, 6 and 9 months). CE and multiple EPs were risk factors for EPs recurrence. The HR for EPs recurrence in the EPs with CE cohort compared with the EPs without CE cohort was 3.06, after adjustment for the number of EPs. CONCLUSIONS: CE was a harmful factor for the recurrence of EPs in premenopausal women after hysteroscopic polypectomy. Thus, routine screening for CE during hysteroscopic polypectomy was needed. Frequent monitoring was needed for multiple EPs as the number of EPs also contributed to polyp recurrence.

Xanthogranulomatous endometritis with unilateral salpingo-oophoritis in a postmenopausal woman masquerading as a malignancy.

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.

Significance of multiple myeloma oncogene 1 immunohistochemistry in chronic endometritis detection in patients with recurrent pregnancy losses: an observational study.

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.

Autophagy Mediates Escherichia Coli-Induced Cellular Inflammatory Injury by Regulating Calcium Mobilization, Mitochondrial Dysfunction, and Endoplasmic Reticulum Stress.

Bovine endometritis is a reproductive disorder that is induced by mucus or purulent inflammation of the uterine mucosa. However, the intracellular control chain during inflammatory injury remains unclear. In the present study, we found that E. coli activated the inflammatory response through the assembly of the NLRP3 inflammasome and activation of the NF-κB p65 subunit in primary bovine endometrial epithelial cells (bEECs). Infection with E. coli also led to an abnormal increase in cytoplasmic calcium and mitochondrial dysfunction. Additionally, live-cell imaging of calcium reporters indicated that the increase in cytosolic calcium mainly was caused by the release of Ca2+ ions stored in the ER and mitochondria, which was independent of extracellular calcium. Cytoplasmic calcium regulates mitochondrial respiratory chain transmission, DNA replication, and biogenesis. Pretreatment with NAC, BAPTA-AM, or 2-APB reduced the expression of IL-1ß and IL-18. Moreover, ERS was involved in the regulation of bovine endometritis and cytosolic calcium was an important factor for regulating ERS in E. coli-induced inflammation. Finally, activation of autophagy inhibited the release of IL-1ß and IL-18, cytochrome c, ATP, ERS-related proteins, and cytoplasmic calcium. Collectively, our findings demonstrate that autophagy mediated E. coli-induced cellular inflammatory injury by regulating cytoplasmic calcium, mitochondrial dysfunction, and ERS.

The menstrual cycle phase impacts the detection of plasma cells and the diagnosis of chronic endometritis in endometrial biopsy specimens.

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 χ2 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.

Baogong decoction treats endometritis in mice by regulating uterine microbiota structure and metabolites.

Endometritis is persistent inflammation caused by bacteria, which can lead to infertility. Although traditional Chinese medicine (TCM) has been used to treat endometritis, the underlying mechanism is still unclear. Here, Baogong Decoction (BGD), a TCM compound, was used to treat mouse endometritis induced by Escherichia coli (E. coli), and then 16S rRNA sequencing and non-targeted metabolomics were used to investigate the change of uterine microbiota and metabolomes in serum and uterine after BGD treatment. Finally, the therapeutic effect of potential metabolites for treating mouse endometritis screened by combined omics analyses was verified using pathological model. The results showed that BGD treatment could effectively treat endometritis associated with the increasing relative abundance of Firmicutes, Bacteroides, Lactobacillus and Lactococcus, and the decreasing relative abundance of Cupriavidus and Proteobacteria. 133 and 130 metabolites were found to be potential biomarkers in serum and uterine tissue respectively. In serum and tissues, dehydroepiandrosterone (DHEA) and catechol were significantly increased in the BGD treatment versus the inflammation group. Results of combined omics analyses demonstrated that DHEA was positively correlated with changes in microbiota. Results of pathological model demonstrated that DHEA could cure endometritis effectively associated with the decreasing infiltration of inflammatory cells and expression of inflammatory factors in the uterus. In summary, our results demonstrated that BGD could cure endometritis in mice by modulating the structure of the uterine microbiota and its metabolites, in which DHEA may be one of the main components of the therapeutic effect of BGD.

Chronic endometritis in recurrent implantation failure: Use of prednisone and IVF outcome.

In recurrent implantation failure patients (RIF), the main criteria for diagnosis of chronic endometritis, is the presence of plasma cells CD138+ in endometrial biopsy. The aim of the present study was to evaluate if treatment with prednisone, in patients with RIF and chronic endometritis, improve IVF outcome. A retrospective study was performed between 2019 and 2020. A total of 27 patients with RIF and an endometrial biopsy positive for CD56+ cells were enrolled. The treatment with prednisone 10 mg per day is began together with controlled ovarian stimulation (COS). Among endometrial biopsies, 13 (48.14%) were positive also for CD138 cells, and an antibiotic treatment was added. In all patients, after therapy, in the subsequent IVF cycle, the clinical pregnancy rate was 25.9% and the live birth rate was 22.2%. Analysing pregnancies according to the percentage of CD 56 cells on endometrial biopsy, the live birth rate in the subgroup of patients with marked endometritis (defined by the presence of >10% CD56+cells) was 29.41%, while in the subgroup with mild endometritis (CD 56 >5% and <10%) was 10%. In the subgroup with mild endometritis with CD 138 positive the live birth was 25%, while in patients with CD 138 negative no live birth were observed. In patients with RIF the count of at least two cell types (CD 138 and CD 56 cells) on endometrial biopsies is advisable. Our study suggests a benefit of prednisone and antibiotic treatment on live birth rate in a subsequent IVF cycle.