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

ObjectivesAs pelvic inflammatory disease (PID) aetiology is not completely understood, we examined the relationship between select novel bacteria, PID and long-term sequelae.MethodsFastidious bacterial vaginosis (BV)-associated bacteria (Sneathia (Leptotrichia) sanguinegens, Sneathia amnionii, Atopobium vaginae and BV-associated bacteria 1 (BVAB1)), as well as Ureaplasma urealyticum and Ureaplasma parvum were identified in cervical and endometrial specimens using organism-specific PCR assays among 545 women enrolled in the PID Evaluation and Clinical Health study. Risk ratios and 95% CIs were constructed to determine associations between bacteria, histologically confirmed endometritis, recurrent PID and infertility, adjusting for age, race, gonorrhoea and chlamydia. Infertility models were additionally adjusted for baseline infertility.ResultsPersistent detection of BV-associated bacteria was common (range 58% for A. vaginae to 82% for BVAB1) and elevated the risk for persistent endometritis (RRadj 8.5, 95% CI 1.6 to 44.6) 30 days post-cefoxitin/doxycycline treatment, independent of gonorrhoea and chlamydia. In models adjusted for gonorrhoea and chlamydia, endometrial BV-associated bacteria were associated with recurrent PID (RRadj 4.7, 95% CI 1.7 to 12.8), and women who tested positive in the cervix and/or endometrium were more likely to develop infertility (RRadj 3.4, 95% CI 1.1 to 10.4). Associations between ureaplasmas and PID sequelae were modest.ConclusionsTo our knowledge, this is the first prospective study to demonstrate that S. sanguinegens, S. amnionii, BVAB1 and A. vaginae are associated with PID, failure of the Centers for Disease Control and Prevention-recommended treatment to eliminate short-term endometritis, recurrent PID and infertility. Optimal antibiotic regimens for PID may require coverage of novel BV-associated microbes.

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

The diagnosis rate of chronic endometritis (CE), closely associated with infertility, recurrent pregnancy loss, and recurrent implantation failure, remains low in clinical practice. The monocyte percentage (MP) has been identified as a biomarker predicting prognosis in various severe diseases. Although monocytes have been linked to clinical endometritis in animals, their associations with CE in infertile patients remains unclear. This cross-sectional study included patients pathologically diagnosed with CE at a single center in 2021. Demographic data, history of abortion, causes of infertility, Ureaplasma urealyticum infection history, laboratory findings, and histological information were recorded. The correlation between MP and CE was investigated using logistic regression analysis, and subgroup analyses were conducted based on age, gravidity, parity, and follicular phase. The cohort consisted of 631 individuals, including 494 patients with CE, corresponding to a CE prevalence of 78%. Univariate logistic regression analysis revealed an inverse correlation between MP and CE risk (odds ratio [OR] = 0.85; 95% confidence interval [CL], 0.76–0.96; P  < 0.01). Multivariate regression after adjusting for all covariates yielded an OR of 0.82 (95% CI 0.71–0.95). Furthermore, the stratified and subgroup analyses yielded consistent results. Sensitivity analyses excluding participants with pathological endometrial changes (OR = 0.83; 95% CI 0.71–0.96), those in the non-follicular phase (OR = 0.78; 95% CI 0.66–0.92), and those with both endometrial abnormality and non-follicular phase status (OR = 0.82; 95% CI 0.7–0.95) further confirmed the correlation between MP and CE risk. MP was significantly associated with CE in infertile participants in models adjusted for all covariates, suggesting that MP may be a valuable parameter for early CE prediction.

Our objectives were to describe and compare the uterine bacterial composition of postpartum Holstein cows diagnosed as healthy (n = 8), subclinical endometritis (SCE; n = 8), or clinical endometritis (CE; n = 5) in the fifth week postpartum. We did metagenomic analyses of 16S rRNA gene sequences from endometrial cytobrush samples at 10, 21, and 35 days in milk (DIM), and endometrial bacterial culture at 35 DIM. Uterine bacterial composition in healthy, SCE, and CE was stable at 10, 21, and 35 DIM. Alpha and beta diversities showed a different uterine microbiome from CE compared to healthy or SCE, but no differences were found between healthy and SCE cows. At the phylum level, the relative abundance of Bacteroidetes and Fusobacteria , and at genera level, of Trueperella was greater in CE than healthy or SCE cows. Trueperella pyogenes was the predominant bacteria cultured in cows with CE, and a wide variety of bacterial growth was found in healthy and SCE cows. Bacteria that grew in culture were represented within the most abundant bacterial genera based on metagenomic sequencing. The uterine microbiota was similar between SCE and healthy, but the microbiome in cows with CE had a loss of bacterial diversity.

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.

To investigate the Interaction between chronic endometritis (CE) caused endometrial microbiota disorder and endometrial immune environment change in recurrent implantation failure (RIF). Transcriptome sequencing analysis of the endometrial of 112 patients was preform by using High-Throughput Sequencing. The endometrial microbiota of 43 patients was analyzed by using 16s rRNA sequencing technology. In host endometrium, CD4 T cell and macrophage exhibited significant differences abundance between CE and non-CE patients. The enrichment analysis indicated differentially expressed genes mainly enriched in immune-related functional terms. and were significantly high infiltration in CE patients, and active in pathways related to carbohydrate metabolism and/or fat metabolism. The increased synthesis of lipopolysaccharide, an important immunomodulator, was the result of microbial disorders in the endometrium. The composition of endometrial microorganisms in CE and non-CE patients were significantly different. and mainly regulated immune cells by interfering with the process of carbohydrate metabolism and/or fat metabolism in the endometrium. CE endometrial microorganisms might regulate Th17 response and the ratio of Th1 to Th17 through lipopolysaccharide (LPS).

The endometrium holds a crucial role in reproduction by supporting blastocyst adhesion, cytotrophoblast invasion and fetal development. Among the various uterine disorders, endometritis, particularly chronic endometritis (CE), has gained attention due to its association with adverse reproductive outcomes (recurrent pregnancy loss (RPL), recurrent implantation failure (RIF), and infertility). The association between CE and adverse reproductive outcomes stresses the necessity for comprehensive diagnostic and therapeutic strategies to optimize fertility outcomes and support individuals in their journey towards parenthood. To explore the relationship between CE and reproductive disorders. Following PRISMA guidelines, a systematic review and meta-analysis using published data from 1990 to 2024 were carried out. A population of 1,038 women was included. Regarding CE-infertility association, a positive correlation was found, with 19.46% CE rate in infertile women compared to 7.7% in controls (OR: 2.96, 95% CI 1.53-5.72, p 0.001). No significant association was observed between RIF and CE (OR: 1.10, 95% CI 0.26-4.61, p 0.90), CE rates in both groups were relatively comparable, with 6.35% in women with RIF and 5.8% in controls. On the opposite, a strong association between CE and RPL was found, reporting a CE rate of 37.6% in RPL cases compared to 16.4% in controls (OR: 3.59, 95% CI 2.46-5.24, p < 0.00001). CE appears to be associated to infertility and RPL, while no significant association was noted in cases of RIF. https://www.crd.york.ac.uk/prospero/#recordDetails PROSPERO, identifier CRD42024541879.

The vaginal and uterine microbiota play important roles in the health of the female reproductive system. However, the interactions among the microbes in these two niches and their effects on uterine health remain unclear. Here we profile the vaginal and uterine microbial samples of 145 women, and combine with deep mining of public data and animal experiments to characterize the microbial translocation in the female reproductive tract and its role in modulating uterine health. Synchronous variation and increasing convergence of the uterine and vaginal microbiome with advancing age are shown. We also find that transplanting certain strains of vaginal bacteria into the vagina of rats induces or reduces endometritis-like symptoms, and verify the damaging or protective effects of certain vaginal bacteria on endometrium. This study clarifies the interdependent relationship of vaginal bacterial translocation with uterine microecology and endometrial health, which will undoubtedly increase our understanding of female reproductive health. Here, the authors present a comparative analyses on vaginal and uterine microbiota in 1223 samples derived from 655 women with chronic endometritis, which, combined with animal experiments, characterize the microbial translocation in the female reproductive tract and its role in modulating uterine health.