Search Results (257)

Background: Recurrent implantation failure (RIF) remains one of the most challenging conditions in reproductive medicine. Although increasing evidence implicates chronic endometritis (CE) and alterations of the endometrial microbiota in impaired implantation, the potential contribution of gastrointestinal dysfunction and intestinal dysbiosis remains poorly characterized. We hypothesized that, in a subgroup of women with pure RIF, reproductive failure may be associated with a broader mucosal phenotype involving both intestinal and endometrial compartments. Objective: To characterize the coexistence of gastrointestinal disorders, intestinal dysbiosis, CE, and endometrial microbial alterations in women diagnosed with pure RIF, and to descriptively report reproductive outcomes observed during subsequent multidisciplinary clinical management. Methods: This retrospective, single-centre, observational, hypothesis-generating study included women who met the strict ESHRE criteria for pure RIF, and were assessed at the “Federico II” IVF Centre, Naples, Italy. Patients underwent multidisciplinary assessment combining reproductive medicine, outpatient hysteroscopy, gastroenterological evaluation according to Rome IV criteria, conventional microbiological investigation and paired intestinal and endometrial microbiome characterization by 16S rRNA sequencing. Following clinical assessment, individualized gastroenterological management was undertaken according to routine practice. Reproductive outcomes were descriptively recorded during follow-up. Results: 19 women were analysed, all of whom met the Rome IV guidelines, and showed hysteroscopic and histologic signs of CE. Gut dysbiosis was identified in 94.7% (18/19) of patients, whereas endometrial microbial alterations were observed in 78.9% (15/19). In 84.2% (16/19) of the cohort, microbial profiles characterized by an abundance of Enterobacteriaceae in the intestinal and/or endometrial compartments were detected. Conventional microbiological positivity was present in less than half of patients, highlighting the distinction between microbiological infection and ecological microbial imbalance. During the follow-up period following completion of the personalized multidisciplinary treatment program, which included the administration of a well-characterized probiotic strain, Escherichia coli Nissle 1917, 11 women (57.9%) achieved a clinical pregnancy. Dysbiosis of the intestine was reported in 94.7% (18 out of 19) of participants, whereas endometrial microbiota disturbances were present in 78.9% (15 out of 19) of subjects. The Enterobacteriaceae-enriched microbiota profiles affecting the intestine and/or endometrium were seen in 84.2% (16 out of 19) of subjects. Out of 19 patients, 11 (57.9%) conceived during the follow-up period after gut-targeted treatment comprising Escherichia coli Nissle 1917. Conclusions: Women who meet strict criteria for pure RIF may represent a clinically identifiable subgroup characterized by the coexistence of gastrointestinal disorders, intestinal dysbiosis, CE, and endometrial microbial alterations. Rather than demonstrating therapeutic efficacy, the present study provides a translational and hypothesis-generating framework supporting the need for prospective validation of this integrated biological phenotype in women with pure RIF before evaluating personalized multidisciplinary management. Prospective controlled studies are warranted to evaluate whether gut-directed interventions may influence reproductive outcomes in this population. Full article

Our first objective was to quantify the associations between health-related events (HRE) before insemination, the relative increase in estrus intensity (REI) at insemination, and the probability of cow-level pregnancy per artificial insemination (P/AI) in organic Holstein dairy cows. Quantifying these associations may aid on-farm decision-making, such as setting the voluntary waiting period, choice of type of semen, do-not-breed and culling decisions. A second objective was to develop predictive models to estimate P/AI based on readily available data, and present common goodness-of-fit results also used in the machine learning community. All data were collected from a certified organic dairy farm in the western USA from 2019 to 2021. Health-related and reproduction data were obtained through Dairy Records Management Systems (DRMS; Raleigh, NC, USA). Activity data were collected using pedometers (IceRobotics, Stirling, UK) mounted on the rear legs. The REI, defined as walking steps per hour before insemination divided by the cow’s baseline steps per hour, was available for 17,238 inseminations from 4759 cows. The REI was categorized as ≤200%, >200–400%, >400–600%, or >600%. The HRE were available for 65,684 inseminations from 13,365 cows. The HRE were categorized as mastitis, metabolic disease (i.e., hypocalcemia, ketosis, displaced abomasum, digestive problems), reproductive disease (i.e, metritis, endometritis, pyometra, retained fetal membranes), lameness, 2 different diseases, ≥3 different diseases, or as healthy (none of these diseases prior to insemination). Combinations (COMBO) between REI categories and 0, 1, or ≥2 HRE were also created. Data were split into training and test sets. The training data were used to fit three logistic regression models that included either HRE, or REI, or COMBO. Each of the three models also included the covariates of 3-mo herd-average P/AI prior to insemination, days in milk, and the fixed effects of parity, insemination season, days after the previous insemination or days to 1st insemination. A random effect accounted for repeated inseminations within cow. Parameter estimates, odds ratios, and the estimated marginal means of the estimated P/AI of the fixed effects were obtained from the logistic regression models. The models’ estimates were applied to the test datasets, and discrimination and calibration statistics were calculated to judge goodness-of-fit. Unadjusted mean P/AI were 0.31, 0.28 and 0.28 for the HRE, REI and COMBO training datasets. For the HRE model, estimated P/AI ranged from 0.20 (≥3 different HRE) to 0.30 (healthy). The estimated P/AI associated with four REI categories were not different from 0.27 in the REI model. The estimated P/AI associated with the combinations of HRE and REI in the COMBO model varied from 0.18 after ≥2 HRE and >200–400% REI, to 0.30 when inseminations were in healthy cows with REI >600%. Inseminations in older cows, in the spring, and outside 18–24 d after the previous insemination were also associated with lower estimated P/AI. The area underneath the Receiver Operating Characteristic curve ranged from 0.57 (COMBO) to 0.60 (HRE) for the test data, indicating fair discrimination ability of the models. Calibration plots showed that the prediction models produced unbiased predicted P/AI. In conclusion, the results showed no conclusive evidence of greater estimated P/AI related to greater REI as a measure of estrus activity. More HRE were associated with lower estimated P/AI. Combinations of low REI and more HRE were associated with notably decreased estimated P/AI. The logistic regression models produced unbiased predicted P/AI. We found no evidence that the strength of the relationship between REI and P/AI depended on the HRE category. The applications of the results are as follows. First, these predictive models may help inform insemination decisions in organic dairy cows, although further external validation is recommended, and the discriminatory performance is weak. Second, a variety of goodness-of-fit statistics were calculated to allow comparisons of the current logistic regression analyses with future analyses made by other machine learning techniques. Full article

Postpartum uterine diseases are among the most prevalent and economically important reproductive disorders affecting dairy cattle worldwide. These conditions, including metritis, clinical and subclinical endometritis, and pyometra, develop during the postpartum transition period when physiological, metabolic, endocrine, and immunological adaptations increase susceptibility to microbial invasion and persistent uterine inflammation. Although bacterial contamination of the postpartum uterus is nearly universal, healthy cows generally restore uterine homeostasis through coordinated immune responses, microbial regulation, and effective uterine involution. Failure of these defense mechanisms results in microbial dysbiosis, impaired endometrial repair, reduced fertility, and substantial economic loss. Major pathogens associated with postpartum uterine disease include Escherichia coli, Trueperella pyogenes, Fusobacterium necrophorum, Prevotella spp., and other anaerobic bacteria that interact synergistically to promote inflammation, tissue damage, and reproductive dysfunction. Advances in next-generation sequencing, metagenomics, and metatranscriptomics have transformed understanding of the postpartum uterine microbiota and host–microbe interactions involved in disease pathogenesis. This review synthesizes current evidence regarding uterine physiology, microbial ecology, immune regulation, virulence mechanisms, dysbiosis, diagnostic approaches, and emerging omics-based technologies relevant to postpartum uterine disease in dairy cattle. Particular emphasis is placed on the ecological and physiological interactions linking microbial succession, endocrine recovery, metabolic stress, and immune competence during the postpartum period. The review further discusses translational opportunities for precision diagnostics, microbiome-informed interventions, antimicrobial stewardship, and integrated herd management strategies to improve reproductive efficiency, animal welfare, and dairy herd sustainability. Full article

The purpose of this review is to highlight the complex influence of antibiotics on human fertility and the need for them not to be underestimated. In creating this review article, data and information from the following international databases were used: PubMed, Scopus and Clarivate Analytics. Only full text articles were used. Antibacterial antibiotics are a group of drugs essential in fighting infections, having multiple mechanisms of action at the level of the bacterial cell; but at the same time they also act on human cells. One of the important actions of antibiotics is on fertility. There are both experimental and clinical data showing the influence of some antibiotics on fertility. There are both positive and negative influences of these drugs on fertility. Some of the most important actions with a positive impact on fertility are: therapy of pelvic infections in women, treatment of endometritis, reduction in post-abortion infections, treatment of infections of the male genital tract—infections that reduce fertility. The most important negative implications of some antibiotics are the direct effects of reducing the production of gametes, decreasing the activity or quality of the gametes, reducing the synthesis of sexual hormones and negative influences on the evolution of pregnancy, including spontaneous abortion in some cases. Other negative influences are produced by the direct action of some antibiotics on the embryo. Some antibiotics such as azithromycin and nitrofurantoin increase the risk of miscarriage. Although only a limited number of antibiotics are known to have an influence on fertility, this influence should not be underestimated in clinical practice. Full article

(1) Background: Chronic endometritis (CE) is a chronic disease of the endometrium characterized by inflammatory infiltration into the endometrial stroma. The diagnosis of CE is complex. Clinical examination and transvaginal ultrasound are not specific for CE. Biopsy is an indispensable tool. Two specific populations can be analyzed at the endometrial level: CD138 positive plasma cells and CD56 positive Natural Killer cells. (2) Methods: Our narrative review was based on an online search with a focus on the last ten years of literature in the English language. (3) Results: Twenty studies on CD138 positive plasma cells and 16 articles on CD56 positive Natural Killer cells highlighted the correlations of CE with diagnostic possibilities and reproductive outcomes. (4) Conclusions: The etiological pathway and management of CE require further scientific studies and investigations. Hysteroscopy is the diagnostic gold standard, but other blind biopsy techniques (i.e., Perma, Pipelle, Novak, etc.) and molecular procedures may help in the diagnosis of chronic endometritis. Full article

Endometritis—inflammation of the endometrial lining—imposes a substantial reproductive and economic burden in both human gynecology and livestock production, where it is a leading cause of recurrent implantation failure in humans and the costliest reproductive disorder in cattle. Conventional management is overwhelmingly antibiotic-based, yet escalating antimicrobial resistance, tissue and milk residues, microbiota disruption and high relapse rates have eroded its efficacy and acceptability, creating an urgent need for mechanism-based, host-directed alternatives. Here we synthesize the expanding evidence positioning dietary flavonoids and traditional Chinese medicine (TCM) formulations as such interventions. Across diverse compounds and preparations, anti-endometriotic activity converges on a tractable set of molecular nodes: TLR4/NF-κB signaling, the NLRP3 inflammasome–pyroptosis axis, the Keap1/Nrf2/HO-1 antioxidant program, PI3K/AKT and PPAR-γ signaling, ferroptosis, and the gut–uterus microbial–metabolite axis. Veterinary field studies report cure rates and fertility outcomes rivaling first-line antibiotics, while integrative case reports show benefit in antibiotic-refractory human chronic endometritis. Translation remains constrained by poor bioavailability, formulation heterogeneity, over-reliance on lipopolysaccharide-only models and a scarcity of randomized trials—barriers now addressable through nanocarrier delivery, network-pharmacology-guided standardization and biomarker-stratified designs. Flavonoids and TCM are best viewed not as substitutes for antibiotics but as a mechanistically rational, multi-target strategy aligned with One Health antimicrobial stewardship. Full article

Uterine infections (metritis and endometritis) are a leading cause of culling and reproductive failure in transition dairy cows, and antibiotic-resistant Gram-negative pathogens limit conventional therapy. This randomized, controlled, multi-farm field trial evaluated whether four intravaginal infusions of a host-adapted lactic acid bacteria (LAB) cocktail (Lactobacillus sakei FUA3089, Pediococcus acidilactici FUA3138, P. acidilactici FUA3140; 10⁸–10⁹ cfu/dose) at −3, −2, +3, and +4 weeks relative to calving reduce periparturient disease and improve milk production. A total of 526 pregnant cows (426 Holstein, 100 Jersey) from four commercial Alberta farms (automatic-milking, parlor, and certified-organic systems) were block-randomized within farm and parity to TRT1 (saline; n = 175), TRT2 (saline + skim milk; n = 176), or TRT3 (LAB cocktail in saline + skim milk; n = 175). Uterine infection incidence was assessed by Metricheck™ mucus scoring and transrectal ultrasonography at +3 and +4 weeks postpartum. Across the principal peripartum infectious outcomes, TRT3 showed a consistent protective effect: uterine infection incidence was lowest in TRT3 (18.8% vs. 25.1% in pooled controls; OR = 0.69; 95% CI, 0.44–1.09; an approximately 25% relative reduction; exact p = 0.12), and this metritis signal was additionally supported by a repeated-measures mixed model accounting for farm, parity, and week (p = 0.0175), although the Bonferroni-adjusted pairwise contrasts were tendencies (adjusted p ≈ 0.12), and the effect did not differ by parity (treatment × lactation interaction, p = 0.97). Subclinical mastitis was numerically lower in TRT3 than in pooled controls (5.3% vs. 8.9%; OR = 0.57; 95% CI, 0.27–1.24; exact p = 0.16), whereas retained placenta, milk fever, displaced abomasum, and lameness showed no clear cow-level treatment effect in the cow-level exact analyses. Milk yield increased significantly in multiparous cows, which produced 4.6 L/day more milk than TRT1 and 3.22 L/day more than TRT2 over the first 50 days in milk (p < 0.01 for both contrasts; treatment × parity interaction, p = 0.01). No effect was seen on milk composition, uterine involution, or reproductive performance. The trial supports intravaginal LAB as a candidate antibiotic-free prophylactic whose response depends on farm- and cow-level contexts and whose mechanisms require confirmation through microbiological and metabolic measurements. Full article

Bovine endometritis remains one of the most significant postpartum uterine disorders. It impairs uterine recovery, compromises fertility, and causes substantial economic losses in dairy production. Growing evidence suggests that the disease cannot be attributed solely to postpartum bacterial contamination; rather, it should be understood as a multifactorial failure to restore uterine homeostasis after calving. This review summarises the latest research findings on six interconnected aspects: the clinical significance of postpartum uterine disease; the diagnostic and biological differences between clinical and subclinical endometritis; the role of microbes in the uterus in health and disease; interactions between the host and uterine bacteria; the mechanisms of persistent inflammatory regulation; and current as well as emerging treatment strategies. Current evidence indicates that postpartum uterine disease is more strongly associated with dysbiosis, reduced microbial diversity, and disturbed microbial succession than with the presence of any single pathogen. Disease progression is driven by complex interplay among microbial ligands, epithelial and stromal immune responses, virulence-associated tissue injury, endocrine disruption, and impaired inflammatory resolution. Furthermore, persistent uterine inflammation is regulated by multilayered networks involving cytokines, prostaglandins, noncoding RNAs, extracellular vesicles, metabolic remodeling, and oxidative stress. Although conventional therapies remain relevant in certain clinical cases, microbiota-oriented approaches, particularly probiotic interventions, have emerged as promising adjunctive strategies for the prevention and control of the condition. Overall, bovine endometritis should be viewed as a disorder caused by disrupted interactions between the host, microbiota and inflammation. Future progress will depend on longitudinal, strain-resolved, and function-oriented studies to enable more precise and less antimicrobial-dependent interventions for postpartum uterine health. Full article

Dairy cows are frequently affected by postpartum uterine infections, such as metritis and endometritis, which negatively impact fertility and cause significant economic losses. The extensive use of antibiotics may alter the reproductive microbiota and contribute to the emergence of antibiotic resistance. This study aimed to isolate lactic acid bacteria (LAB) from healthy vaginal samples of cows and evaluate their antimicrobial activity against uterine pathogens such as Escherichia coli and Salmonella spp. Phenotypic characterization and antibiotic susceptibility testing were performed, along with antagonistic assays using both overlay and well diffusion methods. The results demonstrated strain-dependent inhibitory activity against E. coli, with inhibition zones ranging from 2 to 4 mm depending on the LAB strain and the method used, whereas no inhibitory activity was observed against Salmonella. These findings support the potential application of selected LAB strains in bovine reproductive health management. However, further in vitro and in vivo studies are required to confirm their efficacy, safety, and stability under physiological conditions. Full article

Syringa oblata Lindl. (SOL) has long been used in traditional medicine for inflammatory disorders, yet its molecular actions in reproductive tract inflammation remain poorly defined. This study investigated the phytochemical composition and anti-inflammatory mechanisms of an aqueous SOL leaf extract using murine and cellular models of endometritis. Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) analysis revealed major constituents including rutin, salidroside, and esculetin. In a murine model of bacterial endometritis induced by Escherichia coli and Staphylococcus aureus, SOL markedly attenuated uterine edema, epithelial disruption, leukocyte infiltration, and bacterial burden. Mechanistic analyses demonstrated that SOL suppressed the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) axis and decreased the uterine expression of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). In lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, SOL and its principal monomers significantly reduced nitric oxide (NO) and reactive oxygen species (ROS) production both in the presence and absence of the TLR4 inhibitor TAK-242, suggesting additional modulation of redox-responsive pathways beyond canonical TLR4 signaling. Moreover, SOL selectively decreased the M1 macrophage marker CD86 in uterine tissue without altering CD163, consistent with partial inhibition of pro-inflammatory macrophage polarization. Collectively, these findings indicate that SOL exerts potent antimicrobial, anti-inflammatory, and antioxidative effects through coordinated regulation of innate immune signaling and macrophage activation, supporting its potential as a natural therapeutic candidate for inflammation-associated reproductive disorders. Full article

Endometriosis (EM) and chronic endometritis (CE) are both implicated in female infertility, yet the relationship between them remains incompletely understood. In this narrative review, we synthesize non-systematically selected clinical and mechanistic evidence on EM–CE coexistence, with emphasis on infertility-related settings and diagnostic uncertainty. Available studies, largely from selected infertility cohorts, suggest that CE is identified more often in women with EM, raising the possibility that their coexistence reflects a biologically meaningful association rather than incidental overlap. The two conditions share several abnormalities that may impair reproduction, including persistent inflammation, immune dysregulation, altered cytokine and chemokine signaling, impaired macrophage and natural killer cell function, progesterone resistance, and reduced endometrial receptivity. In addition to the pelvic anatomical distortion and ovarian dysfunction associated with EM, CE may further compromise implantation by impairing decidualization, displacing the window of implantation, and disrupting the local endometrial microenvironment. Both conditions also remain diagnostically challenging. EM is most reliably confirmed by laparoscopy with histologic verification, whereas CE is generally diagnosed by hysteroscopy and endometrial biopsy demonstrating plasma cells. For CE in particular, the lack of standardized diagnostic criteria and uniform CD138 thresholds continues to limit diagnostic consistency. Emerging imaging techniques, molecular biomarkers, microbiota-based approaches, and artificial intelligence-assisted models remain investigational or adjunctive rather than established tools for routine integrated assessment. Taken together, the current evidence is hypothesis-generating and supports selective, phenotype-driven consideration of coexisting EM and CE in infertility care rather than routine dual invasive evaluation. Further studies are required to clarify the mechanisms linking these conditions, define their combined reproductive impact, and determine whether integrated diagnostic and therapeutic strategies can improve fertility outcomes. Full article

Quercetin is a naturally occurring flavonoid found in fruits, vegetables, and teas that is widely available as a dietary supplement. Numerous studies have investigated quercetin’s therapeutic potential across a broad range of diseases and conditions. Collectively, these studies reveal its anti-inflammatory, antioxidant, anti-proliferative, anti-cancer, anti-fibrotic, antibacterial, endocrine-modulating, and senolytic properties, establishing quercetin as a polypharmacologic agent with diverse biological activities. This review describes quercetin’s biochemical properties, bioavailability, and proposed mechanisms of action. It highlights the unique characteristics of the human uterus vs. other species and evaluates published evidence from pre-clinical and clinical studies supporting quercetin’s pleiotropic effects and potential therapeutic benefits for six uterine-related conditions: endometrial cancer, endometriosis, adenomyosis, uterine infections, uterine fibroids, and polycystic ovary syndrome (PCOS). The findings support that quercetin targets multiple endometrial and other uterine cell types and may attenuate key pathological processes relevant to uterine disease. However, robust human clinical evidence supporting quercetin’s efficacy is generally lacking. Critical knowledge gaps and translational barriers to advancing quercetin from a ‘promising preclinical candidate’ into an ‘evidence-based therapeutic’ for improving uterine health are discussed. Full article

The equine reproductive microbiota has emerged as an important factor influencing reproductive health and fertility in both mares and stallions. Traditionally, the equine uterus was considered sterile, and microbial presence was interpreted primarily in the context of infection. However, sequencing-based studies have demonstrated that the reproductive tract, including the uterus and semen, contains detectable microbial communities or microbial DNA signatures, challenging this traditional paradigm. In mares, the vaginal microbiota is consistently dominated by Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria, whereas the uterine environment represents a low-biomass niche in which interpretation is complicated by contamination risk and the inability of sequencing-based methods to distinguish viable from nonviable microorganisms. Culture-based studies consistently identify opportunistic pathogens such as Streptococcus equi subsp. zooepidemicus, Escherichia coli, and Pseudomonas aeruginosa in association with endometritis and persistent breeding-induced endometritis, while sequencing-based studies suggest broader community-level dysbiosis rather than simple pathogen presence. In stallions, semen is not sterile and commonly contains taxa such as Porphyromonas, Corynebacterium, Peptoniphilus, and other opportunistic bacteria that may influence sperm quality and microbial transmission to mares during breeding. However, most reported associations remain correlative, and direct longitudinal evidence for persistent stallion-to-mare microbial transmission is limited. This review synthesizes current evidence on microbial composition, hormonal influences, dysbiosis, and reproductive implications of the equine reproductive microbiota, integrating culture-based and sequencing-based findings while emphasizing methodological limitations associated with low-biomass samples. Improved understanding of these microbial ecosystems may support more evidence-based reproductive diagnostics and microbiome-informed fertility management in horses. Full article

Background/Objectives: Chronic endometritis (CE) is an underrecognized inflammatory disorder associated with infertility, recurrent pregnancy loss, and implantation failure. CD138 immunohistochemistry is widely used to detect endometrial plasma cells; however, background epithelial staining and interobserver variability may limit diagnostic precision. MUM1 (IRF4), a nuclear transcription factor expressed in plasma cells, has emerged as a potential complementary marker. We aimed to systematically evaluate the diagnostic performance of MUM1 immunohistochemistry relative to CD138-based histopathologic reference frameworks for chronic endometritis using a Bayesian meta-analytic framework. Methods: We conducted a systematic review and diagnostic test accuracy meta-analysis in accordance with PRISMA 2020 and PRISMA-DTA guidelines. MEDLINE, Embase, Scopus, and CENTRAL were searched from inception to 28 February 2026. Studies assessing MUM1 immunohistochemistry against predefined histopathologic reference frameworks for CE were eligible. Risk of bias was evaluated using QUADAS-2. A bivariate Bayesian random-effects model was applied to jointly estimate pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR). Results: Six studies (n = 1574 women) were included in the qualitative synthesis, and four provided sufficient 2 × 2 data for quantitative pooling. The pooled sensitivity of MUM1 was 0.876 (95% credible interval (CrI): 0.536–0.976), and the pooled specificity was 0.853 (95% CrI: 0.653–0.930). The pooled positive likelihood ratio was 5.83 (95% CrI: 2.18–12.04), and the negative likelihood ratio was 0.15 (95% CrI: 0.03–0.56), corresponding to a DOR of 40.27 (95% CrI: 5.04–254.59). Credible intervals were wide, reflecting statistical uncertainty related to the limited number of studies and heterogeneity in diagnostic thresholds. Conclusions: MUM1 (IRF4) immunohistochemistry demonstrates potentially favorable comparative diagnostic performance relative to CD138-based reference frameworks, although substantial uncertainty remains due to limited and heterogeneous evidence. As an adjunctive nuclear marker, MUM1 may support histopathologic assessment of chronic endometritis; however, prospective head-to-head studies using harmonized diagnostic criteria and predefined plasma cell thresholds are required before routine implementation can be firmly recommended. Full article

Background: Chronic endometritis (CE) is a subtle, often asymptomatic endometrial inflammation marked by CD138⁺ plasma cell infiltration and linked to recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), and unexplained infertility. Emerging evidence implicates endometrial microbiome dysbiosis in CE. Objective: To systematically review and conduct meta-analysis on the association between CE and endometrial microbiome alterations and their reproductive implications. Methods: We searched MEDLINE, Embase, Web of Science, Scopus, Cochrane CENTRAL, and Google Scholar for studies diagnosing CE via CD138 immunostaining, assessing microbiota with molecular techniques. Data extraction, quality assessment, and meta-analysis were performed. Results: Twenty-two studies including 4022 women were analyzed. CE was associated with reduced prevalence of Lactobacillus-dominated microbiota and increased detection of non-Lactobacillus species, particularly Streptococcus spp., Enterococcus spp., Escherichia coli, Staphylococcus spp., Ureaplasma spp., and Gardnerella vaginalis. In the meta-analysis (2947 women), Enterococcus spp. and Ureaplasma spp. were significantly more prevalent in women with CE, whereas Streptococcus spp., E. coli, Staphylococcus spp. and G. vaginalis showed non-significant trends. Only E. coli and Streptococcus spp. showed significant heterogeneity between-studies. Conclusions: CE is linked to microbial dysbiosis with reduced Lactobacillus dominance and enrichment of potentially pathogenic taxa, notably Enterococcus and Ureaplasma spp. These findings suggest that the endometrial microbiome contributes to chronic inflammation and adverse reproductive outcomes, yet heterogeneity and limited evidence call for standardized diagnostics and robust trials before clinical implementation. Full article