Puerarin inhibits Staphylococcus aureus-induced endometritis through attenuating inflammation and ferroptosis via regulating the P2X7/NLRP3 signalling pathway.

Endometritis is one of the important causes of infertility. Puerarin (PU) can inhibit oxidative stress and reduce inflammation; however, it is unclear whether PU has a protective effect on the endometritis. In our study, we used Staphylococcus aureus to induce mouse endometritis. The PU group (100 mg/kg PU) and the S. aureus + PU group received daily intraperitoneal injection of PU (25, 50 or 100 mg/kg PU). The results showed that S. aureus significantly increased the levels of MPO, TNF-α, IL-1ß and IL-6 in uterine tissue, and increased the expression of p-p65 and p-IκBα proteins in uterine tissue to induce endometritis in mice (p < 0.05). Furthermore, it has been found that S. aureus promotes the occurrence of ferroptosis by reducing GSH and ATP content, increasing MDA and iron content and reducing GPX4 and SLC7A11 protein expression levels (p < 0.05). S. aureus significantly increase the expression of NLRP3, ASC, caspase-1 and P2X7 proteins in uterine tissue (p < 0.05). However, PU obviously reduced the inflammatory response and reversed the changes of ferroptosis and the expression of P2X7 receptor/NLRP3 pathway associated proteins of the uterus induced by S. aureus (p < 0.05). Taken together, these findings emphasize the protective effect of PU on endometritis by regulating the P2X7 receptor/NLRP3 signalling pathway and inhibiting ferroptosis.

Cefoxitin for Intra-amniotic Infections and Endometritis: A Retrospective Comparison to Traditional Antimicrobial Therapy Regimens Within a Healthcare System.

BACKGROUND: Local institutional guidelines and order sets were updated in June 2023 to recommend first-line cefoxitin monotherapy for the treatment of intra-amniotic infections (IAIs) and endometritis. This study evaluated the clinical impact of this change. METHODS: This was a retrospective, observational cohort study in an 11-campus health system comparing clinical outcomes of patients with chorioamnionitis, endometritis, or septic abortion receiving intravenous antimicrobial therapy before and after implementation of first-line cefoxitin monotherapy recommendations for the treatment of these infections. Primary outcome was a composite of serious clinical events postdelivery (ie, intensive care unit admission, death, hospital readmission related to IAI or endometritis within 30 days, additional surgery or procedures, or deep surgical site infection). Baseline characteristics between the pre- and post-cefoxitin groups were compared via Student's t tests for continuous variables and chi-square tests for categorical variables. Outcomes were evaluated via generalized linear modeling. RESULTS: A total of 472 patients were enrolled, 350 (74%) in the pre-cefoxitin group and 122 (26%) in the post-cefoxitin group. Groups were significantly different by race, healthcare payor, and hospital campus. Cefoxitin was rarely used in the pre-cefoxitin group (n = 2, <0.1%) and commonly used in the post-cefoxitin group (n = 112, 91.8%). After controlling for group differences, odds of experiencing serious clinical event postdelivery in the post-cefoxitin group were noninferior to those in the pre-cefoxitin group (adjusted odds ratio, .37; 95% CI, .17-.76; P = .010). CONCLUSIONS: Local institutional guidelines with predominant use of cefoxitin therapy were noninferior to traditional antimicrobial therapy regimens for the treatment of IAI.

Unveiling the protective effects of BMSCs/anti-miR-124-3p exosomes on LPS-induced endometrial injury.

Researchers have reported that miR-124-3p is highly expressed in patients with chronic endometritis. However, the underlying mechanism of miR-124-3p in the development of endometritis remains unclear. This study constructed an in vitro endometrial cell injury model by treating HEECs with 2 µg/mL LPS for 48 h. Then, 1 mg/kg LPS was injected into both sides of the mouse uterus to construct an in vivo endometrial injury model. The expression of miR-124-3p in human endometrial epithelial cells (HEECs) was assessed using RT‒qPCR. Exosomes were separated from bone marrow-derived mesenchymal stem cells (BMSCs) and cocultured with HEECs. A dual-luciferase reporter assay was performed to confirm the relationship between miR-124-3p and DUSP6. The results indicated that LPS inhibited HEEC viability in a time- and dose-dependent manner. The miR-124-3p inhibitor reversed the LPS-induced apoptosis and inhibition of HEEC viability. In addition, miR-124-3p could be transferred from BMSCs to HEECs by exosomes. Exosomes were derived from BMSCs treated with an NC inhibitor (BMSCs/NC Exo) or miR-124-3p inhibitor (BMSCs/anti-miR-124-3p Exo). In addition, BMSCs/anti-miR-124-3p Exo abolished the LPS-induced inhibition of HEEC viability and proliferation by inducing HEEC apoptosis. Moreover, BMSCs/anti-miR-124-3p Exo alleviated the LPS-induced inflammation of HEECs by upregulating DUSP6 and downregulating p-p65 and p-ERK. Furthermore, in an LPS-induced in vivo endometrial injury model, BMSCs/anti-miR-124-3p Exo increased the expression level of DUSP6 and decreased the expression levels of p-p65 and p-ERK. BMSCs/anti-miR-124-3p Exo protected against LPS-induced endometrial damage in vitro and in vivo by upregulating DUSP6 and downregulating p-p65 and p-ERK1/2. This study showed that BMSCs/anti-miR-124-3p Exo might be a potential alternative for the treatment of endometritis.

Metritis and the uterine disease microbiome are associated with long-term changes in the endometrium of dairy cows†.

Cows with metritis (uterine disease) during the first 1 to 2 weeks postpartum have lower pregnancy rates when inseminated later postpartum (typically >10 weeks). We hypothesized that metritis and the disease-associated uterine microbiome have a long-term effect on endometrial gene expression. Changes in gene expression may inform a mechanism through which disease lowers pregnancy rates. A total of 20 cows were enrolled at 1 to 2 weeks postpartum to either metritis (clinical disease; n = 10) or healthy (control; n = 10) groups and randomly assigned to be slaughtered at approximately 80 and 165 dpp (mid-lactation). The microbiome of the reproductive tract was sampled to confirm the presence of pathogens that are typical of metritis. In addition to the original clinical diagnosis, study cows were retrospectively assigned to uterine-disease and control groups based on the composition of their microbiome. There was no effect of early postpartum uterine disease on the uterine microbiome at mid-lactation (time of slaughter). Nonetheless, early postpartum metritis and the disease microbiome were associated with a large number of differentially-expressed genes at mid-lactation primarily in the caruncular compared with the inter-caruncular endometrium. Gene enrichment analysis identified oxidative phosphorylation as the primary pathway increased in caruncular endometrium of diseased cows whereas growth factor signaling pathways were reduced. The current study demonstrated that metritis and a uterine disease microbiome leave a sustained imprint on gene expression in the caruncular endometrium that may explain lower fertility in cows with postpartum uterine disease.

Incidence of uterine infections, major bacteria and antimicrobial resistance in postpartum dairy cows in southern Ethiopia.

BACKGROUND: Uterine infections, primarily caused by bacterial pathogens, pose a significant problem for dairy farmers worldwide, leading to poor reproductive performance and economic losses. However, the bacteria responsible for uterine infections have not been adequately studied, nor has the antibiotic susceptibility of the causative bacteria been frequently tested in Ethiopia. This study aims to estimate the cumulative incidence of uterine infections in postpartum dairy cows, identify bacterial causes and determine antimicrobial susceptibility profile of the isolated bacteria. METHODS: A prospective cohort study was conducted in which 236 cows from 74 dairy farms were monitored biweekly from calving to 90 days postpartum for metritis, endometritis and other disorders. Aseptic uterine swab samples were collected from 40 cows with uterine infections. The samples were cultured, and the isolated bacteria were tested for antimicrobial susceptibility using the disk diffusion method. RESULTS: Out of 236 cows monitored during the postpartum phase, 45 (19.1%) were found to have contracted uterine infection. The cumulative incidence of metritis was 11.4% (n = 27), while the cumulative incidence of endometritis was 7.6% (n = 18). Of the 40 cultured swab samples, 29 (72.5%) had one or more bacteria isolated. The most commonly isolated bacteria were Escherichia coli (45%), coagulase-positive staphylococci (30%), and Klebsiella spp. (22.5%). Other bacterial spp, including Arcanobacterium pyogenes (12.5%), Fusobacterium spp. (12.5%), Enterobacter aerogenes (12.5%), coagulase-negative staphylococci (12.5%), Streptococcus spp. (7.5%), Salmonella spp, (5%) Proteus spp (5%) and Pasteurella spp (2.5%) were also isolated. All of the isolated bacteria demonstrated resistance to at least one of the antimicrobials tested. Multidrug resistance was observed in E. coli, Klebsiella spp., A. pyogenes, and Fusobacterium spp. Gentamicin was found to be the most effective antimicrobial against all bacteria tested, while tetracycline was the least effective of all. CONCLUSION: The study found that a significant proportion of cows in the population were affected by uterine infections and the isolated bacteria developed resistance to several antimicrobials. The study emphasizes the need for responsible use of antimicrobials to prevent the emergence of antimicrobial resistance. It also highlights the importance of raising awareness among dairy farmers to avoid the indiscriminate use of antibiotics and its consequences.

Prostaglandin E2 accumulation is closely associated with S. aureus-infected bovine endometritis.

S. aureus isolated from bacterial bovine endometritis is common in epidemiological reports, but is often ignored as a subclinical pathogenic microorganism. In a previous study, we showed that live S. aureus (LSA) and heat killed S. aureus (HK-SA) induce different inflammatory responses in bovine endometrial tissue, and possibly being associated with the accumulation of prostaglandin E2 (PGE2). Thus, in this study, we varied PGE2 concentrations using inhibitors or agonists in HK-SA-treated bovine endometrial tissues. The results demonstrated that PGE2 has a positive relationship with IL-6, TNF-α, and damage-associated molecular patterns (DAMPs; e.g., HMGB-1 and HABP-1) expression and tissues damage, and is regulated by the EP4-p38 MAPK pathway. We concluded that lipoproteins of S. aureus are associated with PGE2 generation. To further explore the relationship between LSA and PGE2 accumulation, we used the S. aureus strain SA113 lipoprotein knockout (SA113Δlpl) to infect bovine endometrial epithelial cells (BECs). LSA decreased PGE2, cAMP, EP4, IL-6, IL-8, cAMP secretion, and the MAPK and PKA signaling pathways when infected with SA113Δlpl, as compared with SA113-infected groups. Moreover, the adhesion and invasion of BECs were similarly downregulated when lipoproteins in S. aureus were knocked out. The results of this study show that PGE2 is involved in both HK-SA- and LSA-induced inflammatory responses in the bovine endometrium. We suggest that S. aureus infection is associated with bovine endometritis, and although HK-SA and LSA induce different inflammatory responses, the strategy of decreasing PGE2 accumulation is helpful in reducing the inflammation stage caused by S. aureus.

Targeting inflammation for the treatment of endometritis in bovines.

The uterine endometrial surface of bovines is in constant exposureconstantly exposed with to a multitude ofmany microbial populations that changes throughout the post-partum phase in terms of complexity and dynamics. These microbes contribute to the host pathology, leading to severe economic losses along withnd reproductive capabilities. The basic primary interface that occurs between the internal tissues of the body of the hostbetween the host body's internal tissues and the microbes is the endometrial surface of the uterus. As a result of the infinite pathogenic population, there is always a danger for the opportunistic organisms to attack. Therefore, it is paramount that any interactions, especially microbial microbes with the endometrial surface, are regulated by the host cells. However, the inflammatory response as the defense mechanism contributes a pivotal roleis pivotal in host immunity and pathology. The inflammatory cascade and pathways are important essential to eliminate this clinical problem. In this review, we will discuss and explain how the inflammation and the various components of the immune system play their role in host pathology and therapeutic strategies, taking into account the interface between the host and the microbes on the surface of the endometrium. This review is also instrumental in further explanation of inflammatory uterine disease by discussing the response of inflammation to external insult.

Up-regulation of inflammatory, oxidative stress, and apoptotic mediators via inflammatory, oxidative stress, and apoptosis-associated pathways in bovine endometritis.

Endometritis is the inflammation of the endothelial lining of the uterine lumen and is multifactorial in etiology. Escherichia (E.) coli is a Gram-negative bacteria, generally considered as a primary causative agent for bovine endometritis. Bovine endometritis is characterized by the activation of Toll-like receptors (TLRs) by E. coli, which in turn triggers inflammation, oxidative stress, and apoptosis. The objective of this study was to investigate the gene expression of inflammatory, oxidative stress, and apoptotic markers related to endometritis in the uteri of cows. Twenty uterine tissues were collected from the abattoir. Histologically, congestion, edema, hyperemia, and hemorrhagic lesions with massive infiltration of neutrophil and cell necrosis were detected markedly (P < 0.05) in infected uterine samples. Additionally, we identify E. coli using the ybbW gene (177 base pairs; E. coli-specific gene) from infected uterine samples. Moreover, qPCR and western blot results indicated that TLR2, TLR4, proinflammatory mediators, and apoptosis-mediated genes upregulated except Bcl-2, which is antiapoptotic, and there were downregulations of oxidative stress-related genes in the infected uterine tissue. The results of our study suggested that different gene expression regimes related to the immune system reflex were activated in infected uteri. This research gives a novel understanding of active immunological response in bovine endometritis.

Antibiotic cured chronic endometritis remains a risk factor for early pregnancy loss in the subsequent frozen euploid embryo transfer.

RESEARCH QUESTION: Do patients with antibiotic-cured chronic endometritis (CCE) have a comparable pregnancy outcome to those with non-chronic endometritis (NCE) in the subsequent frozen embryo transfer (FET) cycle? DESIGN: A retrospective cohort analysis included 833 patients in their first FET cycles with single euploid embryo transfer. Chronic endometritis (≥5 CD138+ plasma cells per high-power field [CD138+/HPF]) was treated with standard antibiotic therapy. Patients were classified into two groups: the NCE group (n = 611, <5 CD138+/HPF) and the CCE group (n = 222, ≥5 CD138+/HPF and cured after antibiotic treatment). Pregnancy outcomes were compared. NCE group was divided into subgroup 1 (CD138+/HPF = 0) and subgroup 2 (CD138+/HPF = 1-4) for further analysis. RESULTS: The rate of early pregnancy loss (EPL), incorporating all losses before 10 weeks' gestation, was significantly higher in the CCE group than the NCE group (21.2% versus 14.2%, P = 0.016), and the difference was statistically significant (adjusted odds ratio [AOR] 1.68, 95% confidence interval [CI] 1.11-2.55). No significant differences were observed between the two groups with regard to other pregnancy outcomes. In the subgroup analysis, the EPL rate and biochemical pregnancy rate were significantly higher in subgroup 2 than subgroup 1 (17.2% versus 9.4%, AOR 2.21, 95% CI 1.30-3.74; 12.2% versus 6.9%, AOR 2.01, 95% CI 1.09-3.68). CONCLUSIONS: Chronic endometritis cured by standard antibiotic therapy remains a risk factor for EPL in FET cycles, although no differences were found in live birth rates between patients with CCE or with NCE.

Endometrial preparation protocols did not impact pregnancy outcomes of patients with cured chronic endometritis.

RESEARCH QUESTION: Do endometrial preparation protocols have an effect on pregnancy outcomes in patients with cured chronic endometritis? DESIGN: A retrospective study was conducted on 3721 infertile patients from December 2018 to August 2020. Endometrial tissues obtained during the proliferative phase were immunostained for CD138. The presence of CD138-positive cells within the stromal cells indicated chronic endometritis. All patients diagnosed with chronic endometritis received oral antibiotics. Patients underwent endometrial preparation and frozen embryo transfer once chronic endometritis was cured. This study compared various endometrial preparation protocols to assess their effects on pregnancy outcomes. Additionally, it aimed to investigate differences in pregnancy outcomes between patients without chronic endometritis and patients with cured chronic endometritis while following the same endometrial preparation protocol. RESULTS: Almost no differences in pregnancy outcomes were observed between natural cycle, hormone replacement therapy (HRT) and gonadotrophin-releasing hormone agonist-HRT (GnRH agonist-HRT) protocols in patients without chronic endometritis and patients with cured chronic endometritis. The only notable difference was that, among women without chronic endometritis, the early miscarriage rate was higher for the GnRH agonist-HRT protocol (25.8%) compared with the natural cycle (17.4%) and HRT (17.7%) protocols (P = 0.025). However, this difference was not significant after adjusting for confounders (adjusted OR 1.383, 95% CI 0.931-2.055). The live birth rate, clinical pregnancy rate, early miscarriage rate, ectopic pregnancy rate and ongoing pregnancy rate did not differ significantly (P > 0.05) between patients without chronic endometritis and patients with cured chronic endometritis who underwent natural cycle, HRT and GnRH agonist-HRT protocols. CONCLUSION: Endometrial preparation protocols had no impact on pregnancy outcomes in patients with cured chronic endometritis.

Chronic endometritis and the endometrial microbiota: implications for reproductive success in patients with recurrent implantation failure.

BACKGROUND: Chronic endometritis (CE) is associated with poor reproductive outcomes, yet the role of endometrial microbiota in patients with recurrent implantation failure (RIF) and CE remains unclear. This study aims to characterize endometrial microbiota in RIF patients with CE and assess its implications for reproductive outcomes. METHODS: In this prospective study, we enrolled RIF patients both with and without CE. Endometrial and cervical samples were collected for 16 S rRNA gene sequencing. Microbiota composition was compared between groups using diversity indices, phylum, and genus-level analysis. Canonical correlation analysis (CCA) and Spearman's correlation coefficients were used to assess relationships between CE, reproductive outcomes, and microbiota. Predictive functional profiling was performed to evaluate metabolic pathways associated with CE. RESULTS: Endometrial microbiota in CE patients exhibited greater diversity and evenness compared to non-CE patients. Principal coordinates analysis (PCoA) revealed distinct clustering between CE and non-CE groups. Linear discriminant analysis (LDA) identified Proteobacteria, Aminicenantales, and Chloroflexaceae as characteristic of CE, while Lactobacillus, Acinetobacter, Herbaspirillum, Ralstonia, Shewanela, and Micrococcaceae were associated with non-CE. CCA demonstrated associations between CE, adverse reproductive outcomes, and specific bacterial taxa. Microbial metabolic pathways significantly differed between CE and non-CE groups, with enrichment in pathways related to cofactors, vitamins, secondary metabolites, and the immune system in CE patients. CONCLUSION: RIF patients with CE exhibit distinct endometrial microbiota compositions associated with adverse reproductive outcomes. The increased microbial diversity and altered metabolic pathways in CE suggest a potential correlation with reproductive outcomes, although further studies are necessary to elucidate the causal relationship between microbiota alterations and fertility. Modulating the endometrial microbiome may represent a novel therapeutic strategy to improve IVF outcomes in patients with CE.

Prevalence and molecular characterization of extended-spectrum ß-lactamase-producing Escherichia coli isolates from dairy cattle with endometritis in Gansu Province, China.

BACKGROUND: The present study aimed to investigate the prevalence and molecular characterization of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli) isolated from dairy cattle with endometritis in China. The prevalence of ESBL-producing E. coli in sample was detected using ChromID ESBL agar, and genotyping of the ESBL producers was performed by PCR and DNA sequencing. RESULTS: The results revealed that the proportion of positive pathogens tested was 69.76% (180/258) in samples obtained from cows diagnosed with clinical endometritis, with E. coli accounting for 170 out of the 180 positive samples. The infection rate of isolated E. coli was 39.14% (101/258), and co-infections with other pathogens were prevalent. Furthermore, among the 158 E. coli isolates, 50 strains were identified as ESBL producers, with TEM and CTX-M prevalence rates at 78.00% and 32.00%, respectively. Drug sensitivity experiments indicated that 50 isolates of ESBL- producing E. coli were multidrug resistance (MDR), with 48.0% of them exhibiting positive results for both the class 1 integron gene and five gene cassettes associated with resistance to trimethoprim (dfr1 and dfrA17) and aminoglycosides (aadA1, aadA5, and dfrA1), respectively. CONCLUSION: This investigation demonstrated a substantial prevalence and heightened level of antimicrobial resistance among ESBL-producing E. coli isolates derived from dairy cattle infected with endometritis in China.

Can the use of azithromycin during labour reduce the incidence of infection among puerperae and newborns? A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis investigated whether the use of azithromycin during labour or caesarean section reduces the incidence of sepsis and infection among mothers and newborns. DATA SOURCES: We independently searched the PubMed, Web of Science, Cochrane Library and EMBASE databases for relevant studies published before February, 2024. METHODS: We included RCTs that evaluated the effect of prenatal oral or intravenous azithromycin or placebo on intrapartum or postpartum infection incidence. We included studies evaluating women who had vaginal births as well as caesarean sections. Studies reporting maternal and neonatal infections were included in the current analysis. Review Manager 5.4 was used to analyse 6 randomized clinical trials involving 44,448 mothers and 44,820 newborns. The risk of bias of each included study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.Primary outcomes included the incidence of maternal sepsis and all-cause mortality and neonatal sepsis and all-cause mortality; secondary outcomes included maternal (endometritis, wound and surgical site infections, chorioamnionitis, and urinary tract infections) and neonatal outcomes (infections of the eyes, ears and skin). A random-effects model was used to test for overall effects and heterogeneity. RESULTS: The pooled odds ratios (ORs) were as follows: 0.65 for maternal sepsis (95% CI, 0.55-0.77; I2, 0%; P < .00001); 0.62 for endometritis (95% CI, 0.52-0.74; I2, 2%; P < .00001); and 0.43 for maternal wound or surgical site infection (95% CI, 0.24-0.78; P < .005); however, there was great heterogeneity among the studies (I2, 75%). The pooled OR for pyelonephritis and urinary tract infections was 0.3 (95% CI, 0.17-0.52; I2, 0%; P < .0001), and that for neonatal skin infections was 0.48 (95% CI, 0.35-0.65; I2, 0%, P < .00001). There was no significant difference in maternal all-cause mortality or incidence of chorioamnionitis between the two groups. No significant differences were observed in the incidence of neonatal sepsis or suspected sepsis, all-cause mortality, or infections of the eyes or ears. CONCLUSION: In this meta-analysis, azithromycin use during labour reduced the incidence of maternal sepsis, endometritis, incisional infections and urinary tract infections but did not reduce the incidence of neonatal-associated infections, except for neonatal skin infections. These findings indicate that azithromycin may be potentially beneficial for maternal postpartum infections, but its effect on neonatal prognosis remains unclear. Azithromycin should be used antenatally only if the clinical indication is clear and the potential benefits outweigh the harms.

Chronic endometritis multiplies the recurrence risk of endometrial polyps after transcervical resection of endometrial polyps: a prospective study.

BACKGROUND: To investigate the impact of chronic endometritis (CE) on the recurrence of endometrial polyps (EPs) in premenopausal women after transcervical resection of endometrial polyps (TCRP). METHODS: This prospective study enrolled 507 women who underwent TCRP between January 1, 2022 and December 31, 2022. The patients were divided into a CE group (n = 133) and non-CE group (n = 374) based on the expression of CD138 in the endometrium. The EP recurrence rate at 1 year after TCRP was compared between the CE and non-CE groups and between groups with mild CE and severe CE. The impact of CD138 expression by resected EPs on EP recurrence also was investigated. RESULTS: The EP recurrence rate at 1 year post-TCRP was higher in the CE group than in the non-CE group (25.6% vs. 10.4%) and also higher in the severe CE group than in the mild CE group (34.5% vs. 18.7%). Additionally, the EP recurrence rate was higher among patients with CD138-expressing EPs than among those with EPs lacking CD138 expression (30.5% vs. 6.5%). The odds ratio (OR) for EP recurrence in the CE cohort compared with the non-CE cohort was 3.10 (95% confidence interval [CI] 1.84-5.23) after adjustment for EP number and precautions against EP recurrence. The ORs for EP recurrence in patients with mild CE and severe CE were 2.21 (95%CI 1.11-4.40) and 4.32 (95%CI 2.26-8.26), respectively. Similarly, the OR for EP recurrence in cases with CD138-expressing EPs relative to cases with EPs lacking CD138 expression was 6.22 (95%CI 3.59-10.80) after adjustment for EP number and precautions against EP recurrence. CONCLUSIONS: CE multiplied the recurrence rate of EPs in premenopausal women after TCRP, and this effect positively correlated with CE severity. CD138 expression by EPs also was associated with a higher risk for EP recurrence.

Antibiotics improve reproductive outcomes after frozen-thaw embryo transfer for chronic endometritis treatment, especially in those with repeated implantation failure.

PURPOSE: To investigate the impact of antibiotic treatment for chronic endometritis (CE) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycles and the relevant clinical risk factors associated with CE. METHODS: A retrospective cohort analysis was conducted on 1352 patients who underwent hysteroscopy and diagnostic curettage at Nanjing Maternal and Child Health Hospital from July 2020 to December 2021. All patients underwent CD138 immunohistochemical (IHC) testing to diagnose CE, and a subset of them underwent FET after hysteroscopy. Patient histories were collected, and reproductive prognosis was followed up. RESULTS: Out of 1088 patients, 443 (40.7%) were diagnosed with CE. Univariate and multivariate binary logistic regression analyses revealed that parity ≥ 2, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, hydrosalpinx, endometrial polyps, a history of ≥ 2 uterine operations, and RIF were significantly associated with an elevated risk of CE (P < 0.05). Analysis of the effect of CE on pregnancy outcomes in FET cycles after antibiotic treatment indicated that treated CE patients exhibited a significantly lower miscarriage rate (8.7%) and early miscarriage rate (2.9%) than untreated non-CE patients (20.2%, 16.8%). Moreover, the singleton live birth rate (45.5%) was significantly higher in treated CE patients than in untreated non-CE patients (32.7%). Survival analysis revealed a statistically significant difference in the first clinical pregnancy time between treated CE and untreated non-CE patients after hysteroscopy (P = 0.0019). Stratified analysis based on the presence of recurrent implantation failure (RIF) demonstrated that in the RIF group, treated CE patients were more likely to achieve clinical pregnancy than untreated non-CE patients (P = 0.0021). Among hysteroscopy-positive patients, no significant difference was noted in pregnancy outcomes between the treatment and control groups (P > 0.05). CONCLUSION: Infertile patients with a history of parity ≥ 2, hydrosalpinx, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, endometrial polyps, a history of ≥ 2 uterine operations, and RIF are at an increased risk of CE; these patients should be recommended to undergo hysteroscopy combined with CD138 examination before embryo transfer. Antibiotic treatment can improve the reproductive outcomes of FET in patients with CE, especially those with RIF.

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.

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.

Oil-soluble contrast medium bathing attenuated endometrial inflammation and improved endometrial receptivity in women with recurrent implantation failure: a descriptive study.

BACKGROUND: The oil-soluble contrast medium used in hysterosalpingography has been shown to have a fertility-enhancing effect, but the underlying mechanism is unclear, especially regarding the role of window of implantation (WOI). This study aimed to assess the endometrial immunological impact of the WOI before and after bathing with the oil-soluble contrast medium in women with recurrent implantation failure (RIF). METHODS: This descriptive study involved two medical centers between December 18, 2019, and December 30, 2020. We included infertile women who underwent three or more transfer cycles, cumulative transplantation of at least four high-quality cleavage-stage embryos or three high-quality blastocysts without clinical pregnancy, and high-quality frozen embryos that were still available for implantation. Patients received 5 ml of ethiodized poppyseed oil bathing, endometrial biopsy around bathing, and frozen-thawed embryo transfer (FET) within four menstrual cycles after bathing. Patients were excluded if failure to complete anyone. Data on the baseline characteristics and clinical data of the FET cycles were collected, and endometrial biopsy specimens were collected in the luteal phase before and after bathing and subjected to immunohistochemistry. The number of CD56 and CD138 positive cells and H-score of expression of ανß-3 and HOXA10 in endometrium were collected. RESULTS: Thirty-four patients were initially enrolled in the study; ultimately, twelve patients with a median age of 32.5 years (range 27-40 years) completed the research. The median number of embryo transfer cycles was three (range 3-8). A total of 4 of 12 women (33.33%) were diagnosed with chronic endometritis before oil-soluble contrast bathing. After bathing, the median numbers of CD138-positive cells in endometrium decreased from 0.75 (range 0-13.5) to 0.65 (range 0-6), P = 0.035; additionally, the H-score of expression of ανß-3 in endometrium increased from 148.50 ± 31.63 to 175.58 ± 31.83, P < 0.001. The thickness of the endometrium also significantly increased (8.90 ± 1.45 mm vs.10.11 ± 1.98 mm, P = 0.005). However, no consistent changes were found in the expression of CD56 and HOXA10 in the endometrium. Five patients experienced biochemical pregnancies (41.67%), four had clinical pregnancies (33.33%), and three achieved live births following oil-soluble contrast bathing (25%). CONCLUSIONS: These results suggest that oil-soluble contrast medium bathing decreased CD138-positive cells and upregulated expression of ανß-3 during WOI in patients with RIF. This histological impact of endometrium may result in enhanced fertility during FET cycles. Investigating the ability of intrauterine bathing with lower-dosage oil-soluble contrast to improve pregnancy in the RIF population is warranted.

Progesterone profiles in postpartum dairy cows with inflammatory disorders.

The objective of this prospective cohort study was to determine if progesterone (P4) profiles differed between dairy cows with or without inflammatory disorders early postpartum. A total of 708 cows from 2 commercial herds were enrolled 3 wk before parturition and examined for clinical health disorders (difficult calving, retained placenta, metritis, displaced abomasum, mastitis, or lameness) until 5 wk postpartum. Serum haptoglobin (Hp) was measured in blood at 2 and 6 DIM (range ±2 d); metritis was assessed at 4, 8, 11, and 15 DIM; and purulent vaginal discharge and endometritis (≥6% PMN in endometrial cytology sampled by cytobrush) were assessed at 35 ± 3 DIM. As Hp ≥0.8 g/L or endometritis were associated with ovarian dysfunction in previous studies, cows with serum Hp ≥0.8 g/L at either time point and endometritis, regardless of clinical disease, were classified as the cohort with inflammatory disorders (INFLAM; n = 139). Clinically healthy cows without difficult calving, with singleton birth, with Hp <0.8 g/L at both sampling times, without endometritis or purulent vaginal discharge, and BCS ≥3.00 (1 to 5 scale) were classified as healthy (n = 133). Cows with only one of the 2 conditions (high Hp or endometritis) were excluded. Cohorts had serum P4 measured twice weekly from 35 to 70 DIM (±3 d), and the first detected luteal phase (LP) during the sampling period was defined as the period from onset of luteal activity (P4 increase to ≥1 ng/mL) until decline of P4 to <1 ng/mL. The odds of prolonged LP (≥21 d long), average LP length, peak P4, and time to P4 decline (hazard rate) were analyzed using multivariable mixed logistic, linear, or Cox proportional hazard regression models including INFLAM status, parity, sampling day (when applicable), and herd as a random effect considering the covariates of season, milk yield at first DHIA test, and DIM at onset of cyclicity or LP length (when applicable). Cows with INFLAM had greater odds of prolonged LP (LSM ± SEM; 67% vs. 37% ± 7%), greater average LP length (17 vs. 15 ± 2 d), lesser P4 at d 4 (4.6 vs. 5.5 ± 0.3 ng/mL) and d 7 (6.0 vs. 7.7 ± 0.3 ng/mL) of the LP, and lesser peak P4 (6.9 vs. 8.2 ± 0.3 ng/mL) during the LP than healthy cows. Status of INFLAM was associated with time to P4 decline in multiparous but not primiparous cows; the LP of INFLAM multiparous cows was less likely to have luteolysis (P4 decline) by d 14 (adjusted hazard ratio [AHR] and 95% CI: 0.54; 0.31 to 0.94) or by d 21 (AHR: 0.32; 0.12 to 0.84) than in healthy multiparous cows. In conclusion, postpartum cows with markers of systemic inflammation at wk 1 and uterine inflammation at wk 5 had altered luteal function (prolonged LP and lower P4 concentrations) before first breeding, which is a possible pathway linking postpartum health disorders and reduced fertility.

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.