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Background: Intrauterine adhesions (IUAs) are a benign uterine disorder that results in intrauterine adhesions and scarring. This study was conducted to assess the effects of freeze-dried amnion grafts on the concentrations of adhesion-related cytokines in uterine exudates following hysteroscopic adhesiolysis of IUAs. Materials and Methods: This study was a prospective randomized controlled trial. Thirty patients who underwent hysteroscopic adhesiolysis for severe IUAs were enrolled. They were randomly divided into a study group (with freeze-dried amnion graft treatment after surgery, N = 15) and a control group (without a graft, N = 15). After complete separation of adhesions, a Foley balloon containing a freeze-dried amnion graft was inserted into the uterine cavity in the study group, while a Foley balloon with no graft was placed in the control group. Enzyme-linked immunosorbent assays were performed to test adhesion-related cytokine concentrations in uterine exudates, including IL-1β, TNF-α, and VEGF, at different time intervals after surgery. Second-look hysteroscopy was conducted three months after the surgery. On the basis of the American Fertility Society (AFS) scoring system, the level of adhesions was evaluated during hysteroscopy. Results: The postoperative volume of the uterine exudates in the study group was significantly lower than that of the control group (P < 0.05). The adhesion-related cytokine concentrations of TNF-α, VEGF, and IL-1β significantly increased after surgery in both groups. Their concentrations were significantly lower in the study group than in the control group (P < 0.05). Moreover, IL-1β exhibited a long-lasting effect in the study group. AFS scores and readhesion rates were significantly lower in the study group than in the control group after hysteroscopic adhesiolysis of severe IUAs. Conclusion: The application of freeze-dried amnion grafts is beneficial to the postoperative recovery of patients with severe IUAs and may reduce the readhesion rate after hysteroscopic adhesiolysis by lowering adhesion-related cytokines, including TNF-α, VEGF, and IL-1β. [ABSTRACT FROM AUTHOR]

Epithelial ovarian carcinoma (EOC) is one of the most common gynecologic malignancies with a high mortality rate. Serum biomarkers and imaging approaches are insufficient in identifying EOC patients at an early stage. This study is to set up a combination of proteins from serum small extracellular vesicles (sEVs) for the diagnosis of early-stage EOC and to determine its performance. A biomarker for early-stage ovarian cancer (BESOC) cohort was used as a Chinese multi-center population-based biomarker study and registered as a Chinese Clinical Trial ChiCTR2000040136. The sEV protein levels of CA125, HE4, and C5a were measured in 299 subjects. Logistic regression was exploited to calculate the odds ratio and to create the sEV protein model for the predicted probability and subsequently receiver-operating characteristic (ROC) analysis. The combined sEV marker panel of CA125, HE4, and C5a as a sEV model obtained an area under curve (AUC) of 0.912, which was greater than the serum model (0.809), by ROC analysis to identify EOC patients from the whole cohort. With the cutoff of 0.370, the sensitivity and specificity of the sEV model were 0.80 and 0.89, which were much better performance than the serum markers (sensitivity: 0.55~0.66; specificity: 0.59~0.68) and the risk of ovarian malignancy algorithm (ROMA) index approved by the U.S. Food and Drug Administration (sensitivity: 0.65; specificity: 0.61), to identify EOC patients from patients with benign ovarian diseases or other controls. The sEV levels of CA125 significantly differed among early-stage and late-stage EOC (p < 0.001). Moreover, the AUC of ROC to identify early-stage EOC patients was 0.888. Further investigation revealed that the sEV levels of these 3 proteins significantly decreased after cytoreductive surgery (CA125, p = 0.008; HE4, p = 0.025; C5a, p = 0.044). In summary, our study showed that CA125, HE4, and C5a levels in serum sEVs can identify EOC patients at the early stage, elucidating the possibility of using a sEV model for the diagnosis of early-stage EOC. [ABSTRACT FROM AUTHOR]

• The found gene module associates with the ubiquitin-mediated proteolysis pathway. • This gene module drives the proliferation of endometriosis endometrial cells. • GWES of 142 patients and 71 control subjects were analysed in this study. • WGCNA enabled the analysis of co-expression gene clusters rather than single-gene. • The NNET model discovered the clinical value of hub genes for endometriosis. Is abnormal gene module expression in the eutopic endometrium related to the occurrence of endometriosis? Nine datasets of normal and eutopic endometrium were searched and collected through the National Center for Biotechnology Information Gene Expression Omnibus, which included genome-wide expression studies of 71 normal cases and 142 endometriosis cases. Surrogate variable analysis was used for dataset integration. The network module and hub genes were selected by weighted gene co-expression network analysis. Machine learning was used to establish a diagnostic model of endometriosis. A gene module that was most relevant to endometriosis was selected through weighted gene co-expression network analysis. After further analysis of this module, four hub genes that represent the function of this module were selected: SCAF11, KRAS, MDM2 and KIF3A. Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the four hub genes revealed that all of them were most highly correlated with genes enriched in the ubiquitin-mediated proteolysis pathway. Moreover, in the correlation analysis between hub genes and Jab1, SCAF11 was found to be closely related to Jab1. Furthermore, hub genes were effective indicators for clinical diagnosis. The deep machine learning diagnostic model based on hub genes was highly sensitive. The gene module identified is highly correlated with endometriosis. The four hub genes in this module degrade p27kip1 through the ubiquitin-mediated proteolysis pathway to regulate the endometrium cell cycle and affect the development of endometriosis. The hub genes and the deep learning model based on them are valuable for clinical diagnosis. [ABSTRACT FROM AUTHOR]

• Preoperative estrogen therapy may improve the short-term prognosis of IUAs. • There was no sufficient evidence of the effect on reproductive outcomes. • More well-designed, randomized controlled trials are needed. The aim of this systematic review and meta-analysis was to assess the effect of oestrogen therapy as a preoperative intervention for improving clinical outcomes and fertility outcomes in women with intrauterine adhesions (IUA). A systematic search of PubMed, Embase, The Cochrane Library, clinicaltrials.gov, OVID and Chinese databases was carried out to identify relevant studies published before December 2019. Outcomes were expressed as odds ratios and 95% confidence intervals. Five cohort studies with moderate to high methodological quality were included in the meta-analysis. Preoperative oestrogen therapy was strongly associated with better clinical outcome at second-look hysteroscopy (OR 2.72; 95% CI 1.49 to 4.96; P = 0.001); whereas no significant difference was found in menstruation improvement and conception rate (OR 1.45; 95% CI, 0.95 to 2.23; P = 0.09; and OR 0.96; 95% CI 0.60 to 1.54; P = 0.87, respectively). The overall quality of the evidence ranged from moderate to very low. Preoperative oestrogen therapy may improve the short-term prognosis of IUA at second-look hysteroscopy, whereas the long-term prognosis-fertility outcome was similar to the control group. More strictly designed research studies are needed to assess the effectiveness of oestrogen administration before hysteroscopic adhesiolysis. [ABSTRACT FROM AUTHOR]

Background: Hysteroscopic metroplasty of the uterine septum has been the standard treatment strategy to improve reproductive outcomes, but there are still controversies about the appropriateness of metroplasty. In addition, there have been few studies of the factors related to reproductive outcomes of women after surgery. The study aimed to evaluate the reproductive outcomes and the associated risk factors that influence reproductive outcomes after hysteroscopic metroplasty of women with septate uterus and the desire to conceive., Methods: This study was an observational study. Cases were screened by searching electronic patient files, and demographic factors were collected. We conducted telephone follow-ups to collect the postoperative reproductive outcomes. The primary outcome of this study was live birth, and secondary outcomes were ongoing pregnancy, clinical pregnancy, early miscarriage, and preterm birth. Demographic variables included patients' age, body mass index (BMI), the type of septum, infertility and miscarriage history, and complications including intrauterine adhesions, endometrial polyps, endometriosis, and adenomyosis were collected to perform univariate and multivariate analyses to predict the risk factors of reproductive outcomes after surgery treatment., Results: In total, 348 women were evaluated and followed up. There were 95 cases (27.3%, 95/348) with combined infertility, 195 cases (56.0%, 195/348) with miscarriage history, and cases combined with intrauterine adhesions, endometrial polyps, endometriosis, and adenomyosis were 107 (30.7%, 107/348), 53 (15.2%, 53/348), 28 (8.0%, 28/348), and 5 (1.4%), respectively. Following surgery, the live birth rate and clinical pregnancy rate were significantly higher than prior to surgery (84.6% vs 3.7%, p = 0.000; and 78.2% vs 69.5%, p = 0.01, respectively), early miscarriage rate and preterm delivery rate were significantly lower (8.8% vs 80.6%, p = 0.000; and 7.0% vs 66.7%, p =0.000, respectively). After adjusting for body mass index, miscarriage history, and complications, multivariable logistic regression analysis revealed age ≥ 35 years and primary infertility as independent factors that affected postoperative clinical pregnancy (OR 4.025, 95% CI 2.063-7.851, p = 0.000; and OR 3.603, 95% CI 1.903-6.820, p = 0.000; respectively) and ongoing pregnancy (OR 3.420, 95% CI 1.812-6.455, p = 0.000; and OR 2.586, 95% CI 1.419-4.712, p = 0.002; respectively)., Conclusions: Hysteroscopic metroplasty could lead to improved reproductive outcomes of women with septate uterus. Both age and primary infertility were independent factors for postoperative reproductive outcomes., Trial Registration: Chi ECRCT20210343., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chang, Shen, Wang, Guo and Duan.)

Introduction: The endometrial microbiota plays an essential role in the health of the female reproductive system. However, the interactions between the microbes in the endometrium and their effects on adenomyosis remain obscure., Materials and Methods: We profile endometrial samples from 38 women with ( n =21) or without ( n =17) adenomyosis to characterize the composition of the microbial community and its potential function in adenomyosis using 5R 16S rRNA gene sequencing., Results: The microbiota profiles of patients with adenomyosis were different from the control group without adenomyosis. Furthermore, analysis identified Lactobacillus zeae, Burkholderia cepacia, Weissella confusa, Prevotella copri, and Citrobacter freundii as potential biomarkers for adenomyosis. In addition, Citrobacter freundii, Prevotella copri , and Burkholderia cepacia had the most significant diagnostic value for adenomyosis. PICRUSt results identified 30 differentially regulated pathways between the two groups of patients. In particular, we found that protein export, glycolysis/gluconeogenesis, alanine, aspartate, and glutamate metabolism were upregulated in adenomyosis. Our results clarify the relationship between the endometrial microbiota and adenomyosis., Discussion: The endometrial microbiota of adenomyosis exhibits a unique structure and Citrobacter freundii, Prevotella copri , and Burkholderia cepacia were identified as potential pathogenic microorganisms associated with adenomyosis. Our findings suggest that changes in the endometrial microbiota of patients with adenomyosis are of potential value for determining the occurrence, progression, early of diagnosis, and treatment oadenomyosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Duan, Wang, Guo, Wang, Chang, Chen, Shen, Shou and Zhou.)

Background: In a previous study, we reported that amnion promotes endometrial cell growth by regulating cytokines. In this study, hierarchical cluster analysis enabled the evaluation of cytokine expression changes after amnion treatment to be explored by cluster patterns. The role of IL1B on endometrial repair and receptivity was revealed., Methods: A total of 30 patients were recruited in this clinical trial (NCT02496052) of hysteroscopic adhesiolysis. They were randomly allocated into an amnion grafts group (amnion group) and a control group. After hysteroscopic adhesiolysis, a Foley catheter covered with a sterilized freeze-dried amnion graft was inserted into the uterine cavity of the participants in the amnion group, whereas for the control group, a Foley catheter without amnion graft was inserted. After surgery, patient follow-up was done for a year. Uterine exudates were collected every day for seven days after surgery, and analyzed by enzyme-linked immunosorbent assays. Hierarchical cluster analysis was performed to compare expression patterns of each cytokine. Single-gene gene set enrichment analysis and differentially expressed genes enrichment analysis of IL1B were performed using NCBI GEO (N=151) to evaluate its potential mechanisms and impact on endometrial receptivity., Results: Compared to the control group, cytokine expression patterns of the amnion group revealed significant stratifications, which were highly correlated with the expression levels of IL1B on the sixth to seventh day after surgery, improving the pregnant rate. Wilcoxon test revealed significantly low expression levels of IL1B in the reduced endometrial receptivity group compared to the normal group. Moreover, gene set enrichment analysis showed that lysosomes, cell cycle, and calcium signaling pathways were associated with the biological processes in which IL1B plays a role. Screening and enrichment analyses of differentially expressed genes further verified the mechanisms of action of IL1B on endometrial repair and receptivity recovery., Conclusions: Amnion promotes endometrial repair and receptivity by altering the expression levels and patterns of IL1B . Furthermore, by affecting lysosomal, cell cycle, and calcium signaling pathways, IL1B may be one of the factors involved in endometrial repair and receptivity recovery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-21-195). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)