Prevalence of chronic endometritis in infertile women undergoing hysteroscopy and its association with intrauterine abnormalities: A Cross-Sectional study.

OBJECTIVE: Chronic endometritis (CE) is an inflammatory condition with several different risk factors. We aimed to examine whether intrauterine abnormalities, such as endometrial polyps, submucosal myomas, intrauterine adhesions, or a septate uterus, were associated with an increased likelihood of developing chronic endometritis. METHODS: A cross-sectional study was conducted on 335 infertile women who underwent hysteroscopy surgery at the Ayatollah Taleghani Hospital Infertility Center, affiliated by Shahid Beheshti University of Medical Sciences, in 2022. All participants in the study underwent hysteroscopic surgery, which allowed for direct visualization of the intrauterine cavity, and endometrial biopsies were taken for further analysis. To characterize endometritis, plasma cell infiltration was assessed. Patients with ≥5 plasma cells observed in 10 high-power fields were defined as having chronic endometritis. RESULTS: Endometritis was observed in 51.3% of the patients, totaling 172 individuals. Logistic regression analysis revealed that patients with endometrial polyps had 5.2 times higher odds of developing endometritis compared to patients without polyps (95% CI = 2.9, 9.2) (p-value <0.001). Similarly, patients with intrauterine adhesions had a significant increase in the odds of endometritis (OR = 4.6, 95% CI = 2.1, 10.1) (p-value <0.001). CONCLUSIONS: Treatment or removal of endometrial abnormalities through hysteroscopic procedures may help to reduce the risk of chronic endometritis and improve fertility outcomes. Further research is necessary.

Endometrial mesenchymal stromal/stem cells improve regeneration of injured endometrium in mice.

BACKGROUND: The monthly regeneration of human endometrial tissue is maintained by the presence of human endometrial mesenchymal stromal/stem cells (eMSC), a cell population co-expressing the perivascular markers CD140b and CD146. Endometrial regeneration is impaired in the presence of intrauterine adhesions, leading to infertility, recurrent pregnancy loss and placental abnormalities. Several types of somatic stem cells have been used to repair the damaged endometrium in animal models, reporting successful pregnancy. However, the ability of endometrial stem cells to repair the damaged endometrium remains unknown. METHODS: Electrocoagulation was applied to the left uterine horn of NOD/SCID mice causing endometrial injury. Human eMSC or PBS was then injected into the left injured horn while the right normal horn served as controls. Mice were sacrificed at different timepoints (Day 3, 7 and 14) and the endometrial morphological changes as well as the degree of endometrial injury and repair were observed by histological staining. Gene expression of various inflammatory markers was assessed using qPCR. The functionality of the repaired endometrium was evaluated by fertility test. RESULTS: Human eMSC successfully incorporated into the injured uterine horn, which displayed significant morphological restoration. Also, endometrium in the eMSC group showed better cell proliferation and glands formation than the PBS group. Although the number of blood vessels were similar between the two groups, gene expression of VEGF-α significantly increased in the eMSC group. Moreover, eMSC had a positive impact on the regeneration of both stromal and epithelial components of the mouse endometrium, indicated by significantly higher vimentin and CK19 protein expression. Reduced endometrial fibrosis and down-regulation of fibrosis markers were also observed in the eMSC group. The eMSC group had a significantly higher gene expression of anti-inflammatory factor Il-10 and lower mRNA level of pro-inflammatory factors Ifng and Il-2, indicating the role of eMSC in regulation of inflammatory reactions. The eMSC group showed higher implantation sites than the PBS group, suggesting better endometrial receptivity with the presence of newly emerged endometrial lining. CONCLUSIONS: Our findings suggest eMSC improves regeneration of injured endometrium in mice.

Endometrial mesenchymal stromal/stem cells improve regeneration of injured endometrium in mice

BACKGROUND: The monthly regeneration of human endometrial tissue is maintained by the presence of human endometrial mesenchymal stromal/stem cells (eMSC), a cell population co-expressing the perivascular markers CD140b and CD146. Endometrial regeneration is impaired in the presence of intrauterine adhesions, leading to infertility, recurrent pregnancy loss and placental abnormalities. Several types of somatic stem cells have been used to repair the damaged endometrium in animal models, reporting successful pregnancy. However, the ability of endometrial stem cells to repair the damaged endometrium remains unknown. METHODS: Electrocoagulation was applied to the left uterine horn of NOD/SCID mice causing endometrial injury. Human eMSC or PBS was then injected into the left injured horn while the right normal horn served as controls. Mice were sacrificed at different timepoints (Day 3, 7 and 14) and the endometrial morphological changes as well as the degree of endometrial injury and repair were observed by histological staining. Gene expression of various inflammatory markers was assessed using qPCR. The functionality of the repaired endometrium was evaluated by fertility test. RESULTS: Human eMSC successfully incorporated into the injured uterine horn, which displayed significant morphological restoration. Also, endometrium in the eMSC group showed better cell proliferation and glands formation than the PBS group. Although the number of blood vessels were similar between the two groups, gene expression of VEGF-α significantly increased in the eMSC group. Moreover, eMSC had a positive impact on the regeneration of both stromal and epithelial components of the mouse endometrium, indicated by significantly higher vimentin and CK19 protein expression. Reduced endometrial fibrosis and down-regulation of fibrosis markers were also observed in the eMSC group. The eMSC group had a significantly higher gene expression of anti-inflammatory factor Il-10 and lower mRNA level of pro-inflammatory factors Ifng and Il-2, indicating the role of eMSC in regulation of inflammatory reactions. The eMSC group showed higher implantation sites than the PBS group, suggesting better endometrial receptivity with the presence of newly emerged endometrial lining. CONCLUSIONS: Our findings suggest eMSC improves regeneration of injured endometrium in mice.

The role of progesterone receptor membrane component (PGRMC) in the endometrium.

PGRMC is a non-classical receptor that mediates the non-genomic responses to progesterone and is distributed in different subcellular compartments. PGRMC belongs to the membrane-associated progesterone receptor (MAPR) family. Two PGRMC subtypes (PGRMC1 and PGRMC2) have been characterized, and both are expressed in the human endometrium. PGRMC expression is differentially regulated during the menstrual cycle in the human endometrium. Although PGRMC1 is predominantly expressed in the proliferative phase and PGRMC2 in the secretory phase, this expression changes in pathologies such as endometriosis, in which PGRMC2 expression considerably decreases, promoting progesterone resistance. In endometrial cancer, PGRMC1 is overexpressed, its activation induces tumors growth, and confers chemoresistance in the presence of progesterone. Thus, PGRMCs play a key role in progesterone actions in the endometrium.

Accuracy of Transvaginal Ultrasound in the Diagnosis of Intrauterine Lesions.

OBJECTIVE: To evaluate the accuracy of transvaginal ultrasound in the diagnosis of intrauterine lesions, using hysteroscopy as the gold standard. METHODS: This was a prospective observational study with 307 patients. All patients underwent hysteroscopy after a previous transvaginal ultrasound to compare the results. The hysteroscopy was performed by experienced examiners, and transvaginal ultrasounds were performed in various public and private services, which is reflective of routine healthcare practices in obstetrics and gynecology. The sensitivity, specificity, and accuracy of the transvaginal ultrasound were calculated using hysteroscopy as the gold standard. The level of agreement between the two exams was calculated using the Kappa test. RESULTS: The mean age was 56.55 ± 12.3 years. For endometrial polyps, we observed a sensitivity of 39.8%, specificity of 72.7%, accuracy of 52.8%, and Kappa index of 0.11 (p = 0.025). For fibroids, the sensitivity was 46.7%, specificity was 95.0%, accuracy was 87.9%, and Kappa index was 0.46 (p < 0.001). For endometrial thickening, the sensitivity was 68.7%, specificity was 41.7%, accuracy was 47.6%, and Kappa index was 0.06 (p = 0.126). For endometrial atrophy, we found a sensitivity of 6.7%, specificity of 99.3%, accuracy of 90.2%, and Kappa index of 0.10 (p = 0.006). For the other findings, the sensitivity was 15.6%, specificity was 99.6%, accuracy was 87.3%, and Kappa index was 0.23 (P < 0.001). CONCLUSION: Our study demonstrated a low level of accuracy of transvaginal ultrasound for the diagnosis of endometrial lesions, when performed by a non-experienced professional. Thus, it is important to consider the use of hysteroscopy to avoid unnecessary and inappropriate treatments.

OBJETIVO: Avaliar a acurácia do ultrassom transvaginal para o diagnóstico de lesões intrauterinas, tendo a histeroscopia como padrão de referência. MéTODOS: Foi realizado um estudo observacional prospectivo em 307 pacientes, submetidas à histeroscopia após ultrassonografia prévia para comparação dos resultados. A histeroscopia foi realizada por duas médicas com experiência, e os exames de ultrassom foram realizados em diversas fontes, públicas ou privadas, como ocorre no cotidiano da assistência à saúde em nosso meio. Foram avaliados sensibilidade, especificidade e acurácia, tendo a histeroscopia como padrão-ouro. O nível de concordância foi avaliado pelo teste de Kappa. RESULTADOS: A idade média foi de 56,55 ± 12,3 anos. Os resultados para pólipo endometrial foram: sensibilidade 39.8%, especificidade 72,7%, acurácia de 52,8%, e índice Kappa 0,11 (p = 0,025). Para mioma, sensibilidade 46,7%, especificidade 95,0%, acurácia 87,9%, e índice Kappa 0,46 (p < 0,001). Para espessamento endometrial, sensibilidade 68,7%, especificidade 41,7%, acurácia 47,6%, e índice Kappa de 0,06 (p = 0,126). Para atrofia, sensibilidade 6,7%, especificidade 99,3%, acurácia 90,2%, e índice Kappa 0,10 (p = 0,006). Para outros achados, sensibilidade 15,6%, especificidade 99,6%, acurácia 87,3%, e índice Kappa 0,23 (p < 0,001). CONCLUSãO: Nosso estudo demonstrou baixo nível de acurácia da ultrassonografia transvaginal para o diagnóstico de lesões endometriais, quando realizada por profissional não experiente. Assim, é importante considerar o uso da histeroscopia para evitar tratamentos desnecessários e inadequados.

Accuracy of Transvaginal Ultrasound in the Diagnosis of Intrauterine Lesions / Acurácia da ultrasonografia tranvaginal no diagnóstico de lesões intrauterinas

Abstract Objective To evaluate the accuracy of transvaginal ultrasound in the diagnosis of intrauterine lesions, using hysteroscopy as the gold standard. Methods This was a prospective observational study with 307 patients. All patients underwent hysteroscopy after a previous transvaginal ultrasound to compare the results. The hysteroscopy was performed by experienced examiners, and transvaginal ultrasounds were performed in various public and private services, which is reflective of routine healthcare practices in obstetrics and gynecology. The sensitivity, specificity, and accuracy of the transvaginal ultrasound were calculated using hysteroscopy as the gold standard. The level of agreement between the two exams was calculated using the Kappa test. Results Themean age was 56.55±12.3 years. For endometrial polyps, we observed a sensitivity of 39.8%, specificity of 72.7%, accuracy of 52.8%, and Kappa index of 0.11 (p=0.025). For fibroids, the sensitivity was 46.7%, specificity was 95.0%, accuracy was 87.9%, and Kappa index was 0.46 (p<0.001). For endometrial thickening, the sensitivity was 68.7%, specificity was 41.7%, accuracy was 47.6%, and Kappa index was 0.06 (p=0.126). For endometrial atrophy, we found a sensitivity of 6.7%, specificity of 99.3%, accuracy of 90.2%, and Kappa index of 0.10 (p=0.006). For the other findings, the sensitivity was 15.6%, specificity was 99.6%, accuracy was 87.3%, and Kappa index was 0.23 (P<0.001). Conclusion Our study demonstrated a low level of accuracy of transvaginal ultrasound for the diagnosis of endometrial lesions, when performed by a non-experienced professional. Thus, it is important to consider the use of hysteroscopy to avoid unnecessary and inappropriate treatments.

Resumo Objetivo Avaliar a acurácia do ultrassom transvaginal para o diagnóstico de lesões intrauterinas, tendo a histeroscopia como padrão de referência. Métodos Foi realizado um estudo observacional prospectivo em 307 pacientes, submetidas à histeroscopia após ultrassonografia prévia para comparação dos resultados. A histeroscopia foi realizada por duas médicas com experiência, e os exames de ultrassom foram realizados em diversas fontes, públicas ou privadas, como ocorre no cotidiano da assistência à saúde em nosso meio. Foram avaliados sensibilidade, especificidade e acurácia, tendo a histeroscopia como padrão-ouro. O nível de concordância foi avaliado pelo teste de Kappa. Resultados A idade média foi de 56,55±12,3 anos. Os resultados para pólipo endometrial foram: sensibilidade 39.8%, especificidade 72,7%, acurácia de 52,8%, e índice Kappa 0,11 (p=0,025). Para mioma, sensibilidade 46,7%, especificidade 95,0%, acurácia 87,9%, e índice Kappa 0,46 (p<0,001). Para espessamento endometrial, sensibilidade 68,7%, especificidade 41,7%, acurácia 47,6%, e índice Kappa de 0,06 (p=0,126). Para atrofia, sensibilidade 6,7%, especificidade 99,3%, acurácia 90,2%, e índice Kappa 0,10 (p=0,006). Para outros achados, sensibilidade 15,6%, especificidade 99,6%, acurácia 87,3%, e índice Kappa 0,23 (p<0,001). Conclusão Nosso estudo demonstrou baixo nível de acurácia da ultrassonografia transvaginal para o diagnóstico de lesões endometriais, quando realizada por profissional não experiente. Assim, é importante considerar o uso da histeroscopia para evitar tratamentos desnecessários e inadequados.

The role of epigenetic mechanisms in the regulation of gene expression in the cyclical endometrium.

BACKGROUND: The human endometrium is a highly dynamic tissue whose function is mainly regulated by the ovarian steroid hormones estradiol and progesterone. The serum levels of these and other hormones are associated with three specific phases that compose the endometrial cycle: menstrual, proliferative, and secretory. Throughout this cycle, the endometrium exhibits different transcriptional networks according to the genes expressed in each phase. Epigenetic mechanisms are crucial in the fine-tuning of gene expression to generate such transcriptional networks. The present review aims to provide an overview of current research focused on the epigenetic mechanisms that regulate gene expression in the cyclical endometrium and discuss the technical and clinical perspectives regarding this topic. MAIN BODY: The main epigenetic mechanisms reported are DNA methylation, histone post-translational modifications, and non-coding RNAs. These epigenetic mechanisms induce the expression of genes associated with transcriptional regulation, endometrial epithelial growth, angiogenesis, and stromal cell proliferation during the proliferative phase. During the secretory phase, epigenetic mechanisms promote the expression of genes associated with hormone response, insulin signaling, decidualization, and embryo implantation. Furthermore, the global content of specific epigenetic modifications and the gene expression of non-coding RNAs and epigenetic modifiers vary according to the menstrual cycle phase. In vitro and cell type-specific studies have demonstrated that epithelial and stromal cells undergo particular epigenetic changes that modulate their transcriptional networks to accomplish their function during decidualization and implantation. CONCLUSION AND PERSPECTIVES: Epigenetic mechanisms are emerging as key players in regulating transcriptional networks associated with key processes and functions of the cyclical endometrium. Further studies using next-generation sequencing and single-cell technology are warranted to explore the role of other epigenetic mechanisms in each cell type that composes the endometrium throughout the menstrual cycle. The application of this knowledge will definitively provide essential information to understand the pathological mechanisms of endometrial diseases, such as endometriosis and endometrial cancer, and to identify potential therapeutic targets and improve women's health.

The role of KDR in intrauterine adhesions may involve the TGF-ß1/Smads signaling pathway.

The aim of this study was to investigate the role of kinase-insert domain-containing receptor (KDR) in intrauterine adhesions (IUA) and its mechanism. The Case group consisted of 92 patients diagnosed with IUA, and the Control group included 86 patients with uterine septum who had normal endometrium verified with an uteroscope. In addition, 50 rats were randomly assigned into Control, Sham, Model, NC-siRNA, and KDR-siRNA groups. Rats in the Model, NC-siRNA, and KDR-siRNA groups were induced by uterine curettage and lipopolysaccharide (LPS) treatment to establish the IUA model. Then, immunohistochemistry was applied for detection of VEGF and KDR expression, HE staining was used for observation of the endometrial morphology and gland counting, Masson staining for measurement of the degree of endometrial fibrosis, and qRT-PCR and western blot for the expression of KDR, VEGF, MMP-9, as well as TGF-ß1/Smads pathway-related proteins. Compared with the Control group, the mRNA and protein expressions of KDR were significantly higher in IUA endometrial tissues, and the expression of KDR was positively correlated to the severity of IUA. In addition, the injection of si-KDR increased the number of endometrial glands, reduced the area of fibrosis, inhibited mRNA and protein expression of KDR and VEGF, up-regulated the expression of MMP-9 and Smad7, and decreased the expression level of TGF-ß1, p-Smad2, p-Smad3, and Smad4 in rats with IUA. Highly-expressed KDR was related to patients' severity of IUA, and silencing KDR may prevent the occurrence and development of IUA via TGF-ß1/Smads signaling pathway and up-regulating the expression of MMP-9.

Uterine torsion with necrosis of bilateral adnexa in a postmenopausal woman.

Uterine torsion is an uncommon entity that is defined as a rotation of greater than 45° around the longitudinal axis of the uterus. Although cases of uterine torsion among pregnant patients have been mentioned in the literature, torsion of a non-gravid uterus is a rare occurrence. A 73-year-old nulliparous woman with a known fibroid uterus underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy with frozen section of a 17-18 cm pelvic mass seen on CT imaging. The source of the pelvic mass was unclear on imaging, and benign and malignant possibilities were discussed. During the procedure, necrosis of the uterine fundus and bilateral adnexa were seen due to the fundus being torsed with the uterine fibroid being the pivot point. Uterine torsion, though rare, can be the cause of acute pelvic pain in a postmenopausal woman.

The role of KDR in intrauterine adhesions may involve the TGF-ß1/Smads signaling pathway

The aim of this study was to investigate the role of kinase-insert domain-containing receptor (KDR) in intrauterine adhesions (IUA) and its mechanism. The Case group consisted of 92 patients diagnosed with IUA, and the Control group included 86 patients with uterine septum who had normal endometrium verified with an uteroscope. In addition, 50 rats were randomly assigned into Control, Sham, Model, NC-siRNA, and KDR-siRNA groups. Rats in the Model, NC-siRNA, and KDR-siRNA groups were induced by uterine curettage and lipopolysaccharide (LPS) treatment to establish the IUA model. Then, immunohistochemistry was applied for detection of VEGF and KDR expression, HE staining was used for observation of the endometrial morphology and gland counting, Masson staining for measurement of the degree of endometrial fibrosis, and qRT-PCR and western blot for the expression of KDR, VEGF, MMP-9, as well as TGF-β1/Smads pathway-related proteins. Compared with the Control group, the mRNA and protein expressions of KDR were significantly higher in IUA endometrial tissues, and the expression of KDR was positively correlated to the severity of IUA. In addition, the injection of si-KDR increased the number of endometrial glands, reduced the area of fibrosis, inhibited mRNA and protein expression of KDR and VEGF, up-regulated the expression of MMP-9 and Smad7, and decreased the expression level of TGF-β1, p-Smad2, p-Smad3, and Smad4 in rats with IUA. Highly-expressed KDR was related to patients' severity of IUA, and silencing KDR may prevent the occurrence and development of IUA via TGF-β1/Smads signaling pathway and up-regulating the expression of MMP-9.

Comparison of endometrial assessment by transvaginal ultrasonography and hysteroscopy.

OBJECTIVE: To compare transvaginal ultrasonography and hysteroscopy for the diagnosis of endometrial pathologies. METHODS: In the present retrospective cohort study, data were reviewed from women with ultrasonography findings suggestive of endometrial lesions and/or abnormal uterine bleeding who underwent hysteroscopy at a single center in Campinas, Brazil, between January 2011 and December 2013; data were stratified based on reproductive-aged and postmenopausal groups. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ultrasonography and hysteroscopy for the diagnosis of endometrial lesions were determined. Histopathology was used as the gold standard. RESULTS: There were 754 patients included (256 reproductive age, 498 postmenopausal). In the reproductive-age group, ultrasonography had a sensitivity of 96.0%, specificity of 58.0%, PPV of 94.4%, NPV of 66.6%, and accuracy of 91.5%, whereas hysteroscopy had a sensitivity of 91.8%, specificity of 76.6%, PPV of 96.0%, NPV of 60.5%, and accuracy of 89.7% for the diagnosis of endometrial disease. In the postmenopausal group, ultrasonography had a sensitivity of 99.0%, specificity of 19.0%, PPV of 96.1%, NPV of 50.0%, and accuracy of 95.3%, whereas hysteroscopy had a sensitivity of 96.7%, specificity of 86.9%, PPV of 99.2%, NPV of 58.8%, and accuracy of 96.2%. CONCLUSION: Ultrasonography was found to be an effective method for the diagnosis of endometrial disease, especially among postmenopausal women.

Depleted lamin B1: a possible marker of the involvement of senescence in endometriosis?

PROPOSE: Endometriosis is a benign disease characterized by implantation and the growth of endometrial tissue outside the uterine cavity and it shares similarities with cancer. Lamin B1, p16 and p21 play a role on cell cycle regulation, development, cell repair and its activities are related to cancers. Considering the similarities between endometriosis and cancer, the aim of the present cross-sectional study is to detect p16, p21 and Lamin B1 in the ectopic endometrium of patients with endometriosis (n = 8) with eutopic (n = 8) and control endometrium (n = 8) and relate them to the maintenance and development of endometriosis. METHODS: Biopsies were obtained from both eutopic and ectopic, from deep infiltrating lesions, endometrium frozen and used for immunofluorescent (p16) or immunohistochemistry procedures (p16, p21, lamin B1). RESULTS: Detected higher lamin B1 in the eutopic endometrium when compared with ectopic endometrium, with no differences between endometriosis tissue with control endometrium. Similar presence of p16 in all groups of patients and no p21 detection was observed. CONCLUSION: We observed reduced detection of lamin B1 in the ectopic endometrium raising the possibility that the presence of senescent cells might be contributing to the maintenance and progression of endometriosis by apoptosis resistance and peritoneal stress inherent of the disease.

Pathogenesis of uterine diseases in dairy cattle and implications for fertility

Uterine diseases in cattle occur at all stages of the reproduction cycle but the majority of cases is found in the postpartum period. The inflammation of the uterus is generally defined as metritis or endometritis, with several graduations, e.g. puerperal metritis, clinical metritis, clinical or subclinical endometritis. Whether uterine diseases have a negligible, moderate or detrimental effect on fertility is still under discussion and depends on definitions and classification. In the past, it was assumed that the pregnant uterus is free of pathogens, but recent studies found several species including pathogens in the uterus and endometrium of pregnant cows. After parturition, a broad diversity of bacteria with >200 different species has been found in the early postpartum period. Not all of these bacteria, however, are considered as pathogens. Furthermore, bacteriological findings provide only evidence for infection but not for inflammation. For some bacteria, particularly Escherichia coli and Trueperella pyogenes pathogenic mechanism resulting in metritis and endometritis have been elucidated in detail. The role of bacteria that can be regarded as opportunistic or potential pathogens, e.g. Bacillus pumilus, is still under investigation. The understanding of the uterine microbiota and its interactions is increasing with the use of modern high-resolution techniques such as Fouriertransform infrared spectroscopy. Endometrial cytology provides additional information about alterations in the endometrium. Knowledge of innate uterine defense mechanism in cattle has increased a lot in the recent past. It can be speculated that improving or modulating uterine defense mechanism will be part of future prevention and treatment approaches beyond the use of antimicrobials. In this context, cellular and molecular defense mechanisms have been in the focus of interest, e.g. the role of interleukins or mucins. This review gives a short overview on some aspects of recent research on uterine diseases in cattle.

Pathogenesis of uterine diseases in dairy cattle and implications for fertility

Uterine diseases in cattle occur at all stages of the reproduction cycle but the majority of cases is found in the postpartum period. The inflammation of the uterus is generally defined as metritis or endometritis, with several graduations, e.g. puerperal metritis, clinical metritis, clinical or subclinical endometritis. Whether uterine diseases have a negligible, moderate or detrimental effect on fertility is still under discussion and depends on definitions and classification. In the past, it was assumed that the pregnant uterus is free of pathogens, but recent studies found several species including pathogens in the uterus and endometrium of pregnant cows. After parturition, a broad diversity of bacteria with >200 different species has been found in the early postpartum period. Not all of these bacteria, however, are considered as pathogens. Furthermore, bacteriological findings provide only evidence for infection but not for inflammation. For some bacteria, particularly Escherichia coli and Trueperella pyogenes pathogenic mechanism resulting in metritis and endometritis have been elucidated in detail. The role of bacteria that can be regarded as opportunistic or potential pathogens, e.g. Bacillus pumilus, is still under investigation. The understanding of the uterine microbiota and its interactions is increasing with the use of modern high-resolution techniques such as Fouriertransform infrared spectroscopy. Endometrial cytology provides additional information about alterations in the endometrium. Knowledge of innate uterine defense mechanism in cattle has increased a lot in the recent past. It can be speculated that improving or modulating uterine defense mechanism will be part of future prevention and treatment approaches beyond the use of antimicrobials. In this context, cellular and molecular defense mechanisms have been in the focus of interest, e.g. the role of interleukins or mucins. This review gives a short overview on some aspects of recent research on uterine diseases in cattle.(AU)

Analysis of differential genetic expression in endometrial polyps of postmenopausal women.

OBJECTIVES: To evaluate the expression of four genetic markers (PTEN, BCL2, MLH1, and CTNNB1), linked to endometrial carcinogenesis, in endometrial polyps of patients with and without postmenopausal bleeding in order to determine whether symptomatic endometrial polyps have a genetic phenotype similar to that of endometrial cancer. METHODS: Samples were obtained hysteroscopically from endometrial polyps of postmenopausal patients, and the expression of genetic markers involved in the pathogenesis of endometrial cancer (PTEN, BCL2, MLH1, and CTNNB1) was analyzed. The expression of these markers was then compared between patients with and without symptoms, which was characterized as postmenopausal bleeding. Other clinical characteristics of the patients, such as duration of menopause, polyp size, presence of systemic hypertension, diabetes mellitus, and smoking habits were also analyzed. RESULTS: Samples from a total of 60 patients were obtained, as calculated for a test power of 0.80. No statistical differences (p > 0.05) were observed between the two groups concerning the expression of the studied endometrial cancer risk factor genes, or with regard to the clinical aspects evaluated. CONCLUSION: The study found no evidence that symptomatic endometrial polyps have a similar phenotype to type 1 endometrial cancer; further studies are needed in order to establish whether endometrial polyps are in fact true cancer precursors, or simply raise cancer incidence due to a detection bias.

Accuracy of Transvaginal Ultrasonography, Hysteroscopy and Uterine Curettage in Evaluating Endometrial Pathologies.

Objective To evaluate the accuracy of transvaginal ultrasonography, hysteroscopy and uterine curettage in the diagnosis of endometrial polyp, submucous myoma and endometrial hyperplasia, using as gold standard the histopathological analysis of biopsy samples obtained during hysteroscopy or uterine curettage. Methods Cross-sectional study performed at the Hospital Universitário de Brasília (HUB). Data were obtained from the charts of patients submitted to hysteroscopy or uterine curettage in the period from July 2007 to July 2012. Results One-hundred and ninety-one patients were evaluated, 134 of whom underwent hysteroscopy, and 57, uterine curettage. Hysteroscopy revealed a diagnostic accuracy higher than 90% for all the diseases evaluated, while transvaginal ultrasonography showed an accuracy of 65.9% for polyps, 78.1% for myoma and 63.2% for endometrial hyperplasia. Within the 57 patients submitted to uterine curettage, there was an accuracy of 56% for polyps and 54.6% for endometrial hyperplasia. Conclusion Ideally, after initial investigation with transvaginal ultrasonography, guided biopsy of the lesion should be performed by hysteroscopy, whenever necessary, in order to improve the diagnostic accuracy and subsequent clinical management.

Accuracy of Transvaginal Ultrasonography, Hysteroscopy and Uterine Curettage in Evaluating Endometrial Pathologies / Acurácia da ultrassonografia transvaginal, histeroscopia e curetagem uterina na avaliação de patologias endometriais

Abstract Objective To evaluate the accuracy of transvaginal ultrasonography, hysteroscopy and uterine curettage in the diagnosis of endometrial polyp, submucous myoma and endometrial hyperplasia, using as gold standard the histopathological analysis of biopsy samples obtained during hysteroscopy or uterine curettage. Methods Cross-sectional study performed at the Hospital Universitário de Brasília (HUB). Data were obtained from the charts of patients submitted to hysteroscopy or uterine curettage in the period from July 2007 to July 2012. Results One-hundred and ninety-one patients were evaluated, 134 of whom underwent hysteroscopy, and 57, uterine curettage. Hysteroscopy revealed a diagnostic accuracy higher than 90% for all the diseases evaluated, while transvaginal ultrasonography showed an accuracy of 65.9% for polyps, 78.1% for myoma and 63.2% for endometrial hyperplasia. Within the 57 patients submitted to uterine curettage, there was an accuracy of 56% for polyps and 54.6% for endometrial hyperplasia. Conclusion Ideally, after initial investigation with transvaginal ultrasonography, guided biopsy of the lesion should be performed by hysteroscopy, whenever necessary, in order to improve the diagnostic accuracy and subsequent clinical management.

Resumo Objetivo avaliar a acurácia da ultrassonografia transvaginal, da histeroscopia e da curetagem uterina no diagnóstico de pólipo endometrial, mioma submucoso e hiperplasia de endométrio, utilizando como padrão-ouro a análise histopatológica de amostras obtidas por biópsia realizada durante a histeroscopia ou a curetagem. Métodos estudo transversal realizado no Hospital Universitário de Brasília (HUB), cujas informações foram obtidas nos prontuários das pacientes que foram submetidas à histeroscopia ou curetagem uterina no período de julho de 2007 a julho de 2012. Resultados Foram avaliadas 191 pacientes, sendo que 134 foram submetidas à histeroscopia e 57 à curetagem uterina. Observou-se acurácia diagnóstica maior que 90% para todas as patologias avaliadas por histeroscopia, enquanto que por ultrassonografia transvaginal observou-se acurácia de 65,9% para pólipo, 78,1% para mioma e 63,2% para hiperplasia endometrial. Nas 57 pacientes submetidas a curetagem uterina, observou-se acurácia de 56% para pólipo e de 54,6% para hiperplasia endometrial. Conclusão Idealmente, após a investigação inicial com ultrassonografia transvaginal, deveria, sempre que necessário, ser realizada histeroscopia com biópsia guiada da lesão, o que melhoraria a acurácia diagnóstica e posterior conduta clínica.

The value of hysteroscopic biopsy in the diagnosis of endometrial polyps.

Several studies have demonstrated that the combination of hysteroscopy with endometrial biopsy is more accurate in differentiating endometrial polyps from endometrial hyperplasia and cancer. However, blind biopsy not always confirms hysteroscopic findings due to high rates of inadequate or insufficient material. The objective of this clinical, prospective, and comparative study was to establish a correlation between the histological results of office-based endometrial biopsies (hysteroscopically guided and blind) with the surgical polypectomy specimens. We evaluated 82 patients with hysteroscopic diagnosis of endometrial polyp, who randomly underwent hysteroscopically guided biopsy or blind biopsy, referred for surgical resection. A total of 36 women (43.9%) underwent hysteroscopically guided biopsy and 46 women (56.1%) underwent blind biopsy. The sensitivity of hysteroscopically guided biopsy for the diagnosis of endometrial polyps ranged between 35.3 and 36.8%, when carried out at the apex and base of the lesion, compared with 29.2% for blind biopsy. Specificity was 33.3, 50, and 60%, respectively, for each biopsy. The positive predictive values were 75, 77.8, and 87.5%, and negative predictive values were 8.3, 14.3, and 8.1% respectively, compared with surgical polypectomy specimens. The office-based endometrial biopsies had low diagnostic accuracy for endometrial polyps compared with surgical polypectomy specimens.

Common Dysregulated Genes in Endometriosis and Malignancies.

Several authors have investigated the malignant transformation of endometriosis, which supports the hypothesis of the pre-neoplastic state of endometriotic lesions, but there are few data about the pathways and molecular events related to this phenomenon. This review provides current data about deregulated genes that may function as key factors in the malignant transition of endometriotic lesions. In order to do so, we first searched for studies that have screened differential gene expression between endometriotic tissues and normal endometrial tissue of women without endometriosis, and found only two articles with 139 deregulated genes. Further, using the PubMed database, we crossed the symbol of each gene with the terms related to malignancies, such as cancer and tumor, and obtained 9,619 articles, among which 444 were studies about gene expression associated with specific types of tumor. This revealed that more than 68% of the analyzed genes are also deregulated in cancer. We have also found genes functioning as tumor suppressors and an oncogene. In this study, we present a list of 95 informative genes in order to understand the genetic components that may be responsible for endometriosis' malignant transformation. However, future studies should be conducted to confirm these findings.

Common Dysregulated Genes in Endometriosis and Malignancies / Genes comuns desregulados em endometriose e doenças malignas

Abstract Several authors have investigated the malignant transformation of endometriosis, which supports the hypothesis of the pre-neoplastic state of endometriotic lesions, but there are few data about the pathways and molecular events related to this phenomenon. This review provides current data about deregulated genes that may function as key factors in the malignant transition of endometriotic lesions. In order to do so, we first searched for studies that have screened differential gene expression between endometriotic tissues and normal endometrial tissue of women without endometriosis, and found only two articles with 139 deregulated genes. Further, using the PubMed database, we crossed the symbol of each gene with the terms related to malignancies, such as cancer and tumor, and obtained 9,619 articles, among which 444 were studies about gene expression associated with specific types of tumor. This revealed that more than 68% of the analyzed genes are also deregulated in cancer. We have also found genes functioning as tumor suppressors and an oncogene. In this study, we present a list of 95 informative genes in order to understand the genetic components that may be responsible for endometriosis' malignant transformation. However, future studies should be conducted to confirm these findings.

Resumo Vários autores têm estudado transformações malignas em endometriose que suportam a hipótese de um estado pré-neoplásico das lesões endometrióticas; contudo, existem poucos dados sobre as vias e eventos moleculares relacionados a este fenômeno. Esta revisão fornece dados atuais sobre genes desregulados que possam funcionar como fatores-chave para a transição maligna das lesões endometrióticas. Assim, inicialmente, estudos de expressão gênica diferencial em larga escala comparando tecido endometriótico e endométrio normal de mulheres sem endometriose foram procurados, e apenas dois artigos com 139 genes desregulados foram obtidos. Posteriormente, usando o banco de dados do PubMed, foram cruzados os símbolos de cada gene com termos relacionados à malignidade, como câncer e tumor, e 9.619 artigos foram obtidos, dos quais 444 eram estudos sobre expressão de genes associados a tipos específicos de tumor. Isto revela que mais de 68% dos genes analisados eram também desregulados em câncer. Também foram encontrados genes que funcionam como supressor tumoral e um oncogene. Este estudo apresenta uma lista de 95 genes informativos para compreender os componentes genéticos que possam ser responsáveis por transformações malignas na endometriose. Contudo, estudos futuros são necessários para confirmar estes achados.