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The aim of this study was to perform histopathological analysis of residual material in the cannula by endometrial sampling using a Carmen injector, and to compare the results. The study was conducted in the Department of Gynaecology, Mardin Training and Research Hospital, Artuklu/Mardin, Turkiye, from December 2021 to June 2022. The study group consisted of 104 patients who presented to the outpatient clinic with complaints of abnormal uterine bleeding. Endometrial curettage material was collected from all patients using a Carmen injector. The collected material was discharged into the pathology container (Group 1). Subsequently, the residual material remaining in the injector was placed in a separate pathology container (Group 2). Specimens were sent to the pathology laboratory with buffered formol. The pathological evaluation was performed by the same pathologist without revealing the patients' names. Comparative histopathological results of the patients in Group 1 and Group 2 were found to be fully compatible in 64.4% of the patients. In 35.6% of the patients, the histopathological results were different from each other between Group 1 and Group 2. Pathological results were different from each other in 21.2% of patients with incompatible pathology results. In Group 1, 16.7% of the patients were over-diagnosed, while 7.7% of the patients were over-diagnosed in Group 2. It would be beneficial to carefully remove the material remaining in the cannula and send it for pathological examination as it may affect the histopathological results. Key Words: Abnormal uterine bleeding, Probe curettage, Karman cannula, Histopathological evaluation.

Objective: COVID-19 vaccination has been related to menstrual irregularities; however, the effect on postmenopausal women is unknown. The aim of this study was to analyze the prevalence of postmenopausal bleeding (PMB) after COVID-19 vaccination., Methods: A retrospective study was conducted in the Department of Gynecology in Hospital del Mar. Consecutive postmenopausal women with data available and endometrial biopsy were included between February 2021 and January 2022. Patients were stratified between COVID-19 vaccinated and unvaccinated groups. PMB after 30 days from last vaccine dose was considered unrelated to vaccine. Endometrial pathology diagnoses were stratified into benign or malignant. Univariable and multivariable of regression analysis on variables potentially associated with PMB was performed., Results: A total of 381 patients were included, 91 in the vaccinated group and 290 in the unvaccinated group. Prevalence of PMB in the vaccinated group was 75.8% compared to 59.0% in the unvaccinated group ( p  < 0.005). No increase in endometrial malignant pathology was observed among the vaccinated group ( p  = 0.189). Multivariable analysis that correlates factors associated with PMB suggests COVID-19 vaccine and malignant endometrial biopsy as independent risk variables., Conclusions: A higher prevalence of PMB was associated with COVID-19 vaccine. Endometrial histological results showed no association with COVID-19 vaccination, but endometrial biopsy should be performed for PMB.

Objective: To develop predictive models for endometrial hyperplasia and endometrial cancer in patients with recurrent abnormal uterine bleeding (AUB)., Methods: This retrospective cohort study analyzed patients with recurrent AUB who had previous endometrial sampling that showed benign results between January 2013 and December 2021. A model was constructed from the significant factors associated with endometrial hyperplasia and endometrial cancer using multivariate logistic regression. Risk scores were calculated from the log odds of each significant predictive factor and were subsequently subcategorized into risk groups. The overall performance and internal validation of the model were assessed with the area under the receiver operating characteristic curve (AUC) and bootstrap methods., Results: Of the total 456 patients with recurrent AUB, endometrial hyperplasia and endometrial cancer were detected in 8.3% and 2.2% of cases, respectively. The average interval between the first and second endometrial samplings was 25.1 months. Factors significantly associated with endometrial hyperplasia and endometrial cancer included age older than 45 years (odds ratio [OR] 2.86, 95% CI, 1.31-7.03), nulliparity (OR 3.50, 95% CI, 1.76-6.85), a history of endometrial polyp (OR 3.69, 95% CI, 1.93-7.05), and an interval of less than 12 months between sampling (OR 2.36, 95% CI, 1.25-4.42). Predictive factors were scored and categorized into three groups: 0-3, 5-8, and 9-11 points. The corresponding risks for endometrial hyperplasia and endometrial cancer in these groups were 4.7%, 15.5%, and 57.1%, respectively. The AUC was 73.1%, with a mean absolute error of 0.01., Conclusion: Endometrial hyperplasia and endometrial cancer occur at low incidence among one-fifth of patients with AUB who experience recurrent bleeding. Older age, nulliparity, a history of endometrial polyps, and an interval of less than 12 months between samplings are predictive factors for endometrial hyperplasia and endometrial cancer in this cohort., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Abnormal uterine bleeding (AUB) is the most common and frequent presenting complaint in Gynaecology in all age group especially in perimenopausal and postmenopausal women. The spectrum of AUB in women of our country includes a wide varieties of organic pathology. The objective of this study was to assess the role of endometrial thickness as a predictor of endometrial malignancy among the women presenting with AUB. This cross-sectional descriptive type of observational study was conducted among 122 women of perimenopausal (40-50 years) and 87 women of postmenopausal (>50 years) age group presenting with AUB in the Obstetrics and Gynaecology department of Mymensingh Medical College Hospital, Bangladesh from February 2020 to August 2021. These patients were subjected to a detailed history and meticulous general, systemic and local examination. The relevant investigations like Transvaginal Sonography (TVS) followed by endometrial biopsy by dilatation and curettage were done in all study participants. Most of the women were in the age group 41-45 years in perimenopause and 51-55 years in postmenopause. Mean±SD was 45.8±4.1 years in perimenopause and 56.3±6.4 years in postmenopause. There was statistical significance in developing endometrial malignancy regarding risk factors of nulliparity, Hypertention (HTN), Diabetes mellitus (DM) and hormone intake between perimenopause and postmenopause. Endometrial thickness was measured in perimenopause and postmenopause. Mean±SD of Endometrial thickness (ET) in perimenopause and postmenopause was 11.3±4.4mm and 7.2±6.3mm with statistical significance (p<0.001). Sensitivity, specificity, Positive predictive value (PPV), Negative predictive value (NPV) and accuracy of TVS were 85.5%, 67.4%, 81.2%, 73.8% and 78.7% in perimenopause and 85.9%, 20%, 89%, 75% & 83.9% in postmenopause. Cut off limit of ET in detection of endometrial malignancy was 18.5mm with sensitivity 74.8% and specificity 63.6% in perimenopause and 12.2mm with sensitivity 81.0% and specificity 65.8% in postmenopausal women. Women with AUB, endometrial malignancy should be suspected when endometrial thickness on TVS >18.5mm and >12.2mm in perimenopause and postmenopausal age group respectively. TVS has high sensitivity in detection of endometrial malignancy both in perimenopausal and postmenopausal women with AUB and TVS is a reliable, noninvasive method.

To evaluate gene expression associated with unfavorable vaginal bleeding in users of the Etonogestrel (ENG) contraceptive implant. Prospective study involving 100 women who intended to use the ENG implant. Exclusion criteria included abnormal uterine bleeding, inability to attend a 1-year follow-up, and implant removal for reasons unrelated to vaginal bleeding or loss of follow-up. We obtained endometrial biopsies before implant placement and assessed the expression of 20 selected genes. Users maintained a uterine bleeding diary for 12 months post-implant placement. For statistical analysis, we categorized women into those with or without favorable vaginal bleeding at 3 and 12 months. Women with lower CXCL1 expression had a 6.8-fold increased risk of unfavorable vaginal bleeding at 3 months (OR 6.8, 95% CI 2.21-20.79, p < 0.001), while those with higher BCL6 and BMP6 expression had 6- and 5.1-fold increased risks, respectively. By the 12-month follow-up, women with lower CXCL1 expression had a 5.37-fold increased risk of unfavorable vaginal bleeding (OR 5.37, 95% CI 1.63-17.73, p = 0.006). Women with CXCL1 expression < 0.0675, BCL6 > 0.65, and BMP6 > 3.4 had a higher likelihood of experiencing unfavorable vaginal bleeding at 3 months, and CXCL1 < 0.158 at 12 months. Users of ENG contraceptive implants with elevated BCL6 and BMP6 expression exhibited a higher risk of breakthrough bleeding at the 3-month follow-up. Conversely, reduced CXCL1 expression was associated with an elevated risk of bleeding at both the 3 and 12-month follow-ups., (© 2024. The Author(s).)

Background: There has been considerable progress in our understanding of endometriosis, but its pathophysiology remains uncertain. Uncovering the underlying mechanism of the rare instances of endometriosis reported in early postmenarcheal years and in girls before menarche can have wide implications., Methods: We conducted a literature review of all relevant articles on Medline., Results: In the review, we explore the pathogenetic theories of premenarcheal endometriosis, the role of retrograde menstruation in the adult and its potential role in early-onset disease, as well as the factors that argue against the existence of a link between early-onset endometriosis (EOE) and neonatal uterine bleeding (NUB)., Conclusions: As with endometriosis in adult women, the pathogenesis of early-onset disease remains unclear. A link between NUB and EOE is plausible, but there are considerable challenges to collating supporting evidence. The state of our understanding of early uterine development and of the pathophysiology of NUB leaves many unknowns that need exploration. These include proof of the existence of viable endometrial cells or endometrial mesenchymal stem cells in NUB, their passage to the pelvic cavity, their possible response to steroids, and whether they can reside within the pelvic cavity and remain dormant till menarche.

Background: Abnormal uterine bleeding (AUB) refers to any symptomatic deviation from normal menstruation. AUB is a common gynecological disorder in non-pregnant women of reproductive age, accounting for approximately 33% of gynecological outpatient visits. The early diagnosis and management cause of AUB is important because of increased incidence of endometrial carcinoma with rapid growth. Transvaginal ultrasound is non-invasive imaging technique used to find endometrial carcinoma before referring patients for invasive techniques. Dilatation and curettage (D&C) and endometrial biopsy are surgical procedures that scrape the endometrial lining of the uterus for diagnosis and treatment. The aim of this study is to describe the clinicopathologic pattern of endometrial specimens in women with AUB and ultrasonographic correlation., Methods: Tissues from endometrial biopsy and curettage of 411 patients with AUB who referred to Shahid Mohammadi hospital were prospectively selected from 2021 to 2023. Patients were divided into three groups based on age and menstrual status including: premenopausal (18-39 years), perimenopausal (40-49 years) and postmenopausal (≥50 years). The results were correlated to patient's age and other data and evaluated with statistical analysis., Results: During the two-year study period, a total of 411 endometrial specimens with clinical diagnosis of AUB were submitted and the results were analyzed. The youngest patient presenting with AUB was 21 years old, while the oldest was 77 years old. The most common complaint was menorrhagia in 201 (48.0%) out of 411 patients. The most common pathology finding in three groups was polyp in 100 (24.3%) cases. Hormonal effect was the next commonly observed pattern seen in 70 (17.0%) cases. P value was calculated as 0.003 which was significant using chi-square for the trend seen in age., Conclusion: Endometrial sampling is a useful tool for evaluation of women with AUB and referring patients for treatment. Histopathological evaluation of the endometrium is very useful in detecting the etiology of AUB. Transvaginal sonography has high sensitivity in detecting polyps., (© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

The most common presentation of the most common gynaecological malignancy (Endometrial Cancer) is abnormal PV bleeding. Transvaginal sonography (TVS) is the first line investigation to assess the endometrial nature. Four to five (4-5) millimetre endometrial thicknesses is considered as the normal cut off in post menopausal women. But endometrial cancer can be present while endometrial thickness is less than 4mm. The author describes three cases of isolated endometrial cancer in Glangwili General Hospital in Wales, UK that was diagnosed despite endometrial thickness being less than 4mm and a brief review of the literature on its prevalence, risk factors, clinical presentation, diagnosis and therapeutic approach.

DIAGNOSTIC STRATEGY FOR INTRAUTERINE LESIONS The diagnostic strategy for intrauterine lesions is a question that arises very frequently in gynecological consultations. Endometrial cancer is more frequent in postmenopausal women and bleeding is the first clinical sign in more than 90% of cases. Pelvic ultrasound and endometrial biopsy have a very important place in the diagnostic strategy. After a single episode of abnormal uterine bleeding and when the ultrasound estimates the thickness of the endometrium to be less than or equal to 4 mm, it is possible to postpone further uterine exploration. In the event of recurrent abnormal uterine bleeding or when the thickness of the endometrium is greater than 4 mm in a postmenopausal woman, additional uterine explorations (hysteroscopy and histology) are recommended. If endometrial cancer is discovered, the key examination is lumbopelvic MRI., Competing Interests: J. Belghiti déclare des interventions ponctuelles pour Intuitive Surgical. - S. Egels déclare n’avoir aucun lien d’intérêts - G. Canlorbe déclare des liens durables avec Intuitive Surgical et avoir été pris en charge à l’occasion de déplacement pour congrès par Applied Medical.

Background: Menstrual problems with all manifestations ranging from life-threatening bleeding to amenorrhea are considered patterns of abnormal uterine bleeding (AUB), which is until now a popular reason for referral to the gynaecologic clinic and requires a special diagnostic tool., Objective: To assess the accuracy of hysteroscopy in diagnosing endometrial pathologies and to compare it with sonographic and histopathologic reports., Patients and Methods: A prospective study conducted in the Baghdad Teaching Hospital on 60 Iraqi females having varying complaints from abnormal uterine bleeding in pre- and post-menopausal women, infertility, and chronic pelvic pain with normal or abnormal ultrasound findings. Office hysteroscopy was done and an endometrial biopsy was obtained for histopathology for a period of 10 months between September 2020 and June 2021., Results: The current study showed that hysteroscopy was more accurate in diagnosing sensitivity of endometrial poly (100%), fibroids (83%), hyperplasia (84.2%), and cancer (50%) whereas ultrasounds were more accurate in diagnosing sensitivity to endometrial myoma (90%). Hysteroscopy and ultrasound showed low sensitivity in detecting endometrial cancer (50% and 34%, respectively)., Conclusion: Although a transvaginal ultrasound was considered an integral part in the diagnosis of endometrial pathologies, it can be used for initial investigation, however, when suspecting endometrial pathology, hysteroscopy can be more advanced for evaluation, immediate treatment of endometrial masses, and obtaining targeted biopsies. Hysteroscopy showed high sensitivity in detecting endometrial polyps., Competing Interests: The author declares no conflict of interest.

Abnormal uterine bleeding (AUB) is defined as abnormal volume, duration, or frequency of menstrual period and is a common symptom in women of all ages (premenopausal, perimenopausal, and postmenopausal). The acronym PALM-COEIN, introduced by the International Federation of Gynecology and Obstetrics (FIGO), facilitates the evaluation and differential diagnosis of AUB, mostly in premenopausal women with AUB. Endometrial evaluation (including ultrasound or hysteroscopic imaging and tissue sampling) for subtle pathology is proposed in patients who are at high risk for endometrial cancer and in patients at low risk who present with AUB and who present poor correspondence in medical treatment. Many new diagnostic modalities are available in clinicians in order to help the assessment of women presenting with abnormalities in their menstrual pattern. The present study reviews the optimal management of women presenting with AUB, taking into consideration the actual need for invasive management in these women, who of them require it, and who can be diagnosed without histological verification. The importance of endometrial tissue sampling in women who present with AUB as well as the best timing for a clinician to conduct a biopsy are two axons analyzed below, according to the latest worldwide guidelines and major publications about this subject., (© 2021 International Federation of Gynecology and Obstetrics.)

Background: The diagnosis of benign and malignant menopausal endometrial lesions (MEL) is often misled by complicated clinical indicators and ultrasonographic parameters in actual clinical applications., Objective: To investigate the performance of clinical indicators and ultrasonographic parameters in the diagnosis of MEL., Methods: A cohort of 156 enrolled menopausal patients with MEL was divided into benign group (128 cases) and malignant group (28 cases). Two clinical indicators of patient age (PA), abnormal vaginal bleeding (AVB) and three transvaginal ultrasonography (TVS) parameters of endometrial thickness (ET), endometrial uneven echo (EUE) and endometrial blood flow signal (EBFS) were measured for the mathematical modelling. The performance of combined indicators and individual indicators were firstly compared, and then the optimized combined indicators was compared with corresponding individual indicators, respectively., Results: Our experiments verified that the mathematical modelling presented robust capabilities in the diagnosis of MEL with the sensitivity, specificity and AUC of 78.6%, 75.8% and 0.83 for combined indicators, and 75.0%, 81.3% and 0.85 for optimized combined indicators, respectively. The cut off thresholds of PA was 57.5 years, ET was 11.5 mm. Furthermore, the AVB presented the most important risk factor among the optimized indicators of PA, ET and AVB (P< 0.05)., Conclusions: The combined indicators presented better performance in differentiating benign and malignant MEL and the AVB demonstrated the most capability for clinical applications.

Background: Abnormal uterine bleeding requires the investigation of the endometrium. Histology is typically used but there remains room for the improvement and use of cytology., Methods: Women presenting for clinically indicated office endometrial biopsy were prospectively enrolled. Tao endometrial brushing and office endometrial biopsy were performed, and surgical procedure if clinically indicated. Tao brush cytology specimens were blindly reviewed by up to three pathologists, consensus obtained, and scored as: benign, atypical (favor benign), suspicious, positive for malignancy, or non-diagnostic. Cytology and histology were compared to surgical pathology to determine sensitivity, specificity, positive, and negative predictive values to detect AH (atypical hyperplasia) or EC (endometrial cancer)., Results: Clinical indications of 197 enrolled patients included postmenopausal bleeding (90, 45.7%), abnormal uterine bleeding (94, 47.7%), and abnormal endometrium on ultrasound without bleeding (13, 6.6%). Of the 197 patients, 185 (93.9%) had cytology score consensus and a total of 196 (99.5%) had consensus regarding cytology positivity. Surgical pathology diagnoses (N = 85) were 13 (15.3%) FIGO grade 1 or 2 EC, 3 (3.5%) AH, and 69 (81.2%) benign endometrium. Sensitivity and specificity to detect EC or AH were 93.7% and 100%, respectively, via endometrial biopsy; 87.5% and 63.8%, respectively, via endometrial cytology when scores of malignancy, suspicious, or atypical were considered positive., Conclusions: In a high-risk population, Tao brush endometrial cytology showed high sensitivity to detect AH and EC comparable to biopsy histology when considering scores of malignancy, suspicious, atypical, and non-diagnostic. Revisiting the potential value of endometrial cytology in the contemporary era of endometrial diagnostic workup is warranted., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: The aim of this study is to evaluate the quality of the endometrial sample obtained by office endometrial aspiration when performed before or after saline contrast sonohysterography (SCSH) in women with postmenopausal bleeding and a thickened endometrium. To conduct a complete, minimally invasive and cost-effective diagnostic workup in women with postmenopausal bleeding and a thickened endometrium, ideally both the office endometrial sampling and SCSH are performed. However, it is not known whether both tests affect each other when performed one after another., Material and Methods: Women with postmenopausal bleeding and an endometrial thickness >4 mm were eligible. Women were randomized into two groups: one group received endometrial aspiration before SCSH, the other group received SCSH before endometrial aspiration. The primary outcome was the proportion of sufficient endometrial samples. Reliability of the SCSH images and pain during procedures were secondary outcomes., Results: During the inclusion period, 513 eligible women with postmenopausal bleeding visited the participating hospitals, 293 of whom received information about the study. Of these women, 232 (79%) agreed to participate. In the SCSH-aspiration group, 65 women (59%) had a sufficient endometrial sample compared with 70 (67%) in the aspiration-SCSH group (odds ratio 1.46, 95% CI 0.83-2.54, P = .19). The proportion of reliable sonographic images was significantly higher in the SCSH-aspiration group (n = 88, 87%) compared with the aspiration-SCSH group (n = 71, 74%) (OR 2.38, 95% CI 1.38-4.99, P = .02) in the per protocol analysis., Conclusions: This study shows that the quality of an endometrial sample in women with postmenopausal bleeding is not affected by SCSH. Both procedures can be performed in one outpatient visit to perform an optimal diagnostic workup., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objectives: To assess the inter-rater agreement and reliability of using subjective pattern recognition for diagnosing endometrial cancer (EC) on ultrasound in women with postmenopausal bleeding (PMB)., Methods: This was a prospective cross-sectional study conducted at a gynecological rapid-access clinic, between October 2016 and December 2017, in which consecutive women with PMB and endometrial thickness of ≥ 4.5 mm on transvaginal ultrasound examination were included. Women on hormone replacement therapy or tamoxifen and those with a history of primary gynecological malignancy were excluded. Two raters independently performed ultrasound examinations, blinded to each other's findings, and classified women as having uniformly thickened endometrium, benign endometrial polyp or EC, using subjective pattern recognition. Inter-rater reliability of ultrasound diagnosis was assessed using Cohen's kappa (κ) statistic. All women subsequently underwent either outpatient endometrial biopsy, hysteroscopy or hysterectomy., Results: Forty women were included in the study, with a median age of 61 (interquartile range (IQR), 57-69) years and a median endometrial thickness of 11.0 (IQR, 6.2-20.3) mm. Final histological analysis confirmed 16 (40%) women with EC, 16 (40%) with benign endometrial polyp, four (10%) with atrophic endometrium, three (8%) with proliferative endometrium and one (3%) with endometrial hyperplasia. Inter-rater agreement for the ultrasound diagnoses of uniformly thickened endometrium, benign endometrial polyp and EC was 14/16 (87.5%), 22/30 (73.3%) and 28/34 (82.4%), respectively; inter-rater reliability was good (κ = 0.69; 95% CI, 0.49-0.88). When the ultrasound diagnoses were grouped as either cancer or no cancer, inter-rater agreement was 85% and inter-rater reliability was good (κ = 0.78; 95% CI, 0.61-0.95). Rater A correctly identified 14/16 cases of EC and Rater B identified 15/16. EC was misdiagnosed as benign polyps on ultrasound in two women by Rater A and in one woman by Rater B. The overall accuracies of Rater A and Rater B in differentiating between benign endometrial pathologies and malignancy were 90% and 90%, respectively., Conclusions: Our results show good inter-rater reliability of subjective pattern recognition in diagnosing uniformly thickened endometrium, benign endometrial polyp and EC on ultrasound in women with PMB. Our findings should facilitate wider use of subjective pattern recognition in routine clinical practice. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

We report a case of ciliated carcinoma of the endometrium in a 55-yr-old woman with stromal hyperthecosis of the ovaries. The patient presented with postmenopausal uterine bleeding and an endometrial curetting revealed an atypical epithelial proliferation that met the criteria for endometrioid adenocarcinoma notwithstanding an abundance of ciliated cells. Cilia were present not only within typical endometrioid glands but also within microacini of quasi-solid areas as well as inside intracytoplasmic vacuoles. The subsequent hysterectomy specimen demonstrated a well-differentiated adenocarcinoma of the endometrium with a predominance of neoplastic glands lined by ciliated epithelial cells, thus confirming the initial suspicion for ciliated carcinoma. Since the first description of ciliated adenocarcinoma of the endometrium in 1983, only a handful of additional cases have been reported in the literature. We review the spectrum of histologic presentations of this endometrial neoplasm and elaborate on its distinction from cilia-bearing mimickers and its histogenesis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 by the International Society of Gynecological Pathologists.)

Metastasis of breast cancer to the uterus is quite rare. The majority of reported cases have evolved from previously known invasive ductal and lobular carcinomas of the breast. Herein, a rare case of invasive micropapillary carcinoma of the breast that was diagnosed via endometrial biopsy, without a previous diagnosis or history of breast cancer, was presented. A 58-year-old postmenopausal patient, who had no history of cancer, presented with complaints of abnormal uterine bleeding (AUB) that had begun 2 weeks prior. After undergoing transvaginal ultrasonography, endometrial biopsy, tomography, and positron emission tomography/computed tomography, the patient was preliminarily diagnosed with invasive carcinoma of the breast. The biopsy confirmed the diagnosis of metastatic invasive micropapillary carcinoma of the breast. In postmenopausal AUB, endometrial metastasis of breast cancer should be kept in mind, especially in underdeveloped and developing countries where regular breast cancer screening has not been achieved. KEY WORDS: Breast cancer, Endometrium, Metastasis, Micropapillary carcinoma.

Study Objective: Patients who have undergone endometrial ablation may present a diagnostic challenge when they subsequently develop vaginal bleeding, pelvic pain, or postmenopausal bleeding. Extensive scarring of the uterine cavity often precludes evaluation and/or conservative treatment. For further research on this topic, we performed hysteroscopic examination in study subjects a mean duration of 4 years after they had undergone water vapor endometrial ablation., Design: Prospective, multicenter, observational clinical study., Setting: Eight private practice or outpatient sites in the United States and Mexico., Patients: Seventy subjects who had completed their 36-month follow-up in the AEGEA Pivotal Trial., Interventions: Diagnostic hysteroscopy., Measurements and Main Results: The subjects were screened for general health and infection and underwent diagnostic hysteroscopy. Menstrual bleeding status was recorded. The video of the hysteroscopic examination was analyzed by an independent reviewer, who assessed uterine cavity access and visualization of the cornua and tubal ostia as well as characterized adhesions on the basis of the criteria by March et al. An independent reviewer also subjectively assessed whether Pipelle endometrial biopsy or intrauterine device placement would be feasible. Uterine cavity access was achieved in 90% (63/70) of subjects. Among subjects with cavity access, the cornua and ostia were visualized in 79% (50/63) and adhesions were absent in 75% (47/63), with only 2 women having severe adhesions (3%, 2/63). Biopsy was projected to be feasible in 86% (62/70) and intrauterine device placement in 60% (42/70) of all subjects. The subjects' bleeding statuses were not correlated with uterine cavity access. The results were consistent for subjects with large uterine cavities and International Federation of Gynecologic and Obstetrics type II to VI myomas ≤4 cm., Conclusion: Water vapor endometrial ablation preserved an accessible uterine cavity and visualization of the ostia in most subjects, with minimal incidence of severe adhesions, a mean of 4 years after the ablation procedure., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Menopause is characterized by permanent cessation of menstrual periods and is clinically diagnosed after 12 months of complete amenorrhea. It occurs at a median age of 51 years alongside the physiological process of aging, although it can happen at an earlier age for other medical conditions or after surgery (surgical menopause). Due to reduced circulating estrogens and progesterone, the reproductive organs undergo progressive atrophy. This physiologic process of aging is also present at an endometrial level; without the cyclic hormonal actions of the menstrual cycle, the endometrium during menopause becomes atrophic. Postmenopausal bleeding (PMB) is a common gynecologic complaint encountered by the clinician. Endometrial cancer is present in about 10% of patients with PMB. Nevertheless, many other conditions, such as endometrial or cervical polyps, genital atrophy, or non-gynecologic conditions, may also be present. Historically, dilation and curettage (D&C) was the main diagnostic procedure in patients with PMB; however, newer methods of investigation have replaced D&C. The aim of this review is to present an up-to-date analysis of the current evidence for the clinical management of vaginal bleeding in postmenopausal women.

Hysteroscopy is the gold standard for evaluating the uterine cavity, diagnosing intrauterine pathology, and operative intervention for some causes of abnormal uterine bleeding. The American College of Obstetricians and Gynecologists concluded that, when the endometrium measures ≤4 mm with transvaginal ultrasonography, the likelihood that bleeding is secondary to endometrial carcinoma is less than 1% (negative predictive value 99%), and endometrial biopsy is not recommended. Endometrial sampling in this clinical scenario will likely result in insufficient tissue for evaluation and it is reasonable to consider initial management for atrophy. A thickened endometrium on transvaginal ultrasonography (>4 mm in a postmenopausal woman with postmenopausal bleeding) warrants additional evaluation with endometrial sampling. A negative tissue biopsy following 'blind' endometrial sampling in women with postmenopausal bleeding is not considered to be an endpoint, and further evaluation of the endometrial cavity with hysteroscopy to exclude focal disease is imperative.

Objectives: To investigated the metrorrhagia volume-reduction activity, anti-inflammatory activity and repair-promoting activity of Clinopodium chinense (Benth.) O. Kuntze., Methods: An abnormal uterine bleeding (AUB) model was induced via oral administration of mifepristone and misoprostol to pregnant rats, which were treated with the total extract of C. chinense (TEC). After 7 days, the metrorrhagia volume was measured, the levels of TXB2, 6-keto-PGF1α, IL-6 and TNF-α were measured by ELISA, the pathological changes and micro vessel density (MVD) of the endometrium were evaluated using HE and immunofluorescence staining, and the expression of VEGF, MMP-2/9 and TGF-β were assessed by Western blotting. Preliminary phytochemicals were screened and identified by UPLC-Q-TOF-MS., Results: Eleven compounds in C. chinense were identified via comparison to standard substances. The results of animal experiment showed TEC could reduce metrorrhagia volume, alleviate pathological injury and increase MVD to promote recovery of the endometrium; TEC could also increase the levels of TXB2 and the expression of VEGF, TGF-β, decrease the levels of IL-6, TNF-α and the expression of MMP-2/9., Conclusions: TEC showed beneficial effects on treating AUB by reducing metrorrhagia volume, inhibiting the inflammatory response and promoting the repair of the endometrium. Additionally, TEC also showed great haemostatic potential in AUB., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Data supporting a survival advantage of endometrial cancer diagnosed before the onset of postmenopausal bleeding are lacking. This study sought to compare overall survival and disease recurrence between women who were asymptomatic at diagnosis and women who were symptomatic at diagnosis. A systemic search was conducted in databases using the terms: "asymptomatic," "ultrasound," "screening," and "endometrial cancer." Only original research studies that compared characteristics of tumour advancement and survival measures were included. The six articles included in the meta-analysis comprised 2961 patients. Data were collected on study design and period, number and characteristics of participants, and outcomes in terms of tumour histology and survival measures. Higher rates of stage I tumours were shown among asymptomatic patients (relative risk 1.19). The proportion of high-grade histology did not differ between the two groups (relative risk 0.92). The crude pooled estimate for overall survival did not yield statistical significance, nor did recurrence-free survival (which was reported by three studies). In conclusion, endometrial cancer diagnosed in asymptomatic women is not associated with higher survival than in symptomatic women. Invasive procedures in asymptomatic women with incidental ultrasonographic findings should be carefully weighed because no survival advantage is expected., (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Objective: To study influencing factors which cause the endometrial diseases in patients with breast cancer after operation. Methods: A retrospective study was performed on 212 breast cancer post-operation patients with endometrial diseases between June 2006 and January 2018 in Women's Hospital School of Medicine Zhejiang University to analyse the factors which influenced the endometrial diseases. Results: The abnormal uterine bleeding and endometrial thickness were related to the severity of endometrial disease in patients with breast cancer, and they were independent risk factors for breast cancer patients to have endometrial cancer ( P< 0.05) . When the diagnostic cut off value of endometrial thickness was ≥0.49 cm, the sensitivity and specificity to endometrial cancer were 78% and 25%, respectively. The average endometrial thickness was (0.56±0.39) cm in patients who were treated by selective estrogen receptor modulator (SERM) after gynecological surgery, which was significantly thicker than that of aromatase inhibitor (AI) group [ (0.33±0.23) cm] and no treatment group [ (0.44±0.28) cm, P< 0.05]. The endometrial disease recurrent rate and reoperation rate in SERM group were (26.2%, 14.3%) slightly higher than that of AI group (9.5%, 4.8%) and no treatment group (21.6%, 4.9%), but there were not significant differences (all P> 0.05). Conclusions: The clinical symptom of abnormal uterine bleeding and thickening endometrium are risk factors for breast cancer patients to have endometrial cancer. The endometrial thickness has high predictive value for breast cancer patients to diagnose endometrial cancer. The SERM treatment increases the endometrial thickness, recurrent rate and reoperation rate in post-operation patients.

Background: Several methods have been used for evaluation of the endometrial pathology in patients with abnormal uterine bleeding. Endometrial biopsy is one of the primary methods used for diagnostic evaluation, which is a minimally invasive approach. The aim of this study was to compare the adequacy yield of samples obtained by MedGyn® Endosampler with Formal Fractional Curettage., Objective: This study was designed to compare the endometrial tissue quality and diagnostic accuracy between MedGyn® Endosampler and Formal Fractional Curettage in patients with abnormal uterine bleeding., Methods: A total of 85 endometrial tissue samples were tested by the MedGyn® Endosampler, followed by Formal Fractional Curettage, from patients at Phrapokklao Hospital who were eligible for the study and met the inclusion criteria for uterine curettage. Samples were collected between August, 2018 and April, 2019. Both operations were performed by the same investigator. The samples were submitted separately and sent to the same pathologist., Results: The mean age of the patients was 46.92 ± 6.94 years. 91.76% (78/85) of the samples obtained by Formal Fractional Curettage and 89.41% (76/85) of the samples obtained by MedGyn® Endosampler device were adequate for histopathological examination. The difference was not statistically significant (p = 0.317). The pathological results of endometrial tissue from both techniques were the same in 67 patients (78.82%) and different in 14 patients (16.47%). MedGyn® Endosampler was six times more cost effective when compared to Formal Fractional Curettage., Conclusions: Endometrial sampling using MedGyn® Endosampler is a safe, adequate, accurate, cost effective outpatient procedure which precludes general anesthesia. Therefore, it could be an alternative method for endometrial sampling.

Objectives: The feasibility of vaginoscopic hysteroscopy combined with office endometrial biopsy after ultrasonography for management of post-menopausal vaginal bleeding (PMB)., Materials and Methods: A prospective observational study of with PMB whom attending the Outpatient Clinic of Kang Ning Hospital during a four months period (1st Feb to 31st May 2018) was included. Vaginoscopic hysteroscopy was performed with endometrial biopsy after the initial clinical pelvic examination and transvaginal ultrasound examination., Results: A total of 45 consecutive women with PMB was included. The hysteroscopy and endometrial biopsy were successful in 44 out of 45 (98%), a complete view in 82%, adequate tissue was in 91%, only one case was failed both procedures due to pain. The correlation between hysteroscopy and endometrial biopsy by was 100%. The mean operation time was 229 ± 68 s. The most common histological findings was atrophic endometrium 18 (42%). Five endometrial polyps and 2 submucosal leiomyomas were found. One rare case of endometrial carcinosarcoma (2%) was detected. Patients reported less pain for hysteroscopy than endometrial biopsy with rated VAS pain score was 3.5 ± 2.2, with 5 more score in 18%, and for endometrial biopsy 4.2 ± 2 and 33% respectively (p < 0.001). Six cases (13%) experienced vasovagal attacks immediately after the procedure. There is no other complication., Conclusion: The Vaginoscopic hysteroscopy combined endometrial biopsy is safe and feasible for assessment of endometrial pathology with postmenopausal bleeding., (Copyright © 2019. Published by Elsevier B.V.)

Objective: To determine the most effective analgesia for pain relief during the outpatient endometrial biopsy (OEB) or outpatient hysteroscopy with endometrial aspiration (EA)., Design: Systematic review and network meta-analysis of randomized controlled trials., Setting: Not applicable., Patient(s): Pre- or postmenopausal women undergoing OEB or outpatient hysteroscopy with EA for evaluation of uterine pathology., Intervention(s): We conducted an electronic search of the following bibliographic databases: Medline via PubMed, SCOPUS, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL)., Main Outcome Measure(s): The intensity of pain during, immediately after, and 10-30 minutes after procedure assessed by the 10-cm visual analog scale., Result(s): Lidocaine spray was the most effective medication for reducing pain during OEB (P-score = 0.83) and immediately after OEB (P-score = 0.96). On the other hand, naproxen sodium was the most effective medication for reducing pain during outpatient hysteroscopy with EA (P-score = 1.00), followed by misoprostol plus lidocaine (P-score = 0.87)., Conclusion(s): Lidocaine spray, either alone or with topical application of lidocaine, is the most effective medication for reducing the pain during and after the OEB. Naproxen sodium is the most effective analgesic option during outpatient hysteroscopy with EA., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Endometrial biopsy or curetting is indicated for postmenopausal women with abnormal uterine bleeding and/or thickened endometrium. Often, endometrial biopsy or curetting yields limited benign surface endometrium, which may indicate insufficient sampling. This study addresses the clinical outcome and subsequent pathologic diagnoses in postmenopausal women who received this initial diagnosis. Among a total of 370 endometrial biopsy or curetting between 2012 and 2015, 192 (52%) were diagnosed as limited benign surface endometrial epithelium. The women ranged in age from 55 to 91 yr old. Their clinical presentations mainly included postmenopausal bleeding, pelvic pain, and enlarged uterus. Primarily because the initial report was interpreted as "benign," 108 (57%) had no subsequent follow-up. Interestingly, women with an increased endometrial thickness were more likely to receive repeat evaluation. Among the 84 women who underwent follow-up endometrial sampling, 6 (7%) had hyperplasia with atypia or malignancy, 21 (25%) had a repeat diagnosis of limited surface sample, 4 (5%) had insufficient materials, and 53 (63%) had other benign findings. Among the subset of women who did receive subsequent follow-up, endometrial atypia or malignancies are more likely found in those with increased body mass index. In conclusion, a slight majority of women with postmenopausal bleeding and/or thickened endometrium had an initial limited surface endometrial sample. Most had no subsequent endometrial sampling. Among those with subsequent follow-up, the majority had benign findings. The study highlights the inconsistencies in adequacy criteria for endometrial sampling and the lack of standardization of subsequent management.

Objective: In women with postmenopausal bleeding, endometrial polyps are a frequent finding and the risk of a focal (pre)malignancy in a polyp is up to 6%. Because of this reported risk, the detection of polyps in these women, preferably by a minimally invasive method, is important. The aim of this systematic review was to assess the accuracy of saline contrast sonohysterography (SCSH) for diagnosis of endometrial polyps in women with postmenopausal bleeding., Methods: In August 2018, an electronic search was performed of MEDLINE, EMBASE and Web of Science databases to identify all diagnostic studies in which SCSH was used to detect endometrial polyps in postmenopausal women. Studies were included if SCSH was performed to detect endometrial polyps in women with postmenopausal bleeding and if detection of a polyp on hysteroscopy or diagnosis on histopathology was used as a reference standard. Two reviewers assessed methodological quality using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. Two separate analyses were performed for each reference standard. Pooled sensitivity and specificity were calculated using the hierarchical summary receiver-operating characteristics (HSROC) model and HSROC curves were plotted., Results: After selection and quality assessment, five studies were included. Using 'polyps diagnosed with histopathology' as the reference standard, the pooled sensitivity of SCSH was 86.5% (95% CI, 63.6-100%) and the pooled specificity was 91.1% (95% CI, 63.2-100%). Using 'polyps seen on hysteroscopy' as the reference standard, the pooled sensitivity of SCSH was 85.1% (95% CI, 66.9-100%) and the pooled specificity was 84.5% (95% CI, 68.1-100%). Excluding the one study that included women in whom the SCSH examination was reported to be suboptimal, the pooled sensitivity increased to 90.7% (95% CI, 72.8-100%) using hysteroscopy as the reference standard. The sensitivity of hysteroscopy to detect polyps, as reported in two studies, was 81-98%., Conclusions: Provided that the SCSH examination is of optimal quality, it can be considered as a method to stratify women with postmenopausal bleeding for further diagnostic workup and treatment with hysteroscopy. In women without suspicion of a polypoid lesion on SCSH, and with a benign endometrial sample, expectant management should be considered. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To create a prediction model including clinical variables for the prediction of premalignant/malignant endometrial pathology in premenopausal women with abnormal uterine bleeding (AUB)., Methods: This is an observational retrospective study including 240 premenopausal women with AUB referred to diagnostic hysteroscopy. Based on the presence of endometrial hyperplasia (EH) or cancer (EC), the women were divided into cases (EH/EC) and controls (no EH/EC). Univariate, stepwise logistic regression and ROC curve analysis were performed., Results: 12 women had EH/EC (5%). Stepwise logistic regression analysis showed that EH/EC associated significantly with BMI ≥ 30 (OR=7.70, 95% CI 1.90 to 31.17), diabetes (OR=9.71, 95% CI 1.63 to 57.81), and a thickened endometrium (OR=1.20, 95% CI 1.08 to 1.34, criterion > 11 mm). The AUC was 0.854 (95% confidence intervals 0.803 to 0.896, p <0.0001). Considering the pretest probability for EH/EC of 5%, the prediction model with a positive likelihood ratio of 8.14 showed a posttest probability of 30%. The simultaneous presence of two or three risk factors was significantly more common in women with EH/EC than controls (50% vs. 6.6 and 25% vs. 0%, respectively, p <0.0001)., Conclusion: When premenopausal vaginal bleeding occurs in diabetic obese women with ET > 11 mm, the percentage of premalignant/malignant endometrial pathology increases by 25%. It is likely that the simultaneous presence of several risk factors is necessary to significantly increase the probability of endometrial pathology.

Introduction: Our aim was to correlate junctional zone thickening and irregularity (junctional zone disease) and other ultrasonographic features of adenomyosis with the histopathology of the endometrial-myometrial junctional zone., Material and Methods: Consecutively enrolled premenopausal women (n = 110) scheduled for hysterectomy or transcervical endometrial resection due to abnormal uterine bleeding and/or menstrual pain, underwent two- and three-dimensional transvaginal ultrasonography on the day of surgery with the observer blinded to previous diagnosis. Junctional zone maximum thickness (JZ max ), junctional zone maximum irregularity (JZ dif ) and ultrasonographic characteristics of adenomyosis were compared with histopathology of the junctional zone defined as (1) adenomyosis of the inner myometrium, ≥2 mm myometrial invasion without contact to the basal endometrium, (2) serrated junctional zone, >3 mm myometrial invasion with contact to the basal endometrium or (3) linear junctional zone, no or marginal myometrial invasion ≤3 mm with contact to the basal endometrium., Results: Adenomyosis of the inner myometrium, serrated junctional zone and linear junctional zone was present in 29%, 35% and 35% of the women, respectively. Median JZ max and median JZ dif expanded from linear junctional zone (8.5 and 3.3 mm) to serrated junctional zone (10.1 and 4.1 mm) to adenomyosis of the inner myometrium (14.6 and 9.2 mm) (P < 0.05). In addition, the median number of characteristic adenomyosis-like ultrasonographic features increased from the linear junctional zone to the serrated junctional zone to adenomyosis of the inner myometrium (P < 0.05)., Conclusions: A slightly thickened and/or irregular junctional zone corresponds to a histopathologically defined serrated junctional zone. This study emphasizes three distinct appearances of the junctional zone: adenomyosis of the inner myometrium, junctional zone disease (serrated junctional zone) and linear junctional zone. This classification may be useful in future clinical studies., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Abnormal uterine bleeding (AUB) may be acute or chronic and is defined as bleeding from the uterine corpus that is abnormal in regularity, volume, frequency, or duration and occurs in the absence of pregnancy. It is a widespread complaint in the primary care units. The prevalence of abnormal bleeding is up to 30% among women of reproductive age., Objective: To assess the role of CT virtual hysteroscopy in the evaluation of the uterine cavity in cases with abnormal uterine bleeding in reproductive age., Methods: Cross sectional study was performed at Obstetrics and Gynecology Department and Radiology Department, Zagazig University hospitals, Egypt, on 124 women with abnormal uterine bleeding in reproductive age, and their uterine cavity was evaluated by both row multidetector computed tomography (MDCT) scanner and Office hysteroscopy., Results: Mean age of studied group was 28.54 ± 5.99 years, and virtual hysteroscopy showed sensitivity 91.1% and specificity 85.3% in detection of abnormalities within uterine cavity. It showed sensitivity 91.1% and specificity 85.3% in cases of endometrial polyps. It yielded 88.5 % sensitivity and 100 % specificity in cases with submucous fibroids, while it yielded only 57.9 % sensitivity and 82.9% specificity in cases of thick endometrium., Conclusion: Virtual CT hysteroscopy is a good negative test in cases of abnormal uterine bleeding but has some limitations that decrease its sensitivity.

: In clinical practice, although only 3% to 7% of women with postmenopausal bleeding (PMB) will ultimately be found to have cancer, it is the clinician's responsibility to ensure that endometrial cancer is not present. The diagnostic evaluation of PMB has evolved greatly. This Practice Pearl addresses the appropriate evaluation of women with PMB.

The aim of the study is to improve the diagnostic approach in assessing the state of the endometrium with the help of ultrasonic endometrial diagnostics in accordance with the IETА criteria in combination with three-dimensional Doppler indices, calculating the volume of the endometrium, and the 3D reconstruction in postmenopausal women. 167 postmenopausal women underwent a 2D pelvic ultrasound examination and a combined three-dimensional complex pelvic ultrasound examination that included calculation of the volume of the endometrium, three-dimensional dopplerometric indices (vascularization index, blood flow index and vascularization ratio), and 3D-reconstruction mode. In the second stage, the patients underwent hysteroscopy/endometrial bipyroscopy with morphological evaluation of tissue samples, which retrospectively performed analysis of echographic and dopplerometric criteria in patients with benign changes in the endometrium and their comparison with atrophic endometrium. In addition, a comparative analysis of the 2D ultrasound method and its combination with a complex 3D study was carried out. Most of the echographic criteria between the groups of hyperproliferative pathology and endometrial atrophy had statistical differences, but there were no significant differences in comparison with the group of synechia of the uterine cavity and cystic atrophy. While the analysis of Dopplerometric criteria both in the two-dimensional mode and with its combination with trimer techniques demonstrated a statistical difference between the indices in the groups of the endometrial hyperpliphyral pathology and the endometrium atrophy, including its cystic form, and also the synechia of the uterine cavity. Based on the results of the comparative analysis of the ultrasound modes, the combination of 2D study with a complex 3D study increases the sensitivity of the method by 12%, and the specificity by 13%. Three-dimensional echography with the determination of dopplerometric indices and volume of endometrium and 3D reconstruction is highly accurate in the diagnosis of endometrial pathology, its wide practical application at the preoperative stage will allow to improve the quality of diagnostics and to formulate clear criteria for hysteroscopy in postmenopausal women. The results of the study show that the thickness of the endometrium is not an absolute criterion in determining the pathology of the endometrium. The main criterion in the diagnosis of hyperproliferative changes in the endometrium in postmenopause is the presence in it of vascularization.

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., (© 2018 International Federation of Gynecology and Obstetrics.)

Background & Objectives: Transvaginal ultrasonography (TVS) is a non-invasive procedure and can be used as a screening tool among women with abnormal uterine bleeding (AUB). Power Doppler is useful in depicting the vascular architecture better than the conventional Doppler. Hence, this study was conducted to evaluate whether addition of power Doppler to grey scale TVS can replace invasive hysteroscopy for the prediction of endometrial pathology in perimenopausal women with AUB., Methods: One hundred women (>45 yr) with perimenopausal AUB underwent evaluation with TVS, power Doppler and hysteroscopy-guided biopsy after a detailed history and examination. Histopathology was considered as gold standard and other tools such as grey scale TVS with power Doppler and hysteroscopy were compared with it., Results: Fifty six per cent women had no vascularity on power Doppler. Among those who had vascularity, the vascular patterns noted were single-vessel in 18 per cent, scattered-vessel in 15 per cent and multiple-vessel in 11 per cent. The sensitivity, specificity, positive predictive value and negative predictive value of TVS-endometrial thickness with power Doppler in detecting hyperplasia were 50, 86.5, 13.3 and 97.6 per cent, respectively, whereas the same for hysteroscopy were 100, 97.6, 88.1 and 100 per cent, respectively., Interpretation & Conclusions: Addition of power Doppler to grey scale TVS improved the specificity and negative predictive value almost comparable to hysteroscopy for evaluation of AUB, but sensitivity and positive predictive value remained poor., Competing Interests: None

Objectives: Women with recurrent postmenopausal bleeding (PMB) are considered as being at higher risk for endometrial hyperplasia and cancer, and guidelines suggest offering hysterectomy in unexplained cases with repeated negative investigations. This study aims to determine the prevalence of endometrial pathology in women referred with recurrent PMB to help inform clinical practice., Methods: This was an observational study of prospectively collected data over a 5-year period, including 1902 women referred to the PMB clinic. Women were classified into two groups: those with a single referral episode (n = 1517, 79.8%), and women with multiple referrals because of recurrent PMB (n = 385, 20.2%)., Results: The prevalence of endometrial hyperplasia or cancer was 32 (8.3%) in women with multiple referrals and 159 (10.5%) in those with a single referral (p = 0.21). The prevalence of benign polyps was 80 (20.8%) and 214 (14.1%) in the two groups, respectively (p = 0.002). On comparing to women with a single referral, the odds ratio (95% confidence interval) for women with multiple referrals because of recurrent PMB to have endometrial polyps was 1.6 (1.2-2.1)., Conclusion: Women with recurrent PMB had a higher prevalence of endometrial polyps, rather than hyperplasia or cancer, when compared with those with a single referral. Hysteroscopy may be warranted as the first-line investigation, if PMB recurs, to enable polyp diagnosis.

Background: Incidental ultrasonographic findings in asymptomatic postmenopausal women, such as thickened endometrium or polyps, often lead to invasive procedures and to the occasional diagnosis of endometrial cancer. Data supporting a survival advantage of endometrial cancer diagnosed prior to the onset of postmenopausal bleeding are lacking., Objective: To compare the survival of asymptomatic and bleeding postmenopausal patients diagnosed with endometrial cancer., Study Design: This was an Israeli Gynecology Oncology Group retrospective multicenter study of 1607 postmenopausal patients with endometrial cancer: 233 asymptomatic patients and 1374 presenting with postmenopausal bleeding. Clinical, pathological, and survival measures were compared., Results: There was no significant difference between the asymptomatic and the postmenopausal bleeding groups in the proportion of patients in stage II-IV (23.5% vs 23.8%; P = .9) or in high-grade histology (41.0% vs 38.4%; P = .12). Among patients with stage-I tumors, asymptomatic patients had a greater proportion than postmenopausal bleeding patients of stage IA (82.1% vs 66.2%; P < .01) and a smaller proportion received adjuvant postoperative radiotherapy (30.5% vs 40.6%; P = .02). There was no difference between asymptomatic and postmenopausal bleeding patients in the 5-year recurrence-free survival (79.1% vs 79.4%; P = .85), disease-specific survival (83.2% vs 82.2%; P = .57), or overall survival (79.7% vs 76.8%; P = .37)., Conclusion: Endometrial cancer diagnosed in asymptomatic postmenopausal women is not associated with higher survival rates. Operative hysteroscopy/curettage procedures in asymptomatic patients with ultrasonographically diagnosed endometrial polyps or thick endometrium are rarely indicated. It is reasonable to reserve these procedures for patients whose ultrasonographic findings demonstrate significant change over time., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In this study, we aimed to determine the frequency of histopathologic outcomes of solid-organ transplantation in women with abnormal uterine bleeding (AUB) receiving immunosuppressive therapies., Methods: This is a retrospective study including a single-center experience. Data were extracted from hospital records, and solid-organ transplant recipients who were diagnosed with AUB were included., Results: Fifty-five of these patients were renal transplant recipients (79.7%), and 14 were liver transplant recipients (20.3%). Histopathologic examination showed various histopathologic patterns of endometrium in patients with AUB consisting of normal histopathologic findings of endometrium in 31 patients (48.4%); 29 hormonal imbalance during proliferative and secretory phases of menstrual cycle and two atrophic endometrium. Endometrial hyperplasia without atypia was observed in 11 patients (17.2%). Polyp was seen in 22 patients (34.4%); 21 endometrial polyp and one endocervical polyp. There were significant differences in terms of histopathologic findings among the three groups of patients according to different immunosuppressive regimens (P = .029). There was no endometrial hyperplasia in women receiving sirolimus-based immunosuppressive regimens. Moreover, there was no endometrial hyperplasia in the liver transplant recipient group., Conclusions: Sirolimus-based immunosuppressive regimens may be administered to patients who have risk factors for endometrial precancerous lesions, such as endometrial hyperplasia. However, additional well-designed, large-scale studies are warranted to confirm our findings., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective To evaluate the role of transvaginal ultrasound triage in women with a history of tamoxifen treatment who present with post-menopausal bleeding. Study design A retrospective review was undertaken of patients who presented with symptoms of post-menopausal bleeding and underwent ultrasound triage. Endometrial thickness and ultrasonographic features were then correlated with hysteroscopic and histopathological outcome data. The findings and outcomes for women with a history of tamoxifen use (tamoxifen group) were compared to those who had not taken tamoxifen (non-tamoxifen group). Results A total of 614 women with post-menopausal bleeding underwent transvaginal ultrasound triage, of whom 53 had a history of current or previous tamoxifen treatment. An endometrial thickness of ≥5 mm or the presence of other abnormal features was used to triage women to further investigation by hysteroscopy and biopsy. Endometrial thickness was significantly greater in the tamoxifen group (11 mm vs. 6 mm). Nearly all of the tamoxifen group were triaged to further investigation (98.1%), compared with significantly fewer in the non-tamoxifen group (68.3%) Overall, the incidence of endometrial pathology was also significantly higher in tamoxifen patients (43.4% vs. 31.7%). Conclusion For women presenting with post-menopausal bleeding, the use of transvaginal ultrasound as a triage tool is rarely helpful in evaluating women who have a history as tamoxifen use, as most will require further investigation with hysteroscopy and biopsy. A post-menopausal bleeding protocol that omits transvaginal ultrasound for women with a history of tamoxifen use may be an appropriate and effective pathway for managing these patients.

Cancer of the endometrium is the most common type of gynecologic cancer in the United States. Vaginal bleeding is the presenting sign in more than 90% of postmenopausal women with endometrial carcinoma. Clinical risk factors for endometrial cancer, including but not limited to age, obesity, use of unopposed estrogen, specific medical comorbidities (eg, polycystic ovary syndrome, type 2 diabetes mellitus, atypical glandular cells on screening cervical cytology), and family history of gynecologic malignancy also should be considered when evaluating postmenopausal bleeding. The clinical approach to postmenopausal bleeding requires prompt and efficient evaluation to exclude or diagnose endometrial carcinoma and endometrial intraepithelial neoplasia. Transvaginal ultrasonography usually is sufficient for an initial evaluation of postmenopausal bleeding if the ultrasound images reveal a thin endometrial echo (less than or equal to 4 mm), given that an endometrial thickness of 4 mm or less has a greater than 99% negative predictive value for endometrial cancer. Transvaginal ultrasonography is a reasonable alternative to endometrial sampling as a first approach in evaluating a postmenopausal woman with an initial episode of bleeding. If blind sampling does not reveal endometrial hyperplasia or malignancy, further testing, such as hysteroscopy with dilation and curettage, is warranted in the evaluation of women with persistent or recurrent bleeding. An endometrial measurement greater than 4 mm that is incidentally discovered in a postmenopausal patient without bleeding need not routinely trigger evaluation, although an individualized assessment based on patient characteristics and risk factors is appropriate. Transvaginal ultrasonography is not an appropriate screening tool for endometrial cancer in postmenopausal women without bleeding.

Objectives: Abnormal uterine bleeding (AUB) is caused by derangement of physiological processes of tissue growth, shedding and regeneration. It is known that interplay between metalloproteinases (MMP's) and tissue inhibitors of metalloproteinases (TIMP's) may play a crucial role in its occurrence., Aim: To define if expression of proMMP-2, MMP-2 and TIMP-1 in endometrium of women with AUB is dependent on steroid sex hormone concentration and histopathological picture., Materials and Methods: Endometrial scraps were taken from 21 women with AUB and 19 controls. Samples were evaluated in light microscopy by a certified pathologist. Activity of proMMP-2 and MMP-2 proteins levels were evaluated by gelatin zymography and TIMP-1 by reversed zymography. The results has been correlated with serum estradiol and progesterone concentrations in linear regression model., Results: Expression: of proMMP-2 in endometrium of women with AUB is correlated with estradiol concentration and inversely correlated with progesterone levels. It was significantly higher in women with dysfunctional endometrium (p<0.001). Expression of MMP-2 was highest in women with endometrial polyps and longer bleeding (p<0.01), while expression of TIMP-1 was independent from hormone concentration., Conclusion: Lack of correlation between proMMP-2 and MMP-2 levels suggest different pathway of their activation in AUB. ProMMP-2 is up regulated by estradiol and down regulated by progesterone while MMP-2 levels increase with the length of bleeding.

Objective: To estimate intra- and interrater agreement and reliability with regard to describing ultrasound images of the endometrium using the International Endometrial Tumor Analysis (IETA) terminology., Methods: Four expert and four non-expert raters assessed videoclips of transvaginal ultrasound examinations of the endometrium obtained from 99 women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm but without fluid in the uterine cavity. The following features were rated: endometrial echogenicity, endometrial midline, bright edge, endometrial-myometrial junction, color score, vascular pattern, irregularly branching vessels and color splashes. The color content of the endometrial scan was estimated using a visual analog scale graded from 0 to 100. To estimate intrarater agreement and reliability, the same videoclips were assessed twice with a minimum of 2 months' interval. The raters were blinded to their own results and to those of the other raters., Results: Interrater differences in the described prevalence of most IETA variables were substantial, and some variable categories were observed rarely. Specific agreement was poor for variables with many categories. For binary variables, specific agreement was better for absence than for presence of a category. For variables with more than two outcome categories, specific agreement for expert and non-expert raters was best for not-defined endometrial midline (93% and 96%), regular endometrial-myometrial junction (72% and 70%) and three-layer endometrial pattern (67% and 56%). The grayscale ultrasound variable with the best reliability was uniform vs non-uniform echogenicity (multirater kappa (κ), 0.55 for expert and 0.52 for non-expert raters), and the variables with the lowest reliability were appearance of the endometrial-myometrial junction (κ, 0.25 and 0.16) and the nine-category endometrial echogenicity variable (κ, 0.29 and 0.28). The most reliable color Doppler variable was color score (mean weighted κ, 0.77 and 0.69). Intra- and interrater agreement and reliability were similar for experts and non-experts., Conclusions: Inter- and intrarater agreement and reliability when using IETA terminology were limited. This may have implications when assessing the association between a particular ultrasound feature and a specific histological diagnosis, because lack of reproducibility reduces the reliability of the association between a feature and the outcome. Future studies should investigate whether using fewer categories of variable or offering practical training could improve agreement and reliability. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Abnormal uterine bleeding is one of the commonest presenting complaints encountered in a gynecologist's office or primary-care setting. The wider availability of diagnostic tools has allowed prompt diagnosis and treatment of an increasing number of menstrual disorders in an office setting. This White Paper reviews the advantages and disadvantages of transvaginal ultrasound, blind endometrial sampling and diagnostic hysteroscopy. Once a proper diagnosis has been established, appropriate therapy may be embarked upon. Fortunately, only a minority of such patients will have premalignant or malignant disease. When bleeding is sufficient to cause severe anemia or even hypovolemia, prompt intervention is called for. In most of the cases, however, the abnormal uterine bleeding will be disquieting to the patient and significantly affect her 'quality of life'. Sometimes, reassurance and expectant management will be sufficient in such patients. Overall, however, in cases of benign disease, some intervention will be required. The use of oral contraceptive pills especially those with a short hormone-free interval, the insertion of the levonorgestrel intrauterine system, the incorporation of newer medical therapies including antifibrinolytic drugs and selective progesterone receptor modulators and minimally invasive treatments have made outpatient therapy increasingly effective. For others, operative hysteroscopy and endometrial ablation are proven therapeutic tools to provide both long- and short-term relief of abnormal uterine bleeding, thus avoiding, or deferring, hysterectomy.

Objective: To estimate the optimal order of office hysteroscopy and endometrial biopsy when performed successively for evaluation of abnormal uterine bleeding., Methods: Patients undergoing successive office hysteroscopy and endometrial biopsy were included in a single-blind, prospective, randomized trial. The primary outcome was to evaluate the effect of order of procedures on patients' pain score. Prespecified secondary outcomes include procedure duration, hysteroscopic visualization of the uterine cavity, endometrial sample adequacy, and number of attempts at biopsy. Pain scores were assessed using a visual analog scale from 0 to 10 and endometrial sample adequacy was determined from the histopathology report. Hysteroscopy images were recorded. Sample size of 34 per group (n=68) was determined to be adequate to detect a difference of 20% in visual analog scale score between hysteroscopy first (group A) and biopsy first (group B) at α of 0.05 and 80% power., Results: Between October 2015 and January 2017, 78 women were randomized to group A (n=40) and group B (n=38). There was no difference in global pain perception [7 (0-10) vs 7 (0-10); P=.57, 95% CI 5.8-7.1]. Procedure duration [3 (1-9) vs 3 (2-10), P=.32, 95% CI 3.3-4.1] and endometrial sample adequacy (78.9% vs 75.7%, P=.74) were similar in both groups. Group A patients had better endometrial visualization (P<.001) than group B based on the hysteroscopic images: excellent (50% vs 7.9%), good (20% vs 34.2%), and fair (22.5% vs 44.7%); group B participants required fewer endometrial biopsy attempts at obtaining adequate tissue sample (two vs one; P<.001, 1.6-1.9)., Conclusion: Patients having successive office hysteroscopy and endometrial biopsy for evaluation of abnormal uterine bleeding, the global pain perception, and time required are independent of the order in which procedures are performed. Performing hysteroscopy first ensures better image, whereas biopsy first yields adequate tissue sample with fewer attempts., Clinical Trial Registration: ClinicalTrials.gov, NCT02472184.

Purpose: Histological confirmation of endometrial cancer by dilatation/curettage (D/C) in women with postmenopausal bleeding (PMB) can be challenging due to anesthesiological and/or surgical risks. Thus, less invasive methods for diagnostics are required to identify patients with minimal risk for endometrial cancer (EC) to avoid unnecessary surgical intervention. The objective of this single-center cohort study was to assess the diagnostic validity of transvaginal ultrasound (TVUS) measurements of endometrial thickness (ET) in patients with PMB for the detection of EC., Methods: A retrospective analysis of data from patients presenting between January 2005 and August 2014 at the Department of Obstetrics and Gynecology, University Hospital Ulm, Germany, with PMB and subsequent D/C was performed. Complete data with TVUS documentation of ET and histological results of tissue samples were available from 254 patients. In addition, data on age, body mass index (BMI), ASA-score, diabetes, hypertension, and hematological laboratory values (for a smaller subsample) were recorded. To identify independent risk factors, a multivariate logistic regression with endometrial cancer as binary response variable (yes/no) was performed. Diagnostic efficacy data for different ET cutoff points (≤1 to ≤26 mm) were obtained by a receiver operator characteristic (ROC) curve analysis., Results: The multivariate logistic regression revealed a significant independent predictive value for age and ET. However, none of the analyzed ET cutoff points showed optimal diagnostic validity, as all cutoff points with sensitivity rates above 90% (≤1 to ≤5 mm) had false positive rates of 70% and higher., Conclusions: There is no ET cutoff point that provides good diagnostic accuracy and/or reliably excludes the presence of endometrial cancer in patients with PMB. Thus, our data analysis supports the actual German approach of histological evaluation of any PMB to confirm or exclude EC.

Evaluation of the vaginal bleeding of postmenopausal women is crucial to diagnose endometrial lesions. Endometrial thickness measured by transvaginal ultrasonography provides an important reference for diagnosis. Currently, no specific cut-off value of endometrial thickness has been identified to predict the malignant risk for endometrial thickening and postmenopausal women without any symptoms. Most of resected endometrial specimens from postmenopausal women without any symptoms are diagnosed as benign or normal tissues. It seems that postmenopausal women without any symptoms have no need for general screen or intervention of endometrial cancer.

Endometrial biopsy can be used to diagnose endometrial hyperplasia, endometrial cancer, and uterine infections. This cost-effective procedure has minimal side effects, and complications are rare. The purpose of this clinical bulletin is to provide clinicians with guidance about endometrial biopsy including the procedure's advantages and disadvantages, indications and contraindications, and side effects. In addition, step-by-step instructions for performing endometrial biopsy, the equipment required, selection of sampling devices, and care before and after the procedure are discussed., (© 2017 by the American College of Nurse-Midwives.)