Accessory cavitated uterine malformation (ACUM): A scoping review.

INTRODUCTION: Accessory cavitated uterine malformation (ACUM) is a relatively recent term used to describe a noncommunicating, accessory uterine cavity. ACUM have been published under different terms ranging from juvenile cystic adenomyosis to "uterus-like mass". The objective of this study was to systematically identify all cases of ACUM and definitions described in the literature, regardless of label, and identify morphological, epidemiological, and clinical characteristics as well as management, while also highlighting knowledge gaps. MATERIAL AND METHODS: A systematic literature search of three databases was performed, reviewing all records of cystic myometrial lesions. Cases that fitted common definitions for ACUM were included and clinical and imaging characteristics were documented in detail. This work was registered to PROSPERO and reporting followed PRISMA guidelines for scoping reviews. RESULTS: A total of 53 articles were included, comprising 115 cases that met the minimal criteria for ACUM. The median age at onset of symptoms was 17 years, presenting with dysmenorrhea soon after menarche. A total of 19 women were parous. On ultrasound, ACUM appears as unilocular myometrial cysts, usually with ground-glass content. Hemorrhagic content is also observed on magnetic resonance imaging (MRI), with high signal intensity on both T2 and T1-weighted images. Ninety-five (83%) cases were managed surgically, with a trend towards primary nonsurgical options. Although no adverse outcomes were reported, long-term follow-up on subsequent fertility and pregnancy was rare. CONCLUSIONS: Despite its increasing recognition as a clinical entity, ACUM often remains underdiagnosed as it shares similarities with other myometrial masses. We propose a unified terminology and definition for ACUM based on the data in this review. ACUM presents as a cavitated lesion, surrounded by a myometrial mantle, in continuity with the anterolateral uterine wall and located beneath the insertion of the round ligament and the interstitial portion of the fallopian tube. In contrast to other uterine abnormalities, a normal uterine cavity is visualized. Future studies are needed, using a clear definition for ACUM, and prospectively investigating management strategies, including long-term follow-up of patient-reported symptoms, fertility, and pregnancy outcomes.

Intra- and interobserver reproducibility of transvaginal ultrasound for the detection and measurement of endometriotic lesions of the bowel.

INTRODUCTION: The number and invasion depth of endometriotic bowel lesions, total length of bowel affected by endometriosis, lesion-to-anal verge distance, and extent of pouch of Douglas obliteration are important factors in preoperatively determining risk and complexity of endometriosis surgery. The intra- and interobserver reproducibility of transvaginal ultrasound in the evaluation of many of these parameters has not yet been investigated. Our study aimed to assess the intra- and interobserver reproducibility of transvaginal ultrasound between an experienced and less experienced examiner for all of these parameters. MATERIAL AND METHODS: This prospective observational cross-sectional study was conducted between July 2019 and November 2020. Fifty consecutive premenopausal women who underwent transvaginal ultrasound examination in our clinic for the first time, were examined by the same two operators during the same attendance. Outcomes of interest were the inter-rater reproducibility of transvaginal ultrasound for detecting the presence, number, depth and size of bowel endometriotic nodules, lesion-to-anal-verge distance, total length of bowel affected, and pouch of Douglas obliteration. The intraobserver reproducibility was assessed for the continuous parameters. Cohen's kappa (κ) statistic, Cohen's weighted kappa (κ), proportions of agreement, intraclass correlation coefficient (ICC) and Bland-Altman limits of agreement were used to assess the reproducibility of the parameters. RESULTS: The inter-rater agreement and reliability were very good for identifying bowel endometriosis, the number and invasion depth of bowel nodules, determining whether the maximum nodule length was <3 cm, and lesion-to-anal-verge distance <8 cm (proportion of agreement 0.92, 0.94, 0.97, 0.94, 0.96; κ 0.92, 0.91, 0.92, 0.82, 0.89). The inter-rater agreement and reliability were good for assessing pouch of Douglas obliteration (proportion of agreement 0.86, κ 0.80). The intra-rater reliability for the mean nodule diameter (ICC 0.93 and 0.97) and total length of bowel affected (ICC 0.94 and 0.91) were excellent for operators A and B, respectively. The inter-rater reliability for the mean nodule diameter was good (ICC 0.80), and moderate for the total length of bowel affected (ICC 0.70). The Bland-Altman limits of agreement demonstrated clinically acceptable ranges for these two parameters. CONCLUSIONS: This study demonstrated a high intra- and inter-rater reproducibility of transvaginal ultrasound in the diagnosis of bowel endometriosis and measurement of its various components.

Natural progression of deep pelvic endometriosis in women who opt for expectant management.

INTRODUCTION: The natural history of endometriosis is poorly understood, and despite numerous studies, the rate of the disease progression and optimal treatment planning in women who are asymptomatic or experience mild symptoms not requiring treatment are unknown. The aim of this study was to assess the behavior of deep endometriosis in women who are managed expectantly without any medical or surgical intervention. MATERIAL AND METHODS: A retrospective cohort study of women diagnosed with deep endometriosis on transvaginal ultrasound scan at the Department of Gynecology, University College London Hospitals and The Gynecology Ultrasound Centre, London, UK, from April 2007 to April 2022. All women attended for at least two ultrasound scans which were carried out by a single expert ultrasound examiner and at least 6 months apart. The number and position of endometriotic nodules were recorded, and the mean diameter of each nodule was calculated from measurements taken in three orthogonal planes. RESULTS: During the study period, 1922 women were found to have moderate or severe deep endometriosis on pelvic ultrasound examination. A total of 135 premenopausal women who were managed expectantly fitted the inclusion criteria. The median number of endometriotic nodules per woman at the initial visit was 2 (range: 0-7), and the median follow-up time was 666 days (181-2984). In the follow-up period, 50/135 women (37%, 95% CI: 29-46) developed additional nodules or experienced an increase in nodule size, and 17/135 women (13%, 95% CI: 8-19) had a regression in the number or size of the nodules. In the remaining 68/135 women (50%, 95% CI: 42-59) the disease remained static during the follow-up. The median change in mean diameter of nodules during the study period per woman was +0.13 mm (-11.67 - +5.83), with an annual growth rate of +0.09 mm/year (-6.65 - +6.45). CONCLUSIONS: In our study we found evidence of deep endometriosis progression in just over a third of women. In view of this, asymptomatic or mildly symptomatic women diagnosed with deep endometriosis could be reassured that their disease is unlikely to worsen with time.

Patients' and relatives' perspectives on best possible care in the context of developing a multidisciplinary center for endometriosis and adenomyosis: findings from a national survey.

BACKGROUND: Endometriosis and adenomyosis are common benign conditions compromising both physical and psychological health, with a negative impact on quality of life. This survey aimed to establish what the users' perspectives are on best possible care in the context of developing a multidisciplinary center for endometriosis and adenomyosis in Norway. METHODS: An electronic questionnaire was developed in collaboration between the Norwegian Patient's Endometriosis Society (NPES) and gynecologists with special interest in endometriosis and adenomyosis. The questionnaire was distributed digitally to the members of NPES in May 2021. RESULTS: 938 participants answered the questionnaire. Better patient information, long term therapeutic plans and integration of their partners into their care were the main concerns. Multidisciplinary care was a key issue for the majority, with (n = 775) 89% stating a need for a consultation with a psychologist, (n = 744) 86% at least one consultation with a nutritionist, (n = 733) 85% a physiotherapist, and (n = 676) 78% needing a sex therapist and (n = 935) 99,7% consider research and (n = 934) 99,8% consider quality assurance initiated by the endometriosis center to be important. The qualitative analysis of free text answers revealed a great need for updated and easily accessible information, meeting competent health care professionals and being taken seriously/listened to. CONCLUSIONS: This survey shows similar perceptions and a high level of agreement regarding their needs amongst people with endometriosis and/or adenomyosis. This survey supports recommendations by the experts that endometriosis/adenomyosis care should be centralized in specialized, multidisciplinary centers. The results of the present work will be valuable for the future planning and development of a multidisciplinary endometriosis center.

Effect of physical activity and exercise on endometriosis-associated symptoms: a systematic review.

BACKGROUND: Endometriosis is a common benign gynecological disease that has the potential to debilitate due to pain and reduced quality of life. Treatment modalities such as hormones and surgery have limitations and do not treat all dimensions of the problems caused by endometriosis, and physical activity (PA) and exercise have been suggested as alternative treatments. Aim of this study was to perform a systematic review and meta-analysis to assess the effect of PA and exercise on endometriosis-associated symptoms. METHODS: Eleven databases were searched systematically. Study selection, quality assessment, and data extraction were carried out by two independent researchers in accordance with PRISMA guidelines. Eligibility criteria were women with diagnosed endometriosis receiving an intervention (PA and/or exercise). The primary outcome was pain intensity, but all outcomes were accepted. RESULTS: This study screened 1045 citations for eligibility. Four interventional studies were identified, of which one showed fatal design flaws and so was excluded. Three studies, two randomized controlled trials (RCT) and one pre-post study with no control group, involving 109 patients were included in a descriptive synthesis. The interventions included flexibility and strength training, cardiovascular fitness, and yoga, and were performed from one to four times per week for a total duration of 8-24 weeks, with or without supervision. Only one study found improvements in pain intensity. One study showed decreases in stress levels. Due to the heterogeneity of the study outcomes and measures, as well as confounding factors, a quantitative meta-analysis could not be performed. CONCLUSION: The effect of PA and exercise as treatments for endometrioses-associated symptoms could not be determined due to significant limitations of the included studies. Future research should be based on RCTs of high methodological quality, measuring and reporting relevant core outcomes such as pain, improvements in symptoms and quality of life, and acceptability and satisfaction from the perspectives of patients. Furthermore, these outcomes need to be measured using reliable and validated tools. TRIAL REGISTRATION NUMBER: CRD42021233138.

Terminology for describing normally sited and ectopic pregnancies on ultrasound: ESHRE recommendations for good practice.

STUDY QUESTION: What recommendations can be provided to improve terminology for normal and ectopic pregnancy description on ultrasound? SUMMARY ANSWER: The present ESHRE document provides 17 consensus recommendations on how to describe normally sited and different types of ectopic pregnancies on ultrasound. WHAT IS KNOWN ALREADY: Current diagnostic criteria stipulate that each type of ectopic pregnancy can be defined by clear anatomical landmarks which facilitates reaching a correct diagnosis. However, a clear definition of normally sited pregnancies and a comprehensive classification of ectopic pregnancies are still lacking. STUDY DESIGN SIZE DURATION: A working group of members of the ESHRE Special Interest Group in Implantation and Early Pregnancy (SIG-IEP) and selected experts in ultrasound was formed in order to write recommendations on the classification of ectopic pregnancies. PARTICIPANTS/MATERIALS SETTING METHODS: The working group included nine members of different nationalities with internationally recognised experience in ultrasound and diagnosis of ectopic pregnancies on ultrasound. This document is developed according to the manual for development of ESHRE recommendations for good practice. The recommendations were discussed until consensus by the working group, supported by a survey among the members of the ESHRE SIG-IEP. MAIN RESULTS AND THE ROLE OF CHANCE: A clear definition of normally sited pregnancy on ultrasound scan is important to avoid misdiagnosis of uterine ectopic pregnancies. A comprehensive classification of ectopic pregnancy must include definitions and descriptions of each type of ectopic pregnancy. Only a classification which provides descriptions and diagnostic criteria for all possible locations of ectopic pregnancy would be fit for use in routine clinical practice. The working group formulated 17 recommendations on the diagnosis of the different types of ectopic pregnancies on ultrasound. In addition, for each of the types of ectopic pregnancy, a schematic representation and examples on 2D and 3D ultrasound are provided. LIMITATIONS REASONS FOR CAUTION: Owing to the limited evidence available, recommendations are mostly based on clinical and technical expertise. WIDER IMPLICATIONS OF THE FINDINGS: This document is expected to have a significant impact on clinical practice in ultrasound for early pregnancy. The development of this terminology will help to reduce the risk of misdiagnosis and inappropriate treatment. STUDY FUNDING/COMPETING INTERESTS: The meetings of the working group were funded by ESHRE. T.T. declares speakers' fees from GE Healthcare. The other authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A. DISCLAIMER: This Good Practice Recommendations (GPR) document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and where relevant based on the scientific evidence available at the time of preparation. ESHRE's GPRs should be used for informational and educational purposes. They should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. Furthermore, ESHRE's GPRs do not constitute or imply the endorsement, recommendation or favouring of any of the included technologies by ESHRE.

Noninvasive Diagnosis of Adenomyosis: A Structured Review and Meta-analysis of Diagnostic Accuracy in Imaging.

OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate imaging methods used to diagnose adenomyosis. DATA SOURCES: A thorough search was completed through the Cochrane Central Register of Controlled Trials, EMBASE, and PubMed or MEDLINE databases from January 2000 to June 2019. METHODS OF STUDY SELECTION: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Quality Assessment of Diagnostic Accuracy Studies 2 tool, studies reporting the diagnostic accuracy of an imaging method and histopathology as a reference standard were selected and prospectively registered in the International Prospective Register of Systematic Reviews. Statistical analysis was performed using the R-package Meta-Analysis of Diagnostic Accuracy. TABULATION, INTEGRATION, AND RESULTS: Of the 1168 records identified, 10 studies were included in the meta-analysis, and these included 827 patients undergoing 2- or 3-dimensional transvaginal ultrasound (TVUS) and 317 patients undergoing magnetic resonance imaging (MRI). The risk of bias was low or unclear for all Quality Assessment of Diagnostic Accuracy Studies domains. The overall prevalence of adenomyosis was 40%. Overall MRI, 2-dimensional TVUS, 3-dimensional TVUS, and TVUS had the following aggregated diagnostic qualities (95% confidence interval): sensitivity of 78% (70%-84%), 74% (68%-79%), 84% (77%-89%), 78% (73%-82%); specificity of 88% (83%-92%), 76% (71%-79%), 84% (77%-89%), 78% (74%-81%); positive likelihood ratio of 6.8 (4.5%-10%), 3 (2.5%-3.7%), 5.2 (3.6%-7.4%), 3.5 (3%-4.2%); negative likelihood ratio of 0.25 (0.18%-0.35%), 0.34 (0.27%-0.43%), 0.19 (0.13%-0.28%), 0.28 (0.23%-0.34%); and pooled area under the operator curve of 0.77, 0.7, 0.83, 0.73, respectively. The pooled area under the operator curve for all modalities was not significantly different (all: p ≥.4). CONCLUSION: As a result of the systemic review and meta-analysis, we identified TVUS and MRI as good and comparable noninvasive imaging methods for diagnosing adenomyosis, leading us to recommend TVUS as the first-line diagnostic imaging method and MRI as a second-line method, if TVUS is inconclusive.

Diagnosing adenomyosis with MRI: a prospective study revisiting the junctional zone thickness cutoff of 12 mm as a diagnostic marker.

OBJECTIVES: To assess the diagnostic accuracy of a junctional zone (JZ) thickness of ≥ 12 mm and morphological features of the JZ in MRI in diagnosing adenomyosis in a premenopausal study population. METHODS: This single-center, prospective observational study consecutively enrolled 93 premenopausal women suffering from a benign gynecological condition, from September 2014 to August 2016. Institutional review board approval and written consent were obtained. All participants underwent MRI and hysterectomy with a histopathological examination. MR images were evaluated in a blinded fashion by two independent readers. The maximum junctional zone thickness (JZmax), presence of JZmax ≥ 12 mm, and any irregular appearance of the JZ (defined as irregular outer or inner borders, focal thickening, presence of high-intensity signal foci, or fingerlike indentations at the inner border) were documented, and the diagnostic performance was evaluated with the AUC, chi-square test, and multiple regression. RESULTS: Adenomyosis was histopathologically confirmed in 57 (61%) of the women. JZmax was not positively correlated with adenomyosis diagnosis (AUC = 0.57, p = 0.26) and did not differ significantly between those with and without adenomyosis (10.3 vs 10.1 mm, p = 0.88), nor was a cutoff of JZmax ≥ 12 mm (n = 30/57 (53%) vs n = 16/36 (44%), p = 0.29). The presence of an irregular JZ showed the best association with adenomyosis among the evaluated signs (sensitivity 74% (95% CI, 60, 85); specificity 83% (95% CI, 67, 94) (p < 0.001)). CONCLUSIONS: JZmax was not correlated with adenomyosis in the present premenopausal study population, but direct signs of adenomyosis such as irregularities of the JZ provided a good diagnostic accuracy. KEY POINTS: • Measuring the junctional zone thickness is of limited value for diagnosing adenomyosis with MRI and should not be used for diagnosing adenomyosis in premenopausal women with moderate disease severity. • An irregular appearance of the junctional zone, the presence of myometrial cysts, and adenomyoma appear to provide the highest specificity for diagnosing adenomyosis. • A consensus for the definition and reading of the junctional zone is needed.

In Vivo Adenomyosis Tissue Sampling Using a Transvaginal Ultrasound-guided Core Biopsy Technique for Research Purposes: Safety, Feasibility, and Effectiveness.

STUDY OBJECTIVE: To determine if it is possible and safe to obtain adenomyosis tissue in vivo without removing the uterus in order to use it for further molecular investigations of adenomyosis, which would allow investigating the pathogenesis of the disease. DESIGN: A prospective cohort study. SETTING: A university hospital. PATIENTS: Eighty-one premenopausal women scheduled for a hysterectomy because of various benign indications were included. INTERVENTIONS: Ultrasound-guided, transvaginal uterine core biopsy samples were obtained, and the required time was registered. Any trauma to the pelvic organs, blood loss, and other complications were documented during the subsequent hysterectomy. Two biopsy samples were analyzed histopathologically to confirm the presence of adenomyosis, and another 2 were snap frozen using liquid nitrogen for use in further research. Laser microscopic dissection and RNA extraction were performed on the collected samples. MEASUREMENTS AND MAIN RESULTS: Biopsy specimens could be obtained in 80 (99%) of the 81 cases. There was no visible trace of the biopsy retrieval in 20 women (25%), perforation of uterine serosa or peritoneum was present in 56 (70%), and ongoing minor bleeding occurred in 4 (5%). The median amount of bleeding was 2 mL (range, 0-200 mL). No serious complications were observed. The procedure took 6.1 ± 1.9 minutes (mean ± standard deviation). Adenomyosis tissue was obtained in 10 (22%) of the 45 cases with adenomyosis. The inner myometrium with the junctional zone was accessible in all cases. It was possible to produce frozen sections, extract RNA, and dissect single adenomyosis glands with laser microscopic dissection. CONCLUSIONS: No serious complications caused by the uterine biopsies were observed. This technique opens up the possibility of investigating early stages of adenomyosis and the inner myometrium containing the junctional zone independent of hysterectomy specimens.

Development of a clinical prediction model for diagnosing adenomyosis.

OBJECTIVE: To develop a multivariate prediction model for diagnosing adenomyosis using predictors available through transvaginal ultrasonography and clinical examinations. DESIGN: Prospective observational single-center study. SETTING: Teaching university hospital. PATIENT(S): One hundred consecutively enrolled premenopausal women aged 30-50 years, undergoing hysterectomy due to a benign condition and not using hormonal treatment. INTERVENTION(S): Preoperative 2-D and 3-D transvaginal ultrasonography investigations were performed, and the results were documented in a standardized form. Clinical information was collected using a questionnaire. Histopathology confirmed the outcome. MAIN OUTCOME MEASURE(S): Diagnostic performance (sensitivity, specificity, area under the curve (AUC)) of a multivariate prediction model for adenomyosis. Independent diagnostic performance of single predictors and their quantitative effect (ß) in the final model. RESULT(S): The final model showed a good test quality (area under the curve [AUC] = 0.86, [95% confidence interval = 0.79-0.94], optimal cutoff 0.56, sensitivity of 85%, specificity 78%). The following nine predictors were included ([sensitivity, specificity, ß] or [AUC, ß]): presence of myometrial cysts (51%, 86%, ß = 0.86), fan-shaped echo (36%, 92%, ß = 0.54), hyperechoic islets (51%, 78%, ß = 0.62), globular uterus (61%, 83%, ß = 0.2), normal uterine shape (83%, 61%, ß = -0.75), thickest/thinnest ratio for uterine wall (0.61, ß = 0.26), maximum width of the junctional zone in sagittal plane (0.71, ß = 0.1), regular appearance of junctional zone (31%, 92%, ß = -1.0), and grade of dysmenorrhea measured on a verbal numerical rating scale (0.61, ß = 0.08). CONCLUSION(S): We have presented a multivariate model for diagnosing adenomyosis that weights predictors based on their diagnostic significance. The reported findings could aid clinicians who are interpreting the heterogeneous appearance of adenomyosis in ultrasonography. CLINICAL TRIAL REGISTRATION NUMBER: NCT02201719.