Prevalence of deep and ovarian endometriosis in women attending a general gynecology clinic: prospective cohort study.

OBJECTIVES: To assess using transvaginal ultrasound the prevalence of deep and ovarian endometriosis in premenopausal women attending a general gynecology clinic. We also investigated whether the presence of endometriosis was associated with various demographic factors and other pelvic abnormalities. METHODS: This was a prospective observational cohort study carried out between February 2019 and October 2020. Consecutive premenopausal women who attended our general gynecology clinic underwent pelvic ultrasound examination, performed by a single experienced operator. Pregnant women and those with a history of hysterectomy or oophorectomy were excluded. The primary outcome was the prevalence of deep and/or ovarian endometriosis. Secondary outcomes were the anatomical distribution of endometriotic lesions and the association of endometriosis with demographic characteristics and various pelvic abnormalities, which were analyzed using logistic regression and multivariable analysis. RESULTS: A total of 1026 women were included in the final study sample, of whom 194 (18.9% (95% CI, 16.6-21.4%)) had sonographic evidence of deep and/or ovarian endometriosis. Of the 194 women diagnosed with endometriosis, 106 (54.6% (95% CI, 47.4-61.8%)) were diagnosed with endometriotic nodules only, 26 (13.4% (95% CI, 9.0-19.0%)) with ovarian endometriomas only, and 62 (32.0% (95% CI, 25.5-39.0%)) women had evidence of both. There was a total of 348 endometriotic nodules in 168 women, located most frequently in the retrocervical area (166/348; 47.7% (95% CI, 42.4-53.1%)), uterosacral ligaments (96/348; 27.6% (95% CI, 23.0-32.6%)) and bowel (40/348; 11.5% (95% CI, 8.3-15.3%)). Multivariable analysis found significant positive associations between endometriosis and both adenomyosis (odds ratio (OR), 1.72 (95% CI, 1.10-2.69); P = 0.02) and pelvic adhesions (OR, 25.7 (95% CI, 16.7-39.3); P < 0.001), whilst higher parity (OR, 0.44 (95% CI, 0.24-0.81); P = 0.03) and history of Cesarean section (OR, 0.18 (95% CI, 0.06-0.52); P = 0.002) were associated with a lower occurrence of endometriosis. A total of 75/1026 women (7.3% (95% CI, 5.8-9.1%)) underwent laparoscopy within 6 months of pelvic ultrasound examination. There was very good agreement between ultrasound and surgical findings, with a kappa value of 0.84 (95% CI, 0.69-0.99). CONCLUSIONS: Deep and/or ovarian endometriosis was present in nearly one in five women attending a general gynecology clinic. There were significant positive associations with adenomyosis and pelvic adhesions and negative associations with higher parity and previous Cesarean section. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Reproductive outcome in 326 women with unicornuate uterus.

OBJECTIVES: To study the reproductive outcomes of women with a unicornuate uterus and compare them to those of women with no congenital uterine anomaly. METHODS: This was a single-center, retrospective cohort study. Cases were women aged at least 16 years who were diagnosed with a unicornuate uterus on transvaginal/transrectal ultrasound between January 2008 and September 2021. Controls were women with no congenital uterine anomaly matched 1:1 by age and body mass index. The primary outcome was live-birth rate. Secondary outcomes were pregnancy loss (miscarriage, ectopic pregnancy, termination of pregnancy), preterm delivery, mode of delivery and concomitant gynecological abnormalities (endometriosis, adenomyosis, fibroids). RESULTS: Included in the study were 326 cases and 326 controls. Women with a unicornuate uterus had a significantly lower live-birth rate (184/388 (47.4%) vs 229/396 (57.8%); P = 0.004) and higher rates of overall miscarriage (178/424 (42.0%) vs 155/465 (33.3%); adjusted odds ratio (aOR), 2.21 (95% CI, 1.42-3.42), P < 0.001), ectopic pregnancy (26/424 (6.1%) vs 11/465 (2.4%); aOR, 2.52 (95% CI, 1.22-5.22), P = 0.01), preterm delivery (45/184 (24.5%) vs 17/229 (7.4%); aOR, 3.04 (95% CI, 1.52-5.97), P = 0.001) and Cesarean delivery (116/184 (63.0%) vs 70/229 (30.6%); aOR, 2.54 (95% CI, 1.67-3.88), P < 0.001). Rudimentary-horn pregnancies accounted for 7/26 (26.9%) ectopic pregnancies in the study group. Women with a unicornuate uterus were more likely to have endometriosis (17.5% vs 10.7%; P = 0.018) and adenomyosis (26.7% vs 15.6%; P = 0.001), but were not more likely to have fibroids compared with controls. Women with a functional rudimentary horn were more likely to have pelvic endometriosis compared to those without (odds ratio, 2.4 (95% CI, 1.4-4.1), P = 0.002). CONCLUSIONS: Pregnant women with a unicornuate uterus should be classified as high risk. Removal of a functional rudimentary horn should be discussed with the patient to prevent a rudimentary-horn ectopic pregnancy. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Uterine junctional zone and adenomyosis: comparison of MRI, transvaginal ultrasound and histology.

The uterine junctional zone is the subendometrial area in the myometrium that contributes to peristalsis and aids in spermatozoa and blastocyst transport. Alterations in the appearance of the junctional zone on transvaginal sonography (TVS) or magnetic resonance imaging (MRI) are associated with adenomyosis. The lack of standardization of description of its appearance and ill-defined boundaries on both histology and imaging hamper understanding of the junctional zone and limit its role in the diagnosis of adenomyosis. The objectives of this review were to investigate the accordance in definition of the junctional zone across different diagnostic approaches and to examine how imaging findings can be linked to histological findings in the context of diagnosis of adenomyosis. A comprehensive literature review was conducted of articles describing the appearance on imaging and the histological structure of the uterine junctional zone. Our review suggests that the junctional zone is distinguished from the middle and outer myometrium by gradual changes in smooth-muscle cell density, extracellular space, connective tissue, water content and vascular properties. However, while the signal intensity from the junctional zone to the middle myometrium changes abruptly on MRI, the histopathological changes are gradual and its border may be difficult or impossible to distinguish on two-dimensional TVS. Moreover, the thickness of the junctional zone measured on MRI is larger than that measured on TVS. Thus, these two imaging modalities reflect this zone differently. Although a thickened junctional zone is often used to diagnose adenomyosis on MRI, the presence of adenomyosis can be described more accurately as interruptions of the junctional zone by endometrial tissue, which leads to direct signs on imaging such as subendometrial lines and buds on two- and three-dimensional TVS or bright foci on MRI. The histopathological criteria for diagnosis are based on enlargement of the uterus with severe adenomyosis, and might not reflect its early stages. Clinicians should be aware that findings on MRI cannot be extrapolated readily to ultrasound. An understanding of this is necessary when investigating the uterine junctional zone as a functional unit and the association between visualization of direct features of adenomyosis in the junctional zone and clinical symptoms. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Development of a core outcome set and outcome definitions for studies on uterus-sparing treatments of adenomyosis (COSAR): an international multistakeholder-modified Delphi consensus study.

STUDY QUESTION: What outcomes should be reported in all studies investigating uterus-sparing interventions for treating uterine adenomyosis? SUMMARY ANSWER: We identified 24 specific and 26 generic core outcomes in nine domains. WHAT IS KNOWN ALREADY: Research reporting adenomyosis treatment is not patient-centred and shows wide variation in outcome selection, definition, reporting and measurement of quality. STUDY DESIGN, SIZE, DURATION: An international consensus development process was performed between March and December 2021. Participants in round one were 150 healthcare professionals, 17 researchers and 334 individuals or partners with lived experience of adenomyosis from 48 high-, middle- and low-income countries. There were 291 participants in the second round. PARTICIPANTS/MATERIALS, SETTING, METHODS: Stakeholders included active researchers in the field, healthcare professionals involved in diagnosis and treatment, and people and their partners with lived experience of adenomyosis. The core component of the process was a 2-step modified Delphi electronic survey. The Steering Committee analysed the results and created the final core outcome set (COS) in a semi-structured meeting. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 241 outcomes was identified and distilled into a 'long list' of 71 potential outcomes. The final COS comprises 24 specific and 26 generic core outcomes across nine domains, including pain, uterine bleeding, reproductive outcomes, haematology, urinary system, life impact, delivery of care, adverse events and reporting items, all with definitions provided by the Steering Committee. Nineteen of these outcomes will apply only to certain study types. Although not included in the COS, the Steering Committee recommended that three health economic outcomes should be recorded. LIMITATIONS, REASONS FOR CAUTION: Patients from continents other than Europe were under-represented in this survey. A lack of translation of the survey might have limited the active participation of people in non-English speaking countries. Only 58% of participants returned to round two, but analysis did not indicate attrition bias. There is a significant lack of scientific evidence regarding which symptoms are caused by adenomyosis and when they are related to other co-existent disorders such as endometriosis. As future research provides more clarity, the appropriate review and revision of the COS will be necessary. WIDER IMPLICATIONS OF THE FINDINGS: Implementing this COS in future studies on the treatment of adenomyosis will improve the quality of reporting and aid evidence synthesis. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was received for this work. T.T. received a grant (grant number 2020083) from the South Eastern Norwegian Health Authority during the course of this work. T.T. receives personal fees from General Electrics and Medtronic for lectures on ultrasound. E.R.L. is the chairman of the Norwegian Endometriosis Association. M.G.M. is a consultant for Abbvie Inc and Myovant, receives research funding from AbbVie and is Chair of the Women's Health Research Collaborative. S.-W.G. is a board member of the Asian Society of Endometriosis and Adenomyosis, on the scientific advisory board of the endometriosis foundation of America, previous congress chair for the World Endometriosis Society, for none of which he received personal fees. E.S. received outside of this work grants for two multicentre trials on endometriosis from the National Institute for Health Research UK, the Rosetrees Trust, and the Barts and the London Charity, he is a member of the Medicines and Healthcare Products Regulatory Agency (MHRA), Medicines for Women's Health Expert Advisory Group, he is an ambassador for the World Endometriosis Society, and he received personal fees for lectures from Hologic, Olympus, Medtronic, Johnson & Johnson, Intuitive and Karl Storz. M.H. is member of the British Society for Gynaecological Endoscopy subcommittee. No other conflict of interest was declared. TRIAL REGISTRATION NUMBER: N/A.

Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis: results of modified Delphi procedure.

OBJECTIVES: To evaluate whether the Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis need to be better defined and, if deemed necessary, to reach consensus on the updated definitions. METHODS: A modified Delphi procedure was performed among European gynecologists with expertise in ultrasound diagnosis of adenomyosis. To identify MUSA features that might need revision, 15 two-dimensional (2D) video recordings (four recordings also included three-dimensional (3D) still images) of transvaginal ultrasound (TVS) examinations of the uterus were presented in the first Delphi round (online questionnaire). Experts were asked to confirm or refute the presence of each of the nine MUSA features of adenomyosis (described in the original MUSA consensus statement) in each of the 15 videoclips and to provide comments. In the second Delphi round (online questionnaire), the results of the first round and suggestions for revision of MUSA features were shared with the experts before they were asked to assess a new set of 2D and 3D still images of TVS examinations and to provide feedback on the proposed revisions. A third Delphi round (virtual group meeting) was conducted to discuss and reach final consensus on revised definitions of MUSA features. Consensus was predefined as at least 66.7% agreement between experts. RESULTS: Of 18 invited experts, 16 agreed to participate in the Delphi procedure. Eleven experts completed and four experts partly finished the first round. The experts identified a need for more detailed definitions of some MUSA features. They recommended use of 3D ultrasound to optimize visualization of the junctional zone. Fifteen experts participated in the second round and reached consensus on the presence or absence of ultrasound features of adenomyosis in most of the still images. Consensus was reached for all revised definitions except those for subendometrial lines and buds and interrupted junctional zone. Thirteen experts joined the online meeting, in which they discussed and agreed on final revisions of the MUSA definitions. There was consensus on the need to distinguish between direct features of adenomyosis, i.e. features indicating presence of ectopic endometrial tissue in the myometrium, and indirect features, i.e. features reflecting changes in the myometrium secondary to presence of endometrial tissue in the myometrium. Myometrial cysts, hyperechogenic islands and echogenic subendometrial lines and buds were classified unanimously as direct features of adenomyosis. Globular uterus, asymmetrical myometrial thickening, fan-shaped shadowing, translesional vascularity, irregular junctional zone and interrupted junctional zone were classified as indirect features of adenomyosis. CONCLUSION: Consensus between gynecologists with expertise in ultrasound diagnosis of adenomyosis was achieved regarding revised definitions of the MUSA features of adenomyosis and on the classification of MUSA features as direct or indirect signs of adenomyosis. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

A protocol for developing, disseminating, and implementing a core outcome set for adenomyosis research.

Background: Adenomyosis is a common benign gynaecological condition that has been associated with heavy and/or painful periods, subfertility and poor obstetric outcomes including miscarriage and preterm delivery. Studies evaluating treatments for adenomyosis have reported a wide range of outcomes and outcome measures. This variation in outcomes and outcome measures prevents effective data synthesis, thereby hampering the ability of meta-analyses to draw useful conclusions and inform clinical practice. Objectives: Our aim is to develop a minimum set of outcomes to be reported in all future studies that investigate any uterus-sparing intervention for treating uterine adenomyosis. Wide adoption of 'core outcomes' into research on adenomyosis would reduce the heterogeneity of studies and make data synthesis easier. This will ultimately lead to comparable, prioritised, and patient-centred conclusions from meta-analyses and guidelines. Materials and Methods: Outcomes identified from a systematic review of the literature will form a long list, agreed by an international steering group representing key stakeholders, including healthcare professionals, researchers, and public research partners. Through a modified Delphi process, key stakeholders will score outcomes from the agreed long list on a nine-point Likert scale that ranges from 1 (not important) to 9 (critical). Following the Delphi process, the refined outcome set will be finalised by the steering group. Finally, the steering group will develop recommendations for high-quality measures for each outcome. The study was prospectively registered with Core Outcome Measures in Effectiveness Trials Initiative; number 1649. Conclusion: The implementation of the core outcome set for adenomyosis in future trials will enhance the availability of comparable data to facilitate more patient-centred evidence-based care. What is new?: The core outcome set will facilitate the generation of clinically important and patient centred outcomes for studies evaluating treatments for adenomyosis.

A systematic review of outcome reporting and outcome measures in studies investigating uterine-sparing treatment for adenomyosis.

STUDY QUESTION: Which outcomes and outcome measures are reported in interventional trials evaluating the treatment of adenomyosis? SUMMARY ANSWER: We identified 38 studies, reporting on 203 outcomes using 133 outcome measures. WHAT IS KNOWN ALREADY: Heterogeneity in outcome evaluation and reporting has been demonstrated for several gynaecological conditions and in fertility studies. In adenomyosis, previous systematic reviews have failed to perform a quantitative analysis for central outcomes, due to variations in outcome reporting and measuring. STUDY DESIGN SIZE DURATION: A systematic search of Embase, Medline and Cochrane Register of Controlled Trials (CENTRAL) was performed with a timeframe from 1950 until February 2021, following the preferred reporting items for systematic reviews and meta-analysis (PRISMA). PARTICIPANTS/MATERIALS SETTING METHODS: Studies reporting on any uterus-sparing intervention to treat adenomyosis, both prospective and retrospective, were eligible for inclusion. Inclusion criteria were a clear definition of diagnostic criteria for adenomyosis and the modality used to make the diagnosis, a clear description of the intervention, a follow-up time of ≥6 months, a study population of n ≥ 20, a follow-up rate of at least 80%, and English language. The population included premenopausal women with adenomyosis. Risk of bias was assessed using the Evidence Project risk of bias tool. MAIN RESULTS AND THE ROLE OF CHANCE: We included 38 studies (6 randomized controlled trials and 32 cohort studies), including 5175 participants with adenomyosis. The studies described 10 interventions and reported on 203 outcomes, including 43 classified as harms, in 29 predefined domains. Dysmenorrhoea (reported in 82%), heavy menstrual bleeding (HMB) (in 79%) and uterine volume (in 71%) were the most common outcomes. Fourteen different outcome measures were used for dysmenorrhoea and 17 for HMB. Quality of life was reported in 9 (24%) studies, patient satisfaction with treatment in 1 (3%). A clear primary outcome was stated in only 18%. LIMITATIONS REASONS FOR CAUTION: This review includes studies with a high risk of bias. WIDER IMPLICATIONS OF THE FINDINGS: Shortcomings in the definition and choice of outcomes and outcome measures limit the value of the conducted research. The development and implementation of a core outcome set (COS) for interventional studies in adenomyosis could improve research quality. This review suggests a lack of patient-centred research in adenomyosis and people with adenomyosis should be involved in the development and implementation of the COS. STUDY FUNDING/COMPETING INTERESTS: No funds specifically for this work were received. T.T. receives fees from General Electrics for lectures on ultrasound independently of this project. TRIAL REGISTRATION NUMBER: This review is registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42020177466) and the Core Outcome Measures in Effectiveness Trials (COMET) initiative (registration number 1649).