Safety of methotrexate administration in women with pregnancy of unknown location at high risk of ectopic pregnancy.

OBJECTIVES: To evaluate the safety of current guidelines on methotrexate (MTX) administration in women with pregnancy of unknown location (PUL) who are considered to have a high risk of underlying ectopic pregnancy (EP), and to investigate whether implementation of these guidelines would result in inadvertent exposure to MTX of viable intrauterine pregnancies (IUPs). METHODS: This was a retrospective observational study of consecutive clinically stable women who were classified with PUL at the early pregnancy unit of Nepean Hospital, Sydney, Australia, between 2007 and 2021. PUL was defined as a positive pregnancy test in the absence of signs of IUP or EP on transvaginal ultrasound. Patients with a PUL that behaved biochemically like an EP, but for which the location of pregnancy was not confirmed on ultrasound, were eligible for MTX to minimize the risk of subsequent tubal rupture. Criteria discussed in the guidelines of the American College of Obstetricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM), Royal College of Obstetricians and Gynaecologists (RCOG) and National Institute for Health and Care Excellence (NICE) were applied to the PUL database. The number of patients eligible to receive MTX and the number with an underlying viable IUP who would be inadvertently prescribed MTX were calculated. RESULTS: A total of 816 women with PUL were reviewed, of whom 724 had complete data and were included in the final analysis. Six patients had persistent PUL and the remaining 718 had a diagnosis of viable IUP, non-viable IUP, EP or failed PUL. According to the ACOG, ASRM, RCOG and NICE guidelines, the rate of MTX administration among patients with PUL would have been 2.76%, 4.56%, 0.41% and 35.36%, respectively. However, no persistent PUL would have received MTX according to the ACOG, ASRM and RCOG protocols (the NICE protocol identified patients with persistent PUL with a sensitivity of 100%), and the majority of MTX treatments were unnecessary because those patients were later classified as having non-viable IUP or failed PUL. Application of ACOG and ASRM guidance could result theoretically in inadvertent MTX administration to women with an underlying viable IUP at a rate of 4.1/1000 (3/724). CONCLUSIONS: Current guidelines used to predict high risk of EP in the PUL population lead to inadvertent MTX administration to women with an underlying viable IUP. These guidelines should be used wisely to ensure that no wanted pregnancy is exposed to MTX. Women with PUL should be monitored carefully, and MTX should be used judiciously when the location of pregnancy is yet to be confirmed. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Non-invasive imaging techniques for diagnosis of pelvic deep endometriosis and endometriosis classification systems: an International Consensus Statement.

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) and International Deep Endometriosis Analysis (IDEA) group, the European Endometriosis League (EEL), the European Society for Gynaecological Endoscopy (ESGE), the European Society of Human Reproduction and Embryology (ESHRE), the International Society for Gynecologic Endoscopy (ISGE), the American Association of Gynecologic Laparoscopists (AAGL) and the European Society of Urogenital Radiology (ESUR) elected an international, multidisciplinary panel of gynecological surgeons, sonographers and radiologists, including a steering committee, which searched the literature for relevant articles in order to review the literature and provide evidence-based and clinically relevant statements on the use of imaging techniques for non-invasive diagnosis and classification of pelvic deep endometriosis. Preliminary statements were drafted based on review of the relevant literature. Following two rounds of revisions and voting orchestrated by chairs of the participating societies, consensus statements were finalized. A final version of the document was then resubmitted to the society chairs for approval. Twenty statements were drafted, of which 14 reached strong and three moderate agreement after the first voting round. The remaining three statements were discussed by all members of the steering committee and society chairs and rephrased, followed by an additional round of voting. At the conclusion of the process, 14 statements had strong and five statements moderate agreement, with one statement left in equipoise. This consensus work aims to guide clinicians involved in treating women with suspected endometriosis during patient assessment, counseling and planning of surgical treatment strategies. © 2024 The Authors. Published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology, by Universa Press, by The International Society for Gynecologic Endoscopy, by Oxford University Press on behalf of European Society of Human Reproduction and Embryology, by Elsevier Inc. on behalf of American Association of Gynecologic Laparoscopists and by Elsevier B.V.

Non-Invasive Imaging Techniques for Diagnosis of Pelvic Deep Endometriosis and Endometriosis Classification Systems: An International Consensus Statement.

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) and International Deep Endometriosis Analysis (IDEA) group, the European Endometriosis League (EEL), the European Society for Gynaecological Endoscopy (ESGE), the European Society of Human Reproduction and Embryology (ESHRE), the International Society for Gynecologic Endoscopy (ISGE), the American Association of Gynecologic Laparoscopists (AAGL) and the European Society of Urogenital Radiology (ESUR) elected an international, multidisciplinary panel of gynecological surgeons, sonographers and radiologists, including a steering committee, which searched the literature for relevant articles in order to review the literature and provide evidence-based and clinically relevant statements on the use of imaging techniques for non-invasive diagnosis and classification of pelvic deep endometriosis. Preliminary statements were drafted based on review of the relevant literature. Following two rounds of revisions and voting orchestrated by chairs of the participating societies, consensus statements were finalized. A final version of the document was then resubmitted to the society chairs for approval. Twenty statements were drafted, of which 14 reached strong and three moderate agreement after the first voting round. The remaining three statements were discussed by all members of the steering committee and society chairs and rephrased, followed by an additional round of voting. At the conclusion of the process, 14 statements had strong and five statements moderate agreement, with one statement left in equipoise. This consensus work aims to guide clinicians involved in treating women with suspected endometriosis during patient assessment, counseling and planning of surgical treatment strategies.

Addendum to the consensus opinion from the International Deep Endometriosis Analysis (IDEA) group: sonographic evaluation of the parametrium.

Preoperative sonographic staging in patients with suspected parametrial endometriosis is essential to plan the surgical intervention and to anticipate the need for a multidisciplinary approach, and hence optimize surgical outcome. The results of a recent metanalysis suggest that defining more accurately the ultrasonographic criteria of parametrial involvement in endometriosis is needed. The aim of this addendum to the IDEA-consensus is to highlight the sonographic characteristics of the parametrium and identify ultrasound techniques to diagnose deep endometriosis in this area. This article is protected by copyright. All rights reserved.

Diagnostic accuracy of transvaginal ultrasound for detection of endometriosis using International Deep Endometriosis Analysis (IDEA) approach: prospective international pilot study.

OBJECTIVE: To evaluate the diagnostic accuracy of transvaginal ultrasound (TVS) in predicting deep endometriosis (DE) following the International Deep Endometriosis Analysis (IDEA) consensus methodology. METHODS: This was an international multicenter prospective diagnostic accuracy study involving eight centers across six countries (August 2018-November 2019). Consecutive participants with endometriosis suspected based on clinical symptoms or historical diagnosis of endometriosis were included. The index test was TVS performed preoperatively in accordance with the IDEA consensus statement. At each center, the index test was interpreted by a single sonologist. Reference standards were: (1) direct visualization of endometriosis at laparoscopy, as determined by a non-blinded surgeon with expertise in endometriosis surgery; and (2) histological assessment of biopsied/excised tissue. Surgery was performed within 12 months following the index TVS. Accuracy, sensitivity, specificity, positive and negative predictive values (PPV and NPV) and positive and negative likelihood ratios (LR+ and LR-) of TVS in the diagnosis of DE were calculated. RESULTS: Included in the study were 273 participants with complete clinical, TVS, laparoscopic and histological data. Of these, based on histology, 256 (93.8%) were confirmed to have endometriosis, including superficial endometriosis, and 190 (69.6%) were confirmed to have DE. Based on surgical visualization, 207/273 (75.8%) patients had DE. For DE overall, the diagnostic performance of TVS based on surgical visualization as the reference standard was as follows: accuracy, 86.1%; sensitivity, 88.4%; specificity, 78.8%; PPV, 92.9%; NPV, 68.4%; LR+, 4.17; LR-, 0.15, and the diagnostic performance of TVS based on histology as the reference standard was as follows: accuracy, 85.9%; sensitivity, 89.8%; specificity, 75.9%; PPV, 90.4%; NPV, 74.6%; LR+, 3.72; LR-, 0.13. CONCLUSIONS: Using the IDEA consensus methodology provides strong diagnostic accuracy for TVS assessment of DE. We found a higher TVS detection rate of DE overall than that reported by the most recent meta-analysis on the topic (sensitivity, 79%), albeit with a lower specificity. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Strengths and limitations of diagnostic tools for endometriosis and relevance in diagnostic test accuracy research.

Endometriosis is a chronic systemic disease that can cause pain, infertility and reduced quality of life. Diagnosing endometriosis remains challenging, which yields diagnostic delays for patients. Research on diagnostic test accuracy in endometriosis can be difficult due to verification bias, as not all patients with endometriosis undergo definitive diagnostic testing. The purpose of this State-of-the-Art Review is to provide a comprehensive update on the strengths and limitations of the diagnostic modalities used in endometriosis and discuss the relevance of diagnostic test accuracy research pertaining to each. We performed a comprehensive literature review of the following methods: clinical assessment including history and physical examination, biomarkers, diagnostic imaging, surgical diagnosis and histopathology. Our review suggests that, although non-invasive diagnostic methods, such as clinical assessment, ultrasound and magnetic resonance imaging, do not yet qualify formally as replacement tests for surgery in diagnosing all subtypes of endometriosis, they are likely to be appropriate for advanced stages of endometriosis. We also demonstrate in our review that all methods have strengths and limitations, leading to our conclusion that there should not be a single gold-standard diagnostic method for endometriosis, but rather, multiple accepted diagnostic methods appropriate for different circumstances. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Accuracy of sonography for non-invasive detection of ovarian and deep endometriosis using #Enzian classification: prospective multicenter diagnostic accuracy study.

OBJECTIVE: To compare the preoperative detection of endometriosis using transvaginal sonography (TVS) supplemented by transabdominal sonography (TAS) with surgical assessment of disease, using the #Enzian classification for endometriosis. METHODS: This was a prospective multicenter diagnostic accuracy study of women undergoing TVS/TAS and radical surgery for deep endometriosis (DE) at different tertiary referral centers. The localization and grade of severity of the endometriotic lesions and adhesions were described according to the criteria of the #Enzian classification, both at preoperative ultrasound examination and during surgery. According to the #Enzian classification, the small pelvis is divided into three compartments for DE: A (rectovaginal septum and vagina); B (uterosacral and cardinal ligaments, parametrium and pelvic sidewalls); and C (rectum). In addition, further locations (F) are classified as adenomyosis (FA), urinary bladder involvement (FB) and ureteric involvement with signs of obstruction (FU). Other intestinal locations (FI) and other extragenital locations (FO) are also included. Ovarian endometriosis and adhesions at the level of the tubo-ovarian unit are listed as O and T, respectively. The #Enzian grade of severity (Grade 1-3) was determined for #Enzian compartments O, T, A, B and C based on the size of the lesion or the severity of the adhesions. Concordance between preoperative assessment using TVS/TAS and evaluation at surgery was assessed. The sensitivity, specificity, positive and negative predictive values and accuracy of TVS/TAS in the detection of endometriotic lesions/adhesions in the different #Enzian compartments were calculated. RESULTS: In total, 745 women were included in the analysis. Preoperative TVS/TAS and surgical findings showed a concordance rate ranging between 86% and 99% for the presence or absence of endometriotic lesions/adhesions, depending on the evaluated #Enzian compartment. The concordance rate between TVS and surgery ranged between 71% and 92% for different severity grades, in #Enzian compartments O, T, A, B and C. Determining the presence or absence of adhesions at the level of the tubo-ovarian unit and classifying them accurately as Grade 1, 2 or 3 on TVS was more difficult than determining the presence and severity of endometriotic lesions in #Enzian compartments O, A, B and C. The sensitivity of TVS/TAS for the detection of endometriotic lesions ranged from 50% (#Enzian compartment FI) to 95% (#Enzian compartment A), specificity from 86% (#Enzian compartment Tleft ) to 99% (#Enzian compartment FI) and 100% (#Enzian compartments FB, FU and FO), positive predictive value from 90% (#Enzian compartment Tright ) to 100% (#Enzian compartment FO), negative predictive value from 74% (#Enzian compartment Bleft ) to 99% (#Enzian compartments FB and FU) and accuracy from 88% (#Enzian compartment Bright ) to 99% (#Enzian compartment FB). CONCLUSIONS: The localization and severity of endometriotic lesions/adhesions, as described and classified according to the #Enzian classification, can be diagnosed accurately and non-invasively using TVS/TAS. The #Enzian classification provides a uniform classification system for describing endometriotic lesions, which can be used both at TVS/TAS and during surgical evaluation. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Assessing the knowledge of endometriosis diagnostic tools in a large, international lay population: an online survey.

OBJECTIVE: To assess the general population's knowledge regarding the utility and availability of tools to diagnosis endometriosis, with a focus on ultrasound. DESIGN: An international cross-sectional online survey study was performed between August and October 2019. SETTING AND POPULATION: 5301 respondents, representing 73 countries. METHODS: In all, 23 questions survey focused on knowledge of endometriosis diagnosis distributed globally via patient- and community-endometriosis groups using social media. MAIN OUTCOMES AND MEASURES: Descriptive data of the knowledge of diagnostic tools for diagnosing endometriosis, including details about diagnosis using ultrasound. RESULTS: In all, 84.0% of respondents had been previously diagnosed with endometriosis, 71.5% of whom had been diagnosed at the time of surgery. Ultrasound and MRI were the methods of diagnosis in 6.5% and 1.8%, respectively. A total of 91.8%, 28.8% and 16.6% of respondents believed surgery, ultrasound and MRI could diagnose endometriosis, respectively (more than one answer allowed). In those diagnosed by surgery, 21.7% knew about ultrasound as a diagnosis method, whereas in those diagnosed non-surgically, 51.5% knew (P < 0.001). In all, 14.7%, 31.1% and 18.2% stated superficial, ovarian and deep endometriosis could be diagnosed with ultrasound (32.9% stated they did not know which phenotypes of endometriosis could be diagnosed). Lastly, 58.4% of respondents do not believe they could access an advanced ultrasound in their region. CONCLUSIONS: There is a limited appreciation for the role of non-surgical diagnostic tests for endometriosis among lay respondents to this survey. TWEETABLE ABSTRACT: International survey shows limited awareness of lay respondents about non-surgical endometriosis diagnostic tools.

Optimal imaging modality for detection of rectosigmoid deep endometriosis: systematic review and meta-analysis.

OBJECTIVES: To review the accuracy of different imaging modalities for the detection of rectosigmoid deep endometriosis (DE) in women with clinical suspicion of endometriosis, and to determine the optimal modality. METHODS: A search was conducted using PubMed, MEDLINE, Scopus, EMBASE and Google Scholar to identify studies using imaging to evaluate women with suspected DE, published from inception to May 2020. Studies were considered eligible if they were prospective and used any imaging modality to assess preoperatively for the presence of DE in the rectum/rectosigmoid, which was then correlated with the surgical diagnosis as the reference standard. Eligibility was restricted to studies including at least 10 affected and 10 unaffected women. The QUADAS-2 tool was used to assess the quality of the included studies. Mixed-effects diagnostic meta-analysis was used to determine the overall pooled sensitivity and specificity of each imaging modality for rectal/rectosigmoid DE, which were used to calculate the likelihood ratio of a positive (LR+) and negative (LR-) test and diagnostic odds ratio (DOR). RESULTS: Of the 1979 records identified, 30 studies (3374 women) were included in the analysis. The overall pooled sensitivity and specificity, LR+, LR- and DOR for the detection of rectal/rectosigmoid DE using transvaginal sonography (TVS) were, respectively, 89% (95% CI, 83-92%), 97% (95% CI, 95-98%), 30.8 (95% CI, 17.6-54.1), 0.12 (95% CI, 0.08-0.17) and 264 (95% CI, 113-614). For magnetic resonance imaging (MRI), the respective values were 86% (95% CI, 79-91%), 96% (95% CI, 94-97%), 21.0 (95% CI, 13.4-33.1), 0.15 (95% CI, 0.09-0.23) and 144 (95% CI, 70-297). For computed tomography, the respective values were 93% (95% CI, 84-97%), 95% (95% CI, 81-99%), 20.3 (95% CI, 4.3-94.9), 0.07 (95% CI, 0.03-0.19) and 280 (95% CI, 28-2826). For rectal endoscopic sonography (RES), the respective values were 92% (95% CI, 87-95%), 98% (95% CI, 96-99%), 37.1 (95% CI, 21.1-65.4), 0.08 (95% CI, 0.05-0.14) and 455 (95% CI, 196-1054). There was significant heterogeneity and the studies were considered methodologically poor according to the QUADAS-2 tool. CONCLUSIONS: The sensitivity of TVS for the detection of rectal/rectosigmoid DE seems to be slightly better than that of MRI, although RES was superior to both. The specificity of both TVS and MRI was excellent. As TVS is simpler, faster and more readily available than the other methods, we believe that it should be the first-line diagnostic tool for women with suspected DE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Transvaginal sonography determines accurately extent of infiltration of rectosigmoid deep endometriosis.

OBJECTIVE: To investigate the agreement of measurements of the three diameters of rectosigmoid deep endometriosis (DE) lesions between presurgical evaluation using transvaginal sonography (TVS) and postsurgical specimen measurement (PSM). METHODS: This was a prospective observational multicenter study including symptomatic women undergoing surgical treatment for DE involving the rectosigmoid, by either discoid or segmental resection, from April 2017 to December 2019. TVS was performed presurgically to evaluate lesion size (craniocaudal-midsagittal length, anteroposterior thickness and transverse diameter), in accordance with the International Deep Endometriosis Analysis (IDEA) group consensus statement, and was compared with PSM. The agreement of lesion dimensions between the two methods was assessed by Bland-Altman plots and limits of agreement and additionally by the intraclass correlation coefficient (ICC) and Pearson's correlation coefficient. Systematic and proportional bias was assessed using the paired t-test. RESULTS: A total of 207 consecutive women were eligible for inclusion. Forty-one women were excluded, leaving 166 women for final analysis. A total of 123 segmental resections and 46 discoid resections were performed (both procedures were performed in three women). The mean difference between TVS and PSM was 0.90 (95% CI, 0.85-0.95) mm for lesion length measurements, 1.03 (95% CI, 0.98-1.09) mm for lesion thickness measurements and 0.84 (95% CI, 0.79-0.89) mm for transverse diameter measurements. Bland-Altman analysis demonstrated good agreement between the two methods for measurements of lesion length. Furthermore, there was good reliability and correlation between TVS and PSM for lesion length measurements, as demonstrated by an ICC of 0.82 (95% CI, 0.75-0.87) and Pearson's correlation coefficient of 0.72 (95% CI, 0.62-0.80), moderate-to-good reliability and correlation for lesion thickness measurements, with an ICC of 0.76 (95% CI, 0.67-0.82) and Pearson's correlation coefficient of 0.61 (95% CI, 0.51-0.70), and poor-to-moderate reliability and correlation for transverse diameter measurements, with an ICC of 0.58 (95% CI, 0.39-0.71) and Pearson's correlation coefficient of 0.46 (95% CI, 0.33-0.58). CONCLUSION: Preoperative TVS determines accurately rectosigmoid DE lesion length. TVS can thereby contribute to optimal planning of surgical treatment options in women with rectosigmoid DE. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Endometriosis and the microbiome: a systematic review.

BACKGROUND: The aetiology and pathogenesis of endometriosis are still under investigation. There is evidence that there is a complex bidirectional interaction between endometriosis and the microbiome. OBJECTIVE: To systematically review the available literature on the endometriosis-microbiome interaction, with the aim of guiding future inquiries in this emerging area of endometriosis research. SEARCH STRATEGY: MEDLINE, Embase, Scopus and Web of Science were searched through May 2019. A manual search of reference lists of relevant studies was also performed. SELECTION CRITERIA: Published and unpublished literature in any language describing a comparison of the microbiome state in mammalian hosts with and without endometriosis. DATA COLLECTION AND ANALYSIS: Identified studies were screened and assessed independently by two authors. Data were extracted and compiled in a qualitative synthesis of the evidence. MAIN RESULTS: Endometriosis appears to be associated with an increased presence of Proteobacteria, Enterobacteriaceae, Streptococcus spp. and Escherichia coli across various microbiome sites. The phylum Firmicutes and the genus Gardnerella also appear to have an association; however, this remains unclear. CONCLUSIONS: The complex bidirectional relationship between the microbiome and endometriosis has begun to be characterised by the studies highlighted in this systematic review. Laboratory and clinical studies demonstrate that there are indeed differences in the microbiome composition of hosts with and without endometriosis. TWEETABLE ABSTRACT: Review findings show endometriosis associated with increased Proteobacteria, Enterobacteriaceae, Streptococcus and Escherichia coli across various microbiome sites.

Prevalence of negative sliding sign representing pouch of Douglas obliteration during pelvic transvaginal ultrasound for any indication.

OBJECTIVES: Pouch of Douglas (POD) obliteration can be predicted with a high degree of certainty and reproducibility using the dynamic transvaginal ultrasound (TVS) sliding-sign technique. So far, studies on POD obliteration prediction have focused on tertiary-care populations with high prevalence of endometriosis; however, POD obliteration may exist in individuals with asymptomatic endometriosis or other conditions. Our primary aim was to determine the prevalence of a negative sliding sign, representing POD obliteration, in a cohort of patients undergoing TVS for any gynecological indication. METHODS: This was a prospective observational study of consecutive women with an indication for gynecological TVS, conducted at a high-volume ultrasound practice between July and August 2018. Clinical and surgical history, indication for TVS and TVS findings were documented. The prevalence of TVS-confirmed POD obliteration, determined by interpretation of the sliding sign, was calculated for the entire cohort and for the subgroups of women with and without risk factors for endometriosis. High risk for endometriosis was defined as having (1) a TVS referral for endometriosis-like pelvic pain or endometriosis specifically and/or (2) clinical symptoms or signs suggestive of endometriosis. Low risk was defined as the absence of these characteristics. RESULTS: During the study period, 1043 consecutive women underwent TVS. After excluding those who underwent transabdominal ultrasound, had a history of hysterectomy or with missing data, 909 women were analyzed. The prevalence of a negative sliding sign in the entire cohort was 47/909 (5.2%). A negative sliding sign was observed in 22/639 (3.4%) women with a low risk for endometriosis and 25/243 (10.3%) of those with a high risk for endometriosis (difference in proportions, 6.9% (95% CI 2.8-10.9%); P < 0.001). CONCLUSIONS: We have demonstrated an overall prevalence of a negative sliding sign, suggesting POD obliteration, of 5.2% (or 1/20) in women seeking TVS for a gynecological indication. The prevalence of negative sliding sign in low-risk women is not negligible (3.4% or 1/29 women). These women are most likely to have asymptomatic endometriosis or another important etiology of POD obliteration. The prevalence of a negative sliding sign is approximately three-times higher in women with signs and/or symptoms of endometriosis (10.3% vs 3.4%). Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Resultado de supervivencia en una hernia diafragmática congénita grave del lado izquierdo, con y sin oclusión traqueal endoscópica fetal en un país con un tratamiento neonatal subóptimo OBJETIVOS: La obliteración del fondo de saco de Douglas (FSD) puede predecirse con un alto grado de certeza y reproducibilidad usando la técnica del signo deslizante en una ecografía transvaginal dinámica (TVS, por sus siglas en inglés). Hasta ahora, los estudios sobre la predicción de la obliteración del FSD se han centrado en las poblaciones de atención terciaria con alta prevalencia de endometriosis; sin embargo, la obliteración del FSD puede ocurrir en personas con endometriosis asintomática u otras afecciones. El objetivo principal fue determinar la prevalencia de un signo deslizante negativo, como indicador de la obliteración del FSD, en una cohorte de pacientes que se sometieron a TVS por cualquier indicación ginecológica. MÉTODOS: Se trató de un estudio observacional prospectivo de mujeres en una lista consecutiva a quienes se les indicó una TVS ginecológica, realizada en una consulta de ecografía de gran volumen de pacientes entre julio y agosto de 2018. Se documentaron los antecedentes clínicos y quirúrgicos, las indicaciones para la TVS y los hallazgos de la TVS. La prevalencia de la obliteración del FSD confirmada por la TVS, determinada por la interpretación del signo deslizante, se calculó para toda la cohorte y para subgrupos de mujeres con y sin factores de riesgo de endometriosis. El riesgo elevado de endometriosis se definió como el hecho de tener (1) una remisión para TVS debido a dolor pélvico similar a la endometriosis o endometriosis específicamente y/o (2) síntomas o indicios clínicos que sugerían endometriosis. El riesgo bajo se definió como la ausencia de estas características. RESULTADOS: Durante el período de estudio, 1043 mujeres se sometieron a TVS de forma consecutiva. Se analizaron 909 mujeres, tras excluir a las que se sometieron a una ecografía abdominal, las que tenían antecedentes de histerectomía o aquellas para las que faltaban datos. La prevalencia de un signo deslizante negativo en toda la cohorte fue de 47/909 (5,2%). Se observó un signo deslizante negativo en 22/639 (3,4%) de las mujeres con bajo riesgo de endometriosis y en 25/243 (10,3%) de aquellas con alto riesgo de endometriosis (diferencia de proporciones, 6,9% (IC 95%: 2,8-10,9%); P<0,001). CONCLUSIONES: Se demuestra una prevalencia general de un signo deslizante negativo, que sugiere la obliteración del FSD en el 5,2% (o 1/20) de mujeres que se someten a TVS para una indicación ginecológica. La prevalencia del signo deslizante negativo en las mujeres de bajo riesgo no es desdeñable (3,4% o 1/29 mujeres). Estas mujeres son las más propensas a tener endometriosis asintomática u otra etiología importante de obliteración del FSD. La prevalencia de un signo deslizante negativo es aproximadamente tres veces mayor en mujeres con signos y/o síntomas de endometriosis (10,3% vs 3,4%). Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Transvaginal sonography accurately measures lesion-to-anal-verge distance in women with deep endometriosis of the rectosigmoid.

OBJECTIVES: First, to investigate the accuracy of transvaginal sonography (TVS) for presurgical evaluation of the distance between the most caudal part of the endometriotic lesion and the anal verge (lesion-to-anal-verge distance (LAVD)) in women with rectosigmoid deep endometriosis (DE), compared with intraoperative measurement (IOM). Second, to assess the agreement between anastomosis height and LAVD measured using TVS. METHODS: This was a prospective observational multicenter study of symptomatic women who were scheduled for surgical treatment of rectosigmoid DE, by either discoid or segmental resection, between April 2017 and September 2019. Presurgical TVS was performed to evaluate the LAVD in two ways, depending on the level of the lesion. Method 1: for lesions at the level of the rectovaginal septum (RVS), the caudal part of the lesion was identified on TVS and an index finger was placed on the TVS probe at the level of the anal verge. The probe was withdrawn and the distance from the tip of the TVS probe down to the index finger was measured using a ruler, representing the LAVD. Method 2: for lesions above the RVS, the distance between the caudal part of the lesion and the lower lip of the posterior cervix was measured in a frozen image (LAVD-1), and the distance between the lower lip of the posterior cervix and the anal verge (LAVD-2) was measured using Method 1. These two measurements (LAVD-1 and LAVD-2) were added together and the result represented the total LAVD. During surgery, a rectal probe was used to perform IOM of LAVD, which was considered as the gold standard test. Agreement between LAVD measured using TVS and the IOM was assessed using Bland-Altman analysis. The intraclass correlation coefficient (ICC) for absolute agreement and Spearman's correlation coefficient were also calculated. Systematic and proportional bias were tested for significance using the paired t-test. Similar analysis was performed to assess agreement between LAVD measured using TVS and anastomosis height. RESULTS: A total of 147 consecutive women were considered eligible for inclusion. Fourteen women were excluded initially. Thirty-four discoid resections and 102 segmental resections were performed; both procedures were performed in three women. Two more women were excluded from the final analysis because the measurements represented extreme outliers. The mean LAVD measured using TVS was 114.8 ± 36.5 mm and the mean IOM was 116.9 ± 42.3 mm. There was no statistically significant difference between LAVD measured using TVS and IOM (mean difference, -2.12 mm (95% CI, -6.33 to 2.05 mm); P = 0.32). Bland-Altman analysis showed that there was good agreement between the two methods. The ICC was 0.81 (95% CI, 0.74-0.86) and Spearman's correlation coefficient was 0.68 (95% CI, 0.56-0.77). The mean difference between LAVD measured using TVS and anastomosis height was statistically, but not clinically, significant (mean difference, 10.25 mm (95% CI, 5.94-14.32 mm); P = 0.0005), and the ICC was 0.78 (95% CI, 0.66-0.85). CONCLUSIONS: There is good agreement between the LAVD measured using TVS and the IOM in women with rectosigmoid DE. As a consequence, TVS could be useful for estimation of the height of the final surgical anastomosis in women undergoing full-thickness resection for rectosigmoid DE. This is of pivotal importance in reducing the risk of complications and need for a temporary stoma, and could improve patient counseling. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Congenital Uterine Malformation by Experts (CUME): diagnostic criteria for T-shaped uterus.

OBJECTIVES: To identify uterine measurements that are reliable and accurate to distinguish between T-shaped and normal/arcuate uterus, and define T-shaped uterus, using Congenital Uterine Malformation by Experts (CUME) methodology, which uses as reference standard the decision made most often by several independent experts. METHODS: This was a prospectively planned multirater reliability/agreement and diagnostic accuracy study, performed between November 2017 and December 2018, using a sample of 100 three-dimensional (3D) datasets of different uteri with lateral uterine cavity indentations, acquired from consecutive women between 2014 and 2016. Fifteen representative experts (five clinicians, five surgeons and five sonologists), blinded to each others' opinions, examined anonymized images of the coronal plane of each uterus and provided their independent opinion as to whether it was T-shaped or normal/arcuate; this formed the basis of the CUME reference standard, with the decision made most often (i.e. that chosen by eight or more of the 15 experts) for each uterus being considered the correct diagnosis for that uterus. Two other experienced observers, also blinded to the opinions of the other experts, then performed independently 15 sonographic measurements, using the original 3D datasets of each uterus. Agreement between the diagnoses made by the 15 experts was assessed using kappa and percent agreement. The interobserver reliability of measurements was assessed using the concordance correlation coefficient (CCC). The diagnostic test accuracy was assessed using the area under the receiver-operating-characteristics curve (AUC) and the best cut-off value was assessed by calculating Youden's index, according to the CUME reference standard. Sensitivity, specificity, negative and positive likelihood ratios (LR- and LR+) and post-test probability were calculated. RESULTS: According to the CUME reference standard, there were 20 T-shaped and 80 normal/arcuate uteri. Individual experts recognized between 5 and 35 (median, 19) T-shaped uteri on subjective judgment. The agreement among experts was 82% (kappa = 0.43). Three of the 15 sonographic measurements were identified as having good diagnostic test accuracy, according to the CUME reference standard: lateral indentation angle (AUC = 0.95), lateral internal indentation depth (AUC = 0.92) and T-angle (AUC = 0.87). Of these, T-angle had the best interobserver reproducibility (CCC = 0.87 vs 0.82 vs 0.62 for T-angle vs lateral indentation depth vs lateral indentation angle). The best cut-off values for these measurements were: lateral indentation angle ≤ 130° (sensitivity, 80%; specificity, 96%; LR+, 21.3; LR-, 0.21), lateral indentation depth ≥ 7 mm (sensitivity, 95%; specificity, 77.5%; LR+, 4.2; LR-, 0.06) and T-angle ≤ 40° (sensitivity, 80%; specificity, 87.5%; LR+, 6.4; LR-, 0.23). Most of the experts diagnosed the uterus as being T-shaped in 0% (0/56) of cases when none of these three criteria was met, in 10% (2/20) of cases when only one criterion was met, in 50% (5/10) of cases when two of the three criteria were met, and in 93% (13/14) of cases when all three criteria were met. CONCLUSIONS: The diagnosis of T-shaped uterus is not easy; the agreement among experts was only moderate and the judgement of individual experts was commonly insufficient for accurate diagnosis. The three sonographic measurements with cut-offs that we identified (lateral internal indentation depth ≥ 7 mm, lateral indentation angle ≤ 130° and T-angle ≤ 40°) had good diagnostic test accuracy and fair-to-moderate reliability and, when applied in combination, they provided high post-test probability for T-shaped uterus. In the absence of other anomalies, we suggest considering a uterus to be normal when none or only one criterion is met, borderline when two criteria are met, and T-shaped when all three criteria are met. These three CUME criteria for defining T-shaped uterus may aid in determination of its prevalence, clinical implications and best management and in the assessment of post-surgical morphologic outcome. The CUME definition of T-shaped uterus may help in the development of interventional randomized controlled trials and observational studies and in the diagnosis of uterine morphology in everyday practice, and could be adopted by guidelines on uterine anomalies to enrich their classification systems. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Deep endometriosis transvaginal ultrasound in the workup of patients with signs and symptoms of endometriosis: a cost analysis.

OBJECTIVE: Deep endometriosis transvaginal ultrasound (DE TVS) is accurate in the detection of ovarian endometriosis and DE; however, realisation of its full potential and utilisation remains variable. As such, patients may require a two-step surgical approach (diagnostic followed by therapeutic laparoscopy) or experience incomplete surgical treatment. Besides the clinical implications, the economic impact of a two-step approach to diagnosis and treatment on the healthcare system is likely to be significant. We aim to compare the economic costs of two diagnostic models of care for patients with potential endometriosis. DESIGN: Cost analysis using Markov model with 12-month time horizon comparing the economic costs of two diagnostic models. SETTING: The study used a hypothetical population of 1000 women visiting a public tertiary gynaecology clinic. POPULATION: Women with potential endometriosis. Estimates for endometriosis prevalence and severity were drawn from local Australian hospital data. METHODS: The conventional model (M1) includes the basic TVS and diagnostic laparoscopy. The novel model (M2) includes the DE TVS. Probabilistic sensitivity analysis was conducted to capture the uncertainty in the information used to populate the models. MAIN OUTCOME MEASURE: Changes to government, health-service and patient costs with the adoption of the DE TVS compared with standard diagnostic methods. Costs are given in Australian dollars (AU$) and also in pound sterling (£). RESULTS: The total annual cost of the novel model (M2) is AU$12,547,724.03 (£6,826,673.63), cheaper than the conventional model (M1), which cost AU$13,472,161.67 (£7,329,620.15). CONCLUSIONS: For a population of 1000 women, the integration of the DE TVS may save healthcare costs of AU$924,437 (£502,946.17) annually. TWEETABLE ABSTRACT: An endometriosis-focused ultrasound may negate a two-step surgery pathway, including diagnostic surgery, and save healthcare money.

Morphological ultrasound types known as 'blob' and 'bagel' signs should be reclassified from suggesting probable to indicating definite tubal ectopic pregnancy.

OBJECTIVE: In a recent consensus statement on early pregnancy nomenclature by Barnhart, a definite ectopic pregnancy (EP) was defined morphologically on transvaginal sonography (TVS) as an extrauterine gestational sac with yolk sac and/or embryo, with or without cardiac activity, whilst a probable EP was defined as an inhomogeneous adnexal mass ('blob' sign) or extrauterine sac-like structure ('bagel' sign). This study aims to determine whether these ultrasound markers used to define probable EP can be used to predict a definite tubal EP. METHODS: This was a retrospective cohort study of women presenting to the Early Pregnancy Unit (EPU) at Nepean Hospital, Sydney, Australia between November 2006 and June 2016. Women classified with a probable EP or a pregnancy of unknown location (PUL), i.e. with no signs of extra- or intrauterine pregnancy (IUP), at their first TVS were included, whilst those with a definite tubal EP, IUP or non-tubal EP were excluded from the final analysis. The gold standard for tubal EP was histological confirmation of chorionic villi in Fallopian tube removed at laparoscopy. The performance of blob or bagel sign on TVS in the prediction of definite tubal EP was evaluated in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). This was compared with the performance of extrauterine gestational sac with yolk sac and/or embryo on TVS to predict definite tubal EP. RESULTS: During the study period, 7490 consecutive women attended the EPU, of whom 849 were analyzed. At primary TVS, 240/849 were diagnosed with probable EP, of which 174 (72.5%) were classified as blob sign and 66 (27.5%) as bagel sign. The remaining 609/849 were diagnosed with PUL, of which 47 had a final diagnosis of EP (including 24 blob sign, 19 bagel sign and four gestational sac with embryo/yolk sac). 101 of all 198 (51%) blob sign cases and 50 of all 85 (59%) bagel sign cases underwent laparoscopy and salpingectomy; histology proved a tubal EP in 98 (97%) of these blob-sign cases and 48 (96.0%) of the bagel-sign cases. The sensitivity for the blob and bagel signs in the prediction of definite tubal EP was 89.8% and 83.3%, respectively, the specificity was 99.5% and 99.6%, PPV was 96.7% and 95.2% and NPV was 98.3% and 98.6%. This was comparable to the sensitivity of extrauterine gestational sac with yolk sac and/or embryo on TVS in the prediction of definite tubal EP (sensitivity, 84.0%; specificity, 99.9%; PPV, 97.7%; NPV, 99.3% (P = 0.5)). CONCLUSIONS: Blob and bagel signs seem to be the most common presentations of a tubal EP on TVS. Although they cannot be considered as a definitive sign of EP, their PPV is very high (> 95%); such women should therefore be considered at very high risk for having a tubal EP and should be treated as such. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Counting ovarian antral follicles by ultrasound: a practical guide.

This Consensus Opinion summarizes the main aspects of several techniques for performing ovarian antral follicle count (AFC), proposes a standardized report and provides recommendations for future research. AFC should be performed using a transvaginal ultrasound (US) probe with frequency ≥ 7 MHz. For training, we suggest a minimum of 20-40 supervised examinations. The operator should be able to adjust the machine settings in order to achieve the best contrast between follicular fluid and ovarian stroma. AFC may be evaluated using real-time two-dimensional (2D) US, stored 2D-US cine-loops and stored three-dimensional (3D) US datasets. Real-time 2D-US has the advantage of permitting additional maneuvers to determine whether an anechoic structure is a follicle, but may require a longer scanning time, particularly when there is a large number of follicles, resulting in more discomfort to the patient. 2D-US cine-loops have the advantages of reduced scanning time and the possibility for other observers to perform the count. The 3D-US technique requires US machines with 3D capability and the operators to receive additional training for acquisition/analysis, but has the same advantages as cine-loop and also allows application of different imaging techniques, such as volume contrast imaging, inversion mode and semi-automated techniques such as sonography-based automated volume calculation. In this Consensus Opinion, we make certain recommendations based on the available evidence. However, there is no strong evidence that any one method is better than another; the operator should choose the best method for counting ovarian follicles based on availability of resources and on their own preference and skill. More studies evaluating how to improve the reliability of AFC should be encouraged. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Congenital Uterine Malformation by Experts (CUME): better criteria for distinguishing between normal/arcuate and septate uterus?

OBJECTIVES: To assess the level of agreement between experts in distinguishing between septate and normal/arcuate uterus using their subjective judgment when reviewing the coronal view of the uterus from three-dimensional ultrasound. Another aim was to determine the interobserver reliability and diagnostic test accuracy of three measurements suggested by recent guidelines, using as reference standard the decision made most often by experts (Congenital Uterine Malformation by Experts (CUME)). METHODS: Images of the coronal plane of the uterus from 100 women with suspected fundal internal indentation were anonymized and provided to 15 experts (five clinicians, five surgeons and five sonologists). They were instructed to indicate whether they believed the uterus to be normal/arcuate (defined as normal uterine morphology or not clinically relevant degree of distortion caused by internal indentation) or septate (clinically relevant degree of distortion caused by internal indentation). Two other observers independently measured indentation depth, indentation angle and indentation-to-wall-thickness (I:WT) ratio. The agreement between experts was assessed using kappa, the interobserver reliability was assessed using the concordance correlation coefficient (CCC), the diagnostic test accuracy was assessed using the area under the receiver-operating characteristics curve (AUC) and the best cut-off value was assessed using Youden's index, considering as the reference standard the choice made most often by the experts (CUME). RESULTS: There was good agreement between all experts (kappa, 0.62). There were 18 septate and 82 normal/arcuate uteri according to CUME; European Society of Human Reproduction and Embryology (ESHRE)-European Society for Gynaecological Endoscopy (ESGE) criteria (I:WT ratio > 50%) defined 80 septate and 20 normal/arcuate uteri, while American Society for Reproductive Medicine (ASRM) criteria defined five septate (depth > 15 mm and angle < 90°), 82 normal/arcuate (depth < 10 mm and angle > 90°) and 13 uteri that could not be classified (referred to as the gray-zone). The agreement between ESHRE-ESGE and CUME was 38% (kappa, 0.1); the agreement between ASRM criteria and CUME for septate was 87% (kappa, 0.39), and considering both septate and gray-zone as septate, the agreement was 98% (kappa, 0.93). Among the three measurements, the interobserver reproducibility of indentation depth (CCC, 0.99; 95% CI, 0.98-0.99) was better than both indentation angle (CCC, 0.96; 95% CI, 0.94-0.97) and I:WT ratio (CCC, 0.92; 95% CI, 0.90-0.94). The diagnostic test accuracy of these three measurements using CUME as reference standard was very good, with AUC between 0.96 and 1.00. The best cut-off values for these measurements to define septate uterus were: indentation depth ≥ 10 mm, indentation angle < 140° and I:WT ratio > 110% . CONCLUSIONS: The suggested ESHRE-ESGE cut-off value overestimates the prevalence of septate uterus while that of ASRM underestimates this prevalence, leaving in the gray-zone most of the uteri that experts considered as septate. We recommend considering indentation depth ≥ 10 mm as septate, since the measurement is simple and reliable and this criterion is in agreement with expert opinion. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Three-dimensional transvaginal sonographic assessment of uterine volume as preoperative predictor of need to morcellate in women undergoing laparoscopic hysterectomy.

OBJECTIVE: In light of recent statements from the United States Food and Drug Administration warning against the use of power morcellation of uterine leiomyomas during laparoscopy, we sought to evaluate the use of preoperative two- (2D) and three- (3D) dimensional transvaginal ultrasound (US) assessment of uterine volume to predict the need for morcellation in women undergoing laparoscopic hysterectomy (LH). METHODS: This was a prospective observational study performed between October 2008 and November 2011 in a tertiary referral laparoscopic unit. All women scheduled to undergo LH were included and underwent detailed preoperative transvaginal US. Uterine volumes were calculated using 2D-US measurements (ellipsoid formula), and using Virtual Organ Computer-aided AnaLysis (VOCAL™) having acquired 3D-US volumes of the uterus. Age, parity, need to morcellate and final uterine dry weight at histology were recorded. The estimated uterine volumes were then incorporated into a previously published logistic regression model to predict the need to morcellate for both nulliparous and parous women. The probability threshold cut-off of 0.14 (95% sensitivity) was evaluated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and likelihood ratios (LRs). The performance of the models incorporating 2D- and 3D-US calculations were compared with 2D- and 3D-US-generated volumes alone, using receiver-operating characteristics (ROC) curves. RESULTS: Of 76 women who underwent LH during the study period, 79% (n = 60) had complete background and 3D-US data. Their mean age was 43.7 years, 91.7% were parous and 35% underwent morcellation. The greatest uterine volume that did not require morcellation was 404 mL estimated using 3D-US, which corresponded to a uterine volume of 688.8 mL using 2D-US. The smallest uterine volume that required morcellation was 118.9 mL using 3D-US, which corresponded to a uterine volume of 123.4 mL using 2D-US. The 3D-US uterine volume for parous women with a sensitivity of 95% based on ROC-curve analysis was approximately 120 mL, which equated to a predicted probability of morcellation cut-off of 0.14. For this cut-off, specificity was 55.00%, PPV was 51.35%, NPV was 95.65%, LR+ was 2.11 and LR- was 0.09. Areas under the ROC curves for the morcellation logistic regression model were 0.769 (95% CI, 0.653-0.886) and 0.586 (95% CI, 0.419-0.753) using uterine volumes obtained by 3D-US and by 2D-US, respectively, and they were 0.938 (95% CI, 0.879-0.996) and 0.815 (95% CI, 0.681-0.948) using 3D-US and 2D-US volumes alone. CONCLUSIONS: The need to morcellate can be predicted preoperatively using 3D-US uterine volumes obtained by transvaginal US with a fair degree of accuracy. Uteri with volumes smaller than 120 mL at 3D-US are very unlikely to require morcellation. The incorporation of 3D-US-estimated uterine volume into the previously published logistic regression model does not seem to confer any significant improvement when compared with 3D-US uterine volume alone to predict the need to morcellate in women undergoing total LH. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Sonographic evaluation of immobility of normal and endometriotic ovary in detection of deep endometriosis.

OBJECTIVES: To examine the association between ovarian immobility and presence of endometriomas and assess the diagnostic accuracy of transvaginal sonographic (TVS) ovarian immobility in the detection of deep infiltrating endometriosis (DIE). METHODS: This was a multicenter prospective observational study of women presenting with chronic pelvic pain from January 2009 to March 2015. Women with or without history of endometriosis who were scheduled to undergo laparoscopic surgery for endometriosis gave a detailed history and underwent specialized TVS in a tertiary referral unit prior to laparoscopy. During TVS, ovarian mobility and the presence of endometriomas were assessed. The relationship between TVS ovarian mobility, with or without endometriomas, and DIE was correlated with the gold standard, diagnosis of endometriosis at laparoscopy. RESULTS: Included in the analysis were 265 women with preoperative TVS and laparoscopic outcomes. Ovarian immobility on TVS was significantly associated with presence of endometriomas at surgery, with a prevalence of 12.2%, 10.8% and 52.7% for fixation of the left ovary only, the right ovary only and bilateral ovaries, respectively, compared with 4.2%, 3.7% and 7.3% for normal ovaries. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and positive and negative likelihood ratios of TVS ovarian immobility for diagnosis at surgery of immobility of ovaries with endometriomas in the left ovary only were 44.4%, 92.3%, 44.4%, 92.3%, 5.8, 0.6, in the right ovary only were 50.0%, 98.5%, 80.0%, 94.2%, 33.0, 0.5 and bilaterally were 74.4%, 68.6%, 72.5%, 70.6%, 2.4, 0.4, while those for diagnosis of immobility of normal ovaries were 25.0%, 87.9%, 8.3%, 96.4%, 2.1, 0.9 for left ovary only, 14.3%, 92.9%, 7.1%, 96.6%, 2.0, 0.9 for right ovary only and 35.7%, 97.2%, 50.0%, 95.0%, 12.6, 0.7 bilaterally, respectively (P < 0.05 except for normal left and right ovaries with P = 0.2 and 0.4, respectively). The sensitivity, specificity, PPV and NPV for performance of ovarian immobility in the prediction of DIE for all women were 58.3%, 74.1%, 60.6%, 72.2% and in the prediction of need for bowel surgery were 78.2%, 71.1%, 41.3%, 92.6%, respectively. CONCLUSIONS: There is a significant association between ovarian immobility and the presence of endometriomas. Ovarian immobility as a sonographic 'soft marker' of DIE performs better in the presence of endometriomas compared with in normal ovaries. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.