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.

Safety and efficiency of performing transvaginal ultrasound-guided tru-cut biopsy for pelvic masses.

OBJECTIVE: To assess the safety, adequacy and accuracy of transvaginal ultrasound-guided tru-cut biopsy of pelvic masses. METHODS: We performed a retrospective analysis of consecutive women who underwent transvaginal ultrasound-guided tru-cut biopsies between June 2014 and October 2018 at the Department of Obstetrics and Gynecology of the University Hospitals Leuven. Main indications for tru-cut biopsy were tissue collection for diagnosis of pelvic tumors in cases of suspected disseminated disease or recurrence, or tissue banking for research purposes. Data about adverse events occurring within 2 weeks of the procedure (including bleeding, blood transfusion, hospital admission, urgent surgery, pelvic infection or death) were extracted from electronic medical records. Tissue samples were recorded as adequate if tumor identification and immunohistochemistry were possible. Accuracy was defined in patients who underwent surgery as the agreement between histology after tru-cut biopsy and final histology. RESULTS: 176 tru-cut biopsies were performed in 155 patients. Procedure related events were limited to moderate blood loss (<50 ml) without the need for treatment in 4.5%. There were no major complications. Biopsies were deemed adequate for histological evaluation in 84.3% of biopsies performed for diagnostic purposes and in 71.4% of research cases in whom a single tissue cylinder was available for diagnosis. When at least two cylinders were available, diagnostic adequacy increased to >95%. Comparing final histology, the diagnostic accuracy of the tru-cut biopsies was 97.2%. CONCLUSION: Transvaginal tru-cut biopsy for diagnosis of pelvic masses is a safe procedure. To allow an adequate and accurate diagnosis, we advise taking at least 2 core biopsies.

Estimation of the Endometriosis Fertility Index prior to operative laparoscopy.

STUDY QUESTION: Can the Endometriosis Fertility Index (EFI) be estimated accurately before surgery? SUMMARY ANSWER: The EFI can be estimated accurately based on mere clinical/ultrasound information, with some improvement after adding data from diagnostic laparoscopy. WHAT IS KNOWN ALREADY: The EFI is a validated clinical instrument predicting the probability of pregnancy after endometriosis surgery without the use of ART. Being an end-of-surgery-score, it implies the decision for operative laparoscopy to be made in advance-hence, its role in the pre-surgical decision-making process remains to be established. STUDY DESIGN, SIZE, DURATION: Single-cohort prospective observational study in 82 patients undergoing complete endometriosis excision (between June and December 2016). Two methods were used to estimate the final EFI: type A based on non-surgical clinical/ultrasound findings only, and type B based on the combination of non-surgical clinical/ultrasound findings and diagnostic laparoscopy data. To calculate EFI type A, an algorithm was created to translate non-surgical clinical/imaging information into rASRM (revised American Society of Reproductive Medicine)-and EFI points. EFI type A and type B estimates were assessed for their clinical and numerical agreement with the final EFI score. Agreement was defined as clinical if EFI scores were within the same range (0-4, 5-6, 7-10), and numerical if their difference was ≤1. PARTICIPANTS/MATERIALS, SETTING, METHODS: All 82 patients underwent complete laparoscopic CO2-laser excision of any rASRM stage of endometriosis in the Leuven University Fertility Centre (LUFC) of University Hospitals Leuven, a tertiary referral centre for both endometriosis and infertility. An anonymized clinical research file was created. For each patient, three different data sets were created, in order to allow the estimation of the (surgical part) EFI and of the rASRM scores, defined as follows: 'Estimated type A' contained only non-surgical clinical/imaging data, 'Estimated type B' included type A information plus the information of the diagnostic laparoscopy and 'Final EFI' included information of type A, type B and all intra-operative information required to calculate the final EFI. To calculate EFI type A without surgical information, a set of rules was used to translate pre-surgical clinical/imaging information into (rASRM and EFI points). Scoring was done by one person (C.T.), with a time interval of 4 weeks between sessions for each EFI type. Next to the EFI, also rASRM score and stage were calculated. MAIN RESULTS AND THE ROLE OF CHANCE: Agreement rate between estimated EFI type A and final EFI was high for both the clinical (0.915; 95% CI 0.832-0.965) and numerical definition (0.878; 95% CI 0.787-0.940). Agreement rates between estimated EFI type B and final EFI were even higher (clinical (0.988; 95% CI 0.934-1.000), numerical (0.963; 95% CI 0.897-0.992)). LIMITATIONS, REASONS FOR CAUTION: Type A estimation is dependent on high-level gynaecological ultrasound expertise, which may not be available in all clinics. A small number of patients had no prior clinical, ultrasound (hard markers) or surgical confirmation of the diagnosis of endometriosis. When applying the estimated EFI type A in clinical practice, a priori assumptions of the presence or absence of endometriosis will need to be made in adjunct to the estimation of the estimated type A EFI when counselling patients on the potential benefit of an (at least diagnostic) laparoscopy. The level of agreement for type A or B should also be taken into account when counselling patients on the type of efforts undertaken to attempt to diagnose or rule out endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: As this study reports, the EFI can be estimated accurately based on clinical/ultrasound data only without the need for any surgical data. This means that the EFI could be used as an instrument to guide joint physician-patient decision-making between surgery, ART or other fertility management options for the individualized treatment of women with endometriosis-related infertility. STUDY FUNDING/COMPETING INTEREST(S): During this study period, C.T. was supported by FWO (Research Fund Flanders, Grant number 1700816N) and UZ Leuven KOF (University Hospitals Leuven, Klinisch Onderzoeksfonds).The LUFC received unrestricted research grants from Ferring Pharmaceuticals and Merck SA. Gedeon Richter and MSD sponsored travel to and attendance at scientific meetings. C.M. received consultancy fees from Lumenis (paid to KU Leuven, no private revenue). T.D. has been vice-president and head of global medical affairs infertility for the multinational pharmaceutical company Merck (Darmstadt, Germany) since 1 October 2015. He continues his academic appointment on a part-time basis as Professor of Reproductive Medicine at the University of Leuven (KU Leuven). T.D. has been vice-president and head of global medical affairs infertility for the multinational pharmaceutical company Merck (Darmstadt, Germany) since October 2015. He is also a Guest Professor in Reproductive Medicine and Biology at the Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven (University of Leuven), Belgium, and an Adjunct Professor at the Department of Obstetrics and Gynecology in the University of Yale, New Haven, USA. This work was initiated before he joined Merck KGaA in October 2015, and completed during the subsequent years. TRIAL REGISTRATION NUMBER: study registration number at UZ Leuven Clinical Trial Centre: S59221.

IDEAL study: magnetic resonance imaging for suspected deep endometriosis assessment prior to laparoscopy is as reliable as radiological imaging as a complement to transvaginal ultrasonography.

OBJECTIVE: To compare the value of using one-stop magnetic resonance imaging (MRI) vs standard radiological imaging as a supplement to transvaginal ultrasonography (TVS) for the preoperative assessment of patients with endometriosis referred for surgery in a tertiary care academic center. METHODS: This prospective observational study compared the diagnostic value of the standard preoperative imaging practice of our center, which involves expert TVS complemented by intravenous urography (IVU) for the evaluation of the ureters and double-contrast barium enema (DCBE) for the evaluation of the rectum, sigmoid and cecum, with that of expert TVS complemented by a 'one-stop' MRI examination evaluating the upper abdomen, pelvis, kidneys and ureters as well as rectum and sigmoid on the same day, for the preoperative triaging of 74 women with clinically suspected deep endometriosis. The findings at laparoscopy were considered the reference standard. Patients were stratified according to their need for monodisciplinary surgical approach, carried out by gynecologists only, or multidisciplinary surgical approach, involving abdominal surgeons and/or urologists, based on the extent to which endometriosis affected the reproductive organs, bowel, ureters, bladder or other abdominal organs. RESULTS: Our standard preoperative imaging approach and the combined findings of TVS and MRI had similar diagnostic performance, resulting in correct stratification for a monodisciplinary or a multidisciplinary surgical approach of 67/74 (90.5%) patients. However, there were differences between the estimation of the severity of disease by DCBE and MRI. The severity of rectal involvement was underestimated in 2.7% of the patients by both TVS and DCBE, whereas it was overestimated in 6.8% of the patients by TVS and/or DCBE. CONCLUSIONS: Complementary to expert TVS, 'one-stop' MRI can predict intraoperative findings equally well as standard radiological imaging (IVU and DCBE) in patients referred for endometriosis surgery in a tertiary care academic center. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group.

The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Intrauterine transfusion for fetal anemia due to red blood cell alloimmunization: 14 years experience in Leuven.

OBJECTIVE: The purpose of this study is to report on the pregnancy and neonatal outcome of intrauterine transfusion (IUT) for red blood cell (RBC-)alloimmunization. MATERIAL AND METHODS: Retrospective cohort study of all IUT for RBC-alloimmunization in the University Hospital of Leuven, between January 2000 and January 2014. The influence of hydrops, gestational age and technique of transfusion on procedure related adverse events were examined. RESULTS: 135 IUTs were performed in 56 fetuses. In none of the cases fetal or neonatal death occurred. Mild adverse events were noted in 10% of IUTs, whereas severe adverse events occurred in 1.5%. Hydrops and transfusion in a free loop were associated with an increased risk of adverse events whereas gestational age (GA) at transfusion after 34 weeks was not. Median GA at birth was 35.6 weeks and 9% was born before 34 weeks. Besides phototherapy 65.4% required additional neonatal treatment for alloimmune anemia. Non-hematologic complications occurred in 23.6% and were mainly related to preterm birth. CONCLUSION: In experienced hands, IUT for RBC-alloimmunization is a safe procedure in this era. Patients should be referred to specialist centers prior to the development of hydrops. IUT in a free loop of cord and unnecessary preterm birth are best avoided.

Intra-cavitary uterine pathology in women with abnormal uterine bleeding: a prospective study of 1220 women.

OBJECTIVES: Our primary aim was to assess how patients' characteristics, bleeding pattern, sonographic endometrial thickness (ET) and additional features at unenhanced ultrasound examination (UTVS) and at fluid instillation sonography (FIS) contribute to the diagnosis of intracavitary uterine pathology in women presenting with abnormal uterine bleeding (AUB). We further aimed to report the prevalence of pathology in women presenting with AUB. METHODS: 1220 consecutive women presenting with AUB underwent UTVS, colour Doppler imaging (CDI) and FIS. Most women (n = 1042) had histological diagnosis. RESULTS: Mean age was 50 years and 37% were postmenopausal. Of 1220 women 54% were normal, polyps were diagnosed in 26%, intracavitary fibroids in 11%, hyperplasia without atypia in 4% and cancer in 3%. All cancers were diagnosed in postmenopausal (7%) or perimenopausal (1%) women. ET had a low predictive value in premenopausal women (LR+ and LR- of 1.34 and 0.74, respectively), while FIS had a LR+ and LR- of 6.20 and 0.24, respectively. After menopause, ET outperformed all patient characteristics for the prediction of endometrial pathology (LR+ and LR- of 3.13 and 0.24). The corresponding LR+ and LR- were 10.85 and 0.71 for CDI and 8.23 and 0.26 for FIS. CONCLUSION: About half of the women presenting to a bleeding clinic will have pathology. In premenopausal women, benign lesions are often the cause of AUB. For the prediction of intracavitary pathology ET is of little value in premenopausal women. CDI and FIS substantially improve the diagnostic accuracy.

Optimizing the ultrasound visualization of the endometrial-myometrial junction (EMJ).

OBJECTIVES: The aim of this study was to find the best 3D reconstruction technique to visualize the endometrial-myometrial junction (EMJ). METHODS: Retrospective observational study on 240 stored 3D volumes of 80 patients. The first author reconstructed the 2D midcoronal image without volume contrast imaging (VCI), with VCI set at 4 mm and with VCI set at 2 mm. Three images per patient (240 images) were saved and integrated in the web-based electronic data capture software Clinical Data Miner (CDM) (http://cdm.esat.kuleuven.be). Five experienced gynaecologists analysed the images shown in random order. They scored the image quality (good, moderate, poor, insufficient) and described the EMJ of these images using IETA terminology (regular, irregular, interrupted, not defined). One of the examiners (CVP) also re-evaluated the same set of images after 12 days to assess intra-observer variability. RESULTS: The use of VCI significantly improved the recorded subjective image quality. The Fleiss' kappa coefficient for evaluating the inter-observer variability of the EMJ description using coronal view without VCI, with VCI at 4 mm and VCI at 2 mm were 0.36 ± 0.05, 0.34 ± 0.05 and 0.42 ± 0.05, respectively. The corresponding figures for the intra-observer variability were 0.58 ± 0.08, 0.36 ± 0.08 and 0.68 ± 0.07, respectively. DISCUSSION: In this study on 3D reconstructed coronal images of the uterine cavity, the 2 mm VCI slices gave the best quality images of the EMJ.

Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group.

The MUSA (Morphological Uterus Sonographic Assessment) statement is a consensus statement on terms, definitions and measurements that may be used to describe and report the sonographic features of the myometrium using gray-scale sonography, color/power Doppler and three-dimensional ultrasound imaging. The terms and definitions described may form the basis for prospective studies to predict the risk of different myometrial pathologies, based on their ultrasound appearance, and thus should be relevant for the clinician in daily practice and for clinical research. The sonographic features and use of terminology for describing the two most common myometrial lesions (fibroids and adenomyosis) and uterine smooth muscle tumors are presented.

Pain during Fallopian-tube patency testing by hysterosalpingo-foam sonography.

OBJECTIVES: To evaluate perception of pain during Fallopian-tube patency testing by hysterosalpingo-foam sonography (HyFoSy). METHODS: In this cross-sectional study, 216 consecutive women presenting at a university fertility clinic for HyFoSy examination were included. Patients were instructed to take ibuprofen 1 hour before the procedure. Immediately after the procedure, patients filled in a questionnaire concerning discomfort or pain experienced during the process, including a visual analog scale (VAS) score for perception of pain. RESULTS: The median VAS score for perception of pain during transvaginal ultrasound examination and during HyFoSy examination was 1.5 (95% CI, 1.2-1.7) and 3.6 (95% CI, 3.0-4.0), respectively. One-third of women reported that the level of discomfort or pain during HyFoSy examination was similar to that during the preceding transvaginal ultrasound examination and 48% of women considered HyFoSy examination to be neutral/unpleasant, but not painful. There was an inverse association between both patients' age and parity and the pain experienced. CONCLUSIONS: HyFoSy examination is tolerated well and allows for reliable tubal patency testing without exposing the patient to ionizing radiation in an outpatient setting with a low technical failure rate.

Cardiac assessment in fetuses with right-sided congenital diaphragmatic hernia: case-control study.

OBJECTIVE: To evaluate cardiac anatomy and function in fetuses with right-sided congenital diaphragmatic hernia (RCDH), and to compare these values with those of normal controls. METHODS: Fetal echocardiography was performed in 17 consecutive cases with isolated RCDH and 17 gestational age-matched controls. Two-dimensional measurements included ventricular and outflow tract diameters. Doppler ultrasound was used to measure the flow pattern in the ductus venosus and over the pulmonary and aortic valves, right and left ventricular myocardial performance index and the E/A wave ratio over the atrioventricular valves. Stroke volume, cardiac output and shortening fraction were calculated. RESULTS: Median gestational age at evaluation was 27.4 (interquartile range, 24.4-28.9) weeks. RCDH cases had a significantly smaller right ventricle and pulmonary valve diameter. Furthermore, stroke volume and cardiac output from the right ventricle were lower than in controls. Myocardial contractility, however, appeared normal. CONCLUSIONS: Despite significantly reduced right ventricular dimensions and cardiac output, cardiac contractility was normal in a cohort of fetuses with RCDH.

Detection of intracavitary uterine pathology using offline analysis of three-dimensional ultrasound volumes: interobserver agreement and diagnostic accuracy.

OBJECTIVE: To estimate the diagnostic accuracy and interobserver agreement in predicting intracavitary uterine pathology at offline analysis of three-dimensional (3D) ultrasound volumes of the uterus. METHODS: 3D volumes (unenhanced ultrasound and gel infusion sonography with and without power Doppler, i.e. four volumes per patient) of 75 women presenting with abnormal uterine bleeding at a 'bleeding clinic' were assessed offline by six examiners. The sonologists were asked to provide a tentative diagnosis. A histological diagnosis was obtained by hysteroscopy with biopsy or operative hysteroscopy. Proliferative, secretory or atrophic endometrium was classified as 'normal' histology; endometrial polyps, intracavitary myomas, endometrial hyperplasia and endometrial cancer were classified as 'abnormal' histology. The diagnostic accuracy of the six sonologists with regard to normal/abnormal histology and interobserver agreement were estimated. RESULTS: Intracavitary pathology was diagnosed at histology in 39% of patients. Agreement between the ultrasound diagnosis and the histological diagnosis (normal vs abnormal) ranged from 67 to 83% for the six sonologists. In 45% of cases all six examiners agreed with regard to the presence/absence of intracavitary pathology. The percentage agreement between any two examiners ranged from 65 to 91% (Cohen's κ, 0.31-0.81). The Schouten κ for all six examiners was 0.51 (95% CI, 0.40-0.62), while the highest Schouten κ for any three examiners was 0.69. CONCLUSION: When analyzing stored 3D ultrasound volumes, agreement between sonologists with regard to classifying the endometrium/uterine cavity as normal or abnormal as well as the diagnostic accuracy varied substantially. Possible actions to improve interobserver agreement and diagnostic accuracy include optimization of image quality and the use of a consistent technique for analyzing the 3D volumes.

Pre-sampling ultrasound evaluation and assessment of the tissue yield during sampling improves the diagnostic reliability of office endometrial biopsy.

We evaluated the implementation of a strict procedure for endometrium biopsy, including pre-sampling ultrasound examination and assessment of the tissue yield during sampling, in 257 consecutive women with abnormal bleeding. The tissue yield was assessed during sampling and scored from 1 to 4. The median endometrial thickness as measured by ultrasound was 5.0 mm, 5.1 mm, 10.0 mm and 18.7 mm for a tissue yield score of 1, 2, 3 and 4, respectively. The median endometrial thickness at ultrasound and the median tissue yield score was 18.3 mm and score 4 in the endometrial cancer cases, compared with 3.9 mm and score 1, and 14.8 mm and score 3 in the case of endometrial atrophy and hyperplasia, respectively; and 11.5 mm and score 2 in endometrial polyp cases. Overall, 12 cancers were diagnosed. No endometrial cancer was diagnosed during follow-up (median 447 days). A strict office endometrial biopsy procedure contributes to the diagnostic reliability for intracavitary pathology.

Effect of gel-instillation sonography on Doppler ultrasound findings in endometrial polyps.

OBJECTIVE: Saline infusion sonohysterography has been reported to suppress the color signal within the endometrium at color or power Doppler evaluation. The aim of this study was to evaluate if gel-instillation sonography (GIS) affects the power Doppler signal in patients with endometrial polyps. METHODS: Ultrasound volumes of the uterus, obtained by three-dimensional ultrasound imaging of 25 women with histologically confirmed endometrial polyps, were assessed offline by six gynecologists with a special interest in gynecological ultrasound. Each woman contributed four volumes: one gray-scale volume and one power Doppler volume before GIS, and one gray-scale volume and one power Doppler volume at GIS. Power Doppler features before and after gel infusion were compared. RESULTS: At unenhanced ultrasound a pedicle artery was seen in 27-46% of cases, whereas, after gel infusion the examiners reported a pedicle artery in 30-46% of cases (Exact McNemar's test P-values ranged from 0.50 to 1.00). The level of agreement between unenhanced ultrasound and GIS ranged from 59 to 91% (Cohen's kappa values ranged from 0.17 to 0.79). There was no tendency for a pedicle artery to be identified less often at GIS than before gel instillation. CONCLUSION: Gel infusion does not affect the power Doppler signal in patients with endometrial polyps.

Outcome prediction in monochorionic diamniotic twin pregnancies with moderately discordant amniotic fluid.

OBJECTIVE: The aim of this study was to identify predictors of twin-to-twin transfusion syndrome (TTTS) and selective intrauterine growth restriction (sIUGR) in monochorionic diamniotic (MCDA) twin pregnancies with moderate amniotic fluid discordance (mAFD). METHODS: Monochorionic twins with mAFD (n = 45; gestational age, 15-29 weeks) were assessed for extent of fluid discordance, fetal growth discordance and fetal cardiac dysfunction, and were followed longitudinally. A prediction algorithm was constructed for TTTS and sIUGR and validated in an unrelated cohort (n = 52). RESULTS: Cardiac dysfunction could not predict TTTS or sIUGR. Twins below 20 weeks of gestation with a fluid discordance of ≥ 3.1 cm had a risk of TTTS of 85.7%. Sensitivity for TTTS was nevertheless only 55%. An intertwin weight discordance of ≥ 25% had 63% sensitivity and 76% specificity for sIUGR without TTTS. CONCLUSION: The outcome of MCDA twins with mAFD remains unpredictable, yet high-risk and low-risk subgroups for TTTS can be identified based on severity of fluid discordance and gestational age.

Lidocaine does not reduce pain perception during gel instillation sonography or subsequent office hysteroscopy: results of a randomized trial.

BACKGROUND: To evaluate if the addition of lidocaine to the gel used for gel infusion sonohysterography (GIS) reduces pain experienced during GIS or subsequent hysteroscopy. METHODS: A total of 142 consecutive patients were randomized using computer-generated random integers. In 79 patients, GIS was performed with a gel containing lidocaine (Instillagel®) and in 63 patients the gel did not contain lidocaine (Endosgel®). Immediately after GIS, 132 patients (94%) underwent office hysteroscopy. The women were asked to fill in a questionnaire including a 100-mm visual analogue scale (VAS) score after each examination. RESULTS: The mean age (SD) was 50.8 (12.1) years; 58.5% were premenopausal and 15.6% were nulliparous. The median (interquartile range (IR)) VAS score during GIS for all women was 6 (19.5): 8 (21) for the lidocaine group versus 5 (18.2) for those who received gel without lidocaine. The median (IR) VAS scores during hysteroscopy in the total group, the Instillagel group and the Endosgel group were 15.5 (43.2), 24 (35) and 9 (52), respectively. None of the differences were statistically significant. CONCLUSION: The addition of lidocaine to the gel used either for GIS or prior to office hysteroscopy does not reduce the procedure-related pain.