Evaluating the development of endometriosis and adenomyosis lesions over time: An ultrasound study of symptomatic women.

INTRODUCTION: There is a gap in knowledge regarding development of endometriosis and adenomyosis lesions visible at transvaginal ultrasound. The objectives were to evaluate if women with symptoms suggestive of endometriosis or adenomyosis but normal ultrasound examination develop endometriosis or adenomyosis lesions visible at ultrasound over time and if alterations of symptoms over time are associated with ultrasound findings at follow-up. MATERIAL AND METHODS: This was a prospective cohort study of 100 symptomatic women with normal initial ultrasound examination during 2014-2017 who underwent follow-up ultrasound examination in 2022. Symptoms suggestive of endometriosis were assessed using visual analog scale at both examinations and minimal clinically important difference of 10 mm was considered as a significant alteration. An examiner with expertise in advanced ultrasound examination of endometriosis performed transvaginal ultrasound examinations in accordance with the consensus protocol by the International Deep Endometriosis Analysis group. RESULTS: At follow-up ultrasound examination of 100 women, 13 (13% [95% CI 7.1-21.2]) had visible endometriosis or adenomyosis lesions, 8 (8% [95% CI 3.5-15.2]) had endometriosis lesions, and 6 (6% [95% CI 2.2-12.6]) had adenomyosis. At follow-up, women with endometriosis or adenomyosis lesions reported lower intensity of dysmenorrhea and chronic pelvic pain compared to women without lesions (48 mm [IQR 16-79] vs. 73 mm [IQR 46-85] and 45 mm [IQR 26-57] vs. 57 mm [IQR 36-75], p = 0.087 and p = 0.026, respectively). None of the women with endometriosis or adenomyosis lesions reported increased intensity of dysmenorrhea at follow-up, compared to 32/86 women (37%) without lesions (p = 0.008). Increased intensity of chronic pelvic pain tended to be less common in women with lesions compared to those without (3/13 [23%] vs. 35/86 [41%], p = 0.223). CONCLUSIONS: Our findings suggest that in symptomatic women, endometriosis and adenomyosis lesions visible at ultrasound may develop over time. However, majority of women remain having normal ultrasound examinations despite symptoms. Exacerbation of dysmenorrhea or chronic pelvic pain during follow-up was not associated with the development of endometriosis or adenomyosis lesions visible at ultrasound, suggesting that even women with less severe symptoms might benefit from a follow-up ultrasound when indicated.

Prevalence of adenomyosis features in women scheduled for assisted reproductive treatment, using the Morphological Uterus Sonographic Assessment group definitions.

INTRODUCTION: Studies that use standardized ultrasonographic criteria to diagnose adenomyosis in subfertile women are needed. These would improve the understanding of the disease burden and enable further studies on its impact on fertility and assisted reproductive treatment (ART) outcome. The aim of this study was to determine the prevalence of different features of adenomyosis in women scheduled for their first ART, diagnosed at two (2D) and three-dimensional (3D) transvaginal ultrasonography (TVUS) using the revised Morphological Uterus Sonographic Assessment (MUSA) group definitions. MATERIAL AND METHODS: This was a prospective, observational cross-sectional study of subfertile women aged 25 to ≤39 years, that were referred to a university hospital for their first ART between December 2018 and May 2021. Of 1224 eligible women, 1160 women fulfilled the inclusion criteria and consented to participate in the study. All women underwent a systematic 2D and 3D TVUS examination. The primary outcome was the presence of direct and indirect features of adenomyosis, as proposed by the MUSA group. Secondary outcomes were to describe the ultrasonographic characteristics of the different features, as well as any difference in the diagnostics at 2D or 3D TVUS and any association with clinical characteristics such as endometriosis. RESULTS: At least one direct or indirect feature of adenomyosis was observed in 272 (23.4%, 95% confidence interval [CI] 21.0-25.9) women. Direct features that are pathognomonic for the disease were observed in 111 (9.6%, 95% CI, 7.9-11.3) women. Direct features were visible only at 3D TVUS in 56 (4.8%, 95% CI 3.6-6.1) women, that is, 56/111 (50.5%) of women with at least one direct adenomyosis feature. Direct features were more common in women with endometriosis (OR 2.8, 95% CI 1.8-4.3). CONCLUSIONS: We found than one in 10 women scheduled for ART had direct features of adenomyosis at ultrasound examination. The present study suggests that the use of 3D TVUS is an important complement to 2D in the diagnostics of adenomyosis. Our results may further improve the counseling of women scheduled for ART and enables future studies on the impact of different features of adenomyosis on subfertility, ART results and obstetric outcomes.

Prevalence of endometriosis and adenomyosis at transvaginal ultrasound examination in symptomatic women.

INTRODUCTION: Prevalence of endometriosis is commonly reported based on surgery findings and varies widely depending on study population and indication for surgery. Symptoms such as dysmenorrhea, pelvic pain, dyspareunia, dysuria, and dyschezia can be associated with endometriosis and adenomyosis. Transvaginal ultrasound examination is proposed to be the first-line diagnostic method, nevertheless there are no published ultrasound-based studies reporting prevalence of endometriosis and adenomyosis in symptomatic women other than those scheduled for surgery. The aim of this study was to determine the prevalence of endometriosis and adenomyosis as assessed by transvaginal ultrasound in women with symptoms suggestive of endometriosis and adenomyosis. MATERIAL AND METHODS: This is a retrospective cross-sectional study performed at a tertiary-care center including 373 symptomatic women who were systematically examined with transvaginal ultrasound by an experienced ultrasound examiner. Before ultrasound examination women filled in a questionnaire including self-assessment of the severity of their symptoms (dysmenorrhea, chronic pelvic pain, dyspareunia, dysuria, dyschezia) using a visual analog scale. Abnormal findings in the uterus, ovaries, bowel, urinary bladder, uterosacral ligaments, and rectovaginal septum were noted, and their size and location were described. Prevalence of endometriosis, adenomyosis, endometrioma, and deep endometriosis in different anatomical locations was reported. RESULTS: Prevalence of ovarian endometrioma and/or deep endometriosis was 25% and of adenomyosis was 12%. Prevalence of endometrioma was 20% and of deep endometriosis was 9%, for each location being 8% in the bowel, 3% in the uterosacral ligaments, 3% in the rectovaginal septum and 0.5% in the urinary bladder. CONCLUSIONS: In symptomatic women examined with transvaginal ultrasound by an experienced ultrasound examiner, ovarian endometrioma and/or deep endometriosis was found in one of four women and adenomyosis in one of nine women. Deep endometriosis was present in one of 11 women. Despite having symptoms, half of the women had no abnormal ultrasound findings.

Predictors of complete miscarriage after expectant management or misoprostol treatment of non-viable early pregnancy in women with vaginal bleeding.

PURPOSE: To identify predictors of complete miscarriage after expectant management or misoprostol treatment of non-viable early pregnancy in women with vaginal bleeding. METHODS: This was a planned secondary analysis of data from a published randomized controlled trial comparing expectant management with vaginal single dose of 800 µg misoprostol treatment of women with embryonic or anembryonic miscarriage. Predefined variables-serum-progesterone, serum-ß-human chorionic gonadotropin, parity, previous vaginal deliveries, gestational age, clinical symptoms (bleeding and pain), mean diameter and shape of the gestational sac, crown-rump-length, type of miscarriage, and presence of blood flow in the intervillous space-were tested as predictors of treatment success (no gestational sac in the uterine cavity and maximum anterior-posterior intracavitary diameter was ≤ 15 mm as measured with transvaginal ultrasound on a sagittal view) in univariable and multivariable logistic regression. RESULTS: Variables from 174 women (83 expectant management versus 91 misoprostol) were analyzed for prediction of complete miscarriage at ≤ 17 days. In patients managed expectantly, the rate of complete miscarriage was 62.7% (32/51) in embryonic miscarriages versus 37.5% (12/32) in anembryonic miscarriages (P = 0.02). In multivariable logistic regression, the likelihood of success increased with increasing gestational age, increasing crown-rump-length and decreasing gestational sac diameter. Misoprostol treatment was successful in 80.0% (73/91). No variable predicted success of misoprostol treatment. CONCLUSIONS: Complete miscarriage after expectant management is significantly more likely in embryonic miscarriage than in anembryonic miscarriage. Gestational age, crown-rump-length, and gestational sac diameter are independent predictors of success of expectant management. Predictors of treatment success may help counselling women with early miscarriage.

Risk of complications in patients with conservatively managed ovarian tumours (IOTA5): a 2-year interim analysis of a multicentre, prospective, cohort study.

BACKGROUND: Ovarian tumours are usually surgically removed because of the presumed risk of complications. Few large prospective studies on long-term follow-up of adnexal masses exist. We aimed to estimate the cumulative incidence of cyst complications and malignancy during the first 2 years of follow-up after adnexal masses have been classified as benign by use of ultrasonography. METHODS: In the international, prospective, cohort International Ovarian Tumor Analysis Phase 5 (IOTA5) study, patients aged 18 years or older with at least one adnexal mass who had been selected for surgery or conservative management after ultrasound assessment were recruited consecutively from 36 cancer and non-cancer centres in 14 countries. Follow-up of patients managed conservatively is ongoing at present. In this 2-year interim analysis, we analysed patients who were selected for conservative management of an adnexal mass judged to be benign on ultrasound on the basis of subjective assessment of ultrasound images. Conservative management included ultrasound and clinical follow-up at intervals of 3 months and 6 months, and then every 12 months thereafter. The main outcomes of this 2-year interim analysis were cumulative incidence of spontaneous resolution of the mass, torsion or cyst rupture, or borderline or invasive malignancy confirmed surgically in patients with a newly diagnosed adnexal mass. IOTA5 is registered with ClinicalTrials.gov, number NCT01698632, and the central Ethics Committee and the Belgian Federal Agency for Medicines and Health Products, number S51375/B32220095331, and is ongoing. FINDINGS: Between Jan 1, 2012, and March 1, 2015, 8519 patients were recruited to IOTA5. 3144 (37%) patients selected for conservative management were eligible for inclusion in our analysis, of whom 221 (7%) had no follow-up data and 336 (11%) were operated on before a planned follow-up scan was done. Of 2587 (82%) patients with follow-up data, 668 (26%) had a mass that was already in follow-up at recruitment, and 1919 (74%) presented with a new mass at recruitment (ie, not already in follow-up in the centre before recruitment). Median follow-up of patients with new masses was 27 months (IQR 14-38). The cumulative incidence of spontaneous resolution within 2 years of follow-up among those with a new mass at recruitment (n=1919) was 20·2% (95% CI 18·4-22·1), and of finding invasive malignancy at surgery was 0·4% (95% CI 0·1-0·6), 0·3% (<0·1-0·5) for a borderline tumour, 0·4% (0·1-0·7) for torsion, and 0·2% (<0·1-0·4) for cyst rupture. INTERPRETATION: Our results suggest that the risk of malignancy and acute complications is low if adnexal masses with benign ultrasound morphology are managed conservatively, which could be of value when counselling patients, and supports conservative management of adnexal masses classified as benign by use of ultrasound. FUNDING: Research Foundation Flanders, KU Leuven, Swedish Research Council.

Intra- and Inter-Rater Agreement Describing Myometrial Lesions Using Morphologic Uterus Sonographic Assessment: A Pilot Study.

OBJECTIVES: To evaluate the intra- and inter-rater agreement for myometrial lesions using Morphologic Uterus Sonographic Assessment terminology. METHODS: Thirteen raters with high (n = 6) or medium experience (n = 7) assessed 30 3-dimensional ultrasound clips with (n = 20) and without (n = 10) benign myometrial lesions. Myometrial lesions were reported as poorly or well defined and then systematically evaluated for the presence of individual features. The clips were blindly assessed twice (at a 2-month interval). Intra- and inter-rater agreements were calculated with κ statistics. RESULTS: The reporting of poorly defined lesions reached moderate intra-rater agreement (κ = 0.49 [high experience] and 0.47 [medium experience]) and poor inter-rater agreement (κ = 0.39 [high experience] and 0.25 [medium experience]). The reporting of well-defined lesions reached good to very good intra-rater agreement (κ = 0.73 [high experience] and 0.82 [medium experience]) and good inter-rater agreement (κ = 0.75 [high experience] and 0.63 [medium experience]). Most individual features associated with ill-defined lesions reached moderate intra- and inter-rater agreement among highly experienced raters (κ = 0.41-0.60). The least reproducible features were myometrial cysts, hyperechoic islands, subendometrial lines and buds, and translesional flow (κ = 0.11-0.34). Most individual features associated with well-defined lesions reached moderate to good intra- and inter-rater agreement among all observers (κ = 0.41-0.80). The least reproducible features were a serosal contour, asymmetry, a hyperechoic rim, and fan-shaped shadows (κ = 0.00-0.35). CONCLUSIONS: The reporting of well-defined lesions showed excellent agreement, whereas the agreement for poorly defined lesions was low, even among highly experienced raters. The agreement on identifying individual features varied, especially for features associated with ill-defined lesions. Guidelines on minimum requirements for features associated with ill-defined lesions to be interpreted as poorly defined lesions may improve agreement.

Endometriosis diagnosed by ultrasound is associated with lower live birth rates in women undergoing their first in vitro fertilization/intracytoplasmic sperm injection treatment.

OBJECTIVE: To study the cumulative live birth rate (CLBR) after the first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment in women with or without deep-infiltrating endometriosis (DIE) and/or endometrioma diagnosed by transvaginal ultrasonography (TVUS), using the International Deep Endometriosis Analysis (IDEA) group definitions. DESIGN: Prospective observational cohort study at a university hospital. PATIENTS(S): In total, 1,040 women with subfertility aged 25 to ≤39 years were undergoing their first IVF/ICSI treatment between January 2019 and October 2022. Of these, 234 (22.5%; 95% confidence interval [CI], 20.0-25.0) women were diagnosed with DIE and/or endometrioma at systematic TVUS before starting their treatment. INTERVENTION(S): All women underwent their first IVF or ICSI treatment. Fresh and/or frozen embryos from the first cycle were used until pregnancy was achieved or no embryos remained. MAIN OUTCOME MEASURE(S): Cumulative live birth rate after the first IVF/ICSI cycle in women with or without DIE and/or endometrioma. RESULT(S): The CLBR after the first IVF/ICSI treatment in the total cohort of women was 426/1,040 (41.0%; 95% CI, 38.0-44.0). Women with DIE and/or endometrioma had a lower CLBR (78/234, 33.3%; 95% CI, 27.3-39.4) than women without the disease (348/806, 43.2%; 95% CI, 39.8-46.6). The crude relative risk (RR) for cumulative live birth for women with DIE and/or endometrioma was 0.77; 95% CI, 0.63-0.94, and after adjustments were made for age, body mass index, s-antimüllerian hormone, stimulation protocol, and day for embryo transfer, the adjusted RR was 0.63; 95% CI, 0.48-0.82. There was no difference in the number of retrieved mature oocytes, fertilization rate, or good quality embryos between the 2 groups. CONCLUSION: The presence of DIE and/or endometrioma diagnosed by TVUS lowers the chance of live birth in women undergoing their first IVF/ICSI treatment.

External Validation of the Ovarian-Adnexal Reporting and Data System (O-RADS) Lexicon and the International Ovarian Tumor Analysis 2-Step Strategy to Stratify Ovarian Tumors Into O-RADS Risk Groups.

Importance: Correct diagnosis of ovarian cancer results in better prognosis. Adnexal lesions can be stratified into the Ovarian-Adnexal Reporting and Data System (O-RADS) risk of malignancy categories with either the O-RADS lexicon, proposed by the American College of Radiology, or the International Ovarian Tumor Analysis (IOTA) 2-step strategy. Objective: To investigate the diagnostic performance of the O-RADS lexicon and the IOTA 2-step strategy. Design, Setting, and Participants: Retrospective external diagnostic validation study based on interim data of IOTA5, a prospective international multicenter cohort study, in 36 oncology referral centers or other types of centers. A total of 8519 consecutive adult patients presenting with an adnexal mass between January 1, 2012, and March 1, 2015, and treated either with surgery or conservatively were included in this diagnostic study. Twenty-five patients were excluded for withdrawal of consent, 2777 were excluded from 19 centers that did not meet predefined data quality criteria, and 812 were excluded because they were already in follow-up at recruitment. The analysis included 4905 patients with a newly detected adnexal mass in 17 centers that met predefined data quality criteria. Data were analyzed from January 31 to March 1, 2022. Exposures: Stratification into O-RADS categories (malignancy risk <1%, 1% to <10%, 10% to <50%, and ≥50%). For the IOTA 2-step strategy, the stratification is based on the individual risk of malignancy calculated with the IOTA 2-step strategy. Main Outcomes and Measures: Observed prevalence of malignancy in each O-RADS risk category, as well as sensitivity and specificity. The reference standard was the status of the tumor at inclusion, determined by histology or clinical and ultrasonographic follow-up for 1 year. Multiple imputation was used for uncertain outcomes owing to inconclusive follow-up information. Results: Median age of the 4905 patients was 48 years (IQR, 36-62 years). Data on race and ethnicity were not collected. A total of 3441 tumors (70%) were benign, 978 (20%) were malignant, and 486 (10%) had uncertain classification. Using the O-RADS lexicon resulted in 1.1% (24 of 2196) observed prevalence of malignancy in O-RADS 2, 4% (34 of 857) in O-RADS 3, 27% (246 of 904) in O-RADS 4, and 78% (732 of 939) in O-RADS 5; the corresponding results for the IOTA 2-step strategy were 0.9% (18 of 1984), 4% (58 of 1304), 30% (206 of 690), and 82% (756 of 927). At the 10% risk threshold (O-RADS 4-5), the O-RADS lexicon had 92% sensitivity (95% CI, 87%-96%) and 80% specificity (95% CI, 74%-85%), and the IOTA 2-step strategy had 91% sensitivity (95% CI, 84%-95%) and 85% specificity (95% CI, 80%-88%). Conclusions and Relevance: The findings of this external diagnostic validation study suggest that both the O-RADS lexicon and the IOTA 2-step strategy can be used to stratify patients into risk groups. However, the observed malignancy rate in O-RADS 2 was not clearly below 1%.

Number of antral follicles, ovarian volume, and vascular indices in asymptomatic women 20 to 39 years old as assessed by 3-dimensional sonography: a prospective cross-sectional study.

OBJECTIVES: Our aim was to elicit data representative of normal findings on 3-dimensional (3D) transvaginal gray-scale and power Doppler sonography of ovaries in women of fertile age. METHODS: A total of 303 gynecologically asymptomatic white women 20 to 39 years old with spontaneous regular menstrual cycles were examined with transvaginal 3D gray-scale and power Doppler sonography on cycle days 4 to 8. We used a 6- to 12-MHz transducer. The ovarian volume, number and volume of antral follicles of 2 mm or larger, vascularization index, flow index, and vascularization-flow index were calculated using dedicated software. Results are presented separately for women with follicles of 2.0 to 10.0 mm and for those with at least 1 follicle larger than 10.0 mm for 3 age groups: 20 to 29, 30 to 34, and 35 to 39 years. RESULTS: There were 214 women (71%) with follicles of 2.0 to 10.0 mm and 89 (29%) with follicles larger than 10.0 mm. In women with follicles of 2.0 to 10.0 mm, the right ovary was on average 0.8 cm3 larger and contained on average 1.2 more follicles than the left one. The ovarian volume, number of follicles, and total follicular volume decreased significantly with age in both ovaries (P = .000-.029): for the right ovary ovarian volume, the median (range) decreased from 8.4 (3.7-17.3) cm3 at 20 to 29 years to 6.5 (2.4-12.7) cm(3) at 35 to 39 years, the number of follicles from 14 (1-32) at 20 to 29 years to 8 (1-21) at 35 to 39 years, and the total follicular volume from 1.08 (0.01-3.10) cm3 at 20 to 29 years to 0.84 (0.03-2.00) cm3 at 35 to 39 years. The size of the largest follicle and the vascular indices manifested no clear changes with age in any ovary. In women with follicles larger than 10 mm, the number of follicles decreased with age in both ovaries. CONCLUSIONS: We have elicited data representative of normal findings on 3D trans-vaginal sonography of ovaries in gynecologically asymptomatic white women of fertile age. Our gray-scale sonographic results may be used as reference values for general gynecology in populations similar to ours. Vascular indices must be interpreted with caution because of difficulties with standardization.

Prevalence of endometrioma and deep infiltrating endometriosis at transvaginal ultrasound examination of subfertile women undergoing assisted reproductive treatment.

OBJECTIVE: To estimate the prevalence of endometrioma and deep infiltrating endometriosis (DIE), assessed by systematic transvaginal ultrasound examination, in women with subfertility accepted for their first assisted reproductive treatment and to describe the prevalence of endometriotic lesions in different anatomical locations of the pelvis. DESIGN: Cross-sectional study. SETTING: Reproductive Medicine Center, Department of Obstetrics and Gynecology, University hospital. PATIENT(S): A total of 1,191 women with subfertility aged 25-39 years accepted for their first assisted reproductive treatment between December 2018 and May 2021. INTERVENTION(S): All women underwent a systematic transvaginal ultrasound examination. The endometriotic lesions visible on ultrasound examination were described according to the International Deep Endometriosis Analysis group consensus opinion for systematic approach to assess endometriotic lesions. MAIN OUTCOME MEASURE(S): Prevalence of endometrioma and DIE in women with subfertility and prevalence of endometriotic lesions in various anatomical locations of the pelvis. RESULT(S): Endometriosis prevalence was 21.8%, with endometriotic lesions found in 260 of the 1,191 women. Overall, 125 (10.5%) women had endometrioma and 205 (17.2%) women had DIE. Of these 260 women, 197 (75.8% of women with endometriosis) did not have any previous knowledge about having endometriosis. The most common location for endometriotic lesions was the uterosacral ligaments, with lesions found in 151 (12.7%) of all women. The second most common location was the ovaries containing endometrioma, found in 125 (10.5%) women. Most women had 1 (n = 121, 10.2%) or 2 (n = 82, 6.9%) endometriotic lesions. CONCLUSION(S): The prevalence of endometrioma and DIE in women with subfertility, diagnosed by systematic transvaginal ultrasound examination, was 21.8%. Of these, three-fourth of women had no knowledge about the presence of disease.

Risk assessment for endometrial cancer in women with abnormal vaginal bleeding: Results from the prospective IETA-1 cohort study.

OBJECTIVE: To investigate the association between personal history, anthropometric features and lifestyle characteristics and endometrial malignancy in women with abnormal vaginal bleeding. METHODS: Prospective observational cohort assessed by descriptive and multivariable logistic regression analyses. Three features-age, body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters), and nulliparity-were defined a priori for baseline risk assessment of endometrial malignancy. The following variables were tested for added value: intrauterine contraceptive device, bleeding pattern, age at menopause, coexisting diabetes/hypertension, physical exercise, fat distribution, bra size, waist circumference, smoking/drinking habits, family history, use of hormonal/anticoagulant therapy, and sonographic endometrial thickness. We calculated adjusted odds ratio, optimism-corrected area under the receiver operating characteristic curve (AUC), R2 , and Akaike's information criterion. RESULTS: Of 2417 women, 155 (6%) had endometrial malignancy or endometrial intraepithelial neoplasia. In women with endometrial cancer median age was 67 years (interquartile range [IQR] 56-75 years), median parity was 2 (IQR 0-10), and median BMI was 28 (IQR 25-32). Age, BMI, and parity produced an AUC of 0.82. Other variables marginally affected the AUC, adding endometrial thickness substantially increased the AUC in postmenopausal women. CONCLUSION: Age, parity, and BMI help in the assessment of endometrial cancer risk in women with abnormal uterine bleeding. Other patient information adds little, whereas sonographic endometrial thickness substantially improves assessment.

Ovarian borderline tumor presenting as ovarian torsion in a 17-year-old patient: a case report.

BACKGROUND: Ovarian torsion is a gynecological surgical emergency whose diagnosis remains a challenge. Torsion occurs most frequently in women of reproductive age. It is usually associated with the presence of benign masses in the ovary, as malignant tumors are less frequent and less prone to undergo torsion. CASE PRESENTATION: We report the case of a 17-year-old Caucasian patient who presented to the emergency department with lower abdominal pain. Ultrasonography evaluation revealed a unilateral ovarian lesion, 11.2 cm, with features suspicious for malignancy and torsion. The patient was referred for surgical torsion treatment and underwent unilateral salpingo-oophorectomy. The pathology report confirmed a serous borderline ovarian tumor with torsion. CONCLUSIONS: Malignant ovarian torsion in pediatric age groups is rare. Ultrasound examination should be recognized as a powerful tool for diagnosis and management, especially when performed by an experienced ultrasonographer.

Fusion imaging in brain structure measurements on a fetus phantom, combining real-time ultrasound with magnetic resonance imaging.

OBJECTIVES: To assess synchronisation of MRI and US in measuring foetus phantom head structures; inter-method, intra- and inter-observer differences on biparietal diameter (BPD), head diameter, anterio-posterior head diameter (HAP) and lateral ventricle structures (VS). METHODS: Fusion Imaging (FI) has been performed by combining MRI and US simultaneously. Axial scans of 1.5 Tesla MRI on a foetus phantom were acquired and uploaded on a US machine (EPIQ 7G, Philips). A PercuNav US tracker allowed the system to recognise and display the position of the transducer. A fetal phantom tracker was used as a phantom reference. Real-time US of the phantom head was performed by synchronising the uploaded MRI images using different landmarks. Synchronisation has been assessed by taking measurements after rotating the US probe by 90. Measurements were taken by three different observers twice. Differences in measurements between MRI and US, inter-, intra-observer differences in all measurements were assessed. RESULTS: BPD, HAP and VS measurements before rotation were 0.13 ± 0.06 cm, 0.46 ± 0.09 cm and 0.4 ± 0.23 cm (width) and mean 0.6 ± 0.25 cm (length) larger at MRI than at US using any number of landmarks. After US probe rotation VS were 0.3 ± 0.24 cm in width and 0.3 ± 0.27 cm in length. Intra- and inter-observer differences in all measurements were small. CONCLUSIONS: FI showed good synchronisation in measurements. BPD, HAP and VS were larger at MRI than US, likely a result of the way images are generated. Intra-, inter-observer differences between measurements were small. This can be important when reporting geometric measures from FI.

Validation of models to diagnose ovarian cancer in patients managed surgically or conservatively: multicentre cohort study.

OBJECTIVE: To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. DESIGN: Multicentre cohort study. SETTING: 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. PARTICIPANTS: Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up. MAIN OUTCOME MEASURES: Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain. RESULTS: The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125. CONCLUSIONS: Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively. TRIAL REGISTRATION: ClinicalTrials.gov NCT01698632.

The Impact of the Biological Variability or Assay Performance on AMH Measurements: A Prospective Cohort Study With AMH Tested on Three Analytical Assay-Platforms.

This study examined longitudinal, age-related and intra-individual variation in Anti-Müllerian Hormone (AMH) in regular menstruating women and correlated the hormonal levels to the antral follicle count (AFC). The impact of variations on an algorithm for calculation of follitropin-dose for ovarian stimulation were also tested. The study was carried out at a fertility clinic of a tertiary university hospital and had a prospective trial design. Twenty-six healthy women not receiving infertility treatment aged 22 to 50 years participated. Blood sampling for hormonal analysis was done every fifth day throughout three consecutive menstrual cycles, AFC was determined with 3-dimentional ultrasound and AMH measured by different assays from Beckman Coulter, Roche and Ansh Labs. Outcome measures were maximum and minimum difference in absolute and relative terms for each study subject during the test-period, coefficient of variation (Cv) for AMH for each cycle and cycle-day and correlation between AMH and AFC. The impact from variable AMH levels on an algorithm calculating follitrophin-delta dose in ovarian stimulation was explored. A significant longitudinal age-independent variation in AMH-levels and coefficient of variation in cycles and cycle days was found. A strong correlation between AMH-levels and AFC was confirmed and a case of significant divergence between assays was seen. Variations in AMH had a significant impact on an algorithm calculated dosage of gonadotrophins in ovarian stimulation. The finding of a substantial longitudinal variation in AMH question one recording being sufficient in quantifying gonadotrophins for ovarian stimulation, decision making and prognostication related to infertility treatment and counseling. Occasionally, commercial assays may fail to recognize specific AMH cleavage-products.

Ovarian size and vascularization as assessed by three-dimensional grayscale and power Doppler ultrasound in asymptomatic women 20-39 years old using combined oral contraceptives.

BACKGROUND: The aim of this study is to estimate ovarian volume, number and volume of antral follicles, and ovarian power Doppler vascular indices as assessed by three-dimensional (3D) transvaginal grayscale and power Doppler ultrasound in women using combined oral contraceptives (COC). STUDY DESIGN: Two hundred thirteen gynecologically asymptomatic women 20-39 years old using COC were examined with transvaginal 3D grayscale and power Doppler ultrasound on cycle day 4-8 (first cycle day is first day of withdrawal bleeding). We used a Voluson E8 ultrasound system with a 6-12-MHz transvaginal transducer. Ovarian volume, number and volume of antral follicles ≥2 mm, vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were calculated using the virtual organ computer-aided analysis (VOCAL™) and sonography-based automated volume calculation (SonoAVC™) software. Results are described separately for women with follicles 2.0-10.0 mm and for those with at least one follicle >10.0 mm for two age groups: 20-29 years (n=166) and 30-39 years (n=47). Results are also compared between women on monophasic (n=151) and triphasic (n=59) COC, and between women using COC with older (n=110) and newer (n=100) progestins and different doses of estrogen. RESULTS: One hundred eighty-nine (89%) women had follicles 2.0-10.0 mm, and 24 (11%) had follicle(s) >10.0 mm. The proportion of women with follicle(s) >10.0 mm did not differ between women with different types of COC. In women with follicles 2.0-10.0 mm, the right ovary was larger (mean difference 0.5 cm(3) [95% confidence interval 0.22-0.82]) and contained more follicles (mean difference 1.5 [0.52-2.56]) than the left one in the age group 20-29 years. The same differences between the right and left ovary were seen in women 30-39 years old, but they were not statistically significant. In both ovaries, the number of antral follicles 2.0-10.0 mm [median (range)] was significantly higher in women 20-29 than in those 30-39 years old [11 (2-34) vs. 8 (1-26), p=.012 for the right ovary; 9 (0-28) vs. 7 (1-28), p=.035 for the left ovary]. Ovarian volume tended to be smaller in women 20-29 than in those 30-39 years old, but the differences were not statistically significant. Size of the largest follicle, total follicular volume and vascular indices manifested no clear differences between the age groups. For all 378 ovaries with follicles ≤10 mm, ovarian volume ranged from 1 to 16 cm(3) (median 5), total follicular volume ranged from 0.03 to 2.7 cm(3) (median 0.7), VI ranged from 0.0 % to 13.4% (median 0.97), FI ranged from 0 to 38 (median 25), and VFI ranged from 0.0 to 4.7 (median 0.3). CONCLUSIONS: Our results show estimated ranges of 3D grayscale and power Doppler ultrasound measurements in ovaries of women using COC.

Assessment of changes in volume and vascularity of the ovaries during the normal menstrual cycle using three-dimensional power Doppler ultrasound.

BACKGROUND: Our aim was to describe changes in the volume and vascularization of both ovaries, the dominant follicle and the corpus luteum during the normal menstrual cycle using three-dimensional (3D) power Doppler ultrasound. METHODS: Fourteen healthy volunteers underwent serial transvaginal 3D ultrasound examinations of both ovaries on cycle day 2, 3 or 4, then daily from cycle day 9 until follicular rupture and 1, 2, 5, 7 and 12 days after follicular rupture. The volume and vascular indices of the ovaries, the dominant follicle and the corpus luteum were calculated off-line using virtual organ computer-aided analysis (VOCAL) software. RESULTS: The volume of the dominant ovary increased during the follicular phase, decreased after follicular rupture and then increased again during the luteal phase. Vascular indices in the dominant ovary and the dominant follicle/corpus luteum increased during the follicular phase, the vascular flow index (VFI) in the dominant follicle being on average (median) 1.7 times higher on the day before ovulation than 4 days before ovulation (P=0.003). The vascular indices continued to rise after follicular rupture so that VFI in the corpus luteum was on average (median) 3.1 times higher 7 days after ovulation than in the follicle on the day before ovulation (P=0.0002). The volume and vascular indices in the non-dominant ovary manifested no unequivocal changes during the menstrual cycle. CONCLUSIONS: Substantial changes occur in volume and vascularization of the dominant ovary during the normal menstrual cycle. 3D power Doppler ultrasound may become a useful tool for assessing pathological changes in the ovaries, for example, in subfertile patients.