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.

The Risk of Endometrial Malignancy and Other Endometrial Pathology in Women with Abnormal Uterine Bleeding: An Ultrasound-Based Model Development Study by the IETA Group.

OBJECTIVES: The aim of this study was to develop a model that can discriminate between different etiologies of abnormal uterine bleeding. DESIGN: The International Endometrial Tumor Analysis 1 study is a multicenter observational diagnostic study in 18 bleeding clinics in 9 countries. Consecutive women with abnormal vaginal bleeding presenting for ultrasound examination (n = 2,417) were recruited. The histology was obtained from endometrial sampling, D&C, hysteroscopic resection, hysterectomy, or ultrasound follow-up for >1 year. METHODS: A model was developed using multinomial regression based on age, body mass index, and ultrasound predictors to distinguish between: (1) endometrial atrophy, (2) endometrial polyp or intracavitary myoma, (3) endometrial malignancy or atypical hyperplasia, (4) proliferative/secretory changes, endometritis, or hyperplasia without atypia and validated using leave-center-out cross-validation and bootstrapping. The main outcomes are the model's ability to discriminate between the four outcomes and the calibration of risk estimates. RESULTS: The median age in 2,417 women was 50 (interquartile range 43-57). 414 (17%) women had endometrial atrophy; 996 (41%) had a polyp or myoma; 155 (6%) had an endometrial malignancy or atypical hyperplasia; and 852 (35%) had proliferative/secretory changes, endometritis, or hyperplasia without atypia. The model distinguished well between malignant and benign histology (c-statistic 0.88 95% CI: 0.85-0.91) and between all benign histologies. The probabilities for each of the four outcomes were over- or underestimated depending on the centers. LIMITATIONS: Not all patients had a diagnosis based on histology. The model over- or underestimated the risk for certain outcomes in some centers, indicating local recalibration is advisable. CONCLUSIONS: The proposed model reliably distinguishes between four histological outcomes. This is the first model to discriminate between several outcomes and is the only model applicable when menopausal status is uncertain. The model could be useful for patient management and counseling, and aid in the interpretation of ultrasound findings. Future research is needed to externally validate and locally recalibrate the model.

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.

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.

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.

Validation of the Performance of International Ovarian Tumor Analysis (IOTA) Methods in the Diagnosis of Early Stage Ovarian Cancer in a Non-Screening Population.

BACKGROUND: The aim of this study was to assess and compare the performance of different ultrasound-based International Ovarian Tumor Analysis (IOTA) strategies and subjective assessment for the diagnosis of early stage ovarian malignancy. METHODS: This is a secondary analysis of a prospective multicenter cross-sectional diagnostic accuracy study that included 1653 patients recruited at 18 centers from 2009 to 2012. All patients underwent standardized transvaginal ultrasonography by experienced ultrasound investigators. We assessed test performance of the IOTA Simple Rules (SRs), Simple Rules Risk (SRR), the Assessment of Different NEoplasias in the adneXa (ADNEX) model and subjective assessment to discriminate between stage I-II ovarian cancer and benign disease. Reference standard was histology after surgery. RESULTS: 230 (13.9%) patients proved to have stage I-II primary invasive ovarian malignancy, and 1423 (86.1%) had benign disease. Sensitivity and specificity with respect to malignancy (95% confidence intervals) of the original SRs (classifying all inconclusive cases as malignant) were 94.3% (90.6% to 96.7%) and 73.4% (71.0% to 75.6%). Subjective assessment had a sensitivity and specificity of 90.0% (85.4% to 93.2%) and 86.7% (84.9% to 88.4%), respectively. The areas under the receiver operator characteristic curves of SRR and ADNEX were 0.917 (0.902 to 0.933) and 0.905 (0.920 to 0.934), respectively. At a 1% risk cut-off, sensitivity and specificity for SRR were 100% (98.4% to 100%) and 38.0% (35.5% to 40.6%), and for ADNEX were 100% (98.4% to 100%) and 19.4% (17.4% to 21.5%). At a 30% risk cut-off, sensitivity and specificity for SRR were 88.3% (83.5% to 91.8%) and 81.1% (79% to 83%), and for ADNEX were 84.5% (80.5% to 89.6%) and 84.5% (82.6% to 86.3%). CONCLUSION: This study shows that all three IOTA strategies have good ability to discriminate between stage I-II ovarian malignancy and benign disease.

Flow index evaluation of 3-D volume flow images: an in vivo and in vitro study.

Three-dimensional (3-D) ultrasound imaging has improved evaluation of organ circulation and might contribute new information on maternal and fetal blood supply. Flow index (FI) of 3-D color images has been proposed as a measure of perfusion. The aim of this study was to evaluate whether the 3-D FI is a parameter of volume flow and flow velocity in a human vessel and in a flow phantom. A 1-cm-long strip of the uterine artery was recorded in 3-D power Doppler (3D-PD) mode in a cross-sectional study of 170 normal singleton pregnancies between 26 and 42 weeks' gestation. A fixed ultrasound system installation was used during the examination. The VOCAL software integrated in the ultrasound unit calculated vessel volume and FI. Reproducibility of the measurements was tested. The method was also tested on a commercially available flow phantom. Reproducibility measurements gave satisfactory results, both in terms of inter- and intraobserver variation. Unexpectedly, in normal pregnancy, the uterine artery FI decreased slightly with gestation. Uterine artery vessel volume increased, however, with gestational age. A poor correlation was found between the FI and both flow velocity and volume flow in the flow phantom. In conclusion, 3D-PD imaging can give impressive anatomical pictures of organ vascular tree. However, the new FI is poorly related to flow velocity or volume of flow.

Prospective validation of two mathematical models to calculate the risk of endometrial malignancy in patients with postmenopausal bleeding and sonographic endometrial thickness ≥4.5 mm.

AIM: To prospectively validate two mathematical models for calculating the likelihood of endometrial malignancy in patients with postmenopausal bleeding (PMPB), sonographic endometrial thickness (ET) ≥4.5 mm and no fluid in the uterine cavity. METHODS: This is a prospective observational diagnostic validation study performed in a PMPB clinic in a university hospital. Of 860 consecutive patients, 350 fulfilled our inclusion criteria. A standardized history was taken, clinical and transvaginal grey scale and power Doppler ultrasound examinations were performed following a research protocol. The percentage vascularized area of the endometrium at power Doppler examination (VI) was calculated using computer software. The colour content of the endometrial scan was estimated subjectively on a visual analogue scale (VAS). Gold standard was the histological diagnosis of the endometrium. Main outcome measures were area under the receiver operating characteristic curve (AUC), sensitivity and specificity when using the cut-offs suggested in the original study, and calibration curves. RESULTS: Eighty (23%) patients had malignant endometrium. The performance of the models was similar to that in the original study. The model including patient's age, use of hormone therapy, ET and VAS performed best (AUC 0.91; 95% confidence interval [CI] 0.87-0.95; sensitivity 70%, specificity 93%). The model including ET, VI, patient's age and hormone therapy use had AUC 0.89 (95% CI 0.84-0.93; sensitivity 79%; specificity 81%). ET had AUC 0.83 (95% CI 0.78-0.88). The models were reasonably well calibrated. CONCLUSION: On prospective validation both models retained their diagnostic performance. This suggests that they are robust and potentially clinically useful for individualized patient management.

Interobserver agreement in describing the ultrasound appearance of adnexal masses and in calculating the risk of malignancy using logistic regression models.

PURPOSE: To estimate interobserver agreement with regard to describing adnexal masses using the International Ovarian Tumor Analysis (IOTA) terminology and the risk of malignancy calculated using IOTA logistic regression models LR1 and LR2, and to elucidate what explained the largest interobserver differences in calculated risk of malignancy. EXPERIMENTAL DESIGN: One hundred and seventeen women with adnexal masses were examined with transvaginal gray scale and power Doppler ultrasound by two independent experienced sonologists who described the masses using IOTA terminology. The risk of malignancy was calculated using LR1 and LR2. A predetermined risk of malignancy cutoff of 10% indicated malignancy. RESULTS: There were 94 benign, four borderline, and 19 invasively malignant tumors. There was substantial variability between the two sonologists in measurement results and some variability in assessment of categorical variables (agreement 40%-98%, Kappa 0.30-0.91). Interobserver agreement when classifying tumors as benign or malignant was 84% (98/117), Kappa 0.68 for LR1, and for LR2 85% (99/117), Kappa 0.68. When using LR1 and LR2, the interobserver difference in calculated risk was ≥ 25 percentage units in 9% (11/117) and 12% (14/117) of tumors, respectively. Differences in assessment of wall irregularity, acoustic shadowing, color score, and color flow in papillary projections explained most of these largest differences. CONCLUSIONS: Interobserver agreement in classifying tumors as benign or malignant using the risk of malignancy cutoff of 10% for LR1 and LR2 was good. However, because risk estimates may differ substantially between sonologists, one should be cautious with using the risk value for counseling patients about their individual risk.

Quantification of ovarian power Doppler signal with three-dimensional ultrasonography to predict response during in vitro fertilization.

OBJECTIVE: To evaluate whether power Doppler predicts ovarian response to gonadotrophin stimulation during in vitro fertilization (IVF). METHODS: Forty-five women were divided into low-reserve (n = 12) and normal-reserve (n = 33) ovarian groups, according to antral follicle count. Transvaginal three-dimensional power Doppler ultrasonographic examinations were performed after pituitary downregulation and after gonadotrophin stimulation. The antral follicle count, ovarian volume, vascularization index, flow index, vascularization flow index, and mean gray value were measured and related to the number of oocytes retrieved and the pregnancy rate. RESULTS: The number of oocytes retrieved correlated with the antral follicle count (R =.458, P =.004) and ovarian volume (R =.388, P <.016) but not with vascularization index, flow index, vascularization flow index, or mean gray value after pituitary suppression. There was an increase in vascularization index (P <.017), flow index (P <.001), and vascularization flow index (P <.007) during gonadotrophin stimulation in the normal-ovary group but not in the low-ovarian-reserve group. CONCLUSION: According to our results, quantification of power Doppler signal in the ovaries after pituitary suppression does not provide any additional information to predict the subsequent response to gonadotrophin stimulation during IVF. The increase in ovarian power Doppler signal during gonadotrophin stimulation is related to the antral follicle count observed after pituitary suppression.

Comparison of follicular vascularization in normal versus polycystic ovaries during in vitro fertilization as measured using 3-dimensional power Doppler ultrasonography.

OBJECTIVE: The growth of the follicles induced by gonadotropins during IVF treatment is accompanied by physiologic angiogenesis, which is essential for the maturation of the oocytes. We describe the IVF-induced changes in the vascularization and compare normal with polycystic ovaries (PCOs). DESIGN: Prospective study. SETTING: Assisted reproductive unit at a university hospital. PATIENT(S): Sixty women who underwent IVF cycles. INTERVENTION(S): The ovarian vascularization was measured after pituitary down-regulation, FSH stimulation, and hCG-injection using three-dimensional power Doppler ultrasonography. MAIN OUTCOME MEASURE(S): The total ovarian vascularization was divided by the number of follicles. RESULT(S): After pituitary suppression, the ovarian vascularization/follicle was lower in polycystic ovary (PCO) patients. During ovarian stimulation, follicles in PCOs required a lesser amount of FSH to acquire the same level of vascularization than the follicles in normal ovaries. In addition, hCG induced an increase in the follicular vascularization in both normal and PCOs. The follicle count correlated with the total vascularized volume in the ovaries throughout the IVF cycle. CONCLUSION(S): Follicles in PCOs seem to be less vascularized than the follicles in normal ovaries after GnRH treatment but not after gonadotropin stimulation. It is possible that restricted blood supply to the follicles in PCO might be associated with the follicular arrest that is observed. We could confirm that follicles in PCO are more sensitive to gonadotropin stimulation than follicles in normal ovaries.

Side of ovulation and its effects on uterine and ovarian stromal blood flow and reproductive hormones.

OBJECTIVE: Effect of the side of ovulation on uterine, ovarian, and follicular blood flow parameters and various hormone levels. DESIGN: Prospective, observational study. SETTING: Fertility Clinic, St. George's Hospital. PATIENT(S): Nineteen women with regular menstrual cycles. Pulsed Doppler measurements and serum hormonal concentrations during midfollicular, periovulatory, and midluteal phase for three successive cycles. MAIN OUTCOME MEASURE(S): Doppler blood flow and serum hormones. RESULT(S): Doppler blood flow of the ovarian stroma and follicular and uterine arteries showed no differences in the three phases between the right and left sides. Left-side uterine peak systolic velocity (PSV) (right-side PSV, 31.51cm/s; left-side PSV, 37.38 cm/s) during the periovulatory phase tended to be higher in the nondominant ovary; however, this was not quite significant. The serum hormone concentration showed no significant differences. CONCLUSION(S): The side of ovulation did not influence the Doppler blood flow to the ovarian stroma or follicular and uterine arteries. The side of ovulation had no effect on serum FSH, LH, 17beta-estradiol, P, inhibin A, or inhibin B levels.

Effect of pituitary down-regulation on the ovary before in vitro fertilization as measured using three-dimensional power Doppler ultrasound.

OBJECTIVE: To evaluate the changes taking place in the ovaries during pituitary down-regulation. DESIGN: Prospective observational study of women undergoing IVF treatment. SETTING: A tertiary referral center for assisted reproduction. PATIENT(S): Forty women who received the long buserelin acetate treatment protocol. Transvaginal three-dimensional power Doppler ultrasound examinations before and after pituitary down-regulation. INTERVENTION(S): Ovarian volume, number of follicles, vascularization index (VI), flow index (FI), vascularization flow index (VFI), and mean gray value (MG). RESULT(S): Before the pituitary down-regulation, the dominant ovary was larger in volume and had a lower MG than the nondominant ovary. After the down-regulation, there was a significant decrease in the volume and number of follicles and an increase in MG. After pituitary down-regulation, the dominant and nondominant ovaries did not differ from each other in any of the parameters. Polycystic ovaries were larger than normal ones before and after the down-regulation, without any differences in MG, VI, FI, or VFI. Right and left ovaries did not differ from each other after the down-regulation. CONCLUSION(S): The differences observed between dominant and nondominant ovaries seem to disappear after pituitary down-regulation. In addition, polycystic ovaries were always larger than the normal ones, but no differences could be detected in the stromal brightness or vascularity either before or after the administration of GnRH agonist therapy.