This was a prospective cross-sectional study comprising 116 out of 300 women who are suspected of having ovarian lesions on the basis of previous examination, previous clinical or US examination by the obstetric and gynecological surgeon, accidentally discovered ovarian lesion on US examination by non-radiologists, ovarian lesion on computed tomography, high CA125, and clinical symptoms of ovarian lesions such as pelvic pain and back pain, between March 2017 to August 2018. The sample size was calculated using Open Epi software program, version 23.1. A total of 184 patients were excluded from our study when they underwent neoadjuvant chemotherapy before US examination (n = 50), had previous surgery on the ovary (n = 47), and had no pathological reports after surgery (n = 83). This study was approved by our institutional review board. Written informed consent for participation and publication was obtained from each patient after receiving information about the details of the study. Confidentiality of patient’s records was assured and maintained throughout the study. The trial was registered in the US National Library of Medicine, under clinical trial number NCT03175991.
All patients’ pelvises were examined by using the ProSound Alpha 7 ultrasound (Hitachi Aloka Medical America, Inc. Germany) by transvaginal ultrasound in lithotomy position using endovaginal transducer and/or transabdominal ultrasound in the supine position using a 3.75-MHz sector transducer, in transverse and longitudinal plane and evaluated by B-mode ultrasonography, color, and spectral Doppler. Two expert examiners (G.S.S and L.M.R.K), with more than 10 years’ experience in gynecological ultrasound, performed all examinations and stored between one and four representative images on the database.
Sonographic data analysis
A morphologic evaluation was performed according to the International Ovarian Tumor Analysis Group (IOTA) recommendations for the following parameters: wall thickness, septation, papillary projections, presence and echogenicity of solid areas, presence of mixed component, cystic component, and presence of ascites , and intra-abdominal metastases (peritoneal deposits, liver metastasis, and malignant abdominal lymphadenopathy) was also recorded. Pattern recognition analysis was also used for ovarian masses .
Then, the lesion volume was calculated according to the prolate ellipsoid formula (length × width × height × 0.523, expressed in cubic centimeters). Ten cubic centimeters for postmenopausal women and 20 cm3 for premenopausal women were considered as a cutoff point between the normal and suspicious ovarian lesion . This feature was not taken into consideration for assigning a GI-RADS classification.
After the morphologic evaluation was performed, the color Doppler was activated to identify vascular color signals within the tumor with no aliasing. A tumor was considered to have no flow when no signal could be detected. If blood flow was detected, it was stated as “peripheral” (color signals in the tumor wall or periphery of a solid tumor) or “central” (blood flow detected in septa, papillary projections, solid areas, or the central part of a solid tumor). The central blood flow was used for analysis when there was both peripheral and central blood flow. The evaluation of the amount of flow was subjective and stated as scanty, moderate, or abundant . Then, the pulsed Doppler was activated at the lowest pulse repetition frequency to calculate the resistive index (RI) and pulsatility index (PI). The lowest RI was used for analysis when there is more than one vessel. Morphological features considered suspicious of malignancy included thick wall ≥ 3 mm, thick septum ≥ 3 mm, solid papillary projection, solid and mixed component, presence of ascites, intra-abdominal metastasis, and central blood flow.
After the examinations, a combination of morphological features, color and spectral Doppler features, and then the lesion was evaluated according to GI-RADS classification, and the suggested management protocol was based on the risk of malignancy  as follows:
GI-RADS 1 patients did not undergo follow-up on the basis that these lesions are considered to be normal.
GI-RADS 2 patients were treated expectantly and underwent follow-up after 6 weeks on the basis that these lesions were functional.
GI-RADS 3 patients that did not resolve on follow-up by the radiologists on the basis that these lesions are most probably benign and underwent laparoscopic removal of the lesion.
GI-RADS 4 and 5 patients were referred to gynecological oncologists and surgeon for surgical removal on the basis that these lesions were very probably malignant, taking into consideration that the diagnosis of GI-RADS 4 depends on the presence of one or two sonographic findings suggestive of malignancy and three or more sonographic findings suggestive of malignancy in GI-RADS 5.
Finally, the referral to surgery and decision-making was consulted in accordance with a multidisciplinary team meeting (MDT). A definitive histopathological diagnosis was obtained as a gold standard test for all patients with GI-RADS 4 and 5 and 15 cases of GI-RADS 3 patients after laparoscopic or surgical removal of the masses. Resolution of the lesions on follow-up was considered as a gold standard test for all patients with GI-RADS 2 and 21 patients with GI-RADS 3.
A histopathological examination of all the surgical specimens was done. Tissue sections with formalin fixed and paraffin processed were stained with hematoxylin and eosin. Tumors were classified according to the WHO criteria . Borderline tumors were considered as malignant for analytic purposes.
Data was collected and analyzed using SPSS (Statistical Package for the Social Science, version 20, IBM, and Armonk, New York). Continuous data were expressed in the form of mean ± SD or median (range) while nominal data were expressed in the form of frequency (percentage). Categorical variables were compared using the chi-square test, and tumor volumes were compared using the Mann–Whitney U test. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR−) of the GI-RADS system for identifying ovarian masses at high risk of malignancy were calculated using the receiver operating characteristic (ROC) curve. For interrater reliability testing between sonographic findings and histopathological data, Cohen’s kappa (κ) test was used and the result was interpreted as perfect agreement when its value lies between 0.81 and 1.00.