R. Cioffi

Multiple pregnancy with complete hydatidiform mole and coexisting normal fetus: systematic review and meta‐analysis of clinical outcomes from non‐randomized studies

ABSTRACT Objective Complete hydatidiform mole and coexisting normal fetus (CHMCF) is a rare condition for which there is significant heterogeneity in diagnosis, counseling and management of complications. The objective of this study was to summarize the prevalence of clinical outcomes in reported cases of CHMCF. Methods A systematic literature search was conducted in PubMed, Embase and Scopus databases from inception until 1 October 2024. Case series and cohort studies including at least three cases of histologically confirmed CHMCF were included. A random‐effects model was used for meta‐analysis of proportions and heterogeneity was estimated using Higgins' I 2 index. The Newcastle–Ottawa scale and the Joanna Briggs Institute critical appraisal checklist were used to assess study quality, while certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The study was registered in the PROSPERO database (CRD42023431734). Results Quantitative synthesis included 19 studies and 417 cases of CHMCF. Diagnosis was made using ultrasound in 76.0% (95% CI, 58.5–90.6%) of cases and occurred in the first trimester in 52.7% (95% CI, 34.0–71.0%). Symptoms at diagnosis were present in 80.5% (95% CI, 66.1–92.3%) of cases, with vaginal bleeding being the most common symptom both at diagnosis and later in pregnancy. The pooled proportion of elective pregnancy termination was 48.8% (95% CI, 32.7–65.1%), with 6.2% (95% CI, 1.0–13.9%) due to maternal complications. The pooled proportion of live births was 46.5% (95% CI, 36.1–57.1%), with most being delivered by Cesarean section (71.2% (95% CI, 42.4–94.4%)). Preterm birth (< 37 weeks) occurred in 67.8% (95% CI, 44.7–88.1%) of cases, very preterm birth (< 32 weeks) in 12.4% (95% CI, 0.2–33.9%) and miscarriage (fetal death < 24 weeks) in 32.7% (95% CI, 26.1–39.6%). Pre‐eclampsia was present in 17.8% (95% CI, 5.9–32.7%) of cases and postpartum hemorrhage occurred in 42.7% (95% CI, 5.1–84.8%). A small‐for‐gestational‐age neonate (birth weight < 10 th percentile) was delivered in 40.6% (95% CI, 12.9–70.8%) of cases. Rates of neonatal and maternal mortality were negligible. The pooled proportion of gestational trophoblastic neoplasia was 33.8% (95% CI, 25.6–42.5%); among elective terminations, continued pregnancies and live births, the rates were 14.1% (95% CI, 5.4–24.9%), 20.3% (95% CI, 12.0–29.9%) and 5.9% (95% CI, 1.9–11.2%), respectively. The evidence level according to GRADE was low to very low. Conclusions Pregnancies with CHMCF present a high risk of maternal, obstetric and neonatal complications, including miscarriage, pre‐eclampsia, small‐for‐gestational age, postpartum hemorrhage and preterm birth. The risk of developing gestational trophoblastic neoplasia was not clearly mitigated by early pregnancy termination. Early diagnosis, referral to a maternal–fetal medicine unit with expertise in trophoblastic disorders and extensive implementation of screening protocols for preterm birth and pre‐eclampsia are recommended to facilitate timely intervention aimed at outcome improvement. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Additional value of uterine artery Doppler pulsatility index for ultrasound diagnosis of placental site trophoblastic tumor: prospective cohort study

ABSTRACT Objectives The ultrasound diagnosis of placental site trophoblastic tumor (PSTT) is challenging owing to a lack of pathognomonic features. Differential diagnosis from other forms of gestational trophoblastic neoplasia (GTN) is critical owing to major differences in prognosis and treatment. Doppler measurement of uterine artery (UtA) pulsatility index (PI) has been proposed for the diagnosis and management of GTN. The aim of this study was to evaluate the added value of UtA‐PI Doppler measurement during the standard transvaginal ultrasound (TVS) assessment, in patients with PSTT as compared to those with other GTN. Methods This was a single‐center prospective cohort study involving ultrasound assessment of all GTN cases referred to and treated at the trophoblast unit of San Raffaele Hospital, Milan, Italy, between 2011 and 2023. TVS assessment included: grayscale analysis for the detection of myometrial or endometrial abnormalities, color and power Doppler assessment of lesions with scoring of vascularization, and spectral pulsed‐wave Doppler for measurement of mean UtA‐PI from the left and right UtAs. Sonographic findings were compared between patients with PSTT and those with other forms of GTN (postmolar, invasive mole or choriocarcinoma), using non‐parametric two‐tailed statistical analysis. Results A total of 73 GTN cases were recruited, comprising nine (12.3%) with PSTT and 64 (87.7%) with other GTN. A significant difference was detected between other‐GTN and PSTT cases when comparing rates of substantial endometrial vascularity on Doppler (50% vs 0%; P  = 0.013) and mean UtA‐PI measurements (median, 1.5 (interquartile range (IQR), 1.0–2.4) vs 2.2 (IQR, 1.5–2.7); P  = 0.014; area under the receiver‐operating‐characteristics curve, 0.768 (95% CI, 0.610–0.888)). Conclusions This study describes UtA‐PI as a novel and effective marker allowing for the ultrasound differentiation of PSTT from other forms of GTN. The significantly higher mean UtA‐PI and lower endometrial vascularity observed in PSTT as compared with other GTN suggests a unique vascularization pattern, with a potential role in differential diagnosis and management. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fertility sparing surgery in sex-cord stromal tumors: oncological and reproductive outcomes

Sex cord stromal tumors are rare neoplasms, frequently diagnosed in young women often as early-stage disease. In patients who desire to preserve fertility, when possible, unilateral salpingo-oophorectomy with peritoneal surgical staging is a safe alternative to radical treatment. In this review, we analyze the available literature on the obstetrical outcomes after fertility-sparing surgery in a total of 255 patients with sex cord stromal tumors. We found that the spontaneous conception rate in granulosa cells tumor is encouraging (88.5%). In particular, juvenile granulosa cell tumors are associated with a more successful pregnancy rate than adult granulosa cells tumors (11/26 (42.3%) in juvenile granulosa cells tumors compared with 28.5% in adult granulosa cell tumors, respectively.) On the other hand, the results of obstetrical outcomes in Sertoli-Leydig cells tumors are less promising (7/36 (19.4%)). Unfortunately, no evidence on this topic is available for sex cord tumor with annular tubules due to the low incidence. Regarding the oncological outcomes of 900 cases of sex cord stromal tumors treated conservatively, data are reassuring with comparable outcomes between patients treated with conservative and radical surgery. Given the limited available data on this rare tumor, further studies are needed to evaluate the safety of conservative approaches and to define the obstetrical outcomes in this patient population.

Physicians’ Controversies Towards Fertility Preservation in Young Patients with Gynecological Cancer: An MITO Survey

Guidelines on fertility preservation (FP) have been developed to help young women preserve their fertility, which may have been impaired due to cancer. Nevertheless, the correct management of oncological patients of childbearing age remains controversial, especially regarding gynecological malignancies. For this reason, we explored the current knowledge, attitudes, and clinical practices of physicians towards the challenges of FP in this population. A specially developed questionnaire on fertility-related issues in patients with gynecological cancer was administered via email to 167 people, representing 167 centers of the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) group. A total of 56 physicians, who represented 56 out of these 167 centers, responded to our survey (response rate: 33.5%). Approximately half of these physicians stated that they had adequate knowledge about the use of gonadotropin-releasing analog (GnRHa) injections (n = 30; 53.6%), the cryopreservation of oocytes (n = 25; 44.6%), and the cryopreservation of ovarian tissue (n = 27; 48.2%) in patients with gynecological tumors. Meanwhile, regarding (borderline) ovarian tumors, endometrial or cervical cancer, and genetic mutation carriers, attitudes varied substantially. In conclusion, the results of our survey highlight the different perspectives on controversial topics among physicians directly involved in the treatment of these tumors. These findings also demonstrate the lack of evidence on these issues to adequately counsel this specific patient population.

Radiomics‐based ultrasOund Model for differentiating Uterine Sarcomas from leiomyomas ( ROMUS ): a retrospective pilot Multicenter Italian Trials in Ovarian Cancer ( MITO ) study

ABSTRACT Objective To develop machine‐learning models that incorporate clinical information and radiomics features extracted from ultrasound images to distinguish uterine sarcomas from leiomyomas. Methods This retrospective, multicenter, pilot case–control study included 200 patients (100 with a uterine sarcoma and 100 with a usual‐type leiomyoma, i.e. including no benign leiomyoma variants) who underwent preoperative ultrasound examination between January 2010 and June 2022. The patient cohort was split (70:30) into training and validation sets, with the same proportion of leiomyomas and sarcomas in each subset. We extracted radiomics features belonging to different families: intensity‐based statistical features and textural features. The variables used in model building were patient age and the radiomics features that differed statistically significantly between sarcomas and leiomyomas and that were not redundant based on Spearman's correlation coefficient. Logistic regression, random forest, extreme gradient boosting (XGBoost) and support vector machine models were tested in the model development process. We evaluated the performance of the models in differentiating between sarcomas and leiomyomas using the area under the receiver‐operating‐characteristics curve (AUC), accuracy, sensitivity and specificity. We compared these results to those of subjective assessment by the original ultrasound examiner and to those of two independent expert ultrasound examiners who, blinded to clinical history, reviewed the same grayscale ultrasound images as those used for the radiomics analysis. Results Sixty‐three radiomics features were extracted. Of these, eight differed statistically significantly between sarcomas and leiomyomas and were not correlated, so were selected for inclusion in model building. In the validation set, the model that performed best in differentiating between sarcomas and leiomyomas was an XGBoost model integrating patient age and radiomics features. In the validation set, this model had an AUC of 0.93, sensitivity of 0.93 and specificity of 0.83, at a risk‐of‐malignancy cut‐off of 47% (the cut‐off that yielded the highest number of correct classifications based on Youden's index in the training set). The corresponding results for the model integrating only the radiomics features were: AUC of 0.87, sensitivity of 0.87 and specificity of 0.83. Subjective assessment by the original ultrasound examiner had a sensitivity of 0.87 and specificity of 1 in the validation set, while retrospective review of grayscale ultrasound images by ultrasound experts had a sensitivity of 0.87 and specificity of 0.80 (same results for both reviewers). Conclusion A model including eight radiomics features and patient age demonstrated reasonably good discriminative and classification performance for distinguishing uterine sarcomas from leiomyomas. Its classification ability was similar to that of subjective assessment by the original ultrasound examiner, being more sensitive but less specific. To confirm the role of radiomics for discriminating between uterine sarcomas and leiomyomas, large prospective studies including benign leiomyoma variants are needed. If good performance of radiomics models can be confirmed, integrating automated radiomics analysis into ultrasound machine software may help ultrasound examiners to discriminate between sarcomas and benign leiomyomas. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.