Giorgia Mangili

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.

Quality of radiation shapes survival, invasiveness, and migration in ovarian cancer cell lines with different molecular profiles and varying alpha/beta ratios: an in vitro study on behalf of the Multicenter Italian Trials in Ovarian Cancer (MITO) group

The results of radiotherapy (RT) in oligometastatic ovarian cancers (OCs) lead to the query whether it is possible to stratify patients based on tumor hallmarks to ensure the best-personalized RT treatment. To address this question, we designed a preclinical study to evaluate the effects of high and low linear energy transfer (LET) radiation while considering molecular features and alpha/beta ratios of different OC cell lines. Exponentially growing human OVSAHO, OVCAR8, COV362, and OVCAR3 cells cultured in T-25 and T-75 flasks were exposed to different single physical doses of photons, protons, and carbon ion (CIRT) irradiation. We assessed ovarian cells' in vitro response using clonogenic survival (fitted using LQ model), migration by Boyden chamber assay, and invasion through BioCoat Matrigel invasion assay. Following photon irradiation, OVCAR3 was the most radioresistant and OVCAR8 the most radiosensitive cell line. OC cell migration decreased in a dose-dependent manner after irradiation, with CIRT showing the strongest effect, evident by the α/β ratio. The number of invading cells decreased following irradiation with all types. However, the greatest reduction was seen in CIRT, particularly at higher α/β ratios. Proton irradiation demonstrated similar potential to photons but did not match the effects of carbon ions in terms of survival, migration, and invasion

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.

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.