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Objectives: To describe how SARS-CoV-2 infection at the time of delivery affected maternal and neonatal outcomes across four major waves of the COVID-19 pandemic in Italy., Methods: This is a large, prospective, nationwide cohort study collecting maternal and neonatal data in case of maternal peripartum SARS-CoV-2 infection between February 2020 and March 2022. Data were stratified across the four observed pandemic waves., Results: Among 5201 COVID-19-positive mothers, the risk of being symptomatic at delivery was significantly higher in the first and third waves (20.8-20.8%) than in the second and fourth (13.2-12.2%). Among their 5284 neonates, the risk of prematurity (gestational age <37 weeks) was significantly higher in the first and third waves (15.6-12.5%). The risk of intrauterine transmission was always very low, while the risk of postnatal transmission during rooming-in was higher and peaked at 4.5% during the fourth wave. A total of 80% of positive neonates were asymptomatic., Conclusion: The risk of adverse maternal and neonatal outcomes was significantly higher during the first and third waves, dominated by unsequenced variants and the Delta variant, respectively. Postnatal transmission accounted for most neonatal infections and was more frequent during the Omicron period. However, the paucity of symptoms in infected neonates should lead us not to separate the dyad., Competing Interests: Declaration of Competing Interest All authors have no competing interests to declare., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: The impact of cancer on basal fertility and ovarian response to stimulation has not yet been clarified. Evidence on this topic is scarce and conflicting. Aim of this study was to assess the impact of breast cancer stage and grade on the number of retrieved mature oocytes during controlled ovarian stimulation for fertility preservation., Methods: Retrospective cohort study evaluating data on 101 stimulation cycles of women with breast cancer undergoing oocyte cryopreservation categorized according to breast cancer stage (low-stage: I; high-stage:II-III) and grade (low-grade: G1-2; high-grade: G3) using the American Joint Committee on Cancer staging system (VIII edition)., Results: High-stage disease was not associated with worse oocyte retrieval outcomes (median 7 vs 7, p = 0.75). High-grade disease patients showed a significantly lower antral follicle count (AFC) compared to low-grade disease patients (10 vs 13, p = 0.03), and required higher doses of FSH (2612 IU vs 2250 IU; p = 0.03) during stimulation. Median number of vitrified oocytes was 6 in low-grade disease patients and 7 in high-grade disease patients (p = 0.35)., Conclusions: Stage and grade of breast cancer do not impact the number of retrieved mature oocytes. However, higher grade of breast cancer is associated with lower AFC at baseline and need for higher doses of gonadotropin during ovarian stimulation., Competing Interests: Declaration of Competing of interest None declared., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objective: COVID-19 is a global public health emergency. The increasing spread of COVID-19 presents challenges for the clinical care of patients with gynecological tumors. The Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) performed a survey to evaluate the impact of the COVID-19 pandemic on medical treatment of gynecological cancer, with a focus on chemotherapy and oral treatment with poly(ADP)-ribose polymerase inhibitors (PARP-i)., Methods: The survey consisted of a self-administered online questionnaire, sent via email between November 2020 and January 2021 to all members of MITO group., Results: Forty-nine centers completed the questionnaire. The majority of respondents (83%) use screening tests to determine COVID-19 status in patients who were to undergo chemotherapy or oral medications. All respondents to our survey continued cancer therapy in patients who tested negative for COVID-19 during the pandemic. Seventy-three percent of respondents declared they stopped treatment with chemotherapy or PARP-i only after a positive swab and resumed therapy when negative tests were confirmed., Conclusions: COVID-19 positivity impacted patterns of treatment in patients diagnosed with ovarian cancer within the MITO group. Further investigations are needed to evaluate whether these modifications influence oncological clinical outcomes., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To report mode of delivery and immediate neonatal outcome in women infected with COVID-19.Design: Retrospective study.Setting: Twelve hospitals in northern Italy.Participants: Pregnant women with COVID-19-confirmed infection who delivered.Exposure: COVID 19 infection in pregnancy.Methods: SARS-CoV-2-infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co-morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding.Main Outcome and Measures: Data on mode of delivery and neonatal outcome.Results: In all, 42 women with COVID-19 delivered at the participating centres; 24 (57.1%, 95% CI 41.0-72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7-59.0) cases: in eight cases the indication was unrelated to COVID-19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8-61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3-61.6) required oxygen support and 4/19 (21.1%, 95% CI 6.1-45.6) were admitted to a critical care unit. Two women with COVID-19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS-Cov-2 infection. In one case, a newborn had a positive test after a vaginal operative delivery.Conclusions: Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn.Tweetable Abstract: This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to analyze the oncological outcome of stage I malignant ovarian germ cell tumors patients included in the MITO-9 study to identify those who might be recommended routine surveillance alone after complete surgical staging., Methods: MITO-9 was a prospective observational study analyzing data collected between January 2013 and December 2019. Three groups were identified: group A included 13 patients stage IA dysgerminoma and IAG1 immature teratoma; group B included 29 patients with stage IB-C dysgerminomas, IA-C G2-G3 immature teratomas and stage IA mixed malignant ovarian germ cell tumors and yolk sac tumors; and group C included five patients (two patients with stage IC1 and one patient with stage IC2 yolk sac tumors and two patients with mixed-stage IC2 malignant ovarian germ cell tumors)., Results: A total of 47 patients with stage I conservatively treated malignant ovarian germ cell tumors were analyzed. Two patients in group B were excluded from the routine surveillance alone group due to positive surgical restaging. Therefore, a total of 45 patients were included in the study. Median follow-up was 46.2 months (range; 6-83). In total, 14 of 45 patients (31.1%) received chemotherapy, while 31 (68.9%%) underwent surveillance alone. One patient in group A, with stage IA dysgerminoma had a relapse, successfully managed with conservative surgery and chemotherapy. None of the patients in group B and C relapsed. All patients were alive at completion of the study. Overall, among 31 patients (68.9%) who underwent surveillance alone, only one patient relapsed but was treated successfully., Conclusions: Our data showed that close surveillance alone could be an alternative option to avoid adjuvant chemotherapy in properly staged IB-C dysgerminomas, IA-IC G2-G3 immature teratomas, and IA mixed malignant ovarian germ cell tumors with yolk sac tumor component., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Juvenile type granulosa cell tumor (JGCTs) are extremely rare, mainly diagnosed in young women and pre-pubertal girls at stage I disease. Literature is scanty and guidelines regarding the optimal management are still controversial. The aim of this study is to add on the experience of the MITO group (Multicenter Italian Trials in Ovarian Cancer)., Methods: Clinicopathological data from patients with stage I JGCTs were retrospectively collected. Descriptive statistics were used to characterize the patient population. Clinicopathological features and treatment variables were evaluated for association with relapse., Results: Seventeen patients were identified. Surgical approach was laparoscopic and open for 7 (41%) and 10 (59%) patients, respectively. Fertility sparing surgery (FSS) was performed in 15 patients (88%): unilateral salpingo-oophorectomy (USO) in 11 patients, cystectomy with subsequent USO in 2 patients and cystectomy alone in the remaining 2. Adjuvant chemotherapy was given in 2 cases. After a median follow up time of 80 months, no recurrences were registered., Conclusions: Given the available data, minimally invasive surgery is safe in stage I JGCTs. Because of the good prognosis and of the young age of patients, FSS can be chosen in most of the cases. The role of cystectomy deserves further validation. The need of adjuvant chemotherapy in stage I disease is still unclear, even if available data does not seem to support treatment over surveillance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: To evaluate oncological and reproductive outcomes of women undergoing fertility-sparing surgery (FSS) for stage II-III serous borderline ovarian tumors (BOTs)., Methods: A multi-institutional retrospective study was conducted within the MITO Group., Results: A total of 91 patients were recruited. The median follow-up time from primary cytoreduction was 127 months (IQR range 91-179). Forty-nine patients (53.8%) experienced at least one recurrence (median time to first relapse 22 months, IQR range 9.5-57). At univariable analysis, significant predictors of relapse were: size of largest extra-ovarian lesion, peritoneal cancer index, completeness of cytoreduction, type of implants. After multivariable analysis, the size of extra-ovarian lesions and the presence of invasive implants resulted as the only independent predictors of recurrence. Median disease-free survival (DFS) was 96 months (95% CI, 24.6-167.3), while median disease-specific survival (DSS) was not reached. Twenty-nine patients (31.8%) attempted to conceive: 20 (68.9%) achieved at least one pregnancy and 18 (62%) gave birth to a healthy child. At the end of the observation period, 88 patients (96.7%) showed no evidence of disease, 2 (2.2%) were alive with disease, and 1 patient (1.1%) died from BOT., Conclusions: Despite the recurrence high rate, FSS provides good chances of reproductive success with no impact on DSS. The presence of invasive peritoneal implants affects the DFS but not DSS nor reproductive outcome. The risk of recurrence would not seem to be related to the ovarian preservation per se, but to the natural history of the initial peritoneal spread., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Ovarian cancer is the most lethal gynecologic malignancy. Over 5200 new cases of this tumor are diagnosed yearly in Italy, resulting in more than 3600 deaths. In terms of molecular biology, five different ovarian cancer subtypes should be distinguished., Method: This article summarizes the evidence-based guidelines that the Italian Medical Oncology Association (AIOM) has developed with a multidisciplinary panel of experts, including pathologists, gynecologic oncologists, medical oncologists, and radiotherapists, with the support of methodologists, to help clinicians involved in the management of patients with ovarian cancer in their daily clinical practice., Results: The most relevant randomized clinical trials regarding surgery, chemotherapy, and molecularly targeted agents (bevacizumab and PARP inhibitors) in early, advanced, and recurrent disease have been critically analyzed. The levels of evidence and strength of recommendation have been reported for any issue., Conclusion: Women with a clinical suspicion of ovarian cancer should be centralized in referral centers. The BRCA test should be requested for all women with nonmucinous and nonborderline tumors, regardless of age and family history. BRCA testing could be preferentially performed on neoplastic tissue. In the presence of a positive tumor test, a genetic test should always be performed on a blood sample to differentiate between germline mutations, which require counseling and genetic testing of family members, and somatic mutations.

Importance: The management of mother-infant dyads during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic constitutes a major issue for neonatologists. In mothers with SARS-CoV-2 infection, current recommendations suggest either to separate the dyad or encourage protected rooming-in under appropriate precautions. No data are available regarding the risk of mother-to-infant transmission of SARS-CoV-2 during rooming-in., Objective: To evaluate the risk of postnatal transmission of SARS-CoV-2 from infected mothers to their neonates following rooming-in and breastfeeding., Design, Setting, and Participants: A prospective, multicenter study enrolling mother-infant dyads from March 19 to May 2, 2020, followed up for 20 days of life (range, 18-22 days), was performed. The study was conducted at 6 coronavirus disease 2019 maternity centers in Lombardy, Northern Italy. Participants included 62 neonates born to 61 mothers with SARS-CoV-2 infection who were eligible for rooming-in practice based on the clinical condition of the mother and infants whose results of nasopharyngeal swabs were negative at birth., Exposures: Mothers with SARS-CoV-2 infection were encouraged to practice rooming-in and breastfeeding under a standardized protocol to minimize the risk of viral transmission., Main Outcomes and Measures: Clinical characteristics and real-time reverse transcriptase-polymerase chain reaction for SARS-CoV-2 on neonatal nasopharyngeal swabs at 0, 7, and 20 days of life., Results: Of the 62 neonates enrolled (25 boys), born to 61 mothers (median age, 32 years; interquartile range, 28-36 years), only 1 infant (1.6%; 95% CI, 0%-8.7%) was diagnosed as having SARS-CoV-2 infection at postbirth checks. In that case, rooming-in was interrupted on day 5 of life because of severe worsening of the mother's clinical condition. The neonate became positive for the virus on day 7 of life and developed transient mild dyspnea. Ninety-five percent of the neonates enrolled were breastfed., Conclusions and Relevance: The findings of this cohort study provide evidence-based information on the management of mother-infant dyads in case of SARS-CoV-2 maternal infection suggesting that rooming-in and breastfeeding can be practiced in women who are able to care for their infants.

Objective: To report mode of delivery and immediate neonatal outcome in women infected with COVID-19., Design: Retrospective study., Setting: Twelve hospitals in northern Italy., Participants: Pregnant women with COVID-19-confirmed infection who delivered., Exposure: COVID 19 infection in pregnancy., Methods: SARS-CoV-2-infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co-morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding., Main Outcome and Measures: Data on mode of delivery and neonatal outcome., Results: In all, 42 women with COVID-19 delivered at the participating centres; 24 (57.1%, 95% CI 41.0-72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7-59.0) cases: in eight cases the indication was unrelated to COVID-19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8-61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3-61.6) required oxygen support and 4/19 (21.1%, 95% CI 6.1-45.6) were admitted to a critical care unit. Two women with COVID-19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS-Cov-2 infection. In one case, a newborn had a positive test after a vaginal operative delivery., Conclusions: Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn., Tweetable Abstract: This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn., (© 2020 Royal College of Obstetricians and Gynaecologists.)

Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved as maintenance therapy of recurrent ovarian cancer (OC) patients with a BRCA mutation. To achieve the maximum clinical benefit, adherence to olaparib must be persistent. However, in clinical practice, this is challenged by the frequent suboptimal management of toxicities. In view of the expanding use of olaparib also in Italy, physicians must learn how to adequately and promptly manage drug toxicities not to unnecessarily interrupt or reduce the dose. The experts agreed that nausea,vomiting, anemia, and fatigue are the most frequent events experienced by OC patients on olaparib, and that these toxicities usually develop early during treatment, are mainly of grade 1-2 and transient and can be managed with simple non-pharmacological interventions. By sharing their real-world experiences, the panel prepared, for each toxicity, an algorithm organized by grade and besides the procedures indicated in the local label, included supportive care interventions based also on nutritional and lifestyle modifications and psycho-oncology consultation. Moreover, in view of the tablet entry into the Italian market, the full and reduced dosages of capsules and tablets were compared. This practical guidance is intended to be a tool to support especially less-experienced physicians in the management of these complex patients, with the aim to help preventing the worsening of patients' conditions and the unnecessary interruption/reduction of olaparib dosage, which may jeopardize treatment efficacy.

Objective: Borderline ovarian tumours (BOTs) are characterized by the presence of cellular proliferation and nuclear atypia without stromal invasion. Compared to malignant ovarian tumours, BOTs have better prognoses. The most important treatment of BOT is surgery. Considering the good prognosis of BOT, fertility-sparing surgery (FSS) can be considered for young women who desire to preserve fertility. Our study evaluated the pregnancy rate in patients with childbearing desire, the efficacy and risk of recurrence of women affected by BOTs who have undergone FSS., Materials and Methods: Patients characteristics have been restrospectively retrieved for diagnosis made from June 2000 to December 2017 from San Raffaele Hospital and Policlinico Cagliari. Patients underwent FSS for BOT were interviewed about child wishing and pregnancy outcomes., Results: 85 patients were recruited for the study. Median age at diagnosis was 33 years. Unilateral salpingo-oophorectomy was performed in 33 patients (38%), unilateral cystectomy in 40 (47%) and 12 underwent both procedures (14%). 40 women (50%) tried to conceive after surgery. The pregnancy rate was 73% and live birth rate was 67%. Childbearing desire and age at diagnosis were significantly associated with the pregnancy rate., Conclusions: Conservative surgical treatment seems to be a reasonable therapeutic option for women with BOTs who wish to preserve fertility. Our results suggest that the obstetric outcomes after FSS are promising. Maternal desire and the age of diagnosis are the most important factors affecting PR after surgery. Fertility counselling should be an integral part of the clinical management of women with BOT., Competing Interests: Declaration of competing interest Authors declare that they have no conflict of interest., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: To investigate survival outcomes in endometrioid endometrial cancer (EEC) patients with single vs. multiple positive pelvic lymph nodes., Methods: We performed a retrospective evaluation of all consecutive patients with histologically proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1 EEC who underwent primary surgical treatment between 2004 and 2014 at seven Italian gynecologic oncology referral centers. Patients with pre- or intra-operative evidence of extra-uterine disease (including the presence of bulky nodes) and patients with stage IIIC2 disease were excluded, in order to obtain a homogeneous population., Results: Overall 140 patients met the inclusion criteria. The presence of >1 metastatic pelvic node was significantly associated with an increased risk of recurrence and mortality, compared to only 1 metastatic node, at both univariate (recurrence: hazard ratio [HR]=2.19; 95% confidence interval [CI]=1.2-3.99; p=0.01; mortality: HR=2.8; 95% CI=1.24-6.29; p=0.01) and multivariable analysis (recurrence: HR=1.91; 95% CI=1.02-3.56; p=0.04; mortality: HR=2.62; 95% CI=1.13-6.05; p=0.02) and it was the only independent predictor of prognosis in this subset of patients. Disease-free survival (DFS) and disease-specific survival (DSS) were significantly longer in patients with only 1 metastatic node compared to those with more than 1 metastatic node (p=0.008 and 0.009, respectively)., Conclusion: The presence of multiple metastatic nodes in stage IIIC1 EEC represents an independent predictor of worse survival, compared to only one positive node. Our data suggest that EEC patients may be categorized according to the number of positive nodes., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

About 2.7% of patients epithelial ovarian cancers (EOC) are younger than 40 and present with stage I disease. For this subset of women, the issue of fertility sparing surgery (FSS) has become critical. The aim of this survey was to investigate the management of EOC patients desiring to preserve fertility in Italy. A questionnaire consisting of 30 items was developed to evaluate: patient-selection criteria, rate of FSS, patient's counseling- and pregnancy-timing, fertility preservation, obstetrics, and oncologic outcomes. One expert clinician for each of 50 major gynecologic oncology centers was invited to participate. Data were entered into a database and statistically analyzed. 74% of questionnaires were complete. The proportion of EOC patients treated with FSS was <10%, 10%-20% and >20% in 70.3%, 24.3% and 5.4% of cases, respectively. Age, fertility preservation desire, histotype, and stage were considered relevant to select patients for a conservative treatment for 64.8%, 72.9%, and 78.3% of responders, respectively. Only 17 centers (45.9%) resulted to have an assisted reproductive technique service and Obstetrics Department. Our survey highlights discrepancies among oncologists in the management of patients with early EOC undergoing FSS. More efforts should be made to define and broadcast the best management before and after surgery.

Objectives: Gestational trophoblastic neoplasia affects women of reproductive age and is usually treated by chemotherapy. Major concerns related to chemotherapy in young women are the possible infertility, risk of early menopause, and teratogenic effects on subsequent pregnancies. The study's aim was to analyze menstrual and reproductive outcomes of women treated with single-agent versus multiagent chemotherapy for gestational trophoblastic neoplasia., Methods: One-hundred fifty-one patients were treated. Seventy-six patients older than 45 years, with a placental site or epithelioid trophoblastic tumor, undergoing hysterectomy for patient choice, or undergoing human chorionic gonadotropin follow-up at the time of the analysis were excluded. Seventy-five patients were divided into subgroups according to International Federation of Gynecology and Obstetrics score: patients scoring less than 7, receiving single-agent chemotherapy (group A, n = 42); patients scoring 7 or greater, receiving combination treatment (group B, n = 33). Patients' outcomes were compared by univariate and multivariate analyses., Results: Temporary amenorrhea occurred in 33% of group A patients and 66.7% of group B (P = 0.01). Premature menopause occurred in 3 patients in group B (0% vs 9%, P = 0.02). Ten patients in group B underwent salvage hysterectomy. Pregnancy desire did not differ between the 2 groups (P = 0.555). In group A, 57.1% became pregnant; in group B, 36.4% did (P = 0.060). Instead, pregnancy rate was 52.2% among high-risk patients not undergoing hysterectomy (57.1% vs 52.2%, P = 0.449). There was no difference in miscarriage (P = 0.479) and premature birth (P = 0.615) rates. In a multivariate analysis that included age, International Federation of Gynecology and Obstetrics score, chemotherapy type, use of assisted reproductive technologies, previous pregnancies, and pregnancy desire, only age (P = 0.006) and pregnancy desire (P = 0.002) had a significant impact on the probability to have subsequent pregnancies., Conclusions: Except for the risk of premature ovarian failure, a rare adverse effect of combined treatments, both single-agent and multiagent chemotherapy can be safely administered to patients with a desire for childbearing. High-risk patients have worse reproductive outcomes because they undergo hysterectomy more frequently than low-risk patients.

Introduction: Being able to have children could have an important positive effect on the future lives of pediatric cancer survivors. Working at a cancer institute makes us responsible for filling the gaps in our knowledge in this area of patient care., Methods: We describe our activities in a series of young females diagnosed with cancer and evaluated for fertility preservation options. We discuss the developed skills and organization as well as the practical difficulties encountered in managing fertility preservation., Results: Since September 2012, laparoscopy and cryopreservation of cortical ovarian tissue has been performed in 16 girls (with ovary transposition in 3, and after several cycles of chemotherapy in 5) and egg banking in 4 young women (before chemotherapy in 2 and several years after treatment in 2)., Conclusions: Recommendations on fertility preservation indicate that discussing the problems early on is crucial to future success. It is unthinkable to simply provide information and offer the opportunity to choose a fertility preserving technique without helping and accompanying patients and their families in their decisions and choices on the matter.

Objective: To analyze temporal trends of hospital admissions due to molar pregnancies in Italian and non-Italian women in Lombardy during the 1996-2008 period., Methods: A standard form is used to register all discharges from public or private hospitals in Lombardy. Hydatidiform mole (HM) cases were identified when searching the database for code 630 of the International Classification of Diseases, Ninth Revision (ICD-9). Ratios of HM per 100,000 pregnancies in strata of age and nationality were computed., Results: The estimated frequency of HM in Lombardy over the period 1996-2008 was 104.4 per 100,000 pregnancies (SE, 2.8) or 1 case in 935 pregnancies. The frequency of HM tended to decrease in the late 1990s, the crude ratio per 100,000 pregnancies being 127.3 in 1996, 89.3 in 2000, and 113.1 in 2008. The temporal trend analysis, adjusted for age class and geographical origin, showed a significant decrease (P = 0.025). The frequency of HM was 99.8/100,000 pregnancies among Italian women, 112.1/100,000 pregnancies among women from other European countries, 85.1/100,000 pregnancies among women from Africa, 176.9/100,000 pregnancies from South America, and 163.0/100,000 pregnancies among Asian women. Considering the periods 1996-2001 and 2002-2008 separately, the frequency of HMs was largely similar for all groups, except in Asian women: in this group, the frequency of HMs was 242.7/100,000 pregnancies and 120.1/100,000 pregnancies in 1996-2001 and 2002-2008, respectively., Conclusion: Between 1996 and 2008, the HM incidence in Lombardy showed a slight but significant decrease, mostly owing to the decrease of HM incidence among Asian women.

Aims: This study aimed to investigate the outcome of patients with malignant ovarian germ cell tumors (MOGCTs) and to define the risk factors for recurrence., Methods: A total of 123 patients with MOGCTs were retrospectively reviewed among MITO centers. Eighty-one patients had primary treatment in a MITO center, whereas the other 42 were referred for adjuvant chemotherapy or recurrence. The clinicopathologic characteristics were evaluated for association with relapse or death., Results: Median age was 24 years (range, 11-76 years). Forty-nine (39.8%) had dysgerminomas, 35 (28.5%) had immature teratomas, 12 (9.8%) had mixed germ cell tumors, 26 (21.1%) had yolk sac tumors, and 1 (0.8%) had embryonal carcinoma. International Federation of Gynecology and Obstetrics stage distribution was as follows: stage I, 87 (70.7%); stage II, 3 (2.4%); stage III, 29 (23.6%); and stage IV, 4 (3.3%). Fertility-sparing surgery was performed in 92 patients, whereas the remaining 31 received radical surgery; 65.8% of patients received adjuvant chemotherapy. Recurrence rate was 17.8% and the median time to recurrence was 9 months. Univariate and multivariate analyses showed that patient age (>45 years) and treatment outside a referral (MITO) center were the most important predictors of recurrence. The 5-year overall survival rate was 88.8%, with a median follow-up of 61 months. Univariate and multivariate analyses demonstrated that stage greater than I and yolk sac tumors were independent poor prognostic indicators., Conclusions: This study confirms that MOGCTs have excellent prognosis, with 5-year overall survival rates of 95.6% and 73.2% in stage I and advanced stages, respectively. Age older than 45 years and treatment not in a referral center are independent risk factors for recurrence, whereas stage greater than I and yolk sac histology are independent poor prognostic indicators.

Objective: This study was undertaken to evaluate whether the current clinical presentation of hydatidiform mole changed in the recent years compared with an historic group., Study Design: We retrieved 500 patients from our database. We compared the clinical presentation of 189 cases followed-up between 1992-2004 ("later" group) with that of a previous series of 311 patients ("earlier" group, 1970-1982). A Pearson chi2 test was performed analyzing the following variables: uterine volume, ovarian cysts, vaginal bleeding, hyperemesis, preeclampsia, and maternal age; we considered P < .05 to be significant., Results: Uterine volume corrected for gestational age (P < .0001), vaginal bleeding (P < .0001) and presence of ovarian cysts (P = .03) were significantly predominant in the "earlier" group, whereas the incidence of preeclampsia and hyperemesis were not significantly different., Conclusions: The depiction of increased uterine volume, ovarian theca lutein cysts, and vaginal bleeding in hydatidiform mole at presentation is significantly less frequent since the extensive dissemination of ultrasound in obstetrics.

Clinical reports suggested that the use of oral contraceptives (OC) after a molar pregnancy may increase the risk of persistent throphoblastic disease. However, few epidemiologic studies have analyzed the effect of OC use on the risk of developing gestational trophoblastic disease (GTD). To give further information, we have analyzed data from a case-control study on risk factors for GTD. Cases were 268 women with a histologically confirmed diagnosis of complete or partial mole referred to the participating Trophoblastic Disease Centers. A total of 268 subjects were interviewed; 79 cases were classified as partial and 159 as complete mole. Controls were randomly selected women who gave birth to healthy infants at term on randomly selected days in the same network of hospitals in which cases had been identified. A total of 104 cases and 130 controls reported ever OC use, and the corresponding odds ratio (OR) was 1.5 (95% CI, 1.1-2.1). The risk of GTD increases with duration of OC use: the OR was 1.7 (95% CI 1.2-2.6) for ever-users reporting >or=12 months of use. No consistent pattern of risk was observed with time since last OC use. We have analyzed separately the association between OC use and risk of complete and partial moles: no statistically significant difference emerged, but the OR for partial moles was higher (OR 3.0, 95% CI 1.6-8.4) than for complete mole (OR 1.0, 95% CI 1.8). In conclusion, we observed a weak association between OC use and GTD; such a weak association could be explained by factors other than causality.

Objectives: To verify the importance of DNA ploidy on clinical outcome in endometrial carcinoma and to investigate whether the prognostic information obtained by this variable is independent from other clinical-pathologic features., Materials and Methods: Univariate and multivariate analysis of clinical and pathologic prognostic factors obtained from 203 consecutive cases of endometrial cancer, that had been surgically treated in our hospital, were performed., Results: Significant prognostic factors according to the Kaplan-Meier method were age at the time of diagnosis, grade of differentiation, peritoneal cytology, node involvement, vascular invasion, myometrial infiltration and ploidy. At multivariate analysis only DNA ploidy resulted to be an independent variable., Conclusions: In our analysis DNA content is the only parameter which preserved prognostic significance in multivariate analysis.

The risk of gestational trophoblastic disease in relation to frequency of consumption of selected dietary items was evaluated with data from a case-control study conducted in Northern Italy on 148 women with histologically confirmed gestational trophoblastic disease and two control groups, one consisting of 372 obstetric control subjects and one consisting of 406 patients in the hospital for acute, nonobstetric, nongynecologic conditions. Patients with gestational trophoblastic disease tended to consume several foods less frequently, including the major sources of vitamin A and animal protein in the Italian diet. Relative risk estimates were significantly below unity in both control groups for green vegetable, carrot, liver, and cheese consumption and in the obstetric control group only for milk, meat, eggs, fresh fruit, and fish. Inverse relationships emerged between the risk of gestational trophoblastic disease and beta-carotene or retinol intake index. The trend of decreasing risk with increasing intake was significant for beta-carotene consumption. The present findings confirm that various aspects of diet may influence the risk of gestational trophoblastic disease. However, the limitation of available evidence still introduces serious uncertainties in the interpretation of these findings and suggests the potential importance of further epidemiologic and biochemical research to obtain more precise definition of specific dietary correlates of gestational trophoblastic disease.

Background: Lately, one of the major clinical and public health issues has been represented by Coronavirus disease of 2019 (COVID-19) during pregnancy and the risk of transmission of the infection from mother to child. Debate on perinatal management and postnatal care is still ongoing, principally questioning the option of the joint management of mother and child after birth and the safety of breastfeeding. According to the available reports, neonatal COVID-19 appears to have a horizontal transmission and seems to be paucisymptomatic or asymptomatic, compared to older age groups. The aim of this work is to describe a cluster of neonatal COVID-19 and discuss our experience, with reference to current evidence on postnatal care and perinatal management. Methods: This is a retrospective observational case series of five mother-child dyads, who attended the Labor and Delivery Unit of a first-level hospital in Italy, in March 2020. Descriptive statistics for continuous variables consisted of number of observations, mean and the range of the minimum and maximum values. Results: Five women and four neonates tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In one case, the mother-child dyad was separated and the neonate remained negative on two consecutive tests. Two positive neonates developed symptoms, with a predominant involvement of the gastrointestinal tract. Blood tests were unremarkable, except for a single patient who developed mild neutropenia. No complications occurred. Conclusions: We agree that the decision on whether or not to separate a positive/suspected mother from her child should be made on an individual basis, taking into account the parent's will, clinical condition, hospital logistics and the local epidemiological situation. In conformity with literature, in our study, affected neonates were asymptomatic or paucisymptomatic. Despite these reassuring findings, a few cases of severe presentation in the neonatal population have been reported. Therefore, we agree on encouraging clinicians to monitor the neonates with a suspected or confirmed infection. [ABSTRACT FROM AUTHOR]

Grotta Patrizi (Cerveteri, Roma, Lazio) discovered by Patrizi in 1933 is a vast karst network. Excavation by Radmilli revealed an individual burial reliably attributed to the Ceramica a Linee Incise group that contributed to the Neolithization of central and Tyrrhenian Italy around 5000 cal BC. The remains of the individual bore signs of numerous pathological conditions and of trepanation. Expanding on previous studies, a stereomicroscopic examination of the trepanation site suggests new interpretations of the bone changes. This latest analysis confirms the hypothesis that the individual survived an initial complete trepanation, and it specifies the nature and form of the operator's hand movements. A repeat intervention was apparently made during the perimortem period. It can be hypothesized that this intervention was performed after the death of the individual and possibly on the severed head of the deceased, as an integral part of the funerary treatment. If so, this would be the earliest evidence of the practice of ritual trepanation in this chrono‐cultural context. [ABSTRACT FROM AUTHOR]

Objectives: Several studies have investigated the correlation between endometriosis and adverse pregnancy and perinatal outcomes. However, the role of adenomyosis as a risk factor for adverse perinatal outcome in women with endometriosis has yet to be established. The aim of this study was to explore if fetal and maternal outcomes, in particular the incidence of a small-for-gestational-age (SGA) infant, are different in pregnant women with endometriosis only from in those with the concomitant presence of diffuse or focal adenomyosis.Methods: This was a retrospective analysis of data collected prospectively during a 3-year period. We included 206 pregnant women with endometriosis: 148 (71.8%) with endometriosis only, 38 (18.4%) with focal adenomyosis and 20 (9.7%) with diffuse adenomyosis. Adenomyosis was diagnosed using ultrasonography and was classified as focal or diffuse. The study included patients who conceived spontaneously or by an assisted reproductive technique. Demographics, ultrasound variables and outcome were compared between women with endometriosis only and those with diffuse and those with focal adenomyosis. Logistic regression analysis was performed to assess the association of variables with SGA at birth in women with diffuse and those with focal adenomyosis.Results: The three groups were similar in demographic characteristics (age, body mass index, mode of conception). Patients with diffuse adenomyosis compared with those with endometriosis only had significantly lower pregnancy-associated plasma protein A (0.61 vs 0.88 multiple of the median, P < 0.001), higher mean uterine artery pulsatility index in the first (2.23 vs 1.67, P < 0.001) and second (1.30 vs 0.94, P < 0.001) trimesters of pregnancy, and higher incidence of SGA (40% vs 10.8%, P < 0.001). No statistically significant differences were found in patients with focal adenomyosis compared with those with endometriosis only. Logistic regression analysis demonstrated that diffuse adenomyosis (odds ratio = 3.744; 95% CI, 1.158-12.099; P = 0.027) was the only independent risk factor for SGA.Conclusions: The presence of diffuse adenomyosis in pregnant women with endometriosis is strongly associated with delivery of a SGA infant. Women with diffuse adenomyosis should be treated as being at high risk of placental dysfunction, and these pregnancies might therefore need closer monitoring. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical and ultrasound characteristics of three types of rare malignant ovarian germ cell tumor: embryonal carcinoma, non-gestational choriocarcinoma and malignant mixed germ cell tumor., Methods: This was a retrospective multicenter study. From the International Ovarian Tumor Analysis (IOTA) database, we identified patients with a histological diagnosis of ovarian embryonal carcinoma, non-gestational choriocarcinoma or malignant mixed germ cell tumor, who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 2000 and 2020. Additional patients with the same histology were identified from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. Three examiners reviewed all available ultrasound images and described them using pattern recognition., Results: One patient with embryonal carcinoma, five patients with non-gestational ovarian choriocarcinoma and seven patients with ovarian malignant mixed germ cell tumor (six primary tumors and one recurrence) were identified. Seven patients were included in the IOTA studies and six patients were examined outside of the IOTA studies. The median age at diagnosis was 26 (range, 14-77) years. Beta-human chorionic gonadotropin levels were highest in non-gestational choriocarcinomas and alpha-fetoprotein levels were highest in malignant mixed germ cell tumors. Most tumors were International Federation of Gynecology and Obstetrics (FIGO) Stage I (9/12 (75.0%)). All tumors were unilateral, and the median largest diameter was 129 (range, 38-216) mm. Of the tumors, 11/13 (84.6%) were solid and 2/13 (15.4%) were multilocular-solid; 9/13 (69.2%) manifested abundant vascularization on color Doppler examination. Using pattern recognition, the typical ultrasound appearance was a large solid tumor with inhomogeneous echogenicity of the solid tissue and often dispersed cysts which, in most cases, were small and irregular. Some tumors had smooth contours while others had irregular contours., Conclusions: A unilateral, large solid tumor with inhomogeneous echogenicity of the solid tissue and with dispersed small cystic areas in a young woman should raise the suspicion of a rare malignant germ cell tumor. This suspicion can guide the clinician to test tumor markers specific for malignant germ cell tumors. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To investigate the relationships between mortality of infants <32 weeks gestation and neonatal intensive care units' (NICUs) volume of activity, daily number of high-dependent infants (HDIs) and geographical area in Italy. Methods: The study involved 105 neonatal units in 2005. Data were collected prospectically and through monthly cross-sectional investigations. Patients receiving respiratory care were defined as HDIs. Univariate and multivariable methods were used for analysis. Results: Babies enrolled were 4014. The overall mortality was 18.8%. An adjusted nearly two-fold increase in mortality was found in Southern compared to Northern regions. Volume of activity was not associated with mortality. When compared to infants admitted to NICUs in the highest tertile of the median number of HDIs/day (>2.5 patients/day), the adjusted odds ratios were 1.52 (95% CI = 1.14-2.02) for those in the 2nd tertile (1.1-2.5 patients/day) and 1.47 (95% CI = 1.02-2.13) for those in the lowest tertile (≤1 patient/day). After stratification by geographical area, this relationship was present in Southern, to a lesser extent in Central, but not in Northern regions. Conclusions: In Italy, striking geographical differences in mortality of very preterm infants are present. NICUs' average daily number of HDIs is a better predictor of mortality than the volume of activity. [ABSTRACT FROM AUTHOR]

Simple Summary: The development of hypersensitivity reactions to platinum agents in patients with gynecological cancers limits the use of platinum re-treatment for recurrent disease. In those patients who developed a hypersensitivity reactions during treatment with platinum agents it could be safer to undergo allergy diagnosis. This approach includes the in-vivo skin tests before re-exposure to the platinum agent, especially in those patients who have to undergo a 2nd or 3rd line therapy. In our experience, skin test for platinum agents resulted in a simple and sensitive tool for the diagnosis and prevention of hypersensitivity reactions to platinum agents. In addition, this approach identified a sub-group of patients that became sensitized to the platinum agent during the previous platinum-based therapy. Background: Hypersensitivity reactions (HSR)s to platinum agents are increasing in frequency, due to their extensive use and repeated exposures in patients with increased life expectancy. The aims of our study are to analyze the frequency of both type I and type IV HSRs in patients with gynecological cancer treated with (CBDCA) carboplatin and/or (CDDP) cisplatin, to evaluate the role of skin tests in the diagnosis and prevention of HSRs. Methods: From 2011 to 2018, we evaluated 124 consecutive female patients previously treated with CBDCA and/or CDDP for gynecological cancer. All patients, including those with and without HSR to previous platinum-based therapy, underwent in-vivo skin tests for platinum agents before starting the second or more therapeutic lines. To reduce the risk of false negative results, patients with a negative skin test at the first evaluation were re-tested after 3 weeks from the platinum re-exposure. Results: Among the 124 patients evaluated, 58 (47%) experienced HSRs to at least one platinum agent: 35% were to CBDCA, 5% to CDDP, 7% to both. Fifty-six of the 58 HSRs were classified as immediate and two delayed. Skin tests confirmed an IgE-dependent mechanism in 67% of patients with immediate-HSRs to CBDCA and identified a cross-reactivity between platinum agents in 18% of patients. Moreover, among those who had never developed an HSRs during platinum-based therapy, in-vivo skin tests identified 12% of sensitized patients. Conclusions: On the basis of our findings, skin test for platinum agents is a simple and sensitive tool for the diagnosis and prevention of HSRs to CBDCA and/or CDDP and can be useful for detecting possible cross-reactivity among platinum agents. [ABSTRACT FROM AUTHOR]