Reproductive and pregnancy outcomes of fertility-sparing treatments for early-stage endometrial cancer or atypical hyperplasia: A systematic review and meta-analysis

To report the pregnancy outcomes of women with prior endometrial cancer and endometrial hyperplasia managed with fertility-sparing treatments

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6+/-9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; pPeer reviewe

Role of prenatal magnetic resonance imaging in fetuses with isolated mild or moderate ventriculomegaly in the era of neurosonography: international multicenter study

Objectives To assess the role of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses presenting with mild or moderate isolated ventriculomegaly (VM) undergoing multiplanar ultrasound evaluation of the fetal brain. Methods This was a multicenter, retrospective, cohort study involving 15 referral fetal medicine centers in Italy, the UK and Spain. Inclusion criteria were fetuses affected by isolated mild (ventricular atrial diameter, 10.0–11.9 mm) or moderate (ventricular atrial diameter, 12.0–14.9 mm) VM on ultrasound, defined as VM with normal karyotype and no other additional central nervous system (CNS) or extra‐CNS anomalies on ultrasound, undergoing detailed assessment of the fetal brain using a multiplanar approach as suggested by the International Society of Ultrasound in Obstetrics and Gynecology guidelines for the fetal neurosonogram, followed by fetal MRI. The primary outcome of the study was to report the incidence of additional CNS anomalies detected exclusively on prenatal MRI and missed on ultrasound, while the secondary aim was to estimate the incidence of additional anomalies detected exclusively after birth and missed on prenatal imaging (ultrasound and MRI). Subgroup analysis according to gestational age at MRI (< 24 vs ≥ 24 weeks), laterality of VM (unilateral vs bilateral) and severity of dilatation (mild vs moderate VM) were also performed. Results Five hundred and fifty‐six fetuses with a prenatal diagnosis of isolated mild or moderate VM on ultrasound were included in the analysis. Additional structural anomalies were detected on prenatal MRI and missed on ultrasound in 5.4% (95% CI, 3.8–7.6%) of cases. When considering the type of anomaly, supratentorial intracranial hemorrhage was detected on MRI in 26.7% of fetuses, while polymicrogyria and lissencephaly were detected in 20.0% and 13.3% of cases, respectively. Hypoplasia of the corpus callosum was detected on MRI in 6.7% of cases, while dysgenesis was detected in 3.3%. Fetuses with an associated anomaly detected only on MRI were more likely to have moderate than mild VM (60.0% vs 17.7%; P < 0.001), while there was no significant difference in the proportion of cases with bilateral VM between the two groups (P = 0.2). Logistic regression analysis showed that lower maternal body mass index (adjusted odds ratio (aOR), 0.85 (95% CI, 0.7–0.99); P = 0.030), the presence of moderate VM (aOR, 5.8 (95% CI, 2.6–13.4); P < 0.001) and gestational age at MRI ≥ 24 weeks (aOR, 4.1 (95% CI, 1.1–15.3); P = 0.038) were associated independently with the probability of detecting an associated anomaly on MRI. Associated anomalies were detected exclusively at birth and missed on prenatal imaging in 3.8% of cases. Conclusions The incidence of an associated fetal anomaly missed on ultrasound and detected only on fetal MRI in fetuses with isolated mild or moderate VM undergoing neurosonography is lower than that reported previously. The large majority of these anomalies are difficult to detect on ultrasound. The findings from this study support the practice of MRI assessment in every fetus with a prenatal diagnosis of VM, although parents can be reassured of the low risk of an associated anomaly when VM is isolated on neurosonography

Analytic and Diagnostic Performances of Human Papillomavirus E6/E7 mRNA Test on up-to 11-Year-Old Liquid-Based Cervical Samples. A Biobank-Based Longitudinal Study

Human Papillomavirus (HPV) E6/E7 mRNA test demonstrated high specificity in detecting HPV infections, but studies assessing its efficacy in terms of cancer risk stratification are lacking. Follow-up studies are arduous and expensive. Biobank would be the answer to the problem, although data investigating the effects of long-term storage on RNA preservation are still needed. We addressed these issues by retrieving 202 residual liquid-based cervical specimens, collected from 149 women attending cervical cancer screening during the years 2001–2012. Samples were stored in Adriatic Biobank at room temperature and without any handing. After calculation of RNA yield and purity, E6/E7 mRNA test was retrospectively performed on each samples, to assess analytic and diagnostic performances. Using automated extraction procedures, RNA of good quantity and quality was obtained. The mean value of RNA concentration was 27.5 ng/μL. The mean A260/A280 ratio was 2.1. An invalid mRNA test result was found in 11.9% of the specimens. Neither RNA integrity, nor analytic performances of mRNA test were influenced by the year of sample collection. In total, 62.4% of the specimens tested as mRNA positive; among these, 89.2% were CIN2+. E6/E7 mRNA was detected in all Squamous Cervical Cancer (SCC) cases. Percentage of positive samples increased with the severity of histological diagnosis. mRNA testing, showing specificity and predictive values of 75.6% and 84.4%, respectively, significantly improved the corresponding values for DNA testing. Thus, the reflex mRNA test was demonstrated to be suitable to triage women with persistent cervical lesions. A “one sample for all” approach is possible, with practical benefits for Biobank-based long-term longitudinal studies, diseases prevention, prediction, diagnosis and treatment

Outcome of fetuses with congenital parvovirus B19 infection: systematic review and meta-analysis

OBJECTIVE: To explore the outcome of fetuses affected by congenital Parvovirus B19 (PB19) Infection. METHODS: The outcomes observed were: miscarriage, perinatal death (PND), intra-uterine death (IUD), neonatal death (NND), spontaneous resolution of hydrops or fetal anemia, intra-uterine transfusion (IUT), resolution of hydrops or anemia after transfusion, fetal loss following transfusion, abnormal brain scan after birth, abnormal neurodevelopmental outcome. All the observed outcomes were reported in fetuses presenting and in those not presenting signs of hydrops on ultrasound. A sub-group analysis was performed including hydropic and non-hydropic fetuses < and ≥ 20 weeks of gestation respectively. Meta-analyses of proportions and meta-analyses using individual data random-effect logistic regression were used to analyze the data. RESULTS: Thirty-seven observational studies (654 fetuses affected by PB19 infection) were included. The risk of miscarriage (OR: 11.5, 95% CI 2.7-49.7) and PND (OR: 4.2, 95% CI 1.6-11.0) was higher in fetuses affected by PB19 infection presenting compared to those not presenting with hydrops on ultrasound. In fetuses affected by hydrops, spontaneous resolution of the infection, defined as disappearance of hydrops without the need for IUT, occurred in 5.2% (95% CI 2.5-8.8) of cases, while in the group of fetuses not affected by hydrops, resolution occurred in 49.6% (95% CI 20.7-78.6) of cases. IUT was performed in 78.7% (95% CI 66.4-88.8) of hydropic and in 29.6% (95% CI 6.0-61.6) of non-hydropic fetuses affected by congenital PB19 infection and resolution of the infection after IUT occurred in 55.1% (95% CI 34.0-75.3) of fetuses presenting and in 100% (95% CI 57.3-100) of cases not presenting signs of hydrops on ultrasound. The risk of fetal loss after IUT was higher in fetuses affected compared to those not affected by hydrops (OR: 9.8 (95% CI 2.8-34.6). Assessment of neurodevelopmental outcome was affected by the very small number of included cases, thereby precluding the achievement of adequate statistical power. The prevalence of abnormal brain imaging was 9.8% (95% CI 2.5-21.0) in fetuses affected and 0.0% (95% CI 0.0-7.0) in those not affected by hydrops, while the corresponding figures for abnormal neurodevelopmental outcome was 9.5% (95% CI2.6-20.2) and 0.0% (95% 0.0-0.8). CONCLUSION: Hydrops is the main determinant of mortality and adverse perinatal outcome in fetuses affected by PB19 infection. Perinatal outcome in non-hydropic fetuses is generally favorable

Diagnostic accuracy of first-trimester ultrasound in detecting abnormally invasive placenta in high-risk women with placenta previa

OBJECTIVES: To ascertain the diagnostic accuracy of ultrasound in detecting AIP during the first trimester (11-14 weeks of gestation) of pregnancy in women at risk of these conditions. METHODS: Retrospective analysis on prospectively collected data on women at risk for AIP based upon the presence of at least one prior CS and/or uterine surgery and placenta previa who had an ultrasound assessment for AIP since the 11-14 weeks scan. The ultrasound signs explored in the present study were: loss of clear zone, placental lacunae, bladder wall interruption, uterovescical hypervascularity. The potential of ultrasound and different ultrasound signs to predict the different types of AIP was assessed computing the summary estimates of sensitivity, specificity, diagnostic odd ratio, positive and negative likelihood ratios. RESULTS: One hundred and eighty-eight women with placenta previa and at least one previous caesarean section or uterine surgery were included in the study. All the ultrasound signs explored where significantly associated with the occurrence of AIP. Overall, ultrasound had a sensitivity of 84.3% (95% CI 74.7-91.4), a specificity of 61.9 (95% CI 51.9-71.2), a DOR of 8.6 (95% CI 4.1-19.3), a LR+ of 2.2 (95% CI 1.7-2.9) and a LR- of 0.3 (95% CI 0.1-0.4) in detecting AIP, when at least one ultrasound sign was used to make the diagnosis. Using two ultrasound signs to label a case as positive, increased the diagnostic accuracy in terms of specificity, while it did not affect sensitivity. Among the different ultrasound signs, the loss of the clear zone had a sensitivity of 84.4% (95% CI 74.7-91.4) and a specificity of (81.9% (95% CI 73.2-88.7) in detecting AIP, while the corresponding figures for placental lacunae and bladder wall interruption were 78.3% (95% CI 67.9-86.6) and 75.9% (95% CI 65.3-84.) and 81.0% (95% CI 72.1-88.0) and 99.1 (95% CI 94.8-100) respectively. The optimal combination of sensitivity and specificity was achieved when at least two imaging signs of AIP were used in the diagnostic algorithm. CONCLUSION: AIP can be detected since the first trimester of pregnancy in women at risk for this condition and that ultrasound performed between 11 and 14 weeks of gestation has an overall good diagnostic accuracy for detecting all types of AIP. However, these findings are applicable only to women with major placenta previa and prior uterine scar

Diagnostic accuracy of magnetic resonance imaging in detecting the severity of abnormal invasive placenta: a systematic review and meta-analysis

IntroductionAccurate prenatal diagnosis of abnormally invasive placenta (AIP) is fundamental because it significantly reduces maternal morbidities.Material and methodsMedline, Embase, CINAHL and the Cochrane databases were searched. The primary aim of the present review was to elucidate the diagnostic accuracy of prenatal magnetic resonance imaging (MRI) in recognizing the severity of AIP, defined as the depth and topography of invasion. The secondary aim was to ascertain the strength of association between each MRI sign and the depth of placental invasion and to test their individual predictive accuracy in detecting such invasion. Inclusion criteria were studies on women who had prenatal MRI for ultrasound suspicion or the presence of clinical risk factors for AIP. Estimates of sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratio were calculated using the hierarchical summary receiver characteristics curve model, and individual data random-effect logistic regression was used to calculate OR.ResultsTwenty studies (1080 pregnancies undergoing MRI mainly for the ultrasound suspicion of AIP) were included. MRI showed a sensitivity of 94.4% [95% confidence interval (CI) 15.8-99.9], 100% (95% CI 75.3-100) and 86.5% (95% CI 74.2-94.4) for detection of placenta accreta, increta and percreta, respectively; the corresponding values for specificity were 98.8% (95% CI 70.7-100), 97.3% (95% CI 93.3-99.3), 96.8% (95% CI 93.5-98.7). MRI identified 100% of cases with S1 and 100% of those with S2 invasion confirmed at surgery. Among the different MRI signs, intra-placental dark bands showed the best sensitivity for the detection of placenta accreta, increta and percreta; as well as abnormal intra-placental vascularity, uterine bulging was associated with a higher risk of increta and percreta, exophitic mass and bladder tenting with placenta percreta.ConclusionPrenatal MRI has an excellent diagnostic accuracy in identifying the depth and the topography of placental invasion. However, these findings come mainly from studies in which MRI was performed as a secondary imaging tool in women already screened for AIP on ultrasound and might not reflect its actual diagnostic performance in detecting the severity of these disorders

Role of Extracellular Vesicles in Epithelial Ovarian Cancer: A Systematic Review

Extracellular vesicles (EVs) are a heterogeneous group of cell-derived submicron vesicles released under physiological or pathological conditions. EVs mediate the cellular crosstalk, thus contributing to defining the tumor microenvironment, including in epithelial ovarian cancer (EOC). The available literature investigating the role of EVs in EOC has been reviewed following PRISMA guidelines, focusing on the role of EVs in early disease diagnosis, metastatic spread, and the development of chemoresistance in EOC. Data were identified from searches of Medline, Current Contents, PubMed, and from references in relevant articles from 2010 to 1 April 2020. The research yielded 194 results. Of these, a total of 36 papers, 9 reviews, and 27 original types of research were retained and analyzed. The literature findings demonstrate that a panel of EV-derived circulating miRNAs may be useful for early diagnosis of EOC. Furthermore, it appears clear that EVs are involved in mediating two crucial processes for metastatic and chemoresistance development: the epithelial&ndash;mesenchymal transition, and tumor escape from the immune system response. Further studies, more focused on in vivo evidence, are urgently needed to clarify the role of EV assessment in the clinical management of EOC patients