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, prenatal diagnosis, and outcome of posterior placenta accreta spectrum disorders in patients with placenta previa or low-lying placenta: A multicenter study

Introduction: Placenta accreta spectrum (PAS) disorders occur when the definitive placenta develops within the uterus scar area. Although classically PAS develops in the anterior wall of the uterus mainly, it can also develop in the posterior uterine wall. The aim of this study was to report the risk factors, diagnostic accuracy of prenatal imaging, and surgical outcome of pregnancies complicated by posterior PAS in women with placenta previa or low-lying. Material and methods: Secondary analysis of a multicenter prospective study involving 16 referral hospitals in Italy (ADoPAD Study). Inclusion criteria were patients with a posterior low-lying placenta (<20 mm from the internal cervical os) or placenta previa (covering the os), aged ≥18 years undergoing ultrasound assessment at ≥26+0 weeks of gestation. The reference standard for PAS was represented by the failure of placental separation at delivery or by pathological analysis. The primary aim was to report the risk factors associated with the occurrence of posterior PAS. The secondary aims were to evaluate the ability of prenatal ultrasound in detecting posterior PAS and to report its surgical outcome compared to posterior placental previa or low-lying with no PAS and anterior PAS, respectively, and in patients with a prenatal compared to post-natal diagnosis. Univariate and diagnostic accuracy analyses were used to analyze the data. Results: 258 patients were included in the analysis. Posterior PAS occurred in 8.1% (n = 21; 95% CI 5.4-12.1) of patients. There was a higher incidence of one or more prior CS (62% vs. 21%, p < 0.001) and myomectomy with uterine penetration (71.0% vs. 3.4%, p < 0.001) in patients with posterior PAS compared to those with no PAS. In patients with posterior PAS, placenta accreta occurred in 66.67% (14/21), increta in 23.81% (5/21), and percreta in 9.52% (2/21) of cases. Posterior PAS confirmed at birth was diagnosed prenatally by ultrasound in 62% (13/21) of cases. When comparing anterior with posterior PAS, patients with anterior PAS were more likely to have a prior CS (82% vs. 62%; p = 0.0049) and placenta percreta (54% vs. 10%; p < 0.001). Finally, the need for hysterectomy (89% vs. 48%; p < 0.001) was higher, while that of balloon tamponade insertion was lower (17% vs. 52%; p = 0.001) in patients with anterior compared to posterior PAS. Conclusions: Prior uterine surgery in patients with placenta previa or low-lying represents the commonest risk factors for posterior PAS. The diagnostic accuracy of ultrasound in detecting posterior PAS is lower in cases with posterior compared to anterior PAS. Finally, in referral centers, posterior PAS disorders were associated with a lower risk of hysterectomy compared to anterior PAS

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

Maternal and perinatal outcomes of pregnant women with SARS-CoV-2 infection.

OBJECTIVES: To evaluate the maternal and perinatal outcomes of pregnancies affected by SARS-CoV-2 infection. METHODS: This was a multinational retrospective cohort study including women with a singleton pregnancy and laboratory-confirmed SARS-CoV-2 infection, conducted in 72 centers in 22 different countries in Europe, the USA, South America, Asia and Australia, between 1 February 2020 and 30 April 2020. Confirmed SARS-CoV-2 infection was defined as a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab specimens. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit (ICU), use of mechanical ventilation and death. RESULTS: In total, 388 women with a singleton pregnancy tested positive for SARS-CoV-2 on RT-PCR of a nasopharyngeal swab and were included in the study. Composite adverse maternal outcome was observed in 47/388 (12.1%) women; 43 (11.1%) women were admitted to the ICU, 36 (9.3%) required mechanical ventilation and three (0.8%) died. Of the 388 women included in the study, 122 (31.4%) were still pregnant at the time of data analysis. Among the other 266 women, six (19.4% of the 31 women with first-trimester infection) had miscarriage, three (1.1%) had termination of pregnancy, six (2.3%) had stillbirth and 251 (94.4%) delivered a liveborn infant. The rate of preterm birth before 37 weeks' gestation was 26.3% (70/266). Of the 251 liveborn infants, 69/251 (27.5%) were admitted to the neonatal ICU, and there were five (2.0%) neonatal deaths. The overall rate of perinatal death was 4.1% (11/266). Only one (1/251, 0.4%) infant, born to a mother who tested positive during the third trimester, was found to be positive for SARS-CoV-2 on RT-PCR. CONCLUSIONS: SARS-CoV-2 infection in pregnant women is associated with a 0.8% rate of maternal mortality, but an 11.1% rate of admission to the ICU. The risk of vertical transmission seems to be negligible. © 2020 International Society of Ultrasound in Obstetrics and Gynecology

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

Clinical Role of the Detection of Human Telomerase RNA Component Gene Amplification by Fluorescence in situ Hybridization on Liquid-Based Cervical Samples: Comparison with Human Papillomavirus-DNA Testing and Histopathology

Objective: This study was designed to evaluate whether the adjunct of human telomerase RNA component (hTERC) fluorescence in situ hybridization (FISH) analysis to cytological diagnosis and human papillomavirus (HPV)-DNA testing may serve as a predictive marker for distinguishing cervical lesions destined to regress from those at high risk of progression towards invasive cancer. Study Design: hTERC FISH analysis was performed on 54 residual liquid-based cytology specimens obtained from women referred to colposcopy for the detection of atypical squamous cells of undetermined significance or worse (ASCUS+) lesions. Histological diagnosis was considered the gold standard and cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) as the worst outcome. Results: Oncogenic HPV-DNA was found in 96.3% of the specimens. Among these, 38.5% revealed a CIN2+ diagnosis. hTERC gene amplification was detected in 37% of the cases; among these, 70% showed up as CIN2+. hTERC FISH analysis significantly improves the specificity and positive predictive value of HPV-DNA testing, thus differentiating patients with a CIN2+ diagnosis from those with a CIN2- diagnosis. Conclusions: Despite the limitation of a small study sample, our findings provide promising data, indicating the possible role of hTERC analysis in the assessment of the risk of developing cervical cancer. This approach would implement the specificity of DNA testing, avoiding overtreatment at the same time. Prospective follow-up studies are needed with the aim of introducing hTERC FISH into decision-making algorithms

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