Perinatal outcome of monochorionic triamniotic triplet pregnancy: multicenter cohort study.

OBJECTIVE: Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcome and the timing and methods of fetal intervention in these pregnancies. METHODS: This was a multicenter retrospective cohort study of MC triamniotic (TA) triplet pregnancies managed in 21 participating centers around the world from 2007 onwards. Data on maternal age, mode of conception, diagnosis of major fetal structural anomalies or aneuploidy, gestational age (GA) at diagnosis of anomalies, twin-to-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence and or selective fetal growth restriction (sFGR) were retrieved from patient records. Data on antenatal interventions were collected, including data on selective fetal reduction (three to two or three to one), laser surgery and any other active fetal intervention (including amniodrainage). Data on perinatal outcome were collected, including numbers of live birth, intrauterine demise, neonatal death, perinatal death and termination of fetus or pregnancy (TOP). Neonatal data such as GA at birth, birth weight, admission to neonatal intensive care unit and neonatal morbidity were also collected. Perinatal outcomes were assessed according to whether the pregnancy was managed expectantly or underwent fetal intervention. RESULTS: Of an initial cohort of 174 MCTA triplet pregnancies, 11 underwent early TOP, three had an early miscarriage, six were lost to follow-up and one was ongoing at the time of writing. Thus, the study cohort included 153 pregnancies, of which the majority (92.8%) were managed expectantly. The incidence of pregnancy affected by one or more fetal structural abnormality was 13.7% (21/153) and that of TRAP sequence was 5.2% (8/153). The most common antenatal complication related to chorionicity was TTTS, which affected just over one quarter (27.6%; 42/152, after removing a pregnancy with TOP < 24 weeks for fetal anomalies) of the pregnancies, followed by sFGR (16.4%; 25/152), while TAPS (spontaneous or post TTTS with or without laser treatment) occurred in only 4.6% (7/152) of pregnancies. No monochorionicity-related antenatal complication was recorded in 49.3% (75/152) of pregnancies. Survival was apparently associated largely with the development of these complications: there was at least one survivor beyond the neonatal period in 85.1% (57/67) of pregnancies without antenatal complications, in 100% (25/25) of those complicated by sFGR and in 47.6% (20/42) of those complicated by TTTS. The overall rate of preterm birth prior to 28 weeks was 14.5% (18/124) and that prior to 32 weeks' gestation was 49.2% (61/124). CONCLUSION: Monochorionicity-related complications, which can impact adversely perinatal outcome, occur in almost half of MCTA triplet pregnancies, creating a challenge with regard to counseling, surveillance and management. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Risk of fetal loss after chorionic villus sampling in twin pregnancy derived from propensity score matching analysis.

OBJECTIVE: To estimate the risk of fetal loss associated with chorionic villus sampling (CVS) in twin pregnancy, using propensity score analysis. METHODS: This was a multicenter cohort study of women with twin pregnancy undergoing ultrasound examination at 11-13 weeks' gestation, performed in eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. The risk of death of at least one fetus was compared between pregnancies that had and those that did not have CVS, after propensity score matching (1:1 ratio). This procedure created two comparable groups by balancing the maternal and pregnancy characteristics that lead to CVS being performed, similar to how randomization operates in a randomized clinical trial. RESULTS: The study population of 8581 twin pregnancies included 445 that had CVS. Death of one or two fetuses at any stage during pregnancy occurred in 11.5% (51/445) of pregnancies in the CVS group and in 6.3% (515/8136) in the non-CVS group (P < 0.001). The propensity score algorithm matched 258 cases that had CVS with 258 non-CVS cases; there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (odds ratio (OR), 0.81; 95% CI, 0.48-1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss; when the background risk was higher, the risk of fetal loss after CVS decreased (OR, 0.46; 95% CI, 0.23-0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS increased (OR, 2.45; 95% CI, 0.95-7.13). The effects were statistically significantly different (P-value of the interaction = 0.005). For a pregnancy in which the background risk of fetal loss was about 6% (the same as in our non-CVS population), there was no change in the risk of fetal loss after CVS, but, when the background risk was more than 6%, the posterior risk was paradoxically reduced, and when the background risk was less than 6%, the posterior risk increased exponentially; for example, if the background risk of fetal loss was 2.0%, the relative risk was 2.8 and the posterior risk was 5.6%. CONCLUSION: In twin pregnancy, after accounting for the risk factors that lead to both CVS and spontaneous fetal loss and confining the analysis to pregnancies at lower prior risk, CVS seems to increase the risk of fetal loss by about 3.5% above the patient's background risk. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal loss after chorionic villus sampling in twin pregnancy.

OBJECTIVE: To estimate the chorionic villus sampling (CVS)-related risk of fetal loss in twin pregnancy after adjustment for chorionicity, nuchal translucency thickness (NT), intertwin discordance in crown-rump length (CRL), maternal demographic characteristics and serum pregnancy-associated plasma protein-A (PAPP-A) and free ß-human chorionic gonadotropin (ß-hCG). METHODS: This was a multicenter study from eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. Data were obtained prospectively from women with twin pregnancy undergoing routine ultrasound examination at 11-13 weeks' gestation. Multivariable logistic regression analysis with backward stepwise elimination was used to examine whether CVS provided a significant independent contribution to the prediction of risk of fetal loss after adjusting for maternal and pregnancy characteristics, including maternal age, racial origin and weight, method of conception, smoking status, parity, chorionicity, intertwin discordance in CRL, fetal NT ≥ 95th percentile and free ß-hCG and PAPP-A multiples of the median. Similarly, within the CVS group, multivariable logistic regression analysis was used to investigate the effect of the number of intrauterine needle insertions and size of the needle on the risk of fetal loss. RESULTS: The study population of 8581 twin pregnancies undergoing ultrasound examination at 11-13 weeks' gestation included 316 dichorionic and 129 monochorionic twins that had CVS. First, in twin pregnancies undergoing CVS, compared to those not undergoing CVS, there was a 2-fold increased risk of fetal loss at < 24 weeks' gestation and of loss at any stage in pregnancy. Second, the factors providing a significant independent contribution to the prediction of miscarriage or fetal loss in twin pregnancy were increased maternal weight, black racial origin, monochorionicity, and more so monoamnionicity, large intertwin discordance in CRL and increased fetal NT, and, in the case of fetal loss at any stage, there was also a contribution from assisted conception and low serum PAPP-A. Third, after adjustment for maternal and pregnancy characteristics, CVS did not provide a significant contribution to the risk of fetal loss. Fourth, in twin pregnancies that had CVS, there was no significant contribution to fetal loss from the number of intrauterine needle insertions or needle size. CONCLUSION: The 2-fold increased risk of fetal loss following CVS in twin pregnancy can, to a great extent, be explained by maternal and pregnancy characteristics rather than the invasive procedure itself. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of pre-eclampsia in twin pregnancy by maternal factors and biomarkers at 11-13 weeks' gestation: data from EVENTS trial.

OBJECTIVES: First, to validate a previously developed model for screening for pre-eclampsia (PE) by maternal characteristics and medical history in twin pregnancies; second, to compare the distributions of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A) in twin pregnancies that delivered with PE to those in singleton pregnancies and to develop new models based on these results; and, third, to examine the predictive performance of these models in screening for PE with delivery at < 32 and < 37 weeks' gestation. METHODS: Two datasets of prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation were used. The first dataset was from the EVENTS (Early vaginal progesterone for the preVention of spontaneous prEterm birth iN TwinS) trial and the second was from a previously reported study that examined the distributions of biomarkers in twin pregnancies. Maternal demographic characteristics and medical history from the EVENTS-trial dataset were used to assess the validity of risks from our previously developed model. The combined data from the first and second datasets were used to compare the distributional properties of log10 multiples of the median (MoM) values of UtA-PI, MAP, PlGF and PAPP-A in twin pregnancies that delivered with PE to those in singleton pregnancies and develop new models based on these results. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at < 32 and < 37 weeks' gestation. Screening performance was measured by detection rates (DR) and areas under the receiver-operating-characteristics curve. RESULTS: The EVENTS-trial dataset comprised 1798 pregnancies, including 168 (9.3%) that developed PE. In the validation of the prior model based on maternal characteristics and medical history, calibration plots demonstrated very good agreement between the predicted risks and the observed incidence of PE (calibration slope and intercept for PE < 32 weeks were 0.827 and 0.009, respectively, and for PE < 37 weeks they were 0.942 and -0.207, respectively). In the combined data, there were 3938 pregnancies, including 339 (8.6%) that developed PE and 253 (6.4%) that delivered with PE at < 37 weeks' gestation. In twin pregnancies that delivered with PE, MAP, UtA-PI and PlGF were, at earlier gestational ages, more discriminative than in singleton pregnancies and at later gestational ages they were less so. For PAPP-A, there was little difference between PE and unaffected pregnancies. The best performance of screening for PE was achieved by a combination of maternal factors, MAP, UtA-PI and PlGF. In screening by maternal factors alone, the DR, at a 10% false-positive rate, was 30.6% for delivery with PE at < 32 weeks' gestation and this increased to 86.4% when screening by the combined test; the respective values for PE < 37 weeks were 24.9% and 41.1%. CONCLUSIONS: In the assessment of risk for PE in twin pregnancy, we can use the same prior model based on maternal characteristics and medical history as reported previously, but in the calculation of posterior risks it is necessary to use the new distributions of log10 MoM values of UtA-PI, MAP and PlGF according to gestational age at delivery with PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis.

OBJECTIVES: To review clinical validation or implementation studies of maternal blood cell-free (cf) DNA analysis and define the performance of screening for fetal trisomies 21, 18 and 13 and sex chromosome aneuploidies (SCA). METHODS: Searches of PubMed, EMBASE and The Cochrane Library were performed to identify all peer-reviewed articles on cfDNA testing in screening for aneuploidies between January 2011, when the first such study was published, and 31 December 2016. The inclusion criteria were peer-reviewed study reporting on clinical validation or implementation of maternal cfDNA testing in screening for aneuploidies, in which data on pregnancy outcome were provided for more than 85% of the study population. We excluded case-control studies, proof-of-principle articles and studies in which the laboratory scientists carrying out the tests were aware of fetal karyotype or pregnancy outcome. Pooled detection rates (DRs) and false-positive rates (FPRs) were calculated using bivariate random-effects regression models. RESULTS: In total, 35 relevant studies were identified and these were used for the meta-analysis on the performance of cfDNA testing in screening for aneuploidies. These studies reported cfDNA results in relation to fetal karyotype from invasive testing or clinical outcome. In the combined total of 1963 cases of trisomy 21 and 223 932 non-trisomy 21 singleton pregnancies, the weighted pooled DR and FPR were 99.7% (95% CI, 99.1-99.9%) and 0.04% (95% CI, 0.02-0.07%), respectively. In a total of 563 cases of trisomy 18 and 222 013 non-trisomy 18 singleton pregnancies, the weighted pooled DR and FPR were 97.9% (95% CI, 94.9-99.1%) and 0.04% (95% CI, 0.03-0.07%), respectively. In a total of 119 cases of trisomy 13 and 212 883 non-trisomy 13 singleton pregnancies, the weighted pooled DR and FPR were 99.0% (95% CI, 65.8-100%) and 0.04% (95% CI, 0.02-0.07%), respectively. In a total of 36 cases of monosomy X and 7676 unaffected singleton pregnancies, the weighted pooled DR and FPR were 95.8% (95% CI, 70.3-99.5%) and 0.14% (95% CI, 0.05-0.38%), respectively. In a combined total of 17 cases of SCA other than monosomy X and 5400 unaffected singleton pregnancies, the weighted pooled DR and FPR were 100% (95% CI, 83.6-100%) and 0.004% (95% CI, 0.0-0.08%), respectively. For twin pregnancies, in a total of 24 cases of trisomy 21 and 1111 non-trisomy 21 cases, the DR was 100% (95% CI, 95.2-100%) and FPR was 0.0% (95% CI, 0.0-0.003%), respectively. CONCLUSIONS: Screening by analysis of cfDNA in maternal blood in singleton pregnancies could detect > 99% of fetuses with trisomy 21, 98% of trisomy 18 and 99% of trisomy 13 at a combined FPR of 0.13%. The number of reported cases of SCA is too small for accurate assessment of performance of screening. In twin pregnancies, performance of screening for trisomy 21 is encouraging but the number of cases reported is small. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Sonoelastography as method for preliminary evaluation of uterine cervix to predict success of induction of labor.

INTRODUCTION: Induction of labor is a useful practice to solve many obstetric situations but has a large impact on the health of women and their babies and therefore needs to be clearly justified clinically. AIM: To determine the sensitivity of sonoelastography in the evaluation of the cervix to predict the success of induction. MATERIALS AND METHODS: We enrolled 53 subjects preparing for induction of labor. Transvaginal evaluation of cervical length and a sonoelastogram were performed. We preliminarily classified the sonoelastograms into five elastography index (EI) categories and examined the different distribution of cesarean or spontaneous deliveries in various subgroups of EI by χ(2) test and multivariate analysis by logistic regression. RESULTS: Statistical analysis revealed a significant difference of prevalence of spontaneous delivery (EI1-3 82.75%, EI4-5 45.8%) versus cesarean section (EI1-3 17.25%, EI4-5 54.16%) (p = 0.0072). The diagnostic validity of EI was evaluated using the receiver operating characteristic curve and cut-off of the predictive value was EI3. DISCUSSION: The results of our study indicate that sonoelastography is an innovative technique that could allow a more objective preliminary evaluation of the cervix before inducing labor, however further studies with a larger number of subjects and a standardization of image acquisition are necessary.

Uterine endometrioid carcinoma with focal area of choriocarcinomatous differentiation: case report.

PURPOSE OF INVESTIGATION: An endometrioid carcinoma coexisting with choriocarcinomatous differentiation is an uncommon event with an aggressive clinical course and a poor prognosis. MATERIALS AND METHODS: The authors describe an endometrioid carcinoma of the endometrium provided with a focus of choriocarcinoma-like cells in a 50-year-old menstruated woman with a history of abnormal uterine bleeding. A total bilateral hystero-annessectomy was performed. RESULTS: Histopathologic study showed endometrioid adenocarcinoma limited to the endometrium with a single microinvasive (< one mm) choriocarcinomatous focus. Immunohistochemistry established intense reactivity of tumor cells for CK 7 and AE1/AE3, for beta-human chorionic gonadotropin (beta-hCG), and for HER2 confirming the diagnosis. During the clinical course and follow-up, serum levels of beta-hCG were always negative. Up to date the patient is still alive with no evidence of disease. CONCLUSION: Even if endometrioid carcinoma with choriocarcinomatous differentiation is considered highly malignant, occasionally it may have a good prognosis, especially when a non-invasive behaviour is detected together with negative serum beta-hCG levels.

Aggressive angiomyxoma of the vaginal wall at the initial stage: a case report.

Aggressive angiomyxoma (AA) is a rare mesenchimal tumor usually located in the pelvic and perineal region. Less than 30 cases of aggressive angiomyxoma with vaginal location have been reported in the literature up to this date. The authors report the case of a 50-year-old female patient diagnosed with vaginal AA whose characteristics at its initial stage were macroscopically indistinguishable from those of a polypoid lesion. Therefore this case suggests that this type of tumor should be considered as part of the differential diagnosis of vaginal polypoid lesions.

p16INK4a and low-grade cervical intraepithelial neoplasia. Diagnostic and therapeutic implications.

The objectives of this study were to evaluate the evolution of a LSIL associated with p16INK4a overexpression and on the basis of this association, identify patients who would benefit from immediate treatment rather than a later follow-up. Two hundred and forty-five cervical biopsies were studied: 199 (81.2%) were classified CIN 1, 18 (7.4%) CIN 2/3 while 28 (11.4%) were not pathological. Immunohistochemistry revealed that 22 of the 217 CIN samples (11%) were positive for the p16INK4a antigen. The results of the PCR-ELISA for the research and typing of the HPV in these 22 cases were: 14 (63.6%) HPV 16; three (13.6%) HPV 31; 2 (9%) HPV 33; one (4.6%) HPV 43; one (4.6%) HPV 45; one (4.6%) HPV 18. Colposcopic and histological tests performed at four- and eight-month follow-ups in these patients revealed worsening of the initial lesion. Hence, we conclude that immediate therapy would be of benefit in these patients.