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Objective Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vertical transmission has been investigated extensively. Recently, the World Health Organization (WHO) published strict criteria to classify the timing of mother‐to‐child transmission of SARS‐CoV‐2 into different categories. The aim of this study was to investigate the possibility of vertical transmission in asymptomatic SARS‐CoV‐2‐positive women. Methods Pregnant women attending for delivery at a perinatology center in Mexico City, Mexico, who had a SARS‐CoV‐2‐positive nasopharyngeal swab 24–48 h before delivery, were asymptomatic at the time of the test and had an obstetric indication for Cesarean section were eligible for inclusion in this study. Amniotic fluid was collected during Cesarean delivery, and neonatal oral and rectal swabs were collected at birth and at 24 h after birth. SARS‐CoV‐2 detection was carried out using real‐time reverse‐transcription polymerase chain reaction in all samples. Relevant medical information was retrieved from clinical records. The WHO criteria for classifying the timing of mother‐to‐child transmission of SARS‐CoV‐2 were applied to the study population. Results Forty‐two SARS‐CoV‐2‐positive asymptomatic pregnant women fulfilled the inclusion criteria. Twenty‐five (59%) women developed mild disease after discharge. Neonatal death occurred in three (7%) cases, of which one had a positive SARS‐CoV‐2 test at birth and none had coronavirus disease 2019‐related symptoms. There were five (12%) cases with strong evidence of intrauterine transmission of SARS‐CoV‐2, according to the WHO criteria, as amniotic fluid samples and neonatal samples at birth and at 24 h after birth were positive for SARS‐CoV‐2. Our results also showed that 40–60% of infected neonates would have been undetected if only one swab (oral or rectal) was tested. Conclusion This study contributes evidence to reinforce the potential for vertical transmission of SARS‐CoV‐2 even in asymptomatic women and highlights the importance of testing more than one neonatal sample in order to increase the detection rate of SARS‐CoV‐2 in affected cases. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objective To evaluate interobserver agreement for the assessment of local tumor extension in women with cervical cancer, among experienced and less experienced observers, using transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI). Methods The TVS observers were all gynecologists and consultant ultrasound specialists, six with and seven without previous experience in cervical cancer imaging. The MRI observers were five radiologists experienced in pelvic MRI and four less experienced radiology residents without previous experience in MRI of the pelvis. The less experienced TVS observers and all MRI observers underwent a short basic training session in the assessment of cervical tumor extension, while the experienced TVS observers received only a written directive. All observers were assigned the same images from cervical cancer patients at all stages (n = 60) and performed offline evaluation to answer the following three questions: (1) Is there a visible primary tumor? (2) Does the tumor infiltrate > ⅓ of the cervical stroma? and (3) Is there parametrial invasion? Interobserver agreement within the four groups of observers was assessed using Fleiss kappa (κ) with 95% CI. Results Experienced and less experienced TVS observers, respectively, had moderate interobserver agreement with respect to tumor detection (κ (95% CI), 0.46 (0.40–0.53) and 0.46 (0.41–0.52)), stromal invasion > ⅓ (κ (95% CI), 0.45 (0.38–0.51) and 0.53 (0.40–0.58)) and parametrial invasion (κ (95% CI), 0.57 (0.51–0.64) and 0.44 (0.39–0.50)). Experienced MRI observers had good interobserver agreement with respect to tumor detection (κ (95% CI), 0.70 (0.62–0.78)), while less experienced MRI observers had moderate agreement (κ (95% CI), 0.51 (0.41–0.62)), and both experienced and less experienced MRI observers, respectively, had good interobserver agreement regarding stromal invasion (κ (95% CI), 0.80 (0.72–0.88) and 0.71 (0.61–0.81)) and parametrial invasion (κ (95% CI), 0.69 (0.61–0.77) and 0.71 (0.61–0.81)). Conclusions We found interobserver agreement for the assessment of local tumor extension in patients with cervical cancer to be moderate for TVS and moderate‐to‐good for MRI. The level of interobserver agreement was associated with experience among TVS observers only for parametrial invasion. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objectives Increased nuchal translucency (NT) thickness is an antenatal marker of aneuploidy or malformation that can lead to termination of pregnancy. This study assessed the long‐term neurodevelopmental prognosis of infants who had isolated increased NT in utero. Methods This was a prospective cohort study of infants with a NT thickness > 95th percentile in the first trimester, but with a normal karyotype and no major anomalies, and controls with normal NT matched for birth weight, Apgar score, place of birth, parity and gestational age at birth. At 2 years of corrected age, all infants underwent the psychometric Brunet–Lézine test to evaluate their developmental quotient (DQ), overall (global) and specifically for the areas of posture, language, coordination and sociability. Results A total of 203 chromosomally normal infants were included in the increased‐NT group and 208 in the control group. The mean global DQ was significantly lower in the increased‐NT group than in the control group (108.6 ± 9.7 vs 112.8 ± 8.3; P 5 mm in 11%, with a mean global DQ of 108.4, 110.1 and 109.7, respectively. Conclusions Infants who had isolated increased fetal NT in the first trimester had a significantly lower, but normal, DQ at a corrected age of 2 years, when compared with controls. The findings were independent of the infant's sex, fetal NT thickness and the mother's educational level. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objectives To determine the diagnostic accuracy of postmortem magnetic resonance imaging (PM‐MRI) and postmortem ultrasound (PM‐US) for perinatal autopsy in the same patient cohort, and to determine whether PM‐US can provide the same anatomical information as PM‐MRI. Methods In this prospective, 5‐year (July 2014–July 2019) single‐center study, we performed 1.5‐T PM‐MRI and PM‐US in an unselected cohort of perinatal deaths. The diagnostic accuracies of both modalities were calculated, using autopsy as the reference standard. As a secondary objective, the concordance rates between the two imaging modalities for the overall main diagnosis and for five anatomical regions (brain, spine, thorax, heart and abdomen) were calculated. Results During the study period, 136 cases underwent both PM‐US and PM‐MRI, of which 88 (64.7%) also underwent autopsy. There was no significant difference in the rates of concordance with autopsy between the two modalities for overall diagnosis (PM‐US, 86.4% (95% CI, 77.7–92.0%) vs PM‐MRI, 88.6% (95% CI, 80.3–93.7%)) or in the sensitivities and specificities for individual anatomical regions. There were more non‐diagnostic PM‐US than PM‐MRI examinations for the brain (22.8% vs 3.7%) and heart (14.7% vs 5.1%). If an ‘imaging‐only’ autopsy had been performed, PM‐US would have achieved the same diagnosis as 1.5‐T PM‐MRI in 86.8% (95% CI, 80.0–91.5%) of cases, with the highest rates of agreement being for spine (99.3% (95% CI, 95.9–99.9%)) and cardiac (97.3% (95% CI, 92.4–99.1%)) findings and the lowest being for brain diagnoses (85.2% (95% CI, 76.9–90.8%)). Conclusion Although there were fewer non‐diagnostic cases using PM‐MRI than for PM‐US, the high concordance rate for overall diagnosis suggests that PM‐US could be used for triaging cases when PM‐MRI access is limited or unavailable. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objectives To develop and test the performance of computerized ultrasound image analysis using deep neural networks (DNNs) in discriminating between benign and malignant ovarian tumors and to compare its diagnostic accuracy with that of subjective assessment (SA) by an ultrasound expert. Methods We included 3077 (grayscale, n = 1927; power Doppler, n = 1150) ultrasound images from 758 women with ovarian tumors, who were classified prospectively by expert ultrasound examiners according to IOTA (International Ovarian Tumor Analysis) terms and definitions. Histological outcome from surgery (n = 634) or long‐term (≥ 3 years) follow‐up (n = 124) served as the gold standard. The dataset was split into a training set (n = 508; 314 benign and 194 malignant), a validation set (n = 100; 60 benign and 40 malignant) and a test set (n = 150; 75 benign and 75 malignant). We used transfer learning on three pre‐trained DNNs: VGG16, ResNet50 and MobileNet. Each model was trained, and the outputs calibrated, using temperature scaling. An ensemble of the three models was then used to estimate the probability of malignancy based on all images from a given case. The DNN ensemble classified the tumors as benign or malignant (Ovry‐Dx1 model); or as benign, inconclusive or malignant (Ovry‐Dx2 model). The diagnostic performance of the DNN models, in terms of sensitivity and specificity, was compared to that of SA for classifying ovarian tumors in the test set. Results At a sensitivity of 96.0%, Ovry‐Dx1 had a specificity similar to that of SA (86.7% vs 88.0%; P = 1.0). Ovry‐Dx2 had a sensitivity of 97.1% and a specificity of 93.7%, when designating 12.7% of the lesions as inconclusive. By complimenting Ovry‐Dx2 with SA in inconclusive cases, the overall sensitivity (96.0%) and specificity (89.3%) were not significantly different from using SA in all cases (P = 1.0). Conclusion Ultrasound image analysis using DNNs can predict ovarian malignancy with a diagnostic accuracy comparable to that of human expert examiners, indicating that these models may have a role in the triage of women with an ovarian tumor. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., This article's abstract has been translated into Spanish and Chinese. Follow the links from the abstract to view the translations.

Objectives Deep infiltrating endometriosis (DIE) of the rectosigmoid is associated with painful symptoms. When medical treatment is ineffective, surgical resection remains the standard treatment, despite significant risk of adverse events. High‐intensity focused ultrasound (HIFU) is a minimally invasive ablative procedure. Focal One® is a transrectal HIFU (TR‐HIFU) device used in prostate cancer treatment. The primary objective of this study was to confirm the feasibility of treatment with TR‐HIFU in patients presenting with posterior DIE with rectosigmoid involvement. We also assessed its safety and clinical efficacy in this context. Methods This was a non‐controlled, prospective, Phase‐I clinical trial in a French University Hospital which is a multidisciplinary center for management of endometriosis. Included were patients older than 25 years, without plans to conceive within 6 months, who presented with a single lesion of posterior DIE, with rectosigmoid invasion, after failure of hormonal therapy. All lesions were assessed preoperatively using transvaginal sonography and magnetic resonance imaging. Patients completed questionnaires on gynecological and intestinal symptoms (similar to a visual analog scale (VAS)), and on quality of life (Medical Outcomes Study 36‐item short‐form survey (SF‐36) and, for the second half of patients recruited, symptom scoring system for constipation (KESS), female sexual function index (FSFI) and endometriosis health profile short‐version score (EHP‐5)), before, and at 1, 3 and 6 months after, TR‐HIFU treatment with a Focal One real‐time ultrasound‐guided HIFU device. Results Twenty‐three consecutive patients were included in the study between September 2015 and October 2019. All 23 lesions were visualized, giving a detection rate of 100%. Twenty lesions were treated (‘feasibility rate’, 87.0%): in 13 the whole lesion was treated and in seven the lesion was treated partially. The mean duration of the TR‐HIFU procedure was 55.6 min. We observed a significant improvement in VAS score at 6 months, with differences relative to preoperative scores as follows, for: dysmenorrhea (–3.6, P = 0.004), dyspareunia (–2.4, P = 0.006), diarrhea (–3.0, P = 0.006), constipation (–3.0, P = 0.002), dyschezia (–3.2, P = 0.003), false urge to defecate (–3.3, P = 0.007), posterior pelvic pain (–3.8, P = 0.002) and asthenia (–3.8, P = 0.002). There was also a significant improvement in the SF‐36 score, with an increase at 6 months relative to the preoperative score in both the physical component summary (+ 9.3%, P = 0.002) and mental component summary (+ 10.9%, P = 0.017). No major complications occurred during or after any procedure. Conclusions TR‐HIFU therapy for posterior DIE is feasible. If its efficacy and safety are confirmed, it could be a minimally invasive alternative to surgery for the treatment of rectosigmoid endometriosis. © 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objective To investigate the prevalence of three additional ultrasound markers, placental dichotomy, cardiomegaly and ‘starry‐sky’ liver, in monochorionic twin pregnancy with twin anemia–polycythemia sequence (TAPS). Methods All monochorionic twin pregnancies, diagnosed antenatally with TAPS at our center between 2006 and 2019, were reviewed retrospectively for the presence of placental dichotomy, cardiomegaly in the donor twin and a starry‐sky liver in the recipient twin. TAPS was diagnosed based on delta middle cerebral artery (MCA) peak systolic velocity (PSV) > 0.5 multiples of the median. The primary outcome was the prevalence of placental dichotomy, cardiomegaly, starry‐sky liver and at least one of these markers in both spontaneous and post‐laser TAPS. The secondary outcome was the prevalence of these ultrasound markers according to the antenatal stage of TAPS. Results A total of 91 monochorionic twin pregnancies with TAPS were eligible for analysis. Placental dichotomy was observed in 44% (40/91) of TAPS cases. A total of 70% (64/91) of the TAPS donors developed cardiomegaly and a starry‐sky liver was identified in 66% (53/80) of the TAPS recipients. The prevalence of cardiomegaly and starry‐sky liver was roughly comparable between spontaneous and post‐laser TAPS (69% (33/48) vs 72% (31/43) and 64% (25/39) vs 68% (28/41), respectively). Pregnancies with spontaneous TAPS showed a higher prevalence of placental dichotomy compared with post‐laser TAPS (63% (30/48) vs 23% (10/43)). At least one of the three ultrasound markers was detected in 86% (78/91) of TAPS cases, meaning that 14% (13/91) of cases presented solely with discordant MCA‐PSV values. There was a trend towards increased prevalence of all three ultrasound markers with increasing antenatal TAPS stage. Conclusions Placental dichotomy, fetal cardiomegaly and a starry‐sky liver are commonly found in TAPS pregnancy. Investigating the presence of these ultrasound markers can be of additional help in improving antenatal detection of TAPS in monochorionic twin pregnancy. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Objectives Septo‐optic dysplasia (SOD) is a clinical syndrome characterized by varying combinations of optic nerve hypoplasia, pituitary gland hypoplasia and abnormal cavum septi pellucidi. It is suspected on prenatal imaging when there is non‐visualization or hypoplasia of the septal leaflets. Long‐term postnatal outcomes of fetuses with prenatally suspected SOD have been documented poorly. The aims of this study were to describe the natural history of deficient septal leaflets, to quantify the incidence of postnatally confirmed SOD and to document the visual, endocrine and long‐term neurodevelopmental outcomes of these infants. Methods This was an observational retrospective study of all fetuses with prenatal imaging showing isolated septal agenesis, assessed at a single tertiary center over an 11‐year period. Pregnancy, delivery and neonatal outcomes and pre‐ and postnatal imaging findings were reviewed. Neonatal evaluations or fetal autopsy reports were assessed for confirmation of SOD. Ophthalmologic, endocrine, genetic and long‐term developmental evaluations were assessed. Imaging findings and outcome were compared between infants with and those without postnatally confirmed SOD. Results Of 214 fetuses presenting with septal absence on prenatal ultrasound and magnetic resonance imaging (MRI), 18 (8.4%) were classified as having suspected isolated septal agenesis suspicious for SOD. Uniform prenatal MRI findings in cases with suspected SOD included remnants of the leaflets of the cavum septi pellucidi, fused forniceal columns, normal olfactory bulbs and tracts and a normal optic chiasm. Twelve fetuses were liveborn and five (27.8%) had postnatally confirmed SOD. Only two of these five fetuses had additional prenatal imaging features (pituitary cyst, microphthalmia and optic nerve hypoplasia) supporting a diagnosis of SOD. The other three confirmed SOD cases had no predictive prenatal or postnatal imaging findings that reliably differentiated them from cases without confirmed SOD. Visual and endocrine impairments were present in two (40%) and four (80%) cases with confirmed SOD, respectively. In those with visual and/or endocrine impairment, developmental delay (median age at follow‐up, 2.5 (interquartile range, 2.5–7.0) years) was common (80%) and mostly severe. Neonates with isolated septal agenesis and a lack of visual or endocrine abnormalities to confirm SOD had normal development. Conclusions Only a quarter of fetuses with isolated septal agenesis suggestive of SOD will have postnatal confirmation of the diagnosis. Clinical manifestations of SOD are variable, but neurodevelopmental delay may be more prevalent than thought formerly. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objective Estrogen is a well‐established risk factor for various cancers. It causes endometrial proliferation, which is assessed routinely as endometrial thickness (ET) using transvaginal ultrasound (TVS). Only one previous study, restricted to endometrial and breast cancer, has considered ET and the risk of non‐endometrial cancer. The aim of this study was to explore the association between baseline and serial ET measurements and nine non‐endometrial hormone‐sensitive cancers, in postmenopausal women, using contemporary statistical methodology that attempts to minimize the biases typical of endogenous serial data. Methods This was a cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). In the ultrasound arm of UKCTOCS, 50639 postmenopausal women, aged 50–74, underwent annual TVS examination, of whom 38 105 had a valid ET measurement, no prior hysterectomy and complete covariate data, and were included in this study. All women were followed up through linkage to national cancer registries. The effect of ET on the risk of six estrogen‐dependent cancers (breast, ovarian, colorectal, bladder, lung and pancreatic) was assessed using joint models for longitudinal biomarker and time‐to‐event data, and Cox models were used to assess the association between baseline ET measurement and these six cancers in addition to liver cancer, gastric cancer and non‐Hodgkin's lymphoma (NHL). All models were adjusted for current hormone‐replacement therapy (HRT) use, body mass index, age at last menstrual period, parity and oral contraceptive pill use. Results The 38 105 included women had a combined total of 267 567 (median, 8; interquartile range, 5–9) valid ET measurements. During a combined total of 407 838 (median, 10.9) years of follow‐up, 1398 breast, 351 endometrial, 381 lung, 495 colorectal, 222 ovarian, 94 pancreatic, 79 bladder, 62 gastric, 38 liver cancers and 52 NHLs were registered. Using joint models, a doubling of ET increased significantly the risk of breast (hazard ratio (HR), 1.21; 95% CI, 1.09–1.36; P = 0.001), ovarian (HR, 1.39; 95% CI, 1.06–1.82; P = 0.018) and lung (HR, 1.25; 95% CI, 1.02–1.54; P = 0.036) cancers. There were no statistically significant associations between ET and the remaining six cancers. Conclusion Postmenopausal women with high/increasing ET on TVS are at increased risk of breast, ovarian and lung cancer. It is important that clinicians are aware of these risks, as TVS is a common investigation. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Contains fulltext : 220734.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To identify antenatal ultrasound markers that can differentiate between simple and complex gastroschisis and assess their predictive value. METHODS: This was a prospective nationwide study of pregnancies with isolated fetal gastroschisis that underwent serial longitudinal ultrasound examination at regular specified intervals between 20 and 37 weeks' gestation. The primary outcome was simple or complex (i.e. involving bowel atresia, volvulus, perforation or necrosis) gastroschisis at birth. Fetal biometry (abdominal circumference and estimated fetal weight), the occurrence of polyhydramnios, intra- and extra-abdominal bowel diameters and the pulsatility index (PI) of the superior mesenteric artery (SMA) were assessed. Linear mixed modeling was used to compare the individual trajectories of cases with simple and those with complex gastroschisis, and logistic regression analysis was used to estimate the strength of association between the ultrasound parameters and outcome. RESULTS: Of 104 pregnancies with isolated fetal gastroschisis included, four ended in intrauterine death. Eighty-one (81%) liveborn infants with simple and 19 (19%) with complex gastroschisis were included in the analysis. We found no relationship between fetal biometric variables and complex gastroschisis. The SMA-PI was significantly lower in fetuses with gastroschisis than in healthy controls, but did not differentiate between simple and complex gastroschisis. Both intra- and extra-abdominal bowel diameters were larger in cases with complex, compared to those with simple, gastroschisis (P < 0.001 and P < 0.005, respectively). The presence of intra-abdominal bowel diameter >/= 97.7(th) percentile on at least three occasions, not necessarily on successive examinations, was associated with an increased risk of the fetus having complex gastroschisis (relative risk, 1.56 (95% CI, 1.02-2.10); P = 0.006; positive predictive value, 50.0%; negative predictive value, 81.4%). CONCLUSIONS: This large prospective longitudinal study found that intra-abdominal bowel dilatation when present repeatedly during fetal development can differentiate between simple and complex gastroschisis; however, the positive predictive value is low, and therefore the clinical usefulness of this marker is limited. (c) 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objectives To determine the feasibility and tissue yield of a perinatal incisionless ultrasound‐guided biopsy procedure, the INcisionless Targeted Core Tissue (INTACT) technique, in the context of minimally invasive autopsy. Methods Cases of perinatal death in which the parents consented for minimally invasive autopsy underwent postmortem magnetic resonance imaging and an INTACT biopsy procedure, defined as needle biopsy of organs via the umbilical cord, performed under ultrasound guidance. In each case, three cores of tissue were obtained from seven target organs (both lungs, both kidneys, heart, spleen and liver). Biopsy success was predefined as an adequate volume of the intended target organ for pathological analysis, as judged by a pathologist blinded to the case and biopsy procedure. Results Thirty fetuses underwent organ sampling. Mean gestational age was 30 weeks (range, 18–40 weeks) and mean delivery‐to‐biopsy interval was 12 days (range, 6–22 days). The overall biopsy success rate was 153/201 (76.1%) samples, with the success rates in individual organs being highest for the heart and lungs (93% and 91%, respectively) and lowest for the spleen (11%). Excluding splenic samples, the biopsy success rate was 150/173 (86.7%). Histological abnormalities were found in 4/201 (2%) samples, all of which occurred in the lungs and kidneys of a fetus with pulmonary hypoplasia and multicystic kidney disease. Conclusions Incisionless ultrasound‐guided organ biopsy using the INTACT procedure is feasible, with an overall biopsy success rate of over 75%. This novel technique offers the ideal combination of an imaging‐led autopsy with organ sampling for parents who decline the conventional invasive approach. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Objective To assess the predictive value of measures of levator hiatal distension at rest and on maximum Valsalva maneuver for symptoms of vaginal laxity. Methods This was a retrospective study of women seen at a tertiary urogynecological unit. All women underwent a standardized interview, clinical examination and four‐dimensional translabial ultrasound examination. Area, anteroposterior diameter (APD) and coronal diameter (CD) of the levator hiatus were measured at rest and on maximum Valsalva maneuver in the plane of minimal hiatal dimensions using the rendered volume technique, by an operator blinded to all clinical data. The association between levator hiatal measurements and vaginal laxity was assessed, and receiver‐operating‐characteristics (ROC)‐curve analysis was used to determine their predictive value. Results Data from 490 patients were analyzed. Mean age was 58 (range, 18–88) years, and vaginal laxity was reported by 111 (23%) women. Measurements obtained on maximum Valsalva were significantly larger in women who reported vaginal laxity than in those who did not, with mean levator hiatal area, APD and CD of 30.45 ± 8.74 cm2, 7.24 ± 1.16 cm and 5.60 ± 0.89 cm, respectively, in the vaginal‐laxity group, compared with 24.84 ± 8.63 cm2, 6.64 ± 1.22 cm and 5.01 ± 0.97 cm in the no‐laxity group (P

Objectives First, to obtain measurement‐error models for biometric measurements of fetal abdominal circumference (AC), head circumference (HC) and femur length (FL), and, second, to examine the impact of biometric measurement error on sonographic estimated fetal weight (EFW) and its effect on the prediction of small‐ (SGA) and large‐ (LGA) for‐gestational‐age fetuses with EFW 90th percentile, respectively. Methods Measurement error standard deviations for fetal AC, HC and FL were obtained from a previous large study on fetal biometry utilizing a standardized measurement protocol and both qualitative and quantitative quality‐control monitoring. Typical combinations of AC, HC and FL that gave EFW on the 10th and 90th percentiles were determined. A Monte‐Carlo simulation study was carried out to examine the effect of measurement error on the classification of fetuses as having EFW above or below the 10th and 90th percentiles. Results Errors were assumed to follow a Gaussian distribution with a mean of 0 mm and SDs, obtained from a previous well‐conducted study, of 6.93 mm for AC, 5.15 mm for HC and 1.38 mm for FL. Assuming errors according to such distributions, when the 10th and 90th percentiles are used to screen for SGA and LGA fetuses, respectively, the detection rates would be 78.0% at false‐positive rates of 4.7%. If the cut‐offs were relaxed to the 30th and 70th percentiles, the detection rates would increase to 98.2%, but at false‐positive rates of 24.2%. Assuming half of the spread in the error distribution, using the 10th and 90th percentiles to screen for SGA and LGA fetuses, respectively, the detection rates would be 86.6% at false‐positive rates of 2.3%. If the cut‐offs were relaxed to the 15th and 85th percentiles, respectively, the detection rates would increase to 97.0% and the false‐positive rates would increase to 6.3%. Conclusions Measurement error in fetal biometry causes substantial error in EFW, resulting in misclassification of SGA and LGA fetuses. The extent to which improvement can be achieved through effective quality assurance remains to be seen but, as a first step, it is important for practitioners to understand how biometric measurement error impacts the prediction of SGA and LGA fetuses. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Mortality in pregnancy due to coronavirus disease 2019 (COVID-19) is a current health priority in developing countries. Identification of clinical and sociodemographic risk factors related to mortality in pregnant women with COVID-19 could guide public policy and encourage such women to accept vaccination. We aimed to evaluate the association of comorbidities and socioeconomic determinants with COVID-19-related mortality and severe disease in pregnant women in Mexico.This is an ongoing nationwide prospective cohort study that includes all pregnant women with a positive reverse-transcription quantitative polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Mexican National Registry of Coronavirus. The primary outcome was maternal death due to COVID-19. The association of comorbidities and socioeconomic characteristics with maternal death was explored using a log-binomial regression model adjusted for possible confounders.There were 176 (1.35%) maternal deaths due to COVID-19 among 13 062 consecutive SARS-CoV-2-positive pregnant women. Maternal age, as a continuous (adjusted relative risk (aRR), 1.08 (95% CI, 1.05-1.10)) or categorical variable, was associated with maternal death due to COVID-19; women aged 35-39 years (aRR, 3.16 (95% CI, 2.34-4.26)) or 40 years or older (aRR, 4.07 (95% CI, 2.65-6.25)) had a higher risk for mortality, as compared with those aged 35 years. Other clinical risk factors associated with maternal mortality were pre-existing diabetes (aRR, 2.66 (95% CI, 1.65-4.27)), chronic hypertension (aRR, 1.75 (95% CI, 1.02-3.00)) and obesity (aRR, 2.15 (95% CI, 1.46-3.17)). Very high social vulnerability (aRR, 1.88 (95% CI, 1.26-2.80)) and high social vulnerability (aRR, 1.49 (95% CI, 1.04-2.13)) were associated with an increased risk of maternal mortality, while very low social vulnerability was associated with a reduced risk (aRR, 0.47 (95% CI, 0.30-0.73)). Being poor or extremely poor were also risk factors for maternal mortality (aRR, 1.53 (95% CI, 1.09-2.15) and aRR, 1.83 (95% CI, 1.32-2.53), respectively).This study, which comprises the largest prospective consecutive cohort of pregnant women with COVID-19 to date, has confirmed that advanced maternal age, pre-existing diabetes, chronic hypertension, obesity, high social vulnerability and low socioeconomic status are risk factors for COVID-19-related maternal mortality. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Objective To evaluate Sylvian fissure development by assessing Sylvian fissure angles in fetuses with malformation of cortical development (MCD). Methods This was a retrospective study of 22 fetuses with MCD. Cases with a stored three‐dimensional (3D) brain volume acquired at 18 + 0 to 30 + 6 weeks of gestation at an ultrasound‐based research clinic between January 2010 and December 2017 were identified through a database. Of the 22 fetuses, seven had an extracranial abnormality, such as cardiac, renal, gastrointestinal and/or digital anomalies, and five had a minor abnormality such as micrognathia, low‐set ears and/or single umbilical artery. To confirm the final clinical diagnosis of brain abnormality, postmortem histological findings or prenatal or postnatal magnetic resonance images were used. For measurement of Sylvian fissure angle, an anterior coronal plane of the fetal brain on transvaginal 3D volume multiplanar imaging was visualized as a single image from the three orthogonal views. The right and left Sylvian fissure angles were measured between a horizontal reference line (0°) and a line drawn along the upper side of the respective Sylvian fissure. The Sylvian fissure angle on both sides was plotted on the graphs of the reference ranges for gestational age in weeks. Results In 21 (95.5%; 95% CI, 86.8–100.0%) of 22 fetuses with MCD, the Sylvian fissure angle on one or both sides was larger than the 90th percentile of the normal reference. There was one case with apparent focal MCD in the parietal lobe, but the Sylvian fissure angles were normal. A case with apparent unilateral cortical dysplasia and one with apparent unilateral schizencephaly had conspicuous discrepancies between the left and right Sylvian fissure angles. Abnormal genetic test results were obtained in six cases, including four cases with a mutation in a single gene. Conclusions This study has shown that the Sylvian fissures, as defined by the Sylvian fissure angle, have delayed development in most MCD cases prior to the diagnosis of the condition. The Sylvian fissure angle may potentially be a strong indicator for the subsequent development of cortical malformation, before the time point at which the gyri and sulci become obvious on the fetal brain surface. Further research is required to validate these findings. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

OBJECTIVE: To investigate whether the classification of a previous spontaneous preterm birth (sPTB) as preterm labor (PTL) with intact membranes (IM) or as preterm prelabor rupture of membranes (PPROM) impacts the efficacy of cervical pessary or vaginal progesterone for prevention of sPTB in pregnant women with short cervix on transvaginal ultrasound. METHODS: This was a retrospective cohort study of asymptomatic high-risk singleton pregnancies with a short cervix and history of sPTB, treated using Arabin pessary or vaginal progesterone for primary PTB prevention, conducted at four European hospitals. A log-rank test on Kaplan-Meier curves was used to assess the difference in performance of pessary and progesterone, according to history of PTL-IM or PPROM. Linear regression analysis was used to evaluate significant predictors of gestational age at delivery. RESULTS: Between 2008 and 2015, 170 women were treated with a pessary and 88 with vaginal progesterone. In women treated with a pessary, rate of sPTB < 34 weeks was 16% in those with a history of PTL-IM and 55% in those with a history of PPROM. In women treated with progesterone, rate of sPTB < 34 weeks was 13% in those with a history of PTL-IM and 21% in those with a history of PPROM. Treatment with a pessary resulted in earlier delivery in women with previous PPROM than in any other subgroup (P < 0.0001). Linear regression analysis showed a clear effect of PPROM history (P < 0.0001), combination of PPROM history and treatment (P = 0.0003) and cervical length (P = 0.0004) on gestational age at birth. CONCLUSIONS: Cervical pessary may be a less efficacious treatment option for women with previous PPROM; however, these results require prospective validation before change in practice is recommended. Phenotype of previous preterm birth may be an important risk predictor and treatment effect modifier; this information should be reported in future clinical trials. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Objective To identify pregnancies at increased risk for trisomy 13, trisomy 18 or triploidy attributable to low fetal fraction (FF). Methods A FF‐based risk (FFBR) model was built using data from more than 165 000 singleton pregnancies referred for single‐nucleotide polymorphism (SNP)‐based non‐invasive prenatal testing (NIPT). Based on maternal weight and gestational age (GA), FF distributions for normal, trisomy 13, trisomy 18 and triploid pregnancies were constructed and used to adjust prior risks for these abnormalities. A risk cut‐off of ≥ 1% was chosen to define pregnancies at high risk for trisomy 13, trisomy 18 or triploidy (high FFBR score). The model was evaluated on an independent blinded set of pregnancies for which SNP‐based NIPT did not return a result, and for which pregnancy outcome information was gathered retrospectively. Results The evaluation cohort comprised 1148 cases, of which approximately half received a high FFBR score. Compared with rates expected based on maternal age (MA) and GA, cases with a high FFBR score had a significantly increased rate of trisomy 13, trisomy 18 or triploidy combined (5.7% vs 0.7%; P

Infection with SARS‐CoV2 does not spare pregnant women and the possibility of vertical transmission which might lead to fetal damages is pending. Objective We hypothesized that the observed low incidence of perinatal infection could be related to a low expression of the membrane receptor for SARS‐CoV2, ACE2, in the fetal‐placental unit. We evaluated protein expression of ACE2 both in placentas and fetal organs from non‐infected pregnancies across gestation. Methods Discovery study. Immunocytochemistry analysis for ACE2 in organs and placentas were performed in May 2020, in samples from a registered biobank. Five cases of medical termination of pregnancy performed at between 15 and 38 weeks’ in healthy women. Paraffin‐embedded tissues (kidneys, brain, lungs, intestinal tract, heart). Matching tissues from 8‐year‐old children (N=4) were tested as controls. Seven placentas including those of the 5 cases, 1 of a 7‐week miscarriage and 1 of a symptomatic SARS‐COV2 pregnancy at 34 weeks. Tissues’ sections were incubated with rabbit monoclonal anti‐ACE2. Protein expression of ACE2 was detected by immunochemistry. Results ACE2 expression was detected in fetal kidneys, rectum and ileum across gestation and similarly in the pediatric control. It was barely detectable in lungs at 15 weeks’ and not found thereafter. In the pediatric control, ACE2 was only detectable in type 2 pneumocytes. No ACE2 expression was found in the cerebral ependymal, parenchyma nor in cardiac tissues ACE2 was expressed in syncitiotrophoblast and cytotrophoblast from 7th weeks’ onwards and across gestation but not in the amnion. Similar intensity and distribution of ACE2 staining were identified in the mother's SARS‐CoV2 placenta. Conclusions Marked placental expression of ACE2 provides a rationale for vertical transmission at cellular level. Absence of ACE2 expression in the fetal brain and heart is reassuring on the risk of congenital malformation. Clinical follow‐up of infected pregnant women and their children are needed to validate these observations. This article is protected by copyright. All rights reserved.

To examine the characteristics and distribution of possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target cells in the human trophectoderm (TE) and placenta.Bioinformatics analysis was performed based on published single-cell transcriptomic datasets of early TE and first- and second-trimester human placentae. We conducted the transcriptomic analysis of 4198 early TE cells, 1260 first-trimester placental cells and 189 extravillous trophoblast cells (EVTs) from 24-week placentae (EVT_24W) using the SMART-Seq2 method. In addition, to confirm the bioinformatic results, we performed immunohistochemical staining of three first-trimester, three second-trimester and three third-trimester placentae from nine women recruited prospectively to this study. We evaluated the expression of the SARS-CoV-2-related molecules angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2).Via bioinformatic analysis, we identified the existence of ACE2 and TMPRSS2 expression in human TE as well as in first- and second-trimester placentae. In the human TE, 54.4% of TE1 cells, 9.0% of cytotrophoblasts (CTBs), 3.2% of EVTs and 29.5% of syncytiotrophoblasts (STBs) were ACE2-positive. In addition, 90.7% of TE1 cells, 31.5% of CTBs, 22.1% of EVTs and 70.8% of STBs were TMPRSS2-positive. In placental cells, 20.4% of CTBs, 44.1% of STBs, 3.4% of EVTs from 8-week placentae (EVT_8W) and 63% of EVT_24W were ACE2-positive, while 1.6% of CTBs, 26.5% of STBs, 1.9% of EVT_8W and 20.1% of EVT_24W were TMPRSS2-positive. Pathway analysis revealed that EVT_24W cells that were positive for both ACE2 and TMPRSS2 (ACE2 + TMPRSS2-positive) were associated with morphogenesis of branching structure, extracellular matrix interaction, oxygen binding and antioxidant activity. The ACE2 + TMPRSS2-positive TE1 cells were correlated with an increased capacity for viral invasion, epithelial-cell proliferation and cell adhesion. Expression of ACE2 and TMPRSS2 was observed on immunohistochemical staining in first-, second- and third-trimester placentae.ACE2- and TMPRSS2-positive cells are present in the human TE and placenta in all three trimesters of pregnancy, which indicates the possibility that SARS-CoV-2 could spread via the placenta and cause intrauterine fetal infection. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Objective In the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), self‐reported visualization rate (VR) of the ovaries by the sonographer on annual transvaginal sonographic (TVS) examinations was a key quality control (QC) metric. The objective of this study was to assess self‐reported VR using expert review of a random sample of archived images of TVS examinations from UKCTOCS, and then to develop software for measuring VR automatically. Methods A single expert reviewed images archived from 1000 TVS examinations selected randomly from 68 931 TVS scans performed in UKCTOCS between 2008 and 2011 with ovaries reported as ‘seen and normal’. Software was developed to identify the exact images used by the sonographer to measure the ovaries. This was achieved by measuring caliper dimensions in the image and matching them to those recorded by the sonographer. A logistic regression classifier to determine visualization was trained and validated using ovarian dimensions and visualization data reported by the expert. Results The expert reviewer confirmed visualization of both ovaries (VR‐Both) in 50.2% (502/1000) of the examinations. The software identified the measurement image in 534 exams, which were split 2:1:1 providing training, validation and test data. Classifier mean accuracy on validation data was 70.9% (95% CI, 70.0–71.8%). Analysis of test data (133 exams) provided a sensitivity of 90.5% (95% CI, 80.9–95.8%) and specificity of 47.5% (95% CI, 34.5–60.8%) in detecting expert confirmed visualization of both ovaries. Conclusions Our results suggest that, in a significant proportion of TVS annual screens, the sonographers may have mistaken other structures for normal ovaries. It is uncertain whether or not this affected the sensitivity and stage at detection of ovarian cancer in the ultrasound arm of UKCTOCS, but we conclude that QC metrics based on self‐reported visualization of normal ovaries are unreliable. The classifier shows some potential for addressing this problem, though further research is needed. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Objective To evaluate the test performance of 47 biomarkers and ultrasound parameters for the prediction of delivery of a small‐for‐gestational‐age (SGA) infant and adverse perinatal outcome in women presenting with suspected pre‐eclampsia. Methods This was a prospective, multicenter observational study in which 47 biomarkers and ultrasound parameters were measured in 397 women with a singleton pregnancy presenting with suspected preterm pre‐eclampsia between 20 + 0 and 36 + 6 weeks' gestation, with the objective of evaluating them as predictors of subsequent delivery of a SGA infant and adverse perinatal outcome. Women with confirmed pre‐eclampsia at enrollment were excluded. Factor analysis and stepwise logistic regression were performed in two prespecified groups stratified according to gestational age at enrollment. The primary outcome was delivery of a SGA infant with a birth weight, Linked Comment: Ultrasound Obstet Gynecol 2018; 51: 304–305

Objectives To describe our experience with non‐invasive prenatal testing (NIPT) in twin pregnancy. Methods Two sets of maternal blood samples from twin pregnancies were analyzed at our laboratory using NIPT: 115 stored samples from pregnancies with known outcome (Clinical Study A) and 487 prospectively collected samples for which outcomes were requested from providers (Clinical Study B). NIPT was used to screen for the presence of fetal aneuploidy on chromosomes 13, 18, 21, X and Y in all cases, and results were compared with outcomes when known. Results In Clinical Study A, all 115 samples were classified correctly by NIPT: three cases of trisomy 21 (one fetus affected), one of monochorionic trisomy 18 (both fetuses affected) and 111 euploid. In Clinical Study B, a NIPT result was reported for 479 (98.4%) of the 487 samples. Aneuploidy was detected or suspected in nine (1.9%) cases: seven cases of trisomy 21 detected, one case of trisomy 21 suspected and one case with trisomy 21 detected and trisomy 18 suspected. Information on aneuploidy outcome was available for 171 (35.7%) cases in Clinical Study B. Of the nine cases with aneuploidy detected or suspected, six were confirmed to be a true positive in at least one twin based on karyotype or birth outcome and two were suspected to be concordant based on ultrasound findings; the one known discordant result was for the aneuploidy suspected case. No false negatives were reported. Conclusion NIPT performed well in the detection of trisomy 21 in twin pregnancy, with a combined false‐positive frequency for trisomies 13, 18 and 21 of 0% for Clinical Study A and 0.2% for Clinical Study B. © 2016 Illumina. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objective Pre‐eclampsia (PE) is associated with an increased risk of cardiovascular disease later in life. In cases with PE there is a substantial increase in levels of the antiangiogenic factor soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and decreased levels of the proangiogenic factor placental growth factor (PlGF). Elevated levels of sFlt‐1 are also found in individuals with cardiovascular disease. The aims of this study were to assess levels of sFlt‐1, PlGF and the sFlt‐1/PlGF ratio and their correlation with signs of arterial aging by measuring the common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE. Methods Serum sFlt‐1 and PlGF levels were measured using commercially available enzyme‐linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high‐frequency (22‐MHz) ultrasonography in 55 women at PE diagnosis and in 64 women with normal pregnancy at a similar gestational age, with reassessment at 1 year postpartum. Results During pregnancy, higher levels of sFlt‐1, lower levels of PlGF, a thicker intima, a thinner media and a higher I/M ratio of the CCA were found in women with PE vs controls (all P

Objectives To assess the economic impact of introducing into clinical practice in the UK the soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test for guiding the management of pre-eclampsia. Methods We used an economic model estimating the incremental value of information, from a UK National Health Service payer's perspective, generated by the sFlt-1/PlGF ratio test, compared with current diagnostic procedures, in guiding the management of women with suspected pre-eclampsia. The economic model estimated costs associated with the diagnosis and management of pre-eclampsia in pregnant women between 24 + 0 and 36 + 6 weeks' gestation, managed in either a ‘test’ scenario in which the sFlt-1/PlGF test is used in addition to current diagnostic procedures, or a ‘no-test’ scenario in which clinical decisions are based on current diagnostic procedures alone. Test characteristics and resource use were derived from PROGNOSIS, a non-interventional study in women presenting with clinical suspicion of pre-eclampsia. The main outcome measure from the economic model was the cost per patient per episode of care, from first suspicion of pre-eclampsia to birth. Results Introduction of the sFlt-1/PlGF ratio test into clinical practice is expected to result in cost savings of £344 per patient compared with a no-test scenario. Savings are generated primarily through an improvement in diagnostic accuracy and subsequent reduction in unnecessary hospitalization. Conclusions Introducing the sFlt-1/PlGF ratio test into clinical practice in the UK was shown to be cost-saving by reducing unnecessary hospitalization of women at low risk of developing pre-eclampsia. In addition, the test ensures that those women at higher risk are identified and managed appropriately. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objective To compare the standard methods for ultrasound measurement of fetal head circumference (HC) and biparietal diameter (BPD) (outer‐to‐outer (BPDoo) vs outer‐to‐inner (BPDoi) caliper placement), and compare acquisition of these measurements in transthalamic (TT) vs transventricular (TV) planes. Methods This study utilized ultrasound images acquired from women participating in the Oxford arm of the INTERGROWTH‐21st Project. In the first phase of the study, BPDoo and BPDoi were measured on stored images. In the second phase, real‐time measurements of BPD, occipitofrontal diameter (OFD) and HC in TT and TV planes were obtained by pairs of sonographers. Reproducibility of measurements made by the same (intraobserver) and by different (interobserver) sonographers, as well as the reproducibility of caliper placement and measurements obtained in different planes, was assessed using Bland–Altman plots. Results In Phase I, we analyzed ultrasound images of 108 singleton fetuses. The mean intraobserver and interobserver differences were, Linked Comment: Ultrasound Obstet Gynecol 2016; 48: 26–26

Objective To describe the quality assurance (QA) processes and their impact on visualization of postmenopausal ovaries in the ultrasound arm of a multicenter screening trial for ovarian cancer. Methods In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 50 639 women aged 50–74 years were randomized to the ultrasound arm and underwent annual transvaginal ultrasound (TVS) examinations. QA processes were developed during the course of the trial and included regular monitoring of the visualization rate (VR) of the right ovary. Non‐subjective factors identified previously as impacting on VR of the right ovary were included in a generalized estimating equation model for binary outcomes to enable comparison of observed vs adjusted VR between individual sonographers who had undertaken > 1000 scans during the trial and comparison between centers. Observed and adjusted VRs of sonographers and centers were ranked according to the highest VR. Analysis of annual VRs of sonographers and those of the included centers was undertaken. Results Between June 2001 and December 2010, 48 230 of 50 639 women attended one of 13 centers for a total of 270 035 annual TVS scans. One or both ovaries were seen in 228 145 (84.5%) TVS scans. The right ovary was seen on 196 426 (72.7%) of the scans. For the 78 sonographers included in the model, the median difference between observed and adjusted VR was −0.7% (range, −7.9 to 5.9%) and the median change in VR rank after adjustment was 3 (range, 0–18). For the 13 centers, the median difference between observed and adjusted VR was −0.5% (range, −2.2 to 1%), with no change in ranking after adjustment. The median adjusted VR was 73% (interquartile range (IQR), 65–82%) for sonographers and 74.7% (IQR, 67.1–79.0%) for centers. Despite the increasing age of the women being scanned, there was a steady decrease in the number of sonographers with VR < 60% (21.4% in 2002 vs 2.0% in 2010) and an increase in sonographers with VR > 80% (14.3% in 2002 vs 40.8% in 2010). The median VR of the centers increased from 65.5% (range, 55.7–81.0%) in 2001 to 80.3% (range, 74.5–90.9%) in 2010. Conclusions A robust QA program can improve visualization of postmenopausal ovaries and is an essential component of ultrasound‐based ovarian cancer screening trials. While VR should be adjusted for non‐subjective factors that impact on ovarian visualization, subjective factors are likely to be the largest contributors to differences in VR. © 2015 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd. on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.