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Reproductive outcome after cesarean scar pregnancy: A systematic review and meta-analysis

Morlando, Maddalena; Buca, Danilo; Timor-Tritsch, Ilan; Cali, Giuseppe; Palacios-Jaraquemada, Jose; Monteagudo, Ana; Khalil, Asma; Cennamo, Carmen; La Manna, Viviana; Liberati, Marco; D'Amico, Alice; Nappi, Luigi; Colacurci, Nicola; D'Antonio, Francesco
INTRODUCTION/BACKGROUND:To evaluate subsequent reproductive among women with a prior cesarean scar pregnancy (CSP). MATERIAL AND METHODS/METHODS:MEDLINE, Embase and ClinicalTrials.gov databases were searched. Inclusion criteria were women with a prior CSP, defined as the gestational sac or trophoblast within the dehiscence/niche of the previous cesarean section scar or implanted on top of it. The primary outcome was the recurrence of CSP; secondary outcomes were the chance of achieving a pregnancy after CSP, miscarriage, preterm birth, uterine rupture and the occurrence of placenta accreta spectrum disorders. Subgroup analysis according to the management of CSP (surgical vs non-surgical) was also performed. Random effect meta-analyses of proportions were used to analyze the data. RESULTS:Forty-four studies (3598 women with CSP) were included. CSP recurred in 17.6% of women. Miscarriage, preterm birth and placenta accreta spectrum disorders complicated 19.1% (65/341), 10.3% (25/243) and 4.0% of pregnancies, and 67.0% were uncomplicated. When stratifying the analysis according to the type of management, CSP recurred in 21% of women undergoing surgical and in 15.2% of those undergoing non-surgical management. Placenta accreta spectrum disorders complicated 4.0% and 12.0% of cases, respectively. CONCLUSIONS:Women with a prior CSP are at high risk of recurrence, miscarriage, preterm birth and placenta accreta spectrum. There is still insufficient evidence to elucidate whether the type of management adopted (surgical vs non-surgical) can impact reproductive outcome after CSP. Further large, prospective studies sharing an objective protocol of prenatal management and long-term follow up are needed to establish the optimal management of CSP and to elucidate whether it may affect its risk of recurrence and pregnancy outcome in subsequent gestations.
PMID: 32419158
ISSN: 1600-0412
CID: 4494572

ISUOG Practice Guidelines (updated): sonographic examination of the fetal central nervous system. Part 1: performance of screening examination and indications for targeted neurosonography

Malinger, G; Paladini, D; Haratz, K K; Monteagudo, A; Pilu, G L; Timor-Tritsch, I E
PMID: 32870591
ISSN: 1469-0705
CID: 4593832

Cesarean Scar Pregnancy Registry: an international research platform

Kaelin Agten, Andrea; Monteagudo, Ana; Timor-Tritsch, Ilan E; Thilaganathan, Basky
PMID: 31840910
ISSN: 1469-0705
CID: 4243472

Value of first-trimester ultrasound in prediction of third-trimester sonographic stage of placenta accreta spectrum disorder and surgical outcome

Calí, G; Timor-Tritsch, I E; Forlani, F; Palacios-Jaraquemada, J; Monteagudo, A; Kaelin Agten, A; Flacco, M E; Khalil, A; Buca, D; Manzoli, L; Liberati, M; D'Antonio, F
OBJECTIVES:To explore whether early first-trimester ultrasound can predict the third-trimester sonographic stage of placenta accreta spectrum (PAS) disorder and to elucidate whether combining first-trimester ultrasound findings with the sonographic stage of PAS disorder can stratify the risk of adverse surgical outcome in women at risk for PAS disorder. METHODS:This was a retrospective analysis of prospectively collected data from women with placenta previa, and at least one previous Cesarean delivery (CD) or uterine surgery, for whom early first-trimester (5-7 weeks' gestation) ultrasound images could be retrieved. The relationship between the position of the gestational sac and the prior CD scar was assessed using three sonographic markers for first-trimester assessment of Cesarean scar (CS) pregnancy, reported by Calí et al. (crossover sign (COS)), Kaelin Agten et al. (implantation of the gestational sac on the scar vs in the niche of the CS) and Timor-Tritsch et al. (position of the center of the gestational sac below vs above the midline of the uterus), by two different examiners blinded to the final diagnosis and clinical outcome. The primary aim of the study was to explore the association between first-trimester ultrasound findings and the stage of PAS disorder on third-trimester ultrasound. Our secondary aim was to elucidate whether the combination of first-trimester ultrasound findings and sonographic stage of PAS disorder can predict surgical outcome. Logistic regression analysis and area under the receiver-operating-characteristics curve (AUC) were used to analyze the data. RESULTS:One hundred and eighty-seven women with vasa previa were included. In this cohort, 79.6% (95% CI, 67.1-88.2%) of women classified as COS-1, 94.4% (95% CI, 84.9-98.1%) of those with gestational-sac implantation in the niche of the prior CS and 100% (95% CI, 93.4-100%) of those with gestational sac located below the uterine midline, on first-trimester ultrasound, were affected by the severest form of PAS disorder (PAS3) on third-trimester ultrasound. On multivariate logistic regression analysis, COS-1 (odds ratio (OR), 7.9 (95% CI, 4.0-15.5); P < 0.001), implantation of the gestational sac in the niche (OR, 29.1 (95% CI, 8.1-104); P < 0.001) and location of the gestational sac below the midline of the uterus (OR, 38.1 (95% CI, 12.0-121); P < 0.001) were associated independently with PAS3, whereas parity (P = 0.4) and the number of prior CDs (P = 0.5) were not. When translating these figures into diagnostic models, first-trimester diagnosis of COS-1 (AUC, 0.94 (95% CI, 0.91-0.97)), pregnancy implantation in the niche (AUC, 0.92 (95% CI, 0.89-0.96)) and gestational sac below the uterine midline (AUC, 0.92 (95% CI, 0.88-0.96)) had a high predictive accuracy for PAS3. There was an adverse surgical outcome in 22/187 pregnancies and it was more common in women with, compared to those without, COS-1 (P < 0.001), gestational-sac implantation in the niche (P < 0.001) and gestational-sac position below the uterine midline (P < 0.001). On multivariate logistic regression analysis, third-trimester ultrasound diagnosis of PAS3 (OR, 4.3 (95% CI, 2.1-17.3)) and first-trimester diagnosis of COS-1 (OR, 7.9 (95% CI, 4.0-15.5); P < 0.001), pregnancy implantation in the niche (OR, 29.1 (95% CI, 8.1-79.0); P < 0.001) and position of the sac below the uterine midline (OR, 6.6 (95% CI, 3.9-16.2); P < 0.001) were associated independently with adverse surgical outcome. When combining the sonographic coordinates of the three first-trimester imaging markers, we identified an area we call high-risk-for-PAS triangle, which may enable an easy visual perception and application of the three methods to prognosticate the risk for CS pregnancy and PAS disorder, although it requires validation in large prospective studies. CONCLUSIONS:Early first-trimester sonographic assessment of pregnancies with previous CD can predict reliably ultrasound stage of PAS disorder. Combination of findings on first-trimester ultrasound with second- and third-trimester ultrasound examination can stratify the surgical risk in women affected by a PAS disorder. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
PMID: 31788885
ISSN: 1469-0705
CID: 4494352

Cesarean Scar Pregnancy: Diagnosis and Pathogenesis

Timor-Tritsch, Ilan E; Monteagudo, Ana; Calì, Giuseppe; D'Antonio, Francesco; Kaelin Agten, Andrea
Cesarean scar pregnancy is a potentially dangerous consequence of a previous cesarean delivery. If unrecognized and inadequately managed, it can lead to untoward complications throughout all three trimesters of the pregnancy. The rate of occurrence parallels the mounting rate of cesarean sections. The late consequences of cesarean delivery, such as placenta previa and placenta accrete, were known for a long time. However, it took more than a decade for the obstetric community to make the connection between the cesarean scar pregnancy and the placenta accreta spectrum. This article discusses the pathogenesis and diagnosis of cesarean scar pregnancy.
PMID: 31677755
ISSN: 1558-0474
CID: 4178902

Cesarean Scar Pregnancy: Patient Counseling and Management

Timor-Tritsch, Ilan E; Monteagudo, Ana; Calì, Giuseppe; D'Antonio, Francesco; Agten, Andrea Kaelin
There is no universally agreed upon and adopted management protocol supported by professional societies in the United States or around the world for the treatment of cesarean scar pregnancy. There is a wide range of management options in the literature, and many of them can to lead to severe bleeding complications, which can result in loss of fertility or even maternal death. If inadequately managed, it can lead to untoward complications throughout all 3 trimesters of the pregnancy. Early detection of CSP has a paramount clinical importance.
PMID: 31677756
ISSN: 1558-0474
CID: 4178912

Ultrasound and Histopathologic Correlation of Ovarian Cystadenofibromas: Diagnostic Value of the "Shadow Sign"

Timor-Tritsch, Ilan E; Yoon, Esther; Monteagudo, Ana; Ciaffarano, Jeanine; Brandon, Caroline; Mittal, Kushbakhat R; Wallach, Robert C; Boyd, Leslie R
OBJECTIVES/OBJECTIVE:Cystadenofibromas (CAFs) are rare benign ovarian tumors without a widely accepted ultrasound (US) pattern. They are usually described by as thin-walled, unilocular or multilocular, and at times septated cysts with scant blood flow and no solid components. We describe a unique US feature, the "shadow sign," seen in prospectively diagnosed benign CAFs. We also provide the histopathologic basis for this typical US appearance. METHODS:Ultrasound (US) examinations were performed in our obstetric and gynecologic US unit. Pathologic examinations were performed by a dedicated gynecologic pathology team. The US and pathology department's database was searched for the diagnosis of a CAF between 2010 and 2017. RESULTS:We identified 20 patients who underwent transvaginal US examinations with a sole US diagnosis of a CAF, and the tumors were surgically removed. The common US feature across the 20 cases was the presence of hyperechoic avascular shadowing nodules. The correlating histologic features were unilocular or multilocular cysts with a smooth internal wall surface lined by a simple epithelium and occasional robust polypoid fibrous stroma. CONCLUSIONS:This US marker helps in differentiating CAFs from borderline ovarian tumors, which do not show this US feature. We hope that recognizing the suggested shadow sign as an additional descriptor of CAFs will lead to minimizing their unnecessary removal and eliminating additional and unnecessary imaging by computed tomography and magnetic resonance imaging.
PMID: 30927305
ISSN: 1550-9613
CID: 3779052

A new sonographic marker of borderline ovarian tumors: the microcystic pattern of papillary projections and solid components

Timor-Tritsch, Ilan E; Foley, Christine E; Brandon, Caroline; Yoon, Esther; Ciaffarrano, Jeannine; Monteagudo, Ana; Mittal, Kushbakhat; Boyd, Leslie
OBJECTIVE:Accurate diagnosis of borderline ovarian tumors (BOTs) is important to ensure timely and appropriate management, especially in women desiring to preserve fertility. Transvaginal ultrasound (TVUS) is considered the best modality to diagnose adnexal tumors. Sonographic features of BOTs described in the literature include septa, solid components, mural nodules (papillae) and blood vessels within these structures. However, there is no single signature that differentiates BOTs from other adnexal masses. We have identified a microcystic pattern on ultrasound of BOTs. The objective of our study was to evaluate the utility of a new sonographic pattern to describe a novel, yet typical, microcystic pattern of papillary projections, solid components and/or septa as a new ultrasound marker of BOTs and present their histologic confirmation. MATERIAL AND METHODS/METHODS:In this retrospective study, we identified women with a histologic diagnosis of BOT following surgical resection who underwent pre-operative transvaginal ultrasound (TVUS) examination. All images were reviewed for presence or absence of thin-walled, fluid-filled cluster(s) of 1-3-mm cystic formations associated with solid components, papillary projections, and/or septa. Case-matched histopathologic slides of each BOT were examined for the presence of the above-described microcystic features identified on TVUS. To confirm that the microcystic TVUS pattern is unique to BOTs, we randomly selected 20 cases of epithelial cancer and 20 cases of benign cystadenomas from our ultrasound and surgical database. These were also reviewed by the same pathologists. To confirm the novelty of our findings, we searched PubMed for literature published in the English language between 2010 and 2018 to learn if the above described microcystic tissue pattern was previously described. RESULTS:Sixty-seven cases with pre-operative ultrasound that had surgically confirmed BOT on pathologic examination were included in the final analysis. Median age at surgery was 39.8 years. Average size of the BOTs was 60.7mm. Of the 67 BOTs, 47 (70.14%) were serous, 15 (22.38%) were mucinous, and 5 (7.46%) were seromucinous. Sixty (89.7%) of 67 BOTs demonstrated the microcystic pattern in the papillary projections, solid components and/or septa. On ultrasound imaging, 46 of the 47 (97.9%) serous type BOTs had a microcystic pattern compared to 11 of the 15 (73.3%) mucinous and 3 of the 5 (60.0%) seromucinous BOTs. On microscopic evaluation, 60 (89.7%) of 67 samples had characteristic 1-3-mm fluid-filled cysts like those seen on transvaginal ultrasound. Only 7 cases revealed discrepancies between the sonographic and histologic identification of a microcystic pattern. The cystadenomas (we submitted 4 of the 20 pairs we studied for comparison for this article) were mostly unilocular and/or multilocular and largely avascular. None of the 20 cystadenomas or 20 epithelial ovarian malignancies case-matched to histology displayed microcystic characteristics on ultrasound. On review of 23 published articles in the English medical literature containing 163 sonographic pictures of BOT, no description of the microcystic tissue pattern was found. CONCLUSION/CONCLUSIONS:In conclusion, we report a novel sonographic marker of BOTs termed "microcystic pattern" of their papillary projections, solid components and/or septa. This was seen in the majority of both the serous and the mucinous BOT cases. Importantly, based on comparison of sonographic images and histopathology of both benign entities and malignancies, the microcystic appearance appears to be unique to BOTs. No such or similar description was previously provided. We feel utilization of this new marker will help to correctly identify BOTs, discriminating them from ovarian cancers and benign ovarian pathologies, and ensure their appropriate clinical and surgical management.
PMID: 30950132
ISSN: 1469-0705
CID: 3826262

Change in cervical length and spontaneous preterm birth in nulliparous women with a history of loop electrosurgical excision procedure

Gupta, Simi; Chen, Stefanie; Naqvi, Mariam; Saltzman, Daniel H; Rebarber, Andrei; Monteagudo, Ana; Fox, Nathan S
Background: Prior studies have shown an association between history of loop electrode procedures (LEEP) and spontaneous preterm delivery (SPTD) independent of midtrimester cervical length. These studies suggest that there may be other factors beyond an individual cervical length, which contributes to identifying at risk pregnancies. Objective: The objective of this study is to determine the association between change in cervical length and SPTD in women with a history of LEEP. Study design: This is a retrospective cohort study of singleton nulliparous women with a history of LEEP who received serial cervical length measurements at a single institution between 2012 and 2016. Women with serial cervical lengths and available outcome data were included. The cervical length at different gestational ages and rate of change in length was compared with the risk for SPTD < 37 weeks using Student's t-test. Results: One hundred thirty subjects met inclusion criteria for the study. The mean cervical length (35.3 versus 39.8 mm, p = 0.042 at 16 weeks; 32.2 versus 37.8 mm, p < 0.01 at 20 weeks; 29.9 versus 35.6 mm, p = 0.027 at 24 weeks; 21.6 versus 33.4 mm, p < 0.01 at 28 weeks) was significantly different between women who had a SPTD < 37 weeks compared to women who did not. The average rate of change in transvaginal cervical length between 16 to 28 weeks was significantly different between women who had a SPTD < 37 weeks compared to women who did not (-1.4 versus 0.4 mm/wk, p < 0.01). Conclusion: Women with a history of LEEP who had a SPTD < 37 weeks had a shorter cervical length at 16, 20, 24, and 28 weeks' gestation and a higher rate of change in cervical length between 16 and 28 weeks than women without a history of SPTD. Our findings support the concept of the preterm birth syndrome as an evolving biophysical process rather than a distinct event, suggesting improved prediction in the setting of prior history of a LEEP with serial imaging.
PMID: 31416405
ISSN: 1476-4954
CID: 4042702

Early first trimester transvaginal ultrasound is indicated in pregnancies after a previous cesarean delivery: should it be mandated?

Timor-Tritsch, Ilan E; D'Antonio, Francesco; Calỉ, Giuseppe; Palacios-Jaraquemada, Josė; Meyer, Jessica; Monteagudo, Ana
In this opinion article, we provide compelling arguments of why early screening for pregnancies following previous cesarean delivery would be beneficial. First, we provide an overview of the perils of undiagnosed or misdiagnosed cesarean scar pregnancies (CSP), mostly with bleeding, but also with other complications, that may lead to multiple surgeries, uterine artery embolization, loss of fertility and in rare cases of documented deaths. There is well-documented histopathological connection between CSP and the placental adherence spectrum (PAS) suggesting that CSP is a precursor to PAS. We argue that the ultrasound markers to recognize CSP are present in the 1st trimester and that they may go on and become 2nd and 3rd trimester cases of PAS. We stress that early 5-7 weeks ultrasound screening for CSP is strongly indicated (if not mandated) and can be easily implemented alongside several other proven 1st trimester screening tests.
PMID: 30677186
ISSN: 1469-0705
CID: 3610702