Pathologic maternal and neonatal outcomes associated with programmed embryo transfer: potential etiologies and strategies for prevention.

PURPOSE: In the first of two companion papers, we comprehensively reviewed the recent evidence in the primary literature, which addressed the increased prevalence of hypertensive disorders of pregnancy, late-onset or term preeclampsia, fetal overgrowth, postterm birth, and placenta accreta in women conceiving by in vitro fertilization. The preponderance of evidence implicated frozen embryo transfer cycles and, specifically, those employing programmed endometrial preparations, in the higher risk for these adverse maternal and neonatal pregnancy outcomes. Based upon this critical appraisal of the primary literature, we formulate potential etiologies and suggest strategies for prevention in the second article. METHODS: Comprehensive review of primary literature. RESULTS: Presupposing significant overlap of these apparently diverse pathological pregnancy outcomes within subjects who conceive by programmed autologous FET cycles, shared etiologies may be at play. One plausible but clearly provocative explanation is that aberrant decidualization arising from suboptimal endometrial preparation causes greater than normal trophoblast invasion and myometrial spiral artery remodeling. Thus, overly robust placentation produces larger placentas and fetuses that, in turn, lead to overcrowding of villi within the confines of the uterine cavity which encroach upon intervillous spaces precipitating placental ischemia, oxidative and syncytiotrophoblast stress, and, ultimately, late-onset or term preeclampsia. The absence of circulating corpus luteal factors like relaxin in most programmed cycles might further compromise decidualization and exacerbate the maternal endothelial response to deleterious circulating placental products like soluble fms-like tyrosine kinase-1 that mediate disease manifestations. An alternative, but not mutually exclusive, determinant might be a thinner endometrium frequently associated with programmed endometrial preparations, which could conspire with dysregulated decidualization to elicit greater than normal trophoblast invasion and myometrial spiral artery remodeling. In extreme cases, placenta accreta could conceivably arise. Though lower uterine artery resistance and pulsatility indices observed during early pregnancy in programmed embryo transfer cycles are consistent with this initiating event, quantitative analyses of trophoblast invasion and myometrial spiral artery remodeling required to validate the hypothesis have not yet been conducted. CONCLUSIONS: Endometrial preparation that is not optimal, absent circulating corpus luteal factors, or a combination thereof are attractive etiologies; however, the requisite investigations to prove them have yet to be undertaken. Presuming that in ongoing RCTs, some or all adverse pregnancy outcomes associated with programmed autologous FET are circumvented or mitigated by employing natural or stimulated cycles instead, then for women who can conceive using these regimens, they would be preferable. For the 15% or so of women who require programmed FET, additional research as suggested in this review is needed to elucidate the responsible mechanisms and develop preventative strategies.

Microcellular approach for the pathogenesis of placenta accreta spectrum inflammatory versus apoptotic pathways; a thorough look on Treg, dNK and VEGF.

Placenta accreta spectrum (PAS) is a disorder of irregular placental invasion to the surrounding structures, it is a leading cause of maternal morbidity and mortality. This study was theorized to perceive the role of Treg cells and VEGF which appealed to play a role in the pathogenesis of nonstandard extreme placental invasion. The study was carried out on 40 pregnant women; Group I (control group), and Group II (placenta accrete spectrum PAS). Light microscopic, immune-histochemical; CD 56 (NK CELLS) and CD 45 RO (T reg) western blot; P53 and VEGF morphometry and statistical analysis were done. H&E-stained sections revealed Placental tissue in unswerving contact with the myometrium, deficient decidual layer, hemorrhage, congested edematous blood vessels. The mean area percent of collagen, Treg, P53, and VEGF exposed a significant increase in the placenta accreta group when compared to that of control women. Nonetheless, the mean area percent of NK cells displayed a significant decrement PAS cases are associated with low levels of NK cells and increased levels of Treg cells, P 53, and VEGF, promoting the hyperinvasive behavior of trophoblasts of placenta accreta and dysregulate placental vascular remodeling.

Evaluation of maternal serum VEGF, TNF-alpha, IL-4, and IL-10 levels in differentiating placenta accreta spectrum from isolated placenta previa.

OBJECTIVE: Our study aimed to differentiate patients with placenta accreta spectrum (PAS) from those with placenta previa (PP) using maternal serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4), and IL-10. METHODS: The case group consisted of 77 patients with placenta previa, and the control group consisted of 90 non-previa pregnant women. Of the pregnant women in the case group, 40 were diagnosed with PAS in addition to placenta previa and 37 had placenta previa with no invasion. The maternal serum VEGF, TNF-alpha, IL-4, and IL-10 levels were compared between the case and control groups. Then the success of these markers in differentiating between PP and PAS was evaluated. RESULTS: We found the VEGF, TNF-alpha, and IL-4 levels to be higher and the IL-10 level to be lower in the case group compared to the control group (p < 0.001). We observed a statistically significantly lower IL-10 level in the patients with PAS than those with PP (p = 0.029). In the receiver operating characteristic analysis, the optimal cut-off of IL-10 in the detection of PAS was 0.42 ng/mL). In multivariate analysis, the risk of PAS was significant for IL-10 (odds ratio (OR) 0.45, 95 % confidence interval (CI) 0.25-0.79, p = 0.006) and previous cesarean section (OR 2.50, 95 % Cl 1.34-4.66, p = 0.004). The model's diagnostic sensitivity and specificity, including previous cesarean section, preoperative hemoglobin (Hb), TNF-alpha, and IL-10 were 75 % and 72.9 %, respectively. CONCLUSION: The study showed that the IL-10 level was lower in patients with PAS than in those with PP. A statistical model combining risk factors including previous cesarean section, preoperative Hb, TNF-alpha, and IL-10 may improve clinical diagnosis of PAS in placenta previa cases. Cytokines may be used as additional biomarkers to the clinical risk factors in the diagnosis of PAS.

Placenta Accreta Spectrum: Evaluation of classic and non-classic presentations, pathologic grading, and uterine scar dehiscence features in a modern institutional series.

INTRODUCTION: The aim of this study is to document the distribution of classic versus non-classic presentation of Placenta Accreta Spectrum (PAS) disorders as well as grading categories by the Society for Pediatric Pathology (SPP) and FIGO systems in an institutional cohort of gravid hysterectomies. We also document the prevalence of uterine scar as a histologic correlate for uterine scar dehiscence, a phenomenon raised by some as central to PAS pathogenesis. METHODS: PAS cases were assigned grade and designated as classic (anterior lower uterine segment implantation, prior C-section) or non-classic (implantation away from anterior lower uterine segment and/or no prior C-section). Features of dehiscence (uterine window, histologic evidence of scar) were recorded. RESULTS: Sixty-two patients were included: 76 % had prior C-section; 55 % had other forms of uterine instrumentation. Classic PAS was recorded in 52 % patients; notably, 48 % had non-classic presentation; of these, all but one had prior instrumentation (curettage, myomectomy, laparoscopy). Uterine window was described in 53 % classic and 23 % non-classic PAS. Scar was demonstrated in 31 % classic and 23 % non-classic PAS; trichrome/reticulin stains were confirmatory. 32 % cases were SPP grade 1, 18 % grade 2, 18 % grade 3a and 32 % grade 3d. Grade 3 was significantly more common in classic (72 %) than non-classic (27 %) PAS. DISCUSSION: While most PAS patients have classic presentation, a large subset does not; in addition, scar tissue is not identified histologically in most PAS hysterectomies; in these settings, PAS cannot be fully attributed to scar dehiscence. Uterine instrumentation often precedes non-classic PAS reinforcing the concept of decidual disruption as central to PAS pathogenesis. PAS grading as defined correlates with presentation (classic vs non-classic).

Placental lakes vs lacunae: spot the differences.

Sonographic sonolucencies are anechoic areas surrounded by tissue of normal echogenicity, commonly found in the placental parenchyma during the second and third trimesters of pregnancy. The ultrasound appearance of lakes and lacunae derives from the low echogenicity of villous-free areas within the placental parenchyma, filled with maternal blood of varying velocities. In normal placentation, lakes usually start appearing as soon as maternal blood begins to flow freely within the intervillous space at the end of the first trimester, whereas, in accreta placentation, lacunae develop progressively during the second trimester. Larger lakes are found mainly in areas of lower villous density under the fetal plate or in the marginal areas, but can also be found in the center of a lobule above the entry of a spiral artery. Lakes of variable size, position and shape are of no clinical significance, except if they transform into echogenic cystic lesions, which have been associated with poor fetal growth and placental malperfusion. Lacunae are formed by the distortion of one or more placental lobules developing inside a uterine scar, resulting from high-volume, high-velocity flows from the radial/arcuate arteries, and are associated with a high probability of placenta accreta spectrum at birth. They often present with ultrasound signs of uterine remodeling following scarring. Lakes and lacunae can coexist within the same placenta and both will change in size and shape as pregnancy advances. Better understanding of the etiopathology of placental sonolucent spaces and associated morphological changes is necessary to identify patients at risk of subsequent complications during pregnancy and/or at delivery. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Placenta accreta spectrum in early and late pregnancy from an imaging perspective. A scoping review.

Placenta accreta spectrum (PAS) disorders (with increasing order of the depth of invasion: accreta, increta, percreta) are quite challenging for the purpose of diagnosis and treatment. Pathological examination or imaging evaluation are not very dependable when considered as stand-alone diagnostic tools. On the other hand, timely diagnosis is of great importance, as maternal and fetal mortality drastically increases if patient goes through the third phase of delivery in a not well-suited facility. A multidisciplinary approach for diagnosis (incorporating clinical, imaging, and pathological evaluation) is mandatory, particularly in complicated cases. For imaging evaluation, the diagnostic modality of choice in most scenarios is ultrasound (US) exam; patients are referred for MRI when US is equivocal, inconclusive, or not visualizing placenta properly. Herewith, we review the reported US and MRI features of PAS disorders (mainly focusing on MRI), going over the normal placental imaging and imaging pitfalls in each section, and lastly, covering the imaging findings of PAS disorders in the first trimester and cesarean section pregnancy (CSP).

[Prenatal diagnosis of placenta acretta by ultrasound and its histopathological association]. / Diagnóstico prenatal de acretismo placentario por ultrasonido y su asociación histopatológica.

Background: Anomalous adhesions of the placenta, known as placenta accreta and its variants, are the cause of obstetric hemorrhages that put the pregnant woman at risk. Accretism is strongly associated with a history of uterine surgery (cesarean section, myomectomy, curettage), as well as ultrasonographic signs, such as the presence and size of placental lacunae, loss of the placenta/bladder interface, location on the anterior face of the placenta, and presence of Doppler flow; these markers can be assessed by prenatal ultrasound. Objective: To analyze the association of prenatal diagnosis of placenta accreta by ultrasound with the histopathological result using the Tovbin index. Material and methods: Observational, cross-sectional and analytical study. 63 patients who had placenta accreta data by ultrasound measured with the Tovbin index and by means of the histopathological result obtained from the platform of the Mexican Institute for Social Security (IMSS) were included. The association between the two studies with the presence of placenta accreta was analyzed. Results: 63 patients were analyzed; the Tovbin index was positive in 89% of the patients with a diagnosis of placenta accreta confirmed by histopathology. Both the Tovbin index and the histopathology report showed a statistically significant association with a p value of 0.04 for the diagnosis of placenta accreta. Conclusion: The Tovbin index as an ultrasonographic prenatal diagnosis of placenta accreta has a statistically significant association with histopathology diagnosis.

Introducción: las adherencias anómalas de la placenta, conocidas como acretismo, y sus variantes son causa de hemorragias obstétricas que ponen en riesgo a la gestante. El acretismo se asocia firmemente con antecedentes de cirugías uterinas (cesárea, miomectomía, legrados), así como con signos ultrasonográficos como presencia y tamaño de lagunas placentarias, pérdida de la interfaz placenta/vejiga, localización en cara anterior de la placenta y presencia de flujo Doppler; estos marcadores pueden ser valorados mediante ecografía prenatal. Objetivo: analizar la asociación de diagnóstico prenatal de acretismo placentario por ultrasonido con el resultado histopatológico utilizando el Índice de Tovbin. Material y métodos: estudio observacional, transversal y analítico. Se incluyeron 63 pacientes que tenían datos de acretismo placentario por ultrasonido medido con el Índice de Tovbin y mediante el resultado histopatológico obtenido de la plataforma del Instituto Mexicano del Seguro Social. Se analizó la asociación de ambos estudios con la presencia de acretismo placentario. Resultados: se analizaron 63 pacientes; el Índice de Tovbin fue positivo en un 89% de las pacientes con diagnóstico de acretismo placentario confirmado por histopatología. Tanto el Índice de Tovbin como el reporte de histopatología mostraron una asociación estadísticamente significativa con un valor de p de 0.04 para el diagnóstico de acretismo placentario. Conclusión: el Índice de Tovbin como diagnóstico prenatal ultrasonográfico de acretismo placentario tiene asociación estadísticamente significativa con el diagnóstico de histopatología.

Prediction of placenta accreta spectrum in patients with placenta previa using a clinical, US and MRI combined model: A retrospective study with external validation.

PURPOSE: To build and validate a predictive model of placental accreta spectrum (PAS) in patients with placenta previa (PP) combining clinical risk factors (CRF) with US and MRI signs. METHOD: Our retrospective study included patients with PP from two institutions. All patients underwent US and MRI examinations for suspicion of PAS. CRF consisting of maternal age, cesarean section number, smoking and hypertension were retrieved. US and MRI signs suggestive of PAS were evaluated. Logistic regression analysis was performed to identify CRF and/or US and MRI signs associated with PAS considering histology as the reference standard. A nomogram was created using significant CRF and imaging signs at multivariate analysis, and its diagnostic accuracy was measured using the area under the binomial ROC curve (AUC), and the cut-off point was determined by Youden's J statistic. RESULTS: A total of 171 patients were enrolled from two institutions. Independent predictors of PAS included in the nomogram were: 1) smoking and number of previous CS among CRF; 2) loss of the retroplacental clear space at US; 3) intraplacental dark bands, focal interruption of the myometrial border and placental bulging at MRI. A PAS-prediction nomogram was built including these parameters and an optimal cut-off of 14.5 points was identified, showing the highest sensitivity (91%) and specificity (88%) with an AUC value of 0.95 (AUC of 0.80 in the external validation cohort). CONCLUSION: A nomogram-based model combining CRF with US and MRI signs might help to predict PAS in PP patients, with MRI contributing more than US as imaging evaluation.

Bleeding after childbirth / miscarriage - practical notes on the examination of biopsy material.

Postpartum haemorrhage is a significant cause of maternal morbidity and mortality worldwide. The pathologist encounters only a limited spectrum of causes leading to postpartum haemorrhage. The most common causes are retained placenta and placental site subinvolution. Both of these lesions can be diagnosed from material obtained by uterine curettage. Morbidly adherent placenta (placenta accreta spectrum) is a less frequent subject of investigation, the diagnosis of which can be reliably established only on the basis of histological examination of uterine specimens after hysterectomy.

Placenta previa percreta with surrounding organ involvement: a proposal for management.

Placenta accreta spectrum encompasses cases where the placenta is morbidly adherent to the myometrium. Placenta percreta, the most severe form of placenta accreta spectrum (grade 3E), occurs when the placenta invades through the myometrium and possibly into surrounding structures next to the uterine corpus. Maternal morbidity of placenta percreta is high, including severe maternal morbidity in 82.1% and mortality in 1.4% in the recent nationwide U.S. statistics. Although cesarean hysterectomy is commonly performed for patients with placenta accreta spectrum, conservative management is becoming more popular because of reduced morbidity in select cases. Treatment of grade 3E disease involving the urinary bladder, uterine cervix, or parametria is surgically complicated due to the location of the invasive placenta deep in the maternal pelvis. Cesarean hysterectomy in this setting has the potential for catastrophic hemorrhage and significant damage to surrounding organs. We propose a step-by-step schema to evaluate cases of grade 3E disease and determine whether immediate hysterectomy or conservative management, including planned delayed hysterectomy, is the most appropriate treatment option. The approach includes evaluation in the antenatal period with ultrasound and magnetic resonance imaging to determine suspicion for placenta previa percreta with surrounding organ involvement, planned cesarean delivery with a multidisciplinary team including experienced pelvic surgeons such as a gynecologic oncologist, intra-operative assessment including gross surgical field exposure and examination, cystoscopy, and consideration of careful intra-operative transvaginal ultrasound to determine the extent of placental invasion into surrounding organs. This evaluation helps decide the safety of primary cesarean hysterectomy. If safely resectable, additional considerations include intra-operative use of uterine artery embolization combined with tranexamic acid injection in cases at high risk for pelvic hemorrhage and ureteral stent placement. Availability of resuscitative endovascular balloon occlusion of the aorta is ideal. If safe resection is concerned, conservative management including planned delayed hysterectomy at around 4 weeks from cesarean delivery in stable patients is recommended.

The Need for Presurgical Evaluation for Placenta Accreta Spectrum.

Staging or grading of placenta accreta spectrum has historically relied on histopathologic evaluation of placental and uterine specimens. This approach has limited utility, since it is retrospective in nature and does not allow for presurgical planning. Here, we argue for a paradigm shift to use of clinical and imaging characteristics to define the presurgical stage. We summarize past attempts at staging, and define a new data-driven approach to determining the stage prior to delivery. Use of this model may help hospitals direct patients to the most appropriate level of care for workup and management of placenta accreta spectrum. KEY POINTS: · Staging systems that rely on histopathologic grade (accreta, increta, percreta) are unhelpful in antenatal planning for placenta accreta spectrum.. · Past attempts at pre-delivery (pre-surgical) staging have failed to account for key factors that contribute to risk and morbidity.. · We developed a data-driven model that could be easily incorporated as a decision aid into clinical practice to help clinicians decide an individual patient's risk for placenta accreta spectrum..

Imaging the Uterus in Placenta Accreta Spectrum Disorder.

Antenatal diagnosis of placenta accreta spectrum (PAS) improves maternal and neonatal outcomes by allowing for multidisciplinary planning and preparedness. Ultrasound is the primary imaging tool. Simplification and standardization of placental evaluation and reporting terminology allows improved communication and understanding between teams. Prior to 10 weeks of gestation, gestational sac position and least myometrial thickness surrounding the gestational sac help PAS diagnosis very early in pregnancy. Late first-, second-, and third-trimester evaluation includes comprehensive evaluation of the placenta, transabdominal and transvaginal with partially full maternal urinary bladder, and by color Doppler. Subsequently, the sonologist should indicate whether the evaluation was optimal or suboptimal; the level of suspicion as low, moderate, or high; and the extent as focal, global, or extending beyond the uterus. Other complementary imaging modalities such as 3D-power Doppler ultrasound, magnetic resonance imaging (MRI), and vascular topography mapping strive to improve antenatal placental evaluation but remain investigational at present. KEY POINTS: · Antenatal imaging, primarily using ultrasound with partially full maternal urinary bladder, is an essential means of evaluation of those at risk for PAS.. · Simplification and standardization of placental evaluation and reporting will allow improved communication between the multidisciplinary teams.. · Gestational sac location prior to 10 weeks of gestation and four markers after that (placental lacunae and echostructure, myometrial thinning, hypoechoic zone with or without bulging between placenta and myometrium, and increased flow on color Doppler)..

Factors Limiting Magnetic Resonance Imaging Diagnosis of Placenta Accreta Spectrum.

OBJECTIVE: Placenta accreta spectrum (PAS) disorders are characterized by an abnormal adherence of the placenta to the uterine myometrium. Magnetic resonance imaging (MRI) is an important adjunct in antenatal diagnosis. We sought to determine if there are patient and MRI characteristics that limit the accuracy of PAS diagnosis and degree of invasion. STUDY DESIGN: We conducted a retrospective cohort analysis of patients who were evaluated for PAS by MRI from January 2007 to December 2020. Patient characteristics evaluated included number of prior cesarean deliveries, history of dilation and curettage (D&C) or dilation and evacuation (D&E), short interval pregnancy less than 18 months, and delivery body mass index (BMI). All patients were followed until delivery and MRI diagnosis was compared with final histopathology. RESULTS: Of the 353 patients with suspected PAS, 152 (43%) underwent MRI evaluation and were included in the final analysis. In patients who underwent MRI evaluation, 105 (69%) had confirmed PAS on pathology. Patient characteristics were similar between groups and not associated with accuracy of MRI diagnosis. MRI was accurate in diagnosing PAS and the associated degree of invasion in 83 (55%) patients. Accuracy was associated with lacunae (8 vs. 0%, p = 0.02), abnormal bladder interface (25 vs. 6%, p = 0.002), and T1 hyperintensity (13 vs. 1%, p = 0.002). Of the 69 (45%) patients in whom MRI was inaccurate, overdiagnosis was seen in 44 (64%) patients and underdiagnosis in 25 (36%) patients. Overdiagnosis was significantly associated with dark T2 bands (45 vs. 22%, p = 0.005). Underdiagnosis was associated with earlier gestational age at MRI (28 vs. 30 weeks, p = 0.049) and lateral placentation (16 vs. 2.4%, p = 0.025). CONCLUSION: Patient factors did not change MRI accuracy of PAS diagnosis. MRI is associated with a significant overdiagnosis of PAS when dark T2 bands are present, and underdiagnose PAS when performed earlier in gestation or when lateral placentation is present. KEY POINTS: · Patient factors are not associated with MRI accuracy of PAS diagnosis.. · MRI overdiagnoses PAS invasion when there are dark T2 bands.. · MRI underdiagnoses PAS invasion when performed earlier in gestation.. · Underdiagnosis of PAS is associated with lateral placentation..

YKL-40 promotes proliferation and invasion of HTR-8/SVneo cells by activating akt/MMP9 signalling in placenta accreta spectrum disorders.

YKL-40 is a secreted glycoprotein that can promote invasion, angiogenesis and inhibit apoptosis, and was highly expressed in a variety of tumours. In this paper, we investigated the impacts of YKL-40 on proliferation and invasion in HTR-8/SVneo cells during placenta accreta spectrum disorders (PAS) development. The levels of YKL-40 protein in late-pregnant placental tissue were detected using immunohistochemistry and Western blotting, and gene expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion and apoptosis abilities of HTR-8/SVneo cells were detected by cell counting kit-8 (CCK-8), Transwell, scratch assay, and flow cytometry, respectively. Our current results showed that YKL-40 was significantly increased in the PAS group compared to the normal control group (P < 0.01). Biological function experiments showed that YKL-40 significantly promoted the proliferation, migration and invasion of HTR-8/SVneo cells, and inhibited cell apoptosis. Knockdown of YKL-40 inhibited the activation of Akt/MMP9 signalling in trophoblast cells. These data suggested that YKL-40 might be involved in the progression of PAS, which may be attributed to the regulation of Akt/MMP9 signalling pathway.

What is already known on this subject? YKL-40 is a secretory glycoprotein that can promote invasion, angiogenesis, and inhibit apoptosis and was highly expressed in a variety of tumours. Trophoblast cells resemble tumour cells in their migration and invasion.What the results of this study add? YKL-40 expression was significantly up-regulated in PAS. CCK-8 assays showed that YKL-40 remarkably enhanced the viability of HTR-8/SVneo cells. Scratch and Transwell assays demonstrated that YKL-40 significantly promoted the migration and invasion of HTR-8/SVneo cells. Additionally, YKL-40 attenuated apoptosis in HTR-8/SVneo cells.What the implications are of these findings for clinical practice and/or further research? Akt/MMP9 was involved in the regulation of YKL-40 on trophoblast invasion, which may provide theoretical basis and new ideas for the drug blocking intervention of placenta accreta.

[Clinical and morphological characteristics of the atypical placentation spectrum in the uterus]. / Kliniko-morfologicheskaya kharakteristika spektra atipichnoi platsentatsii v matke.

BACKGROUND: The concern of the global community of gynecologists and obstetricians (FIGO) regarding the increase in the number of caesarean sections has resulted in the creation of a new classification, Placenta Accreta Spectrum (PAS), which presents degrees of villus invasion into the uterine wall. OBJECTIVE: Compare the main types of atypical placentation (AP) with the stages of PAS, to supplement and unify the clinical and morphological criteria AP. MATERIAL AND METHODS: Surgical material was examined from 73 women after metroplasty (n=61) and hysterectomies (n=12) from the regions of Russia, Moscow and the Moscow region for ingrown villi and from 10 women with a typical placenta location during the first cesarean section. A targeted cutting of material from the uteroplacental region was used, at least 10-12 pieces, with further H&E and Mallory staining. RESULTS: In the classification of AP, the terms «placenta accreta¼, «increta¼, «percreta¼ should be retained. It is necessary to single out pl. previa as a separate type. Attention is focused on the need to assess the depth of villi invasion accompanied by a layer of fibrinoid, the volume of scar tissue and the degree of disorganization of the myometrial bundles, the state of the vessels in the serous membrane. A new type of AP has been proposed - a sharp thinning of the lower segment of the uterus, due to the scar failure and the pressure of the growing amniotic sac, leading to atrophy and necrosis of the myometrium. CONCLUSION: An integrated approach should be used to classify atypical placentation, taking into account not only the depth of villus invasion, but also anatomical and pathogenic factors in order to develop targeted methods of surgical treatment.

Assessment of ultrasound features of placenta accreta spectrum in women at high risk: association with outcome and interobserver concordance.

OBJECTIVES: To evaluate the prenatal ultrasound features associated with operative complications and to assess the interobserver agreement of prenatal ultrasound assessment with histopathologic confirmation of placenta accreta spectrum (PAS) in a cohort of high-risk patients with detailed intraoperative and histopathologic data. METHODS: This was a retrospective multicenter cohort study of patients at high risk of PAS referred for specialist perinatal care and management between January 2019 and May 2022. Deidentified ultrasound images were reviewed independently by two experienced operators blinded to clinical details, intraoperative features, outcome and histopathologic findings. The diagnosis of PAS was confirmed by failure of detachment of one or more placental cotyledons from the uterine wall at delivery, and the absence of decidua with distortion of the uteroplacental interface by fibrinoid deposition on histologic examination of the accretic areas obtained by guided sampling of partial myometrial resection or hysterectomy specimens. Patients were categorized as having a low or high likelihood of PAS at birth. Interobserver agreement of prenatal ultrasound assessment with histopathologic confirmation of PAS was assessed using the kappa statistic. Primary outcome was major operative morbidity (blood loss ≥ 2000 mL, unintentional injury to the viscera, admission to intensive care unit or death). RESULTS: A total of 102 women at high risk of PAS were referred, of whom 66 had evidence of PAS at birth and 36 did not. When blinded to other clinical details, the examiners agreed on the low or high probability of PAS, according to ultrasound features, in 75/102 cases (73.5%). The kappa statistic was 0.47 (95% CI, 0.28-0.66), showing moderate agreement. Morbidity was twice as common with concordant prenatal diagnosis of PAS vs concordant diagnosis of not PAS. Concordant assessment of high probability of PAS was associated with the highest morbidity (66.6%) and a very high (97.6%) likelihood of histopathologic confirmation. CONCLUSIONS: The probability of histopathologic confirmation is very high with concordant prenatal assessment suggestive of PAS. The interobserver agreement for preoperative assessment with histopathologic confirmation of PAS is only moderate. Morbidity is associated with both histopathologic diagnosis and concordant antenatal assessment of PAS. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Identification of altered miRNAs and their targets in placenta accreta.

Placenta accreta spectrum (PAS) is one of the major causes of maternal morbidity and mortality worldwide with increasing incidence. PAS refers to a group of pathological conditions ranging from the abnormal attachment of the placenta to the uterus wall to its perforation and, in extreme cases, invasion into surrounding organs. Among them, placenta accreta is characterized by a direct adhesion of the villi to the myometrium without invasion and remains the most common diagnosis of PAS. Here, we identify the potential regulatory miRNA and target networks contributing to placenta accreta development. Using small RNA-Seq followed by RT-PCR confirmation, altered miRNA expression, including that of members of placenta-specific miRNA clusters (e.g., C19MC and C14MC), was identified in placenta accreta samples compared to normal placental tissues. In situ hybridization (ISH) revealed expression of altered miRNAs mostly in trophoblast but also in endothelial cells and this profile was similar among all evaluated degrees of PAS. Kyoto encyclopedia of genes and genomes (KEGG) analyses showed enriched pathways dysregulated in PAS associated with cell cycle regulation, inflammation, and invasion. mRNAs of genes associated with cell cycle and inflammation were downregulated in PAS. At the protein level, NF-κB was upregulated while PTEN was downregulated in placenta accreta tissue. The identified miRNAs and their targets are associated with signaling pathways relevant to controlling trophoblast function. Therefore, this study provides miRNA:mRNA associations that could be useful for understanding PAS onset and progression.

Bladder involvement in placenta accreta spectrum disorder with placenta previa: MRI findings and outcomes correlation.

BACKGROUND: Placental accreta spectrum (PAS) disorder with bladder involvement can be associated with maternal and neonatal morbidity. Magnetic resonance imaging (MRI) may provide accurate preoperative diagnoses. OBJECTIVE: This study had 2 aims: to retrospectively review the MRI findings for bladder involvement in PAS with placental previa and to correlate bladder involvement with maternal and neonatal outcomes. MATERIALS AND METHODS: MRI images of 48 patients with severe PAS (increta and percreta) with placenta previa/low-lying placenta were evaluated by 2 experienced radiologists blinded to the final diagnoses. Nine MRI findings and stepwise logistic regression analysis were assessed to identify predictive MRI findings for bladder involvement. The correlations between PAS patients with bladder involvement and clinical outcomes were analyzed using Fisher's exact test. RESULTS: Of the 48 patients, 27 did not have bladder involvement, while 21 did. Logistic regression analysis identified 2 predictive MRI features for bladder involvement. They were abnormal vascularization (OR,6.94; 95 %CI,1.05-45.75) and loss of the chemical shift line at the uterovesical interface (OR, 4.41; 95 %CI, 0.63-30.98). The sensitivity and specificity of the combined MRI features were 38.1 % and 100 %, respectively (p = 0.001). A significant correlation was found between bladder involvement and massive blood loss during surgery (p = 0.022). CONCLUSIONS: PAS with bladder involvement was significantly correlated with massive surgical blood loss. Prenatally, the disorder was predicted with high specificity by the combination of loss of chemical shift artifacts in the steady-state free precession sequence and abnormal vascularization at the uterovesical interface on MRI.

Systematic review and meta-analysis on placenta accreta spectrum disorders in twin pregnancies: risk factors, detection rate and histopathology.

INTRODUCTION: The occurrence of PAS has been recently associated with the presence of twin pregnancy. Aim of this review is to report the risk factors, histopathological correlation, diagnostic accuracy of prenatal ultrasound and clinical outcome of twin pregnancies complicated by placenta accreta spectrum (PAS) disorders. EVIDENCE ACQUISITION: PubMed, Embase, Cinahl, Clinical Trial.Gov and Google Scholar databases were searched. Inclusion criteria were studies on twin pregnancies complicated by PAS. The outcomes explored were risk factors for PAS (including placenta previa, prior uterine surgery or assisted reproductive technology, ART), histopathology (placenta accreta and increta/percreta), detection rate of prenatal ultrasound and clinical outcome, including need for blood transfusion, hysterectomy, emergency or scheduled Cesarean delivery (CD), and maternal death. Random effect meta-analyses of proportions were sued to combine the data. EVIDENCE SYNTHESIS: Two studies considering 103 pregnancies were included in this systematic review: 41.86% (95% CI 27.0-57.9) of twin pregnancies complicated by PAS disorders had a prior CD, 28.22% (95% CI 13.4-46.0) presented placenta previa and 58.14% (95% CI 42.1-73.0) of twin pregnancies were conceived by ART. 74.49% (95% CI 41.6-96.5) of PAS in twin pregnancies were placenta accreta, while 25.51% (95% CI 3.5-58.4) were placenta increta or percreta. Prenatal diagnosis of PAS in twin pregnancies was accomplished only in 27.91% (95% CI 15.3-43.7) of cases. Finally, only one study consistently reported the clinical outcome of PAS in twins. 31.67% (95% CI 20.3-45.0) of women required blood transfusion, 26.67% (95% CI 16.1-39.7) had hysterectomy, while there was no case of maternal death. 44.19% of women had an emergency CD. CONCLUSIONS: There is still limited evidence on the clinical course of PAS disorders in twin pregnancies. Placenta previa, prior uterine surgery (mainly CD), and ART are the most commonly risk factors for PAS disorders in twins. Prenatal diagnosis of PAS in twins is lower compared to what reported in singleton. Finally, about 30% of women with a twin pregnancy complicated by PAS required blood transfusion and hysterectomy.