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.

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.

[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.

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.

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.

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.

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.

Overexpressed LAMC2 promotes trophoblast over-invasion through the PI3K/Akt/MMP2/9 pathway in placenta accreta spectrum.

BACKGROUND: Placenta accreta spectrum (PAS) is an ongoing major iatrogenic public health challenge with devastating obstetric complications, but its underlying molecular pathogenesis remains poorly illuminated. LAMC2 is reported to regulate tumor cells proliferation and invasion, yet has not been explored in placenta trophoblast cells. This study investigated LAMC2 expression and its contribution in the etiology of PAS. METHODS: Quantitative polymerase chain reaction, western blot, and immunohistochemistry were performed to detect the expression of LAMC2 in placentas. Cell proliferation, invasion, migration, and apoptosis were monitored by CCK8 assay, wound healing assay, transwell invasion assay, and flow cytometry assay. Western blot was conducted to confirm the pertinent proteins level of PI3K/Akt/MMP2/9 pathway in HTR8/SVneo cells. RESULTS: LAMC2 was predominantly expressed in placental villous syncytiotrophoblasts and cytotrophoblasts. LAMC2 mRNA and protein expression were substantially upregulated in placental tissues with PAS compared to those with pernicious placenta previa without PAS. LAMC2 overexpression eminently boosted HTR8/SVneo cells proliferation, invasion, and migration, but inhibited apoptosis, accompanied by elevated protein expression of MMP2, MMP9, and phosphorylated Akt (pAkt). Knockdown of LAMC2 yielded the converse results. Additionally, when treated with LY294002, the effects of LAMC2 overexpression on proliferation, migration, invasion, and apoptosis of HTR8/SVneo cells were abolished and concomitantly the elevated pAkt, MMP2, and MMP9 proteins induced by LAMC2 overexpression were eliminated. CONCLUSION: Our study highlighted the involvement of LAMC2 in the pathogenesis of PAS by activating the PI3K/Akt/MMP2/9 signaling pathway to stimulate trophoblast over-invasion. These findings provide a new target for the diagnosis and disease stratification of PAS.

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.

Assessment of postpartum haemorrhage for placenta accreta: Is measurement of myometrium thickness and dark intraplacental bands using MRI helpful?

BACKGROUND: This study aimed to investigate the predictive values of magnetic resonance imaging (MRI) myometrial thickness grading and dark intraplacental band (DIB) volumetry for blood loss in patients with placenta accreta spectrum (PAS). METHODS: Images and clinical data were acquired from patients who underwent placenta MRI examinations and were diagnosed with PAS from March 2015 to January 2021. Two radiologists jointly diagnosed, processed, and analysed the MR images of each patient. The analysis included MRI-based determination of placental attachment, as well as myometrial thickness grading and DIB volumetry. The patients included in the study were divided into three groups according to the estimated blood loss volume: in the general blood loss (GBL) group, the estimated blood loss volume was < 1000 ml; in the massive blood loss (MBL) group, the estimated blood loss volume was ≥ 1000 ml and < 2000 ml; and in the extremely massive blood loss (ex-MBL) group, the estimated blood loss volume was ≥ 2000 ml. The categorical, normally distributed, and non-normally distributed data were respectively analysed by the Chi-square, single-factor analysis of variance, and Kruskal-Wallis tests, respectively. The verification of correlation was completed by Spearman correlation analysis. The evaluation capabilities of indicators were assessed using receiver operating characteristic curves. RESULTS: Among 75 patients, 25 were included in the GBL group, 26 in the MBL group, and 24 in the ex-MBL group. A significant negative correlation was observed between the grade of myometrial thickness and the estimated blood loss (P < 0.001, ρ = - 0.604). There was a significant positive correlation between the volume of the DIB and the estimated blood loss (P < 0.001, ρ = 0.653). The areas under the receiver operating characteristic curve of the two MRI features for predicting blood loss ≥ 2000 ml were 0.776 and 0.897, respectively. CONCLUSIONS: The grading and volumetric MRI features, myometrial thickness, and volume of DIB, can be used as good prediction indicators of the risk of postpartum haemorrhage in patients with PAS.

New insights into the etiopathology of placenta accreta spectrum.

Placenta accreta has been described as a spectrum of abnormal attachment of villous tissue to the uterine wall, ranging from superficial attachment to the inner myometrium without interposing decidua to transmural invasion through the entire uterine wall and beyond. These descriptions have prevailed for more than 50 years and form the basis for the diagnosis and grading of accreta placentation. Accreta placentation is essentially the consequence of uterine remodeling after surgery, primarily after cesarean delivery. Large cesarean scar defects in the lower uterine segment are associated with failure of normal decidualization and loss of the subdecidual myometrium. These changes allow the placental anchoring villi to implant, and extravillous trophoblast cells to migrate, close to the serosal surface of the uterus. These microscopic features are central to the misconception that the accreta placental villous tissue is excessively invasive and have led to much confusion and heterogeneity in clinical data. Progressive recruitment of large arteries in the uterine wall, that is, helicine, arcuate, and/or radial arteries, results in high-velocity maternal blood entering the intervillous space from the first trimester of pregnancy and subsequent formation of placental lacunae. Recently, guided sampling of accreta areas at delivery has enabled accurate correlation of prenatal imaging data with intraoperative features and histopathologic findings. In more than 70% of samples, there were thick fibrinoid depositions between the tip of most anchoring villi and the underlying uterine wall and around all deeply implanted villi. The distortion of the uteroplacental interface by these dense depositions and the loss of the normal plane of separation are the main factors leading to abnormal placental attachment. These data challenged the classical concept that placenta accreta is simply owing to villous tissue sitting atop the superficial myometrium without interposed decidua. Moreover, there is no evidence in accreta placentation that the extravillous trophoblast is abnormally invasive or that villous tissue can cross the uterine serosa into the pelvis. It is the size of the scar defect, the amount of placental tissue developing inside the scar, and the residual myometrial thickness in the scar area that determine the distance between the placental basal plate and the uterine serosa and thus the risk of accreta placentation.

Failure of placental detachment in accreta placentation is associated with excessive fibrinoid deposition at the utero-placental interface.

BACKGROUND: The main histopathologic diagnostic criteria for the diagnosis of placenta accreta for more than 80 years has been the finding of a direct attachment of the villous tissue to the superficial myometrium or adjacent to myometrial fibers without interposing decidua. There have been very few detailed histopathologic studies in pregnancies complicated by placenta accreta spectrum disorders and our understanding of the pathophysiology of the condition remains limited. OBJECTIVE: To prospectively evaluate the microscopic changes used in grading and to identify changes that might explain the abnormal placental tissue attachment. STUDY DESIGN: A total of 40 consecutive cesarean delivery hysterectomy specimens for placenta previa accreta at 32 to 37 weeks of gestation with at least 1 histologic slide showing deeply implanted villi were analyzed. Prenatal ultrasound examination included placental location, myometrial thickness, subplacental vascularity and lacunae. Macroscopic changes of the lower segment were recorded during surgery and areas of abnormal placental adherence were sampled for histology. In addition, 7 hysterectomy specimens with placenta in-situ from the Boyd Collection at 20.5 to 32.5 weeks were used as controls. RESULTS: All 40 patients had a history of at least 2 previous cesarean deliveries and presented with a mainly anterior placenta previa. Of note, 37 (92.5%) cases presented with increased subplacental vascularity, 31 (77.5%) cases with myometrial thinning and all with lacunae. Furthermore, 20 (50%) cases presented with subplacental hypervascularity, lacunae score of >3, and lacunae feeder vessels. Intraoperative findings included anterior lower segment wall increased vascularization in 36 (90.0%) cases and extended area of dehiscence in 18 (45.0%) cases. Immediate gross examination of hysterectomy specimens showed an abnormally attached areas involving up to 30% of the basal plate, starting at <2 cm from the dehiscence area in all cases. Histologic examination found deeply implanted villi in 86 (53.8%) samples with only 17 (10.6%) samples presenting with villous tissue reaching at least half the uterine wall thickness. There were no villi crossing the entire thickness of the uterine wall. There was microscopic evidence of myometrial scarification in all cases. Dense fibrinoid deposits, 0.5 to 2 mm thick, were found at the utero-placental interface in 119 (74.4%) of the 160 samples between the anchoring villi and the underlying uterine wall at the accreta areas and around all deeply implanted villi. In the control group, the Nitabuch stria and basal plate became discontinuous with advancing gestation and there was no evidence of fibrinoid deposition at these sites. CONCLUSION: Samples from accreta areas at delivery present with a thick fibrinoid deposition at the utero-placental interface on microscopic examination independently of deeply implanted villous tissue in the sample. These changes are associated with distortion of the Nitabuch membrane and might explain the loss of parts of the physiological site of detachment of the placenta from the uterine wall in placenta accreta spectrum. These findings indicate that accreta placentation is more than direct attachment of the villous tissue to the superficial myometrium and support the concept that accreta villous tissue is not truly invasive.

Doppler evaluation of normal and abnormal placenta.

Doppler techniques are needed for the evaluation of the intraplacental circulation and can be of great value in the diagnosis of placental anomalies. Highly sensitive Doppler techniques can differentiate between the maternal (spiral arteries) and fetal (intraplacental branches of the umbilical artery) components of the placental circulation and assist in the evaluation of the placental functional units. A reduced number of placental functional units can be associated with obstetric complications, such as fetal growth restriction. Doppler techniques can also provide information on decidual vessels and blood movement. Abnormal decidual circulation increases the risk of placenta accreta. Doppler evaluation of the placenta greatly contributes to the diagnosis and clinical management of placenta accreta, vasa previa, placental infarcts, placental infarction hematoma, maternal floor infarction, massive perivillous fibrin deposition and placental tumors. However, it has a limited role in the diagnosis and clinical management of placental abruption, placental hematomas, placental mesenchymal dysplasia and mapping of placental anastomoses in monochorionic twin pregnancies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Clinical Analysis of Improved Particle Swarm Algorithm-Based Magnetic Resonance Imaging Diagnosis of Placenta Accreta.

The magnetic resonance imaging (MRI) image processing capabilities were investigated based on the improved particle swarm optimization (IPSO) algorithm, and the clinical application analysis of MRI images in the diagnosis of placenta accreta (PA) was evaluated in this study. The MRI uterine images were detected on the basis of IPSO. Besides, the clinical data of 89 patients with PA were selected and collected, who were diagnosed by clinical cesarean section surgery and pathological comprehensive diagnosis in hospital from January 2018 to July 2020. Then, all of them underwent the ultrasound (US) and MRI examinations, and the differences of sensitivity, specificity, and accuracy between MRI and US under IPSO in the diagnosis of PA were compared, as well as the differences in the diagnosis of adhesive, implantable, and penetrated PA. The results showed that the difference in detection between IPSO-based MRI images and US images was not statistically substantial (p > 0.05), but the number of initial detections was higher than the number of US examination. MRI examination had higher sensitivity and specificity in the diagnosis of PA during pregnancy, especially for implantable PA, compared with US examination (p < 0.05). In conclusion, MRI images based on the improved particle swarm optimization algorithm showed a good application effect in the diagnosis of placental implantation diseases, which was worthy of further promotion in clinical practice.

Role of Ultrasound and MRI in Diagnosis of Severe Placenta Accreta Spectrum Disorder: An Intraindividual Assessment With Emphasis on Placental Bulge.

BACKGROUND. The "placental bulge" sign (focal area of myometrial-placental bulging beyond the normal uterine contour) on ultrasound (US) or MRI is postulated to represent deeper venous invasion in placenta accreta spectrum (PAS) disorder and may represent severe PAS. OBJECTIVE. The purpose of this study was to evaluate the diagnostic performance and interobserver agreement of US and MRI features for diagnosis of severe PAS, with an emphasis on the placental bulge sign. METHODS. This retrospective study included 62 pregnant women (mean age, 33.2 ± 5.5 [SD] years) with clinically suspected PAS who underwent both US and MRI. Five readers (two maternal-fetal medicine specialists for US, three abdominal radiologists for MRI) independently reviewed images for the given modality, blinded to the final diagnosis, and recorded the presence of a range of findings (nine on US, eight on MRI), including placental bulge. Intraoperative and pathologic findings were used to separate patients into those with and without severe PAS according to International Federation of Gynecology and Obstetrics classification. Diagnostic performance of US and MRI findings for severe PAS was evaluated, multivariable logistic regression was performed, and interob-server agreement was assessed. RESULTS. A total of 58.1% (36/62) of patients had severe PAS. On US, the finding with the highest accuracy for severe PAS was placental bulge (85.5%), which had a sensitivity of 91.7% and specificity of 76.9%. On MRI, the finding with highest accuracy was also placental bulge (90.3%), which had a sensitivity of 94.4% and specificity of 84.6%. In the multivariable regression analysis, placental bulge was an independent predictor of severe PAS on US (odds ratio [OR], 8.94; p = .02) and MRI (OR, 45.67; p = .003). Interobserver agreement analysis showed a kappa value for placental bulge of 0.48 for MRI and 0.40 for US. Given wide 95% CIs, differences among features for a given modality and differences between modalities were not statistically significant. CONCLUSION. The findings suggest a strong performance of placental bulge in diagnosing severe PAS on both US and MRI, with a potentially stronger performance on MRI. Nonetheless, interobserver agreement remains suboptimal for both modalities. CLINICAL IMPACT. Accurate prenatal diagnosis of severe PAS by imaging could help guide maternal counseling and selection of either hysterectomy or uterine-preserving surgery.

Enhanced expression of αVß3 integrin in villus and extravillous trophoblasts of placenta accreta.

BACKGROUND: Placenta accreta is one of the most serious complications in obstetrics and gynecology. Villous trophoblasts (VT) and extravillous trophoblasts (EVT) play a central role in normal placentation. Placenta accreta is characterized by abnormal invasion of EVT cells through the uterine layers, due to changes in several parameters, including adhesion proteins. Although αvß3 integrin is a central adhesion molecule, participating in multiple invasive pathological conditions including cancer, data on placenta accreta are lacking. OBJECTIVE: To study the expression pattern of αvß3 integrin in placenta accreta in comparison with normal placentas. STUDY DESIGN: We collected tissue samples from placentas defined as percreta, the most severe presentation of placenta accreta and from normal control placentas (n = 10 each). The samples underwent protein extractions for analyses of αvß3 expression by Western blots (WB) and a parallel tissue assessment by immunohistochemistry (IHC). RESULTS: WB results indicated significantly elevated αvß3 integrin expression in the percreta samples compared to normal placentas. These elevated levels were mainly contributed by EVT cells, as demonstrated by IHC. αvß3 integrin demonstrated a classical membranal expression in the VT cells, whereas a uniformly distributed expression was documented in the EVT cells. These patterns of the αvß3 integrin localization were similar in both accreta and normal placental samples. CONCLUSIONS: Enhanced αvß3 integrin expression, mainly in extra villous trophoblasts of placenta percreta, implies for a role of this adhesion molecule in pathological placentation.