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Placenta accreta spectrum in early and late pregnancy from an imaging perspective. A scoping review.Radiologia 2023Placenta accreta spectrum (PAS) disorders (with increasing order of the depth of invasion: accreta, increta, percreta) are quite challenging for the purpose of diagnosis... (Review)
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).
Topics: Pregnancy; Humans; Female; Placenta Accreta; Placenta; Cesarean Section; Magnetic Resonance Imaging
PubMed: 38049252
DOI: 10.1016/j.rxeng.2023.02.001 -
International Journal of Molecular... Sep 2023Placenta accreta is a high-risk condition causing obstetric crisis and hemorrhage; however, its pathogenesis remains unknown. We aimed to identify the factors...
Placenta accreta is a high-risk condition causing obstetric crisis and hemorrhage; however, its pathogenesis remains unknown. We aimed to identify the factors contributing to trophoblast invasiveness and angiogenic potential, which in turn drive the pathogenesis of placenta accreta. We focused on the transforming growth factor (TGF)-β1-Smad pathway and investigated the intrinsic relationship between the time- and dose-dependent inhibition of the ubiquitinating enzyme UCHL5 using bAP15, a deubiquitinase inhibitor, after TGF-β1 stimulation and the invasive and angiogenic potential of two cell lines, gestational choriocarcinoma cell line JEG-3 and trophoblast cell line HTR-8/SVneo. UCHL5 inhibition negatively regulated TGF-β1-induced Smad2 activation, decreasing extravillous trophoblast invasiveness. Smad1/5/9 and extracellular signal-regulated kinase (ERK) were simultaneously activated, and vascular endothelial growth factor was secreted into the trophoblast medium. However, extravillous trophoblast culture supernatant severely impaired the vasculogenic potential of human umbilical vein endothelial cells. These results suggest that the downstream ERK pathway and Smad1/5/9 potentially regulate the TGF-β1-Smad pathway in extravillous trophoblasts, whereas Smad2 contributes to their invasiveness. The abnormal invasive and angiogenic capacities of extravillous cells, likely driven by the interaction between TGF-β1-Smad and ERK pathways, underlie the pathogenesis of placenta accreta.
Topics: Female; Pregnancy; Humans; Transforming Growth Factor beta; Transforming Growth Factor beta1; Placenta Accreta; Cell Line, Tumor; Vascular Endothelial Growth Factor A; Cysteine Proteases; Extracellular Signal-Regulated MAP Kinases; Human Umbilical Vein Endothelial Cells; Ubiquitin Thiolesterase
PubMed: 37762005
DOI: 10.3390/ijms241813706 -
BMC Pregnancy and Childbirth Aug 2023A previous study investigated the effect of adenomyosis on perinatal outcomes. Some studies have reported varying effect of adenomyosis on pregnancy outcomes in some...
BACKGROUND
A previous study investigated the effect of adenomyosis on perinatal outcomes. Some studies have reported varying effect of adenomyosis on pregnancy outcomes in some patients and dependence on the degree and subtype of uterine lesions. To elucidate the impact of adenomyosis on perinatal outcomes.
METHODS
This large-scale cohort study used the perinatal registry database of the Japan Society of Obstetrics and Gynecology. A dataset of 203,745 mothers who gave birth between January 2020 and December 2020 in Japan was included in the study. The participants were divided into two groups based on the presence or absence of adenomyosis. Information regarding the use of fertility treatment, delivery, obstetric complications, maternal treatments, infant, fetal appendages, obstetric history, underlying diseases, infectious diseases, use of drugs, and maternal and infant death were compared between the groups.
RESULTS
In total, 1,204 participants had a history of adenomyosis and 151,105 did not. The adenomyosis group had higher rates of uterine rupture (0.2% vs. 0.01%, P = 0.02) and placenta accreta (2.0% vs. 0.5%, P < 0.001) than the non-adenomyosis group. A history of adenomyosis (odds ratio: 2.26; 95% confidence interval: 1.43-3.27; P < 0.001), uterine rupture (odds ratio: 3.45; 95% confidence interval: 0.89-19.65; P = 0.02), placental abruption (odds ratio: 2.11; 95% confidence interval: 1.27-3.31; P < 0.01), and fetal growth restriction (odds ratio: 2.66; 95% confidence interval: 2.00-3.48; P < 0.01) were independent risk factors for placenta accreta.
CONCLUSION
Adenomyosis in pregnancies is associated with an increased risk of placenta accreta, uterine rupture, placental abruption, and fetal growth restriction.
TRIAL REGISTRATION
Institutional Review Board of Tottori University Hospital (IRB no. 21A244).
Topics: Pregnancy; Female; Humans; Cohort Studies; Abruptio Placentae; Uterine Rupture; Placenta Accreta; Fetal Growth Retardation; Retrospective Studies; Placenta; Adenomyosis
PubMed: 37568120
DOI: 10.1186/s12884-023-05895-w -
Biomarker Research Jun 2024Placenta accreta spectrum disorders (PAS) are a severe complication characterized by abnormal trophoblast invasion into the myometrium. The underlying mechanisms of PAS...
Single-cell and spatial transcriptomics reveal alterations in trophoblasts at invasion sites and disturbed myometrial immune microenvironment in placenta accreta spectrum disorders.
BACKGROUND
Placenta accreta spectrum disorders (PAS) are a severe complication characterized by abnormal trophoblast invasion into the myometrium. The underlying mechanisms of PAS involve a complex interplay of various cell types and molecular pathways. Despite its significance, both the characteristics and intricate mechanisms of this condition remain poorly understood.
METHODS
Spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq), were performed on the tissue samples from four PAS patients, including invasive tissues (ST, n = 3; scRNA-seq, n = 4), non-invasive normal placenta samples (ST, n = 1; scRNA-seq, n = 2). Three healthy term pregnant women provided normal myometrium samples (ST, n = 1; scRNA-seq, n = 2). ST analysis characterized the spatial expression landscape, and scRNA-seq was used to identify specific cellular components in PAS. Immunofluorescence staining was conducted to validate the findings.
RESULTS
ST slices distinctly showed the myometrium in PAS was invaded by three subpopulations of trophoblast cells, extravillous trophoblast cells, cytotrophoblasts, and syncytiotrophoblasts, especially extravillous trophoblast cells. The pathways enriched by genes in trophoblasts, smooth muscle cells (SMC), and immune cells of PAS were mainly associated with immune and inflammation. We identified elevated expression of the angiogenesis-stimulating gene PTK2, alongside the cell proliferation-enhancing gene EGFR, within the trophoblasts of PAS group. Trophoblasts mainly contributed the enhancement of HLA-G and EBI3 signaling, which is crucial in establishing immune escape. Meanwhile, SMC regions in PAS exhibited upregulation of immunomodulatory markers such as CD274, HAVCR2, and IDO1, with CD274 expression experimentally verified to be increased in the invasive SMC areas of the PAS group.
CONCLUSIONS
This study provided information of cellular composition and spatial organization in PAS at single-cell and spatial level. The dysregulated expression of genes in PAS revealed a complex interplay between enhanced immune escape in trophoblasts and immune tolerance in SMCs during invasion in PAS. These findings will enhance our understanding of PAS pathogenesis for developing potential therapeutic strategies.
PubMed: 38831319
DOI: 10.1186/s40364-024-00598-6 -
American Journal of Obstetrics and... Apr 2024Placenta accreta spectrum disorders are associated with severe maternal morbidity and mortality. Placenta accreta spectrum disorders involve excessive adherence of the...
BACKGROUND
Placenta accreta spectrum disorders are associated with severe maternal morbidity and mortality. Placenta accreta spectrum disorders involve excessive adherence of the placenta preventing separation at birth. Traditionally, this condition has been attributed to excessive trophoblast invasion; however, an alternative view is a fundamental defect in decidual biology.
OBJECTIVE
This study aimed to gain insights into the understanding of placenta accreta spectrum disorder by using single-cell and spatially resolved transcriptomics to characterize cellular heterogeneity at the maternal-fetal interface in placenta accreta spectrum disorders.
STUDY DESIGN
To assess cellular heterogeneity and the function of cell types, single-cell RNA sequencing and spatially resolved transcriptomics were used. A total of 12 placentas were included, 6 placentas with placenta accreta spectrum disorder and 6 controls. For each placenta with placenta accreta spectrum disorder, multiple biopsies were taken at the following sites: placenta accreta spectrum adherent and nonadherent sites in the same placenta. Of note, 2 platforms were used to generate libraries: the 10× Chromium and NanoString GeoMX Digital Spatial Profiler for single-cell and spatially resolved transcriptomes, respectively. Differential gene expression analysis was performed using a suite of bioinformatic tools (Seurat and GeoMxTools R packages). Correction for multiple testing was performed using Clipper. In situ hybridization was performed with RNAscope, and immunohistochemistry was used to assess protein expression.
RESULTS
In creating a placenta accreta cell atlas, there were dramatic difference in the transcriptional profile by site of biopsy between placenta accreta spectrum and controls. Most of the differences were noted at the site of adherence; however, differences existed within the placenta between the adherent and nonadherent site of the same placenta in placenta accreta. Among all cell types, the endothelial-stromal populations exhibited the greatest difference in gene expression, driven by changes in collagen genes, namely collagen type III alpha 1 chain (COL3A1), growth factors, epidermal growth factor-like protein 6 (EGFL6), and hepatocyte growth factor (HGF), and angiogenesis-related genes, namely delta-like noncanonical Notch ligand 1 (DLK1) and platelet endothelial cell adhesion molecule-1 (PECAM1). Intraplacental tropism (adherent versus non-adherent sites in the same placenta) was driven by differences in endothelial-stromal cells with notable differences in bone morphogenic protein 5 (BMP5) and osteopontin (SPP1) in the adherent vs nonadherent site of placenta accreta spectrum.
CONCLUSION
Placenta accreta spectrum disorders were characterized at single-cell resolution to gain insight into the pathophysiology of the disease. An atlas of the placenta at single cell resolution in accreta allows for understanding in the biology of the intimate maternal and fetal interaction. The contributions of stromal and endothelial cells were demonstrated through alterations in the extracellular matrix, growth factors, and angiogenesis. Transcriptional and protein changes in the stroma of placenta accreta spectrum shift the etiologic explanation away from "invasive trophoblast" to "loss of boundary limits" in the decidua. Gene targets identified in this study may be used to refine diagnostic assays in early pregnancy, track disease progression over time, and inform therapeutic discoveries.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Placenta Accreta; Endothelial Cells; Placenta; Placenta Diseases; Abruptio Placentae; Intercellular Signaling Peptides and Proteins; Decidua; Endothelium
PubMed: 38296740
DOI: 10.1016/j.ajog.2023.10.001 -
Cureus May 2024Placenta previa poses significant risks to maternal and perinatal health, yet its management remains challenging. This comprehensive review synthesizes current evidence... (Review)
Review
Placenta previa poses significant risks to maternal and perinatal health, yet its management remains challenging. This comprehensive review synthesizes current evidence on maternal and perinatal outcomes in placenta previa, addressing its epidemiology, pathophysiology, diagnosis, and management strategies. Placenta previa complicates pregnancies, with increasing incidence linked to factors such as advanced maternal age and rising cesarean rates. Maternal complications, including hemorrhage and placenta accreta spectrum disorders, pose substantial risks. At the same time, perinatal outcomes are marked by increased rates of preterm birth, intrauterine growth restriction, and neonatal morbidity and mortality. Timely diagnosis and appropriate management, including antenatal corticosteroids and multidisciplinary care, are critical for optimizing outcomes. Future research should focus on improving diagnostic methods, evaluating novel interventions, and assessing long-term neurodevelopmental outcomes. This review underscores the importance of informed clinical practice and ongoing research efforts to enhance outcomes for women and infants affected by placenta previa.
PubMed: 38841031
DOI: 10.7759/cureus.59737 -
European Journal of Radiology Nov 2023To 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...
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.
Topics: Pregnancy; Humans; Female; Placenta Accreta; Placenta Previa; Placenta; Retrospective Studies; Cesarean Section; Magnetic Resonance Imaging
PubMed: 37801998
DOI: 10.1016/j.ejrad.2023.111116 -
Case Reports in Women's Health Sep 2023
PubMed: 37954226
DOI: 10.1016/j.crwh.2023.e00521 -
The Journal of Maternal-fetal &... Dec 2023To demonstrate the surgical and morbidity differences between upper and lower parametrial placenta invasion (PPI).
OBJECTIVE
To demonstrate the surgical and morbidity differences between upper and lower parametrial placenta invasion (PPI).
MATERIALS AND METHODS
Forty patients with placenta accreta spectrum (PAS) into the parametrium underwent surgery between 2015 and 2020. Based on the peritoneal reflection, the study compared two types of parametrial placental invasion (PPI), upper or lower. Surgical approach to PAS follows a conservative-resective method. Before delivery, surgical staging by pelvic fascia dissection established a final diagnosis of placental invasion. In upper PPI cases, the team attempted to repair the uterus after resecting all invaded tissues or performing a hysterectomy. In cases of lower PPI, experts performed a hysterectomy in all cases. The team only used proximal vascular (aortic occlusion) control in cases of lower PPI. Surgical dissection for lower PPI started finding the ureter in the pararectal space, ligating all the tissues (placenta and newly formed vessels) to create a tunnel to release the ureter from the placenta and placenta suppletory vessels. Overall, at least three pieces of the invaded area were sent for histological analysis.
RESULTS
Forty patients with PPI were included, 13 in the upper parametrium and 27 in the lower parametrium. MRI indicated PPI in 33/40 patients; in three, the diagnosis was presumed by ultrasound or medical background. The intrasurgical staging categorizes 13 cases of PPI performed and finds diagnosis in seven undetected cases. The expertise team completed a total hysterectomy in 2/13 upper PPI cases and all lower PPI cases (27/27). Hysterectomies in the upper PPI group were performed by extensive damage of the lateral uterine wall or with a tube compromise. Ureteral injury ensued in six cases, corresponding to cases without catheterization or incomplete ureteral identification. All aortic vascular proximal control (aortic balloon, internal aortic compression, or aortic loop) was efficient for controlling bleeding; in contrast, ligature of the internal iliac artery resulted in a useless procedure, resulting in uncontrollable bleeding and maternal death (2/27). All patients had antecedents of placental removal, abortion, curettage after a cesarean section, or repeated D&C.
CONCLUSIONS
Lower PAS parametrial involvement is uncommon but associated with elevated maternal morbidity. Upper and lower PPI has different surgical risks and technical approaches; consequently, an accurate diagnosis is needed. The clinical background of manual placental removal, abortion, and curettage after a cesarean or repeated D&C could be ideally studied to diagnose a possible PPI. For patients with high-risk antecedents or unsure ultrasound, a T2 weight MRI is always recommended. Performing comprehensive surgical staging in PAS allows the efficient diagnosis of PPI before using some procedures.
Topics: Pregnancy; Humans; Female; Placenta Accreta; Cesarean Section; Peritoneum; Placenta; Hysterectomy; Retrospective Studies; Morbidity
PubMed: 36966802
DOI: 10.1080/14767058.2023.2183764 -
Reproductive Health Aug 2023Most treatments for postpartum haemorrhage (PPH) lack evidence of effectiveness. New innovations are ubiquitous but have not been synthesized for ready access. (Review)
Review
BACKGROUND
Most treatments for postpartum haemorrhage (PPH) lack evidence of effectiveness. New innovations are ubiquitous but have not been synthesized for ready access.
NARRATIVE REVIEW
Pubmed 2020 to 2021 was searched on 'postpartum haemorrhage treatment', and novel reports among 755 citations were catalogued. New health care strategies included early diagnosis with a bundled first response and home-based treatment of PPH. A calibrated postpartum blood monitoring tray has been described. Oxytocin is more effective than misoprostol; addition of misoprostol to oxytocin does not improve treatment. Heat stable carbetocin has not been assessed for treatment. A thermostable microneedle oxytocin patch has been developed. Intravenous tranexamic acid reduces mortality but deaths have been reported from inadvertent intrathecal injection. New transvaginal uterine artery clamps have been described. Novel approaches to uterine balloon tamponade include improvised and purpose-designed free-flow (as opposed to fixed volume) devices and vaginal balloon tamponade. Uterine suction tamponade methods include purpose-designed and improvised devices. Restrictive fluid resuscitation, massive transfusion protocols, fibrinogen use, early cryopreciptate transfusion and point-of-care viscoelastic haemostatic assay-guided blood product transfusion have been reported. Pelvic artery embolization and endovascular balloon occlusion of the aorta and pelvic arteries are used where available. External aortic compression and direct compression of the aorta during laparotomy or aortic clamping (such as with the Paily clamp) are alternatives. Transvaginal haemostatic ligation and compression sutures, placental site sutures and a variety of novel compression sutures have been reported. These include Esike's technique, three vertical compression sutures, vertical plus horizontal compression sutures, parallel loop binding compression sutures, uterine isthmus vertical compression sutures, isthmic circumferential suture, circumferential compression sutures with intrauterine balloon, King's combined uterine suture and removable retropubic uterine compression suture. Innovative measures for placenta accreta spectrum include a lower uterine folding suture, a modified cervical inversion technique, bilateral uterine artery ligation with myometrial excision of the adherent placenta and cervico-isthmic sutures or a T-shaped lower segment repair. Technological advances include cell salvage, high frequency focussed ultrasound for placenta increta and extra-corporeal membrane oxygenation.
CONCLUSIONS
Knowledge of innovative methods can equip clinicians with last-resort options when faced with haemorrhage unresponsive to conventional methods.
Topics: Female; Pregnancy; Humans; Postpartum Hemorrhage; Oxytocin; Misoprostol; Placenta; Hemostatics
PubMed: 37568196
DOI: 10.1186/s12978-023-01657-1