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Molecular Medicine Reports May 2024Placenta accreta spectrum (PAS) is one of the most dangerous complications in obstetrics, which can lead to severe postpartum bleeding and shock, and even necessitate...
Pigment epithelium‑derived factor inhibits proliferation, invasion and angiogenesis, and induces ferroptosis of extravillous trophoblasts by targeting Wnt‑β‑catenin/VEGF signaling in placenta accreta spectrum.
Placenta accreta spectrum (PAS) is one of the most dangerous complications in obstetrics, which can lead to severe postpartum bleeding and shock, and even necessitate uterine removal. The abnormal migration and invasion of extravillous trophoblast cells (EVTs) and enhanced neovascularization occurring in an uncontrolled manner in time and space are closely related to the abnormal expression of pro‑angiogenic and anti‑angiogenic factors. The pigment epithelium‑derived factor (PEDF) is a multifunctional regulatory factor that participates in several important biological processes and is recognized as the most efficient inhibitor of angiogenesis. The present study aimed to explore the effects of PEDF on EVT phenotypes and the underlying mechanisms in PAS. HTR‑8/SVneo cells were transfected to overexpress or knock down PEDF. Cell proliferation and invasion were assessed using Cell Counting Kit‑8, 5‑ethynyl‑2'‑deoxyuridine and Transwell assays. angiogenesis was analyzed using tube formation assays. The degree of ferroptosis was assessed by evaluating the levels of lipid reactive oxygen species, total iron, Fe, malondialdehyde and reduced glutathione using commercial kits. The expression levels of biomarkers of ferroptosis, angiogenesis, cell proliferation and Wnt signaling were examined by western blotting. PEDF overexpression decreased the proliferation, invasion and angiogenesis, and induced ferroptosis of EVTs. Activation of Wnt signaling with BML‑284 and overexpression of vascular endothelial growth factor (VEGF) reversed the PEDF overexpression‑induced suppression of cell proliferation, invasion and tube formation. PEDF overexpression‑induced ferroptosis was also decreased by Wnt agonist treatment and VEGF overexpression. It was predicted that PEDF suppressed the proliferation, invasion and angiogenesis, and increased ferroptosis in EVTs by decreasing Wnt‑β‑catenin/VEGF signaling. The findings of the present study suggested a novel regulatory mechanism of the phenotypes of EVTs and PAS.
Topics: Pregnancy; Humans; Female; Vascular Endothelial Growth Factor A; Extravillous Trophoblasts; beta Catenin; Trophoblasts; Placenta Accreta; Wnt Signaling Pathway; Angiogenesis; Ferroptosis; Cell Proliferation; Cell Movement; Placenta; Eye Proteins; Nerve Growth Factors; Serpins
PubMed: 38488028
DOI: 10.3892/mmr.2024.13199 -
Medical Science Monitor : International... Mar 2024BACKGROUND Placenta accreta syndrome (PAS) can lead to severe obstetric bleeding, and can be life-threatening. This study aimed to assess the precision of radiomics... (Meta-Analysis)
Meta-Analysis
BACKGROUND Placenta accreta syndrome (PAS) can lead to severe obstetric bleeding, and can be life-threatening. This study aimed to assess the precision of radiomics features derived from magnetic resonance imaging (MRI) for diagnosing PAS. MATERIAL AND METHODS A comprehensive search was conducted in the databases PubMed, Embase, Web of Science, and the Cochrane library from inception to October 2023. We included diagnostic accuracy studies utilizing radiomics-MRI in PAS patients, with histopathology serving as the reference standard. The overall diagnostic odds ratio (DOR), sensitivity, specificity, and area under the curve (AUC) were computed to gauge the diagnostic accuracy of MRI-based radiomic features in PAS patients. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies 2. Statistical analyses were carried out using Stata 14.2, MetaDiSc 1.4, and Review Manager 5.3 software. RESULTS Seven studies involving 672 patients were incorporated. The aggregated DOR, sensitivity, specificity, and AUC for radiomics in detecting PAS were 78% (confidence interval32, 191), 87% (76%, 93%), 92% (89%, 94%), and 0.93 (0.91-0.95), respectively. The meta-analysis revealed notable heterogeneity among the included studies, with no evidence of a threshold effect. Subgroup analysis demonstrated that, in comparison to manual segmentation and validation groups with ≤100 cases and internal validation datasets, automated segmentation, validation groups with >100 cases, and external validation datasets exhibited superior diagnostic performance . CONCLUSIONS Our findings indicate that MRI-based radiomic features perform well in assessing the diagnostic risk of PAS during prenatal diagnosis. This noninvasive and convenient tool may prove valuable in facilitating the identification of PAS.
Topics: Female; Pregnancy; Humans; Placenta Accreta; Radiomics; Area Under Curve; Databases, Factual; Magnetic Resonance Imaging
PubMed: 38486373
DOI: 10.12659/MSM.943461 -
Cureus Feb 2024Introduction Placenta accreta is an important factor responsible for maternal morbidity and mortality and is commonly associated with emergent postpartum hysterectomy....
Introduction Placenta accreta is an important factor responsible for maternal morbidity and mortality and is commonly associated with emergent postpartum hysterectomy. The precise prenatal diagnosis of affected pregnancies allows optimal obstetric management. Ultrasonography (USG) and magnetic resonance imaging (MRI) are the only diagnostic modalities available for the prenatal diagnosis of placenta accreta. Objective This study aims to evaluate the accuracy of USG and MRI in diagnosing adherent placenta. Methods Thirty females with placenta previa or a history of previous cesarean sections were evaluated with USG at 28-30 weeks, followed by MRI. The findings of USG and MRI were compared with the intra-operative findings (gold standard) as determined at surgery and by pathological examination. Results Abnormal bridging vessel (n = 24; 80%) was the most common finding seen on USG, whereas abnormal bulge (n = 22; 73.3%) and heterogenous placenta (n = 21; 70%) were the most common findings seen on MRI. The sensitivity of USG and MRI was in the range of 86.7%-92.9% and 92.9%-100%, respectively, in diagnosing three types of adherent placenta. The positive predictive values (PPV) of USG and MRI were in the range of 86.7%-86.7% and 93.8%-100%, respectively, in diagnosing three types of adherent placenta. The accuracy of USG and MRI was in the range of 86.7%-96.7% and 96.7%-100%, respectively, in diagnosing three types of adherent placenta. Conclusion MRI helps to accurately classify placental invasion according to depth, as can be seen from the results of the present study, where the MRI technique was more accurate in diagnosing three types of adherent placenta.
PubMed: 38465149
DOI: 10.7759/cureus.53856 -
European Journal of Obstetrics,... May 2024Assisted reproductive technology (ART), especially frozen-thawed embryo transfer (FET) in a hormone replacement cycle (HRC), is a risk factor for placenta accreta...
OBJECTIVE
Assisted reproductive technology (ART), especially frozen-thawed embryo transfer (FET) in a hormone replacement cycle (HRC), is a risk factor for placenta accreta spectrum (PAS). This study aimed to clarify the risk factors for PAS related to the maternal background and ART techniques in pregnancies achieved after FET in an HRC.
STUDY DESIGN
We performed a case-control study in two tertiary perinatal centres in Japan. Among 14,028 patients who delivered at ≥24 weeks of gestation or were transferred after delivery to two tertiary perinatal centres between 2010 and 2021, 972 conceived with ART and 13,056 conceived without ART. PAS was diagnosed on the basis of the FIGO classification for the clinical diagnosis of PAS or retained products of conception after delivery at ≥24 weeks of gestation. We excluded women with fresh embryo transfer, FET with a spontaneous ovulatory cycle, a donor oocyte cycle, and missing details of the ART treatment. Finally, among women who conceived after FET in an HRC, 62 with PAS and 340 without PAS were included in this study. Multivariate logistic regression models were used for case-control comparisons, with adjustment for maternal age at delivery, parity, endometriosis or adenomyosis, the number of previous uterine surgeries of caesarean section, myomectomy, endometrial polypectomy or endometrial curettage, placenta previa, the stage of transferred embryos, and endometrial thickness at the initiation of progestin administration.
RESULTS
PAS was associated with ≥2 previous uterine surgeries (adjusted odds ratio, 3.57; 95 % confidence interval, 1.60-7.97) and the stage of embryo transfer (blastocysts: adjusted odds ratio, 2.89; 95 % confidence interval, 1.15-7.26). In patients with <2 previous uterine surgeries, PAS was associated with an endometrial thickness of <7.0 mm (adjusted odds ratio, 5.18; 95 % confidence interval, 1.10-24.44).
CONCLUSION
Multiple uterine surgeries and the transfer of blastocysts are risk factors for PAS in pregnancies conceived after FET in an HRC. In women with <2 previous uterine surgeries, a thin endometrium before FET is also a risk factor for PAS in these pregnancies.
Topics: Pregnancy; Female; Humans; Placenta Accreta; Case-Control Studies; Cesarean Section; Embryo Transfer; Progestins; Cryopreservation; Risk Factors; Retrospective Studies
PubMed: 38458035
DOI: 10.1016/j.ejogrb.2024.02.040 -
American Journal of Obstetrics &... May 2024In recent years, there has been a significant rise in cases of placenta accreta spectrum, a group of life-threatening placental disorders that can arise during... (Review)
Review
In recent years, there has been a significant rise in cases of placenta accreta spectrum, a group of life-threatening placental disorders that can arise during childbirth. Early detection plays a crucial role in facilitating meticulous delivery planning, ultimately leading to a reduction in mortality and morbidity rates and improved overall outcomes. Although third-trimester ultrasound has traditionally been the primary method for prenatal screening for placenta accreta spectrum, it often falls short in identifying cases or diagnosis is too late for optimal delivery planning. Emerging evidence has highlighted the option of early detection of placenta accreta spectrum indicators during the first trimester of pregnancy. This comprehensive review delves into our current knowledge of sonographic assessment of the uterine cervicoisthmic complex in the first trimester, examining the location and appearance of cesarean scars and exploring first-trimester screening strategies, ultimately paving the way for improved maternal and neonatal outcomes.
Topics: Humans; Placenta Accreta; Pregnancy; Female; Pregnancy Trimester, First; Ultrasonography, Prenatal; Cesarean Section; Cicatrix; Early Diagnosis; Cervix Uteri
PubMed: 38447672
DOI: 10.1016/j.ajogmf.2024.101329 -
AJOG Global Reports Feb 2024Placenta accreta spectrum disorders are a complex range of placental pathologies that are associated with significant maternal morbidity and mortality. A diagnosis of...
BACKGROUND
Placenta accreta spectrum disorders are a complex range of placental pathologies that are associated with significant maternal morbidity and mortality. A diagnosis of placenta accreta spectrum relies on ultrasonographic findings with modest positive predictive value. Exosomal microRNAs are small RNA molecules that reflect the cellular processes of the origin tissues.
OBJECTIVE
We aimed to explore exosomal microRNA expression to understand placenta accreta spectrum pathology and clinical use for placenta accreta spectrum detection.
STUDY DESIGN
This study was a biomarker analysis of prospectively collected samples at 2 academic institutions from 2011 to 2022. Plasma specimens were collected from patients with suspected placenta accreta spectrum, placenta previa, or repeat cesarean deliveries. Exosomes were quantified and characterized by nanoparticle tracking analysis and western blotting. MicroRNA were assessed by polymerase chain reaction array and targeted single quantification. MicroRNA pathway analysis was performed using the Ingenuity Pathway Analyses software. Placental biopsies were taken from all groups and analyzed by polymerase chain reaction and whole cell enzyme-linked immunosorbent assay. Receiver operating characteristic curve univariate analysis was performed for the use of microRNA in the prediction of placenta accreta spectrum. Clinically relevant outcomes were collected from abstracted medical records.
RESULTS
Plasma specimens were analyzed from a total of 120 subjects (60 placenta accreta spectrum, 30 placenta previa, and 30 control). Isolated plasma exosomes had a mean size of 71.5 nm and were 10 times greater in placenta accreta spectrum specimens (20 vs 2 particles/frame). Protein expression of exosomes was positive for intracellular adhesion molecule 1, flotilin, annexin, and CD9. MicroRNA analysis showed increased detection of 3 microRNAs (mir-92, -103, and -192) in patients with placenta accreta spectrum. Pathway interaction assessment revealed differential regulation of p53 signaling in placenta accreta spectrum and of erythroblastic oncogene B2 or human epidermal growth factor 2 in control specimens. These findings were subsequently confirmed in placental protein analysis. Placental microRNA paralleled plasma exosomal microRNA expression. Biomarker assessment of placenta accreta spectrum signature microRNA had an area under the receiver operating characteristic curve of 0.81 (<.001; 95% confidence interval, 0.73-0.89) with a sensitivity and specificity of 89.2% and 80%, respectively.
CONCLUSION
In this large cohort, plasma exosomal microRNA assessment revealed differentially expressed pathways in placenta accreta spectrum, and these microRNAs are potential biomarkers for the detection of placenta accreta spectrum.
PubMed: 38440154
DOI: 10.1016/j.xagr.2024.100319 -
Medical Science Monitor : International... Mar 2024BACKGROUND The incidence of placenta accreta spectrum disorder (PAS) has been increasing in past decades, and women with PAS are a high-risk maternal population. This...
Efficacy of Bakri Intrauterine Balloon in Managing Postpartum Hemorrhage: A Comparative Analysis of Vaginal and Cesarean Deliveries with Placenta Accreta Spectrum Disorders.
BACKGROUND The incidence of placenta accreta spectrum disorder (PAS) has been increasing in past decades, and women with PAS are a high-risk maternal population. This study aimed to explore the performance of Bakri intrauterine balloon tamponade (IUBT) in the treatment of postpartum hemorrhage (PPH), among those with and without PAS. MATERIAL AND METHODS The outcomes of 198 women who underwent treatment for PPH using IUBT were retrospectively analyzed. The demographics and maternal outcomes were analyzed for vaginal and cesarean births, with PAS and without PAS. RESULTS Compared to women with vaginal births (n=130), women who underwent cesarean births (n=68) showed a higher proportion of age ≥35 years (χ²=6.85, P=0.013), multiple births (χ²=13.60, P<0.001), preeclampsia (χ²=9.81, P=0.002), use of transabdominal IUBT (χ²=84.12, P<0.001) and pre-IUBT interventions (χ²=41.61, P<0.001), but had less infused volume of physiological saline (t=6.41, P<0.001). Women with PAS (n=105) showed a higher rate of pre-IUBT intervention (χ²=4.96, P=0.029) and transabdominal IUBT placement (χ²=9.37, P=0.002) than non-PAS women (n=93). The 36 women with PAS (n=36) showed a higher rate of preeclampsia (χ²=4.80, P=0.029), pre-IUBT intervention (χ²=5.90, P=0.015), and transabdominal IUBT placement (χ²=14.94, P<0.001) and a shorter duration from delivery to Bakri insertion (χ²=3.31, P=0.002), than non-PAS women (n=32). CONCLUSIONS PAS was a major cause of PPH at 198 vaginal and cesarean births. An accurate and timely pre-IUBT intervention and Bakri IUBT placement was critical for controlling PPH in cesarean births, especially in women with PAS.
Topics: Pregnancy; Humans; Female; Adult; Placenta Accreta; Postpartum Hemorrhage; Pre-Eclampsia; Retrospective Studies; Cesarean Section
PubMed: 38433445
DOI: 10.12659/MSM.943072 -
American Journal of Obstetrics and... Mar 2024The prevalence of placenta accreta spectrum, a potentially life-threatening condition, has exhibited a significant global rise in recent decades. Effective screening...
BACKGROUND
The prevalence of placenta accreta spectrum, a potentially life-threatening condition, has exhibited a significant global rise in recent decades. Effective screening methods and early identification strategies for placenta accreta spectrum could enable early treatment and improved outcomes. Endometrial thickness plays a crucial role in successful embryo implantation and favorable pregnancy outcomes. Extensive research has been conducted on the impact of endometrial thickness on assisted reproductive technology cycles, specifically in terms of pregnancy rates, live birth rates, and pregnancy loss rates. However, limited knowledge exists regarding the influence of endometrial thickness on placenta accreta spectrum.
OBJECTIVE
This study aimed to evaluate the association between preimplantation endometrial thickness and the occurrence of placenta accreta spectrum in women undergoing assisted reproductive technology cycles.
STUDY DESIGN
A total of 4637 women who had not undergone previous cesarean delivery and who conceived by in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment and subsequently delivered at the Third Affiliated Hospital of Guangzhou Medical University between January 2008 and December 2020 were included in this study. To explore the relationship between endometrial thickness and placenta accreta spectrum, we used smooth curve fitting, threshold effect, and saturation effect analysis. Multivariate logistic regression analysis was performed to evaluate the independent association between endometrial thickness and placenta accreta spectrum while adjusting for potential confounding factors. Propensity score matching was performed to reduce the influence of bias and unmeasured confounders. Furthermore, we used causal mediation effect analysis to investigate the mediating role of endometrial thickness in the relationship between gravidity and ovarian stimulation protocol and the occurrence of placenta accreta spectrum.
RESULTS
Among the 4637 women included in this study, pregnancies with placenta accreta spectrum (159; 3.4%) had significantly thinner endometrial thickness (non-placenta accreta spectrum, 10.08±2.04 mm vs placenta accreta spectrum, 8.88±2.21 mm; P<.001) during the last ultrasound before embryo transfer. By using smooth curve fitting, it was found that changes in endometrial thickness had a significant effect on the incidence of placenta accreta spectrum up to a thickness of 10.9 mm, beyond which the effect plateaued. Then, the endometrial thickness was divided into the following 4 groups: ≤7, >7 to ≤10.9, >10.9 to ≤13, and >13 mm. The absolute rates of placenta accreta spectrum in each group were 11.91%, 3.73%, 1.35%, and 2.54%, respectively. Compared with women with an endometrial thickness from 10.9 to 13 mm, the odds of placenta accreta spectrum increased from an adjusted odds ratio of 2.27 (95% confidence interval, 1.33-3.86) for endometrial thickness from 7 to 10.9 mm to an adjusted odds ratio of 7.15 (95% confidence interval, 3.73-13.71) for endometrial thickness <7 mm after adjusting for potential confounding factors. Placenta previa remained as an independent risk factor for placenta accreta spectrum (adjusted odds ratio, 11.80; 95% confidence interval, 7.65-18.19). Moreover, endometrial thickness <7 mm was still an independent risk factor for placenta accreta spectrum (adjusted odds ratio, 3.91; 95% confidence interval, 1.57-9.73) in the matched cohort after PSM. Causal mediation analysis revealed that approximately 63.9% of the total effect of gravidity and 18.6% of the total effect of ovarian stimulation protocol on placenta accreta spectrum were mediated by endometrial thickness.
CONCLUSION
The findings of our study indicate that thin endometrial thickness is an independent risk factor for placenta accreta spectrum in women without previous cesarean delivery undergoing assisted reproductive technology treatment. The clinical significance of this risk factor is slightly lower than that of placenta previa. Furthermore, our results demonstrate that endometrial thickness plays a significant mediating role in the relationship between gravidity or ovarian stimulation protocol and placenta accreta spectrum.
PubMed: 38432419
DOI: 10.1016/j.ajog.2024.02.301 -
European Heart Journal. Case Reports Feb 2024Antenatal cardiovascular disease is a major cause of maternal morbidity and mortality. Severe rheumatic mitral stenosis is especially poorly tolerated during pregnancy.
Case report of pregnancy complicated by severe pulmonary hypertension from mitral stenosis and placenta accreta spectrum disorder: management of two life-threatening conditions.
BACKGROUND
Antenatal cardiovascular disease is a major cause of maternal morbidity and mortality. Severe rheumatic mitral stenosis is especially poorly tolerated during pregnancy.
CASE SUMMARY
We present a young woman with severe pulmonary hypertension secondary to rheumatic mitral stenosis. She presented at 25 weeks 4 days gestation for evaluation of a pregnancy complicated by placenta accreta spectrum disorder. Invasive hemodynamic testing was carried out to delineate her hemodynamics, and a multidisciplinary cardio-obstetrics team collaborated closely with the patient and her partner to create a management plan. Ultimately, the patient was initiated on veno-arterial extracorporeal membrane oxygenation and underwent caesarean section delivery followed by hysterectomy and subsequent valve replacement surgery.
DISCUSSION
This case describes the treatment options considered to balance the risk of decompensation in the setting of severe pulmonary hypertension with hemorrhage associated with placenta accreta spectrum disorder. It highlights the importance of a multidisciplinary, team-based approach to the management of high-risk cardiac conditions throughout pregnancy.
PubMed: 38425728
DOI: 10.1093/ehjcr/ytae055 -
Scientific Reports Feb 2024Placenta accreta spectrum (PAS) has become a significant life-threatening issue due to its increased incidence and associated morbidity and mortality. Pregnancy is often...
Placenta accreta spectrum (PAS) has become a significant life-threatening issue due to its increased incidence and associated morbidity and mortality. Pregnancy is often associated with states of anaemia, and severe maternal haemorrhage represents a major risk factor for red blood cell (RBC) transfusion. The present study retrospectively analyzed the prevalence of anaemia, transfusion requirements and outcome in women with PAS. Using data from the German Statistical Office pregnant patients with deliveries hospitalized between January 2012 and December 2021 were included. Primary outcome was the prevalence of anemia and administration of RBCs. Secondary outcome were complications in women with PAS who received RBC transfusion. In total 6,493,606 pregnant women were analyzed, of which 38,060 (0.59%) were diagnosed with PAS. The rate of anaemia during pregnancy (60.36 vs. 23.25%; p < 0.0001), postpartum haemorrhage (47.08 vs. 4.41%; p < 0.0001) and RBC transfusion rate (14.68% vs. 0.72%; p < 0.0001) were higher in women with PAS compared to women without PAS. Women with PAS who had bleeding and transfusion experienced significantly more peripartum complications than those who did not. A multiple logistic regression revealed that the probability for RBC transfusion in all pregnant women was positively associated with anaemia (OR 21.96 (95% CI 21.36-22.58)). In women with PAS, RBC transfusion was positively associated with the presence of renal failure (OR 11.27 (95% CI 9.35-13.57)) and congestive heart failure (OR 6.02 (95% CI (5.2-7.07)). Early anaemia management prior to delivery as well as blood conservation strategies are crucial in women diagnosed with PAS.
Topics: Female; Humans; Pregnancy; Erythrocyte Transfusion; Placenta Accreta; Retrospective Studies; Anemia; Blood Transfusion; Placenta; Hysterectomy
PubMed: 38424178
DOI: 10.1038/s41598-024-55531-6