Ultrasound-histopathologic features of the utero-placental interface in placenta accreta spectrum.

The objective of this study was to evaluate the relationship between utero-placental vascular changes on ultrasound imaging and histopathologic findings according to the grade of villous invasion in placenta accreta spectrum (PAS). The ultrasound features of 31 patients with singleton pregnancies diagnosed prenatally with low-lying/placenta previa accreta were compared with histopathology findings following caesarean hysterectomy (n = 25) or partial myometrial resection (n = 6). The number and degree of transformation of arteries within the superficial layer of myometrium were recorded. Cytokeratin 7 (CK7) immunohistochemistry was used to complement H&E analysis. All 31 patients presented with loss of clear zone, myometrial thinning and placenta lacunae. Subplacental hypervascularity and lacunae feeder vessels were found in 25 and nine cases, respectively. Large recent intervillous thromboses were found in one case with adherent villi and 12 cases with invasive villi, and showed a significantly different distribution according to lacunae scores. Thick basal plate fibrinoid deposits were found in all the areas of abnormally adherent and invasive villous tissue There was no significant difference in the mean count of partially remodeled vessels or vessels completely lacking remodeling according to the lacunae score and grade of placental invasiveness. EVT cells were arranged in superficial confluent sheets or superficial irregular clusters, or were scattered deep below the basal plate. Placental ultrasound and histopathologic features associated with PAS are more pronounced in invasive cases suggesting that they are secondary to the haemodynamic effects of abnormally deep placentation and transformation of the radial and arcuate arteries.

Jauniaux E ，Zosmer N ，Subramanian D ，Shaikh H ，Burton GJ ... -  《-》

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

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. To prospectively evaluate the microscopic changes used in grading and to identify changes that might explain the abnormal placental tissue attachment. 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. 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. 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.

Jauniaux E ，Hussein AM ，Elbarmelgy RM ，Elbarmelgy RA ，Burton GJ ... -  《-》

Prospective evaluation of impact of post-Cesarean section uterine scarring in perinatal diagnosis of placenta accreta spectrum disorder.

Standardized ultrasound imaging and pathology protocols have recently been developed for the perinatal diagnosis of placenta accreta spectrum (PAS) disorders. The aim of this study was to evaluate prospectively the effectiveness of these standardized protocols in the prenatal diagnosis and postnatal examination of women presenting with a low-lying placenta or placenta previa and a history of multiple Cesarean deliveries (CDs). This was a prospective cohort study of 84 consecutive women with a history of two or more prior CDs presenting with a singleton pregnancy and low-lying placenta/placenta previa at 32-37 weeks' gestation, who were referred for perinatal care and management between 15 January 2019 and 15 December 2020. All women were investigated using the standardized description of ultrasound signs of PAS proposed by the European Working Group on abnormally invasive placenta. In all cases, the ultrasound features were compared with intraoperative and histopathological findings. Areas of abnormal placental attachment were identified during the immediate postoperative gross examination and sampled for histological examination. The data of a subgroup of 32 women diagnosed antenatally as non-PAS who had complete placental separation at birth were compared with those of 39 cases diagnosed antenatally as having PAS disorder that was confirmed by histopathology at delivery. Of the 84 women included in the study, 42 (50.0%) were diagnosed prenatally as PAS and the remaining 42 (50.0%) as non-PAS on ultrasound examination. Intraoperatively, 66 (78.6%) women presented with a large or extended area of dehiscence and 52 (61.9%) with a dense tangled bed of vessels or multiple vessels running laterally and craniocaudally in the uterine serosa. A loss of clear zone was recorded on grayscale ultrasound imaging in all 84 cases, while there was no case with bladder-wall interruption or with a focal exophytic mass. Myometrial thinning (< 1 mm) in at least one area of the anterior uterine wall was found in 41 (97.6%) of the 42 cases diagnosed as non-PAS on ultrasound and 37 (88.1%) of the 42 diagnosed antenatally as PAS. Histological samples were available for all 48 hysterectomy specimens with abnormal placental attachment and for the three cases managed conservatively with focal myometrial resection and uterine reconstruction. Villous tissue was found directly attached to the superficial myometrium (placenta creta) in six of these cases and both creta villous tissue and deeply implanted villous tissue within the uterine wall (placenta increta) were found in the remaining 45 cases. There was no evidence of percreta placentation on histology in any of the PAS cases. Comparison of the main antenatal ultrasound signs and perioperative macroscopic findings between the two subgroups correctly diagnosed antenatally (32 non-PAS and 39 PAS) showed no significant difference with respect to the distribution of myometrial thinning and the presence of a placental bulge on ultrasound and of anterior uterine wall dehiscence intraoperatively. Compared with the non-PAS subgroup, the PAS subgroup showed significantly higher placental lacunae grade (P < 0.001) and more often hypervascularity of the uterovesical/subplacental area (P < 0.001), presence of bridging vessels (P = 0.027) and presence of lacunae feeder vessels (P < 0.001) on ultrasound examination, and increased vascularization of the anterior uterine wall intraoperatively (P < 0.001). Remodeling of the lower uterine segment following CD scarring leads to structural abnormalities of the uterine contour on both ultrasound examination and intraoperatively, independently of the presence of accreta villous tissue on microscopic examination. These anatomical changes are often reported as diagnostic of placenta percreta, including cases with no histological evidence of PAS. Guided histological examination could improve the overall diagnosis of PAS and is essential to obtain evidence-based epidemiologic data. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Hussein AM ，Elbarmelgy RA ，Elbarmelgy RM ，Thabet MM ，Jauniaux E ... -  《-》

Placenta accreta spectrum: pathophysiology and evidence-based anatomy for prenatal ultrasound imaging.

Placenta accreta spectrum is a complex obstetric complication associated with high maternal morbidity. It is a relatively new disorder of placentation, and is the consequence of damage to the endometrium-myometrial interface of the uterine wall. When first described 80 years ago, it mainly occurred after manual removal of the placenta, uterine curettage, or endometritis. Superficial damage leads primarily to an abnormally adherent placenta, and is diagnosed as the complete or partial absence of the decidua on histology. Today, the main cause of placenta accreta spectrum is uterine surgery and, in particular, uterine scar secondary to cesarean delivery. In the absence of endometrial reepithelialization of the scar area the trophoblast and villous tissue can invade deeply within the myometrium, including its circulation, and reach the surrounding pelvic organs. The cellular changes in the trophoblast observed in placenta accreta spectrum are probably secondary to the unusual myometrial environment in which it develops, and not a primary defect of trophoblast biology leading to excessive invasion of the myometrium. Placenta accreta spectrum was separated by pathologists into 3 categories: placenta creta when the villi simply adhere to the myometrium, placenta increta when the villi invade the myometrium, and placenta percreta where the villi invade the full thickness of the myometrium. Several prenatal ultrasound signs of placenta accreta spectrum were reported over the last 35 years, principally the disappearance of the normal uteroplacental interface (clear zone), extreme thinning of the underlying myometrium, and vascular changes within the placenta (lacunae) and placental bed (hypervascularity). The pathophysiological basis of these signs is due to permanent damage of the uterine wall as far as the serosa, with placental tissue reaching the deep uterine circulation. Adherent and invasive placentation may coexist in the same placental bed and evolve with advancing gestation. This may explain why no single, or set combination of, ultrasound sign(s) was found to be specific for the depth of abnormal placentation, and accurate for the differential diagnosis between adherent and invasive placentation. Correlation of pathological and clinical findings with prenatal imaging is essential to improve screening, diagnosis, and management of placenta accreta spectrum, and standardized protocols need to be developed.

Jauniaux E ，Collins S ，Burton GJ 《-》

Development of the utero-placental circulation in cesarean scar pregnancies: a case-control study.

Cesarean scar pregnancies carry a high risk of pregnancy complications including placenta previa with antepartum hemorrhage, placenta accreta spectrum, and uterine rupture. To evaluate the development of utero-placental circulation in the first half of pregnancy in ongoing cesarean scar pregnancies and compare it with pregnancies implanted in the lower uterine segment above a previous cesarean delivery scar with no evidence of placenta accreta spectrum at delivery STUDY DESIGN: This was a retrospective case-control study conducted in 2 tertiary referral centers. The study group included 27 women who were diagnosed with a live cesarean scar pregnancy in the first trimester of pregnancy and who elected to conservative management. The control group included 27 women diagnosed with an anterior low-lying placenta or placenta previa at 19 to 22 weeks of gestation who had first and early second trimester ultrasound examinations. In both groups, the first ultrasound examination was carried out at 6 to 10 weeks to establish the pregnancy location, viability, and to confirm the gestational age. The utero-placental and intraplacental vasculatures were examined using color Doppler imaging and were described semiquantitatively using a score of 1 to 4. The remaining myometrial thickness was recorded in the study group, whereas the ultrasound features of a previous cesarean delivery scar including the presence of a niche were noted in the controls. Both the cesarean scar pregnancies and the controls had ultrasound examinations at 11 to 14 and 19 to 22 weeks of gestation. The mean color Doppler imaging vascularity score in the ultrasound examination at 6 to 10 weeks was significantly (P<.001) higher in the cesarean scar pregnancy group than in the controls. High vascularity scores of 3 and 4 were recorded in 20 of 27 (74%) cases of the cesarean scar pregnancy group. There was no vascularity score of 4, and only 3 of 27 (11%) controls had a vascularity score of 3. In 15 of the 27 (55.6%) cesarean scar pregnancies, the residual myometrial thickness was <2 mm. In the ultrasound examination at 11 to 14 weeks, there was no significant difference between the groups in the number of cases with an increased subplacental vascularity. However, 12 cesarean scar pregnancies (44%) presented with 1 or more placental lacunae whereas there was no case with lacunae in the controls. Of the 18 cesarean scar pregnancies that progressed into the third trimester, 10 of them were diagnosed with placenta previa accreta at birth, including 4 creta and 6 increta. In the 19 to 22 weeks ultrasound examination, 8 of the 10 placenta accreta spectrum patients presented with subplacental hypervascularity, out of which 6 showed placental lacunae. The vascular changes in the utero-placental and intervillous circulations in cesarean scar pregnancies are due to the loss of the normal uterine structure in the scar area and the development of placental tissue in proximity of large diameter arteries of the outer uterine wall. The intensity of these vascular changes, the development of placenta accreta spectrum, and the risk of uterine rupture are probably related to the residual myometrial thickness of the scar defect at the start of pregnancy. A better understanding of the pathophysiology of the utero-placental vascular changes associated with cesarean scar pregnancies should help in identifying those cases that may develop major complications. It will contribute to providing counseling for women about the risks associated with different management strategies.

Jauniaux E ，Zosmer N ，De Braud LV ，Ashoor G ，Ross J ，Jurkovic D ... -  《-》