Vasa previa in singleton pregnancies: diagnosis and clinical management based on an international expert consensus.

BACKGROUND: There are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies. OBJECTIVE: This study aimed to systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions and a Delphi technique. STUDY DESIGN: A 4-round focus group discussion and a 3-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected on the basis of their publication record on vasa previa. First, we convened a focus group discussion panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A 3-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa, which the experts were asked to rate on a 5-point Likert scale (from "strongly disagree"=1 to "strongly agree"=5). Consensus was defined as a median score of 5. Following responses to each round, any statements that had median scores of ≤3 were deemed to have had no consensus and were excluded. Statements with a median score of 4 were revised and re-presented to the experts in the next round. Consensus and nonconsensus statements were then aggregated. RESULTS: A total of 68 international experts were invited to participate in the study, of which 57 participated. Experts were from 13 countries on 5 continents and have contributed to >80% of published cohort studies on vasa previa, as well as national and international society guidelines. Completion rates were 84%, 93%, and 91% for the first, second, and third rounds, respectively, and 71% completed all 3 rounds. The panel reached a consensus on 26 statements regarding the diagnosis and key points of management of vasa previa, including the following: (1) although there is no agreement on the distance between the fetal vessels and the cervical internal os to define vasa previa, the definition should not be limited to a 2-cm distance; (2) all pregnancies should be screened for vasa previa with routine examination for placental cord insertion and a color Doppler sweep of the region over the cervix at the second-trimester anatomy scan; (3) when a low-lying placenta or placenta previa is found in the second trimester, a transvaginal ultrasound with Doppler should be performed at approximately 32 weeks to rule out vasa previa; (4) outpatient management of asymptomatic patients without risk factors for preterm birth is reasonable; (5) asymptomatic patients with vasa previa should be delivered by scheduled cesarean delivery between 35 and 37 weeks of gestation; and (6) there was no agreement on routine hospitalization, avoidance of intercourse, or use of 3-dimensional ultrasound for diagnosis of vasa previa. CONCLUSION: Through focus group discussion and a Delphi process, an international expert panel reached consensus on the definition, screening, clinical management, and timing of delivery in vasa previa, which could inform the development of new clinical guidelines.

Ambient air pollution and adverse birth outcomes: A review of underlying mechanisms.

Epidemiological data provide varying degrees of evidence for associations between prenatal exposure to ambient air pollutants and adverse birth outcomes (suboptimal measures of fetal growth, preterm birth and stillbirth). To assess further certainty of effects, this review examines the experimental literature base to identify mechanisms by which air pollution (particulate matter, nitrogen dioxide and ozone) could cause adverse effects on the developing fetus. It likely that this environmental insult impacts multiple biological pathways important for sustaining a healthy pregnancy, depending upon the composition of the pollutant mixture and the exposure window owing to changes in physiologic maturity of the placenta, its circulations and the fetus as pregnancy ensues. The current body of evidence indicates that the placenta is a target tissue, impacted by a variety of critical processes including nitrosative/oxidative stress, inflammation, endocrine disruption, epigenetic changes, as well as vascular dysregulation of the maternal-fetal unit. All of the above can disturb placental function and, as a consequence, could contribute to compromised fetal growth as well increasing the risk of stillbirth. Furthermore, given that there is often an increased inflammatory response associated with preterm labour, inflammation is a plausible mechanism mediating the effects of air pollution on premature delivery. In the light of increased urbanisation and an ever-changing climate, both of which increase ambient air pollution and negatively affect vulnerable populations such as pregnant individuals, it is hoped that the collective evidence may contribute to decisions taken to strengthen air quality policies, reductions in exposure to air pollution and subsequent improvements in the health of those not yet born.

Evaluation of maternal serum protein biomarkers in the prenatal evaluation of placenta accreta spectrum: A systematic scoping review.

INTRODUCTION: Placenta accreta spectrum (PAS) is an increasingly commonly reported condition due to the continuous increase in the rate of cesarean deliveries (CD) worldwide; however, the prenatal screening for pregnant patients at risk of PAS at birth remains limited, in particular when imaging expertise is not available. MATERIAL AND METHODS: Two major electronic databases (MEDLINE and Embase) were searched electronically for articles published in English between October 1992 and January 2023 using combinations of the relevant medical subject heading terms and keywords. Two independent reviewers selected observational studies that provided data on one or more measurement of maternal blood-specific biomarker(s) during pregnancies with PAS at birth. PRISMA Extension for Scoping Review (PRISMA-ScR) was used to extract data and report results. RESULTS: Of the 441 reviewed articles, 29 met the inclusion criteria reporting on 34 different biomarkers. 14 studies were retrospective and 15 prospective overall including 18 251 participants. Six studies had a cohort design and the remaining a case-control design. Wide clinical heterogeneity was found in the included studies. In eight studies, the samples were obtained in the first trimester; in five, the samples were collected on hospital admission for delivery; and in the rest, the samples were collected during the second and/or third trimester. CONCLUSIONS: Measurements of serum biomarkers, some of which have been or are still used in screening for other pregnancy complications, could contribute to the prenatal evaluation of patients at risk of PAS at delivery; however, important evidence gaps were identified for suitable cutoffs for most biomarkers, variability of gestational age at sampling and the potential overlap of the marker values with other placental-related complications of pregnancy.

Surgical evacuation combined with Shirodkar cervical suture and selective uterine artery embolization: A fertility preserving treatment for 10-15 weeks' live cesarean scar ectopic pregnancies.

INTRODUCTION: Cesarean scar ectopic pregnancies (CSEPs) are associated with significant maternal morbidity and termination is often recommended in the early first trimester. Management of more advanced cases is challenging due to higher risks of major intraoperative hemorrhage. Hysterectomy is currently the intervention of choice for advanced cases. This study aimed to investigate if advanced live CSEPs could be managed effectively conservatively using suction curettage and interventional radiology. MATERIAL AND METHODS: A retrospective single-center cohort study was performed. A total of 371 women diagnosed with CSEP were identified between January 2008 and January 2023. A total of 6% (22/371) women had an advanced live CSEP with crown-rump length (CRL) of ≥40 mm (≥10 weeks' gestation). Of these, 77% (17/22) opted for surgical intervention, whilst the remaining five continued their pregnancies. A preoperative ultrasound was performed in each patient. All women underwent suction curettage under ultrasound guidance and insertion of Shirodkar cervical suture as a primary hemostatic measure combined with uterine artery embolization (UAE) if required. The primary outcome was rate of blood transfusion. Secondary outcomes were estimated intraoperative blood loss, UAE, intensive care unit admission, reintervention, hysterectomy, hospitalization duration and rate of retained products of conception. Descriptive statistics were used to describe these variables. RESULTS: Median CRL of the 17 patients included was 54.1 mm (range: 40.0-85.7) and median gestational age based on CRL was 12 + 3 weeks (range: 10 + 6-15 + 0). On preoperative ultrasound scan placental lacunae were recorded in 76% (13/17) of patients and color Doppler score was ≥3 in 67% (10/15) of patients. At surgery, Shirodkar cervical suture was used in all cases. It was successful in achieving hemostasis by tamponade in 76% (13/17) of patients. In the remaining 24% (4/17) patients tamponade failed to achieve complete hemostasis and UAE was performed to stop persistent arterial bleeding into the uterine cavity. Median intraoperative blood loss was 800 mL (range: 250-2500) and 41% (7/17) women lost >1000 mL. 35% (6/17) needed blood transfusion. No women required hysterectomy. CONCLUSIONS: Surgical evacuation with Shirodkar cervical suture and selective UAE is an effective treatment for advanced live CSEPs.

The human placenta: new perspectives on its formation and function during early pregnancy.

The placenta has evolved to support the development of the embryo and fetus during the different intrauterine periods of life. By necessity, its development must precede that of the embryo. There is now evidence that during embryogenesis and organogenesis, the development of the human placenta is supported by histotrophic nutrition secreted from endometrial glands rather than maternal blood. These secretions provide a plentiful supply of glucose, lipids, glycoproteins and growth factors that stimulate rapid proliferation and differentiation of the villous trophoblast. Furthermore, evidence from endometrial gland organoids indicates that expression and secretion of these products are upregulated following sequential exposure to oestrogen, progesterone and trophoblastic and decidual hormones, in particular prolactin. Hence, a feed-forward signalling dialogue is proposed among the trophoblast, decidua and glands that enables the placenta to stimulate its own development, independent of that of the embryo. Many common complications of pregnancy represent a spectrum of disorders associated with deficient trophoblast proliferation. Increasing evidence suggests that this spectrum is mirrored by one of impaired decidualization, potentially compromising histotroph secretion through diminished prolactin secretion and reduced gland function. Optimizing endometrial wellbeing prior to conception may therefore help to prevent common pregnancy complications, such as miscarriage, growth restriction and pre-eclampsia.

Perinatal assessment of complex cesarean delivery: beyond placenta accreta spectrum.

Multiple cesarean deliveries are known to be associated with long-term postoperative consequences because of a permanent defect of the lower uterine segment wall and the development of thick pelvic adhesions. Patients with a history of multiple cesarean deliveries often present with large cesarean scar defects and are at heightened risk in subsequent pregnancies of cesarean scar ectopic pregnancy, uterine rupture, low-lying placenta or placenta previa, and placenta previa accreta. Moreover, large cesarean scar defects will lead to progressive dehiscence of the lower uterine segment with the inability to effectively reapproximate hysterotomy edge and repair at birth. Major remodeling of the lower uterine segment associated with true placenta accreta spectrum at birth, whereby the placenta becomes inseparable from the uterine wall, increases the rates of perinatal morbidity and mortality, especially when undiagnosed before delivery. Ultrasound imaging is currently not routinely used to evaluate the surgical risks of patients with a history of multiple cesarean deliveries, beyond the risk assessment of placenta accreta spectrum. Independent of accreta placentation, a placenta previa under a scarred, thinned partially disrupted lower uterine segment, covered by thick adhesions with the posterior wall of the bladder, poses a surgical risk and requires fine dissection and surgical expertise; however, data on the use of ultrasound to evaluate uterine remodeling and adhesions between the uterus and other pelvic organs are scarce. In particular, transvaginal sonography has been underused, including in patients with a high probability of placenta accreta spectrum at birth. Based on the best available knowledge, we discuss the role of ultrasound imaging in identifying the signs suggestive of major remodeling of the lower uterine segment and in mapping the changes in the uterine wall and pelvis, to enable the surgical team to prepare for all different types of complex cesarean deliveries. The need for postnatal confirmation of the prenatal ultrasound findings for all patients with a history of multiple cesarean deliveries, regardless of the diagnosis of placenta previa and placenta accreta spectrum, is discussed. We propose an ultrasound imaging protocol and a classification of the level of surgical difficulty at elective cesarean delivery to stimulate further research toward the validation of ultrasound signs by which these signs may be applied to improve surgical outcomes.

The role of transvaginal ultrasound in the third-trimester evaluation of patients at high risk of placenta accreta spectrum at birth.

BACKGROUND: Transvaginal ultrasound imaging has become an essential tool in the prenatal evaluation of the lower uterine segment and anatomy of the cervix, but there are only limited data on the role of transvaginal ultrasound in the management of patients at high risk of placenta accreta spectrum at birth. OBJECTIVE: This study aimed to evaluate the role of transvaginal sonography in the third trimester of pregnancy in predicting outcomes in patients with a high probability of placenta accreta spectrum at birth. STUDY DESIGN: This was a retrospective analysis of prospectively collected data of patients presenting with a singleton pregnancy and a history of at least 1 previous cesarean delivery and patients diagnosed prenatally with an anterior low-lying placenta or placenta previa delivered electively after 32 weeks of gestation. All patients had a least 1 detailed ultrasound examination, including transabdominal and transvaginal scans, within 2 weeks before delivery. Of note, 2 experienced operators, blinded to the clinical data, were asked to make a judgment on the likelihood of placenta accreta spectrum as a binary, low or high-probability of placenta accreta spectrum, and to predict the main surgical outcome (conservative vs peripartum hysterectomy). The diagnosis of accreta placentation was confirmed when one or more placental cotyledons could not be digitally separated from the uterine wall at delivery or during the gross examination of the hysterectomy or partial myometrial resection specimens. RESULTS: A total of 111 patients were included in the study. Abnormal placental tissue attachment was found in 76 patients (68.5%) at birth, and histologic examination confirmed superficial villous attachment (creta) and deep villous attachment (increta) in 11 and 65 cases, respectively. Of note, 72 patients (64.9%) had a peripartum hysterectomy, including 13 cases with no evidence of placenta accreta spectrum at birth because of failure to reconstruct the lower uterine segment and/or excessive bleeding. There was a significant difference in the distribution of placental location (X2=12.66; P=.002) between transabdominal and transvaginal ultrasound examinations, but both ultrasound techniques had similar likelihood scores in identifying accreta placentation that was confirmed at birth. On transabdominal scan, only a high lacuna score was significantly associated (P=.02) with an increased chance of hysterectomy, whereas on transvaginal scan, significant associations were found between the need for hysterectomy and the thickness of the distal part of the lower uterine segment (P=.003), changes in the cervix structure (P=.01), cervix increased vascularity (P=.001), and the presence of placental lacunae (P=.005). The odds ratio for peripartum hysterectomy were 5.01 (95% confidence interval, 1.25-20.1) for a very thin (<1-mm) distal lower uterine segment and 5.62 (95% confidence interval, 1.41-22.5) for a lacuna score of 3+. CONCLUSION: Transvaginal ultrasound examination contributes to both prenatal management and the prediction of surgical outcomes in patients with a history of previous cesarean delivery with and without ultrasound signs suggestive of placenta accreta spectrum. Transvaginal ultrasound examination of the lower uterine segment and cervix should be included in clinical protocols for the preoperative evaluation of patients at risk of complex cesarean delivery.

The impact of preoperative ultrasound and intraoperative findings on surgical outcomes in patients at high risk of placenta accreta spectrum.

OBJECTIVE: To assess whether preoperative ultrasound imaging and intraoperative features predict surgical outcomes in patients at high risk for placenta accreta spectrum (PAS). DESIGN: Cohort study. SETTING: Cairo University Maternity, Egypt. POPULATION OR SAMPLE: Pregnant patients with one or more prior caesarean deliveries presenting with a low-lying/placenta praevia with or without PAS confirmed by histopathology. METHODS: Logistic regression and multivariable analyses. MAIN OUTCOMES MEASURES: Need for primary caesarean hysterectomy, numbers of red blood cell (RBC) units transfused and patients requiring transfusion of >5 units. RESULTS: Ninety consecutive records were reviewed, including 58 (64.4%) PAS cases. Sixty (66.7%, 95% confidence interval (CI) 56-76) required hysterectomy. Odds of hysterectomy were significantly (p = 0.005) increased with complete praevia. Significantly higher odds of hysterectomy were associated with subplacental hypervascularity (7.23, 95% CI 2.72-19.2, p < 0.001), lacunar scores 2+ and 3+ (12.6, 95% CI 4.15-38.5, p < 0.001), lacunar feeder vessels (5.69, 95% CI 1.77-18.3, p = 0.004) or bridging vessels (2.00, 95% CI 1.29-3.10, p = 0.002) on ultrasound, and increased lower segment vascularization at laparotomy (5.42, 95% CI 2.09-14.1, p = 0.001). Transfusion >5 RBC units was associated with number of lacunae (odds ratio [OR] 1.48, 95% CI 1.14-1.93, p = 0.004) and presence of feeder vessels (OR 1.62, 95% CI 1.24-2.11, p = 0.001). The multivariable analysis indicated that parity, placental location and PAS were significantly (p = 0.007; p = 0.01; p < 0.001, respectively) associated with hysterectomy. CONCLUSIONS: Preoperative ultrasound imaging can assist in triaging and counselling patients regarding the odds of PAS, intraoperative blood losses and need for hysterectomy, and intraoperative features can assist the surgeon in evaluating the need for multidisciplinary support.

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.

Searching for placenta percreta: a prospective cohort and systematic review of case reports.

BACKGROUND: Placenta percreta is described as the most severe grade of placenta accreta spectrum and accounts for a quarter of all cases of placenta accreta spectrum reported in the literature. OBJECTIVE: We investigated the hypothesis that placenta percreta, which has been described clinically as placental tissue invading through the full thickness of the uterus, is a heterogeneous category with most cases owing to primary or secondary uterine abnormality rather than an abnormally invasive form of placentation. STUDY DESIGN: We have evaluated the agreement between the intraoperative findings using the International Federation of Gynecology and Obstetrics classification with the postoperative histopathology diagnosis in a prospective cohort of 101 consecutive singleton pregnancies presenting with a low-lying placenta or placenta previa, a history of at least 1 prior cesarean delivery and ultrasound signs suggestive of placenta accreta spectrum. Furthermore, a systematic literature review of case reports of placenta percreta, which included histopathologic findings and gross images, was performed. RESULTS: Samples for histologic examination were available in 80 of 101 cases of the cohort, which were managed by hysterectomy or partial myometrial resection. Microscopic examination showed evidence of placenta accreta spectrum in 65 cases (creta, 9; increta, 56). Of 101 cases included in the cohort, 44 (43.5%) and 54 (53.5%) were graded as percreta by observer A and observer B, respectively. There was a moderate agreement between observers. Of note, 11 of 36 cases that showed no evidence of abnormal placental attachment at delivery and/or microscopic examination were classified as percreta by both observers. The systematic literature review identified 41 case reports of placenta percreta with microscopic images and presenting symptomatology, suggesting that most cases were the consequence of a uterine rupture. The microscopic descriptions were heterogeneous, and all descriptions demonstrated histology of placenta creta rather than percreta. CONCLUSION: Our study supported the concept that placenta accreta is not an invasive disorder of placentation but the consequence of postoperative surgical remodeling or a preexisting uterine pathology and found no histologic evidence supporting the existence of a condition where the villous tissue penetrates the entire uterine wall, including the serosa and beyond.

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.

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

BACKGROUND: Cesarean scar pregnancies carry a high risk of pregnancy complications including placenta previa with antepartum hemorrhage, placenta accreta spectrum, and uterine rupture. OBJECTIVE: 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. RESULTS: 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. CONCLUSION: 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.

Prospective Evaluation of the Ultrasound Signs Proposed for the Description of Uterine Niche in Nonpregnant Women.

OBJECTIVES: To evaluate the new ultrasound-based signs for the diagnosis of post-cesarean section uterine niche in nonpregnant women. METHODS: We investigated prospectively a cohort of 160 consecutive women with one previous term cesarean delivery (CD) between December 2019 and 2020. All women were separated into two subgroups according to different stages of labor at the time of their CD: subgroup A (n = 109; 68.1%) for elective CD and CD performed in latent labor at a cervical dilatation (≤4 cm) and subgroup B (n = 51; 31.9%); for CD performed during the active stage of labor (>4 cm). RESULTS: Overall, the incidence of a uterine niche was significantly (P < .001) higher in women who had an elective (20/45; 44.4%) compared with those who had an emergent (21/115; 18.3%) CD. Compared with subgroup B, subgroup A presented with a significantly (P = .012) higher incidence of uterine niche located above the vesicovaginal fold and with a significantly (P = .0002) lower proportion of cesarean scar positioned below the vesicovaginal fold. There was a significantly (P < .001) higher proportion of women with a residual myometrial thickness (RMT) > 3 mm in subgroup A than in subgroup B and a significant negative relationship was found between the RMT and the cervical dilatation at CD (r = -0.22; P = .008). CONCLUSIONS: Sonographic cesarean section scar assessment indicates that the type of CD and the stage of labor at which the hysterotomy is performed have an impact on the location of the scar and the scarification process including the niche formation and RMT.

Placentation in the Human and Higher Primates.

Placentation in humans is precocious and highly invasive compared to other mammals. Implantation is interstitial, with the conceptus becoming completely embedded within the endometrium towards the end of the second week post-fertilization. Villi initially form over the entire surface of the chorionic sac, stimulated by histotrophic secretions from the endometrial glands. The secondary yolk sac never makes contact with the chorion, and a choriovitelline placenta is never established. However, recent morphological and transcriptomic analyses suggest that the yolk sac plays an important role in the uptake of nutrients from the coelomic fluid. Measurements performed in vivo demonstrate that early development takes place in a physiological, low-oxygen environment that protects against teratogenic free radicals and maintains stem cells in a multipotent state. The maternal arterial circulation to the placenta is only fully established around 10-12 weeks of gestation. By then, villi have regressed over the superficial, abembryonic pole, leaving the definitive discoid placenta, which is of the villous, hemochorial type. Remodeling of the maternal spiral arteries is essential to ensure a high-volume but low-velocity inflow into the mature placenta. Extravillous trophoblast cells migrate from anchoring villi and surround the arteries. Their interactions with maternal immune cells release cytokines and proteases that are key to remodeling, and a successful pregnancy.

HYPOXIA AND REPRODUCTIVE HEALTH: Oxygen and development of the human placenta.

Development of the human placenta takes place in contrasting oxygen concentrations at different stages of gestation, from ~20 mmHg during the first trimester rising to ~60 mmHg at the start of the second trimester before gradually declining to ~40 mmHg at term. In view of these changes, the early placenta has been described as 'hypoxic'. However, placental metabolism is heavily glycolytic, supported by the rich supply of glucose from the endometrial glands, and there is no evidence of energy compromise. On the contrary, the trophoblast is highly proliferative, with the physiological low-oxygen environment promoting maintenance of stemness in progenitor populations. These conditions favour the formation of the cytotrophoblastic shell that encapsulates the conceptus and interfaces with the endometrium. Extravillous trophoblast cells on the outer surface of the shell undergo an epithelial-mesenchymal transition and acquire invasive potential. Experimental evidence suggests that these changes may be mediated by the higher oxygen concentration present within the placental bed. Interpreting in vitro data is often difficult, however, due to the use of non-physiological oxygen concentrations and trophoblast-like cell lines or explant models. Trophoblast is more vulnerable to hyperoxia or fluctuating levels of oxygen than to hypoxia, and some degree of placental oxidative stress likely occurs in all pregnancies towards term. In complications of pregnancy, such as early-onset pre-eclampsia, malperfusion generates high levels of oxidative stress, causing release of factors that precipitate the maternal syndrome. Further experiments are required using genuine trophoblast progenitor cells and physiological concentrations to fully elucidate the pathways by which oxygen regulates placental development.

Impact of the COVID-19 Pandemic on Excess Perinatal Mortality and Morbidity in Israel.

OBJECTIVE: The 2020 COVID-19 pandemic has been associated with excess mortality and morbidity in adults and teenagers over 14 years of age, but there is still limited evidence on the direct and indirect impact of the pandemic on pregnancy. We aimed to evaluate the effect of the first wave of the COVID-19 pandemic on obstetrical emergency attendance in a low-risk population and the corresponding perinatal outcomes. STUDY DESIGN: This is a single center retrospective cohort study of all singleton births between February 21 and April 30. Prenatal emergency labor ward admission numbers and obstetric outcomes during the peak of the first COVID-19 pandemic of 2020 in Israel were compared with the combined corresponding periods for the years 2017 to 2019. RESULTS: During the 2020 COVID-19 pandemic, the mean number of prenatal emergency labor ward admissions was lower, both by daily count and per woman, in comparison to the combined matching periods in 2017, 2018, and 2019 (48.6 ± 12.2 vs. 57.8 ± 14.4, p < 0.0001 and 1.74 ± 1.1 vs. 1.92 ± 1.2, p < 0.0001, respectively). A significantly (p = 0.0370) higher rate of stillbirth was noted in the study group (0.4%) compared with the control group (0.1%). All study group patients were negative for COVID-19. Gestational age at delivery, rates of premature delivery at <28, 34, and 37 weeks, pregnancy complications, postdate delivery at >40 and 41 weeks, mode of delivery, and numbers of emergency cesarean deliveries were similar in both groups. There was no difference in the intrapartum fetal death rate between the groups. CONCLUSION: The COVID-19 pandemic stay-at-home policy combined with patient fear of contracting the disease in hospital could explain the associated higher rate of stillbirth. This collateral perinatal damage follows a decreased in prenatal emergency labor ward admissions during the first wave of COVID-19 in Israel. KEY POINTS: · Less obstetrical ER attendance is observed during the pandemic.. · There is a parallel increase in stillbirth rate.. · Stillbirth cases tested negative for COVID-19.. · Lockdown and pandemic panic are possible causes..

Classification and reporting guidelines for the pathology diagnosis of placenta accreta spectrum (PAS) disorders: recommendations from an expert panel.

The terminology and diagnostic criteria presently used by pathologists to report invasive placentation is inconsistent and does not reflect current knowledge of the pathogenesis of the disease or the needs of the clinical care team. A consensus panel was convened to recommend terminology and reporting elements unified across the spectrum of PAS specimens (i.e., delivered placenta, total or partial hysterectomy with or without extrauterine tissues, curetting for retained products of conception). The proposed nomenclature under the umbrella diagnosis of placenta accreta spectrum (PAS) replaces the traditional categorical terminology (placenta accreta, increta, percreta) with a descriptive grading system that parallels the guidelines endorsed by the International Federation of Gynaecology and Obstetrics (FIGO). In addition, the nomenclature for hysterectomy specimens is separated from that for delivered placentas. The goal for each element in the system of nomenclature was to provide diagnostic criteria and guidelines for expected use in clinical practice.

Physical resolution of tubal ectopic pregnancy on ultrasound imaging following successful expectant management.

RESEARCH QUESTION: What is the time required for complete physical resolution of tubal ectopic pregnancies diagnosed on ultrasound imaging in women undergoing successful expectant management? DESIGN: A prospective observational cohort study of 177 women who had successful expectant management of tubal ectopic pregnancy, who attended a single Early Pregnancy Unit between January 2014 and December 2018. All participants were monitored until their serum beta-human chorionic gonadotrophin (beta-HCG) dropped to non-pregnant concentrations and with 2-weekly follow-up ultrasound scans until resolution of the pregnancy. RESULTS: A total of 112/177 (63.3%, 95% confidence interval [CI] 55.7-70.4) of tubal ectopic pregnancies were indiscernible on ultrasound 2 weeks after serum beta-HCG had returned to non-pregnant concentrations. In 8/177 (4.5%, 95% CI 2.0-8.7), physical resolution took longer than 78 days. There was a positive correlation between biochemical and physical resolution of tubal ectopic pregnancy (r = 0.21, P = 0.006). CONCLUSIONS: Physical resolution of tubal ectopic pregnancy is often prolonged and is positively correlated with initial and maximum beta-HCG concentrations. Results of this study indicate that beta-HCG resolution cannot be used as the end-point of expectant management of tubal ectopic pregnancy, which should be considered when counselling women and planning for future pregnancies.

A new methodologic approach for clinico-pathologic correlations in invasive placenta previa accreta.

BACKGROUND: The development of new management strategies for women presenting with placenta accreta spectrum requires quality epidemiology data, which have so far been limited by the high variability in clinical and histopathologic data confirming the diagnosis at birth. OBJECTIVE: To evaluate the role of a new methodologic approach for the correlation of clinical and pathological data for women with a history of prior cesarean delivery diagnosed prenatally with placenta previa accreta. MATERIALS AND METHODS: A modified pathologic technique for gross examination of hysterectomy specimens with placenta in situ consisting of intraoperative examination, immediate postoperative examination, and guided histologic sampling was used prospectively in a cohort of 24 patients with singleton pregnancies complicated by placenta low-lying/placenta previa accreta. Maternal characteristics, detailed ultrasound findings, surgical outcomes, and histopathologic examination were compared with those of a group of 24 patients with similar clinical characteristics and in whom a standard pathologic examination method was used. RESULTS: The median reporting time for obtaining the complete histopathology results including the microscopic examination was significantly shorter (7 versus 15 days; P < .001) and the median number of samples taken for histologic examination significantly lower (4 versus 14 samples; P < .001) in the study group than in the controls. The number of histologic slides showing villous invasion was significantly higher (2 versus 1 slide; P = .002), and the ratio of the number of samples taken to the numbers of slides confirming villous invasion was significantly lower (2 versus 9; P < .001) in the study group than in the controls. In all cases in the study group, intraoperative examination identified a dense tangled bed of vessels or multiple vessels running laterally and cranio-caudally in the uterine serosa above the placental insertion that were no longer visible during immediate gross postoperative examination of the hysterectomy specimens. Immediate postoperative dissection enables the differential diagnosis between focal and large increta areas, and between abnormally adherent placenta and invasive placenta accreta. CONCLUSION: Valuable clinical information on the serosal vascularity, uterine dehiscence, and extension of the accreta area is added with the description of the macroscopic examination during the surgical procedure and immediate dissection of the specimen. This methodological approach is cost-effective and increases the quality of the histologic sampling. It thus provides more accurate correlations with the clinical data and more accurate epidemiologic data collection. Perinatal pathologists should be part of multidisciplinary teams involved the management placenta accreta spectrum disorders.

RNA-seq reveals conservation of function among the yolk sacs of human, mouse, and chicken.

The yolk sac is phylogenetically the oldest of the extraembryonic membranes. The human embryo retains a yolk sac, which goes through primary and secondary phases of development, but its importance is controversial. Although it is known to synthesize proteins, its transport functions are widely considered vestigial. Here, we report RNA-sequencing (RNA-seq) data for the human and murine yolk sacs and compare those data with data for the chicken. We also relate the human RNA-seq data to proteomic data for the coelomic fluid bathing the yolk sac. Conservation of transcriptomes across the species indicates that the human secondary yolk sac likely performs key functions early in development, particularly uptake and processing of macro- and micronutrients, many of which are found in coelomic fluid. More generally, our findings shed light on evolutionary mechanisms that give rise to complex structures such as the placenta. We identify genetic modules that are conserved across mammals and birds, suggesting these modules are part of the core amniote genetic repertoire and are the building blocks for both oviparous and viviparous reproductive modes. We propose that although a choriovitelline placenta is never established physically in the human, the placental villi, the exocoelomic cavity, and the secondary yolk sac function together as a physiological equivalent.