Delivery outcomes in the subsequent pregnancy following the conservative management of placenta accreta spectrum disorder: a systematic review and meta-analysis.

OBJECTIVE: Cesarean hysterectomy is generally presumed to decrease maternal morbidity and mortality secondary to placenta accreta spectrum disorder. Recently, uterine-sparing techniques have been introduced in conservative management of placenta accreta spectrum disorder to preserve fertility and potentially reduce surgical complications. However, despite patients often expressing the intention for future conception, few data are available regarding the subsequent pregnancy outcomes after conservative management of placenta accreta spectrum disorder. Thus, we aimed to perform a systematic review and meta-analysis to assess these outcomes. DATA SOURCES: PubMed, Scopus, and Web of Science databases were searched from inception to September 2022. STUDY ELIGIBILITY CRITERIA: We included all studies, with the exception of case studies, that reported the first subsequent pregnancy outcomes in individuals with a history of placenta accreta spectrum disorder who underwent any type of conservative management. METHODS: The R programming language with the "meta" package was used. The random-effects model and inverse variance method were used to pool the proportion of pregnancy outcomes. RESULTS: We identified 5 studies involving 1458 participants that were eligible for quantitative synthesis. The type of conservative management included placenta left in situ (n=1) and resection surgery (n=1), and was not reported in 3 studies. The rate of placenta accreta spectrum disorder recurrence in the subsequent pregnancy was 11.8% (95% confidence interval, 1.1-60.3; I2=86.4%), and 1.9% (95% confidence interval, 0.0-34.1; I2=82.4%) of participants underwent cesarean hysterectomy. Postpartum hemorrhage occurred in 10.3% (95% confidence interval, 0.3-81.4; I2=96.7%). A composite adverse maternal outcome was reported in 22.7% of participants (95% confidence interval, 0.0-99.4; I2=56.3%). CONCLUSION: Favorable pregnancy outcome is possible following successful conservation of the uterus in a placenta accreta spectrum disorder pregnancy. Approximately 1 out of 4 subsequent pregnancies following conservative management of placenta accreta spectrum disorder had considerable adverse maternal outcomes. Given such high incidence of adverse outcomes and morbidity, patient and provider preparation is vital when managing this population.

External Validation of a Multivariable Prediction Model for Placenta Accreta Spectrum.

BACKGROUND: Placenta accreta spectrum (PAS) is a disorder of abnormal placentation associated with severe postpartum hemorrhage, maternal morbidity, and mortality. Predelivery prediction of this condition is important to determine appropriate delivery location and multidisciplinary planning for operative management. This study aimed to validate a prediction model for PAS developed by Weiniger et al in 2 cohorts who delivered at 2 different United States tertiary centers. METHODS: Cohort A (Brigham and Women's Hospital; N = 253) included patients with risk factors (prior cesarean delivery and placenta previa) and/or ultrasound features of PAS presenting to a tertiary-care hospital. Cohort B (Columbia University Irving Medical Center; N = 99) consisted of patients referred to a tertiary-care hospital specifically because of ultrasound features of PAS. Using the outcome variable of surgical and/or pathological diagnosis of PAS, discrimination (via c-statistic), calibration (via intercept, slope, and flexible calibration curve), and clinical usefulness (via decision curve analysis) were determined. RESULTS: The model c-statistics in cohorts A and B were 0.728 (95% confidence interval [CI], 0.662-0.794) and 0.866 (95% CI, 0.754-0.977) signifying acceptable and excellent discrimination, respectively. The calibration intercept (0.537 [95% CI, 0.154-0.980] for cohort A and 3.001 [95% CI, 1.899- 4.335] for B), slopes (0.342 [95% CI, 0.170-0.532] for cohort A and 0.604 [95% CI, -0.166 to 1.221] for B), and flexible calibration curves in each cohort indicated that the model underestimated true PAS risks on average and that there was evidence of overfitting in both validation cohorts. The use of the model compared to a treat-all strategy by decision curve analysis showed a greater net benefit of the model at a threshold probability of >0.25 in cohort A. However, no net benefit of the model over the treat-all strategy was seen in cohort B at any threshold probability. CONCLUSIONS: The performance of the Weiniger model is variable based on the case-mix of the population with regard to PAS clinical risk factors and ultrasound features, highlighting the importance of spectrum bias when applying this PAS prediction model to distinct populations. The model showed benefit for predicting PAS in populations with substantial case-mix heterogeneity at threshold probability of >25%.

Incidence and Clinical Implications of Placenta Accreta Spectrum after Treatment for Asherman Syndrome.

STUDY OBJECTIVE: To investigate the incidence, predictors, and clinical implications of placenta accreta spectrum (PAS) in pregnancies after hysteroscopic treatment for Asherman syndrome (AS). DESIGN: This is a retrospective cohort study, conducted through a telephone survey and chart review. SETTING: Minimally invasive gynecologic surgery center in an academic community hospital. PATIENTS: Database of 355 patients hysteroscopically treated for AS over 4 years. We identified patients who achieved pregnancy past the first trimester and evaluated the incidence and predictors for PAS as well as associated clinical implications. INTERVENTIONS: Telephone survey. MEASUREMENTS AND MAIN RESULTS: We identified 97 patients meeting the inclusion criteria. Among these patients, 23 (23.7%) patients had PAS. History of cesarean delivery was the only variable statistically significantly associated with having PAS (adjusted odds ratio 4.03, 95% confidence interval 1.31-12.39). PAS was diagnosed antenatally in 3 patients (14.3%), with patients having placenta previa more likely to be diagnosed (p <.01). Nine patients (39.13%) with PAS required cesarean hysterectomy, which is 9.3% of those with a pregnancy that progressed past the first trimester. Factors associated with cesarean hysterectomy were the etiology of AS (dilation and evacuation after the second trimester pregnancy or postpartum instrumentation, p <.01), invasive placenta (increta or percreta, p <.05), and history of morbidly adherent placenta in previous pregnancies (p <.05). Two patients with PAS (9.5%) had uterine rupture, and another 2 (9.5%) experienced uterine inversion. CONCLUSION: There is a high incidence of PAS and associated morbidity in pregnancies after hysteroscopic treatment for AS. There is a low rate of antenatal diagnosis as well as a lack of reliable clinical predictors, which both stress the importance of clinical awareness, careful counseling, and delivery planning.

Knowledge Gaps in Placenta Accreta Spectrum.

Since its first description early in the 20th Century, placenta accreta and its variants have changed substantially in incidence, risk factor profile, clinical presentation, diagnosis and management. While systematic use of diagnostic tools and a multidisciplinary team care approach has begun to improve patient outcomes, the condition's pathophysiology, epidemiology, and best practices for diagnosis and management remain poorly understood. The use of large databases with broadly accepted terminology and diagnostic criteria should accelerate research in this area. Future work should focus on non-traditional phenotypes, such as those without placenta previa-preventive strategies, and long term medical and emotional support for patients facing this diagnosis. KEY POINTS: · Placenta accreta spectrum research may be improved with standardized terminology and use of large databases.. · Placenta accreta prediction should move beyond ultrasound with the addition of biomarkers, and needs to extend to those without traditional risk factors.. · Future research should identify practices that can prevent future accreta development..

General Management Considerations for Placenta Accreta Spectrum.

The ideal management of a patient with placenta accreta spectrum (PAS) includes close antepartum management culminating in a planned and coordinated delivery by an experienced multidisciplinary PAS team. Coordinated team management has been shown to optimize outcomes for mother and infant. This section provides a consensus overview from the Pan-American Society for the Placenta Accreta Spectrum regarding general management of PAS.

The Association between Placenta Accreta Spectrum Severity and Incidence of Small for Gestational Age Neonates.

OBJECTIVE: The aim of the study is to evaluate whether pathologic severity of placenta accreta spectrum (PAS) is correlated with the incidence of small for gestational age (SGA) and neonatal birthweight. STUDY DESIGN: This was a multicenter cohort study of viable, non-anomalous, singleton gestations delivered with histology-proven PAS. Data including maternal history, neonatal birthweight, and placental pathology were collected and deidentified. Pathology was defined as accreta, increta, or percreta. The primary outcome was rate of SGA defined by birth weight less than the 10th percentile. The secondary outcomes included incidence of large for gestational age (LGA) babies as defined by birth weight greater than the 90th percentile as well as incidence of SGA and LGA in preterm and term gestations. Statistical analysis was performed using Chi-square, Kruskal-Wallis, and log-binomial regression. Increta and percreta patients were each compared with accreta patients. RESULTS: Among the cohort of 1,008 women from seven United States centers, 865 subjects were included in the analysis. The relative risk (RR) of SGA for increta and percreta did not differ from accreta after adjusting for confounders (adjusted RR = 0.63, 95% confidence interval [CI]: 0.36-1.10 for increta and aRR = 0.72, 95% CI: 0.45-1.16 for percreta). The results were stratified by placenta previa status, which did not affect results. There was no difference in incidence of LGA (p = 1.0) by PAS pathologic severity. The incidence of SGA for all PAS patients was 9.2% for those delivered preterm and 18.7% for those delivered at term (p = 0.004). The incidence of LGA for all PAS patients was 12.6% for those delivered preterm and 13.2% for those delivered at term (p = 0.8203). CONCLUSION: There was no difference in incidence of SGA or LGA when comparing accreta to increta or percreta patients regardless of previa status. Although we cannot suggest causation, our results suggest that PAS, regardless of pathologic severity, is not associated with pathologic fetal growth in the preterm period. KEY POINTS: · PAS severity is not associated with SGA in the preterm period.. · PAS severity is not associated with LGA.. · Placenta previa does not affect the incidence of SGA in women with PAS..

Surgical Techniques for the Management of Placenta Accreta Spectrum.

The surgical management of placenta accreta spectrum (PAS) is often challenging. There are a variety of techniques and management options described in the literature ranging from uterine sparing to cesarean hysterectomy. Following the inaugural meeting of the Pan-American Society for Placenta Accreta Spectrum a multidisciplinary group collaborated to describe collective recommendations for the surgical management of PAS. In this manuscript, we outline individual components of the procedure and provide suggested direction at key points of a cesarean hysterectomy in the setting of PAS. KEY POINTS: · The surgical management of PAS requires careful planning and expertise.. · Multidisciplinary team care for pregnancies complicated by PAS can decrease morbidity and mortality.. · Careful surgical techniques can minimize risk of significant hemorrhage by avoiding pitfalls..

Uterine rupture and factors associated with adverse outcomes.

PURPOSE: To review cases of uterine rupture and identify risk factors associated with adverse outcomes. METHODS: This study is a retrospective cohort of complete uterine ruptures diagnosed in a large hospital system in Massachusetts between 2004 and 2018. Baseline demographics, labor characteristics and outcomes of uterine rupture were collected from medical records. RESULTS: A total of 173 cases of uterine rupture were identified. There were 30 (17.3%) women with an unscarred uterus, while 142 (82.1%) had a scarred uterus. Adverse outcomes (n = 89, 51.4% of cases) included 26 (15.0%) hysterectomies, 55 (31.8%) blood transfusions, 18 (10.4%) bladder/ureteral injuries, 5 (2.9%) reoperations, 25 (14.5%) Apgar scores lower than 5 at 5 min and 9 (5.2%) perinatal deaths. Uterine rupture of a scarred uterus was associated with decreased risk of hemorrhage (OR 0.40, 95% CI 0.17-0.93), blood transfusion (OR 0.27, 95% CI 0.11-0.69), hysterectomy (OR 0.23, 95% CI 0.08-0.69) and any adverse outcome (OR 0.34, 95% CI 0.13-0.91) compared with unscarred rupture. Uterine rupture during vaginal delivery was associated with increased risk of transfusion (OR 6.55, 95% CI 1.53-28.05) and hysterectomy (OR 8.95, 95% CI 2.12-37.72) compared with emergent C-section. CONCLUSIONS: Although rare, uterine rupture is associated with adverse outcomes in over half of cases. Unscarred rupture and vaginal delivery demonstrate increased risk of adverse outcomes, highlighting the need for early diagnosis and operative intervention.

Tranexamic acid administered during cesarean delivery in high-risk patients: maternal pharmacokinetics, pharmacodynamics, and coagulation status.

BACKGROUND: Tranexamic acid is frequently administered for postpartum hemorrhage. The World Health Organization recommends 1 g intravenous dosing, repeated once after 30 minutes for ongoing bleeding. Understanding the pharmacokinetics and pharmacodynamics of tranexamic acid in patients at high risk of postpartum hemorrhage may enable dosage tailoring for optimal antifibrinolysis with minimal adverse events, such as thrombosis or renal cortical necrosis. OBJECTIVE: This study aimed to report tranexamic acid pharmacokinetics and pharmacodynamics after 1 g intravenous dosing during cesarean delivery in patients at risk of hemorrhage. The primary endpoint was tranexamic acid plasma concentration of >10 µg/mL, known to inhibit 80% of fibrinolysis. In addition, the correlation between patient demographics and rotational thromboelastometry coagulation changes were analyzed. STUDY DESIGN: In this prospective study, 20 women aged 18 to 50 years, ≥23 weeks of gestation undergoing cesarean delivery with at least 1 major (placenta previa, suspected placenta accreta spectrum, or active bleeding) or 2 minor (≥2 previous cesarean deliveries, previous postpartum hemorrhage, chorioamnionitis, polyhydramnios, macrosomia, obesity, or suspected placental abruption) risk factors for postpartum hemorrhage were recruited. The exclusion criteria were allergy to tranexamic acid, inherited thrombophilia, previous or current thrombosis, seizure history, renal or liver dysfunction, anticoagulation, or category III fetal heart tracing. Tranexamic acid 1 g was administered after umbilical cord clamping. Blood samples were drawn at 3, 7, 15, and 30 minutes and then at 30-minute intervals up to 5 hours. Plasma concentrations were evaluated as mean (standard error). Serial rotational thromboelastometry was performed and correlated with tranexamic acid plasma concentrations. RESULTS: The median age of participants was 37.5 years (interquartile range, 35.0-39.5), and the median body mass index was 28.6 kg/m2 (interquartile range, 24.9-35.0). The median blood loss (estimated or quantitative) was 1500 mL (interquartile range, 898.5-2076.0). Of note, 9 of 20 (45%) received a transfusion of packed red blood cells. The mean peak tranexamic acid plasma concentration at 3 minutes was 59.8±4.7 µg/mL. All patients had a plasma concentration >10 µg/mL for 1 hour after infusion. Plasma concentration was >10 µg/mL in more than half of the patients at 3 hours and fell <10 µg/mL in all patients at 5 hours. There was a moderate negative correlation between body mass index and the plasma concentration area under the curve (r=-0.49; 95% confidence interval, -0.77 to -0.07; P=.026). Rotational thromboelastometry EXTEM maximum clot firmness had a weak positive correlation with longitudinal plasma concentration (r=0.32; 95% confidence interval, 0.21-0.46; P<.001). EXTEM maximum clot lysis was 0% after infusion in 18 patients (90%), and no patient in the study demonstrated a maximum lysis of >15% at any interval from 3 minutes to 5 hours. There was no significant correlation between EXTEM clot lysis at 30 minutes and longitudinal tranexamic acid plasma concentrations (r=0.10; 95% confidence interval, -0.20 to 0.19; P=.252). CONCLUSION: After standard 1 g intravenous dosing of tranexamic acid during cesarean delivery in patients at high risk of hemorrhage, a plasma concentration of ≥10 µg/mL was sustained for at least 60 minutes. Plasma tranexamic acid levels correlated inversely with body mass index. The concurrent use of rotational thromboelastometry may demonstrate tranexamic acid's impact on clot firmness but not a hyperfibrinolysis-derived trigger for therapy.

Introduction of a Novel System for Quantitating Blood Loss After Vaginal Delivery: A Retrospective Interrupted Time Series Analysis With Concurrent Control Group.

BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. While volumetric and gravimetric blood loss measurement techniques have been shown to increase PPH detection compared to visual estimation of blood loss (vBL), a combination of these methods has not been evaluated. The primary aim of this study was to compare the change in odds of PPH detection after vaginal delivery (VD; the intervention series) versus cesarean delivery (CD; the control series) before versus after implementation of a device (Triton L&D, Gauss Surgical, Inc, Los Altos, CA) that combines gravimetric and volumetric estimation of blood loss (tBL). METHODS: After institutional review board (IRB) approval, patients were identified who had a VD or CD at our institution 3 months before and 3 months after the implementation of a tBL device for VD. The levels and trends in odds of PPH detection (the primary outcome, defined as blood loss ≥500 mL for VD and ≥1000 mL for CD) were compared within and between delivery methods before and after implementation of the device. Secondary outcomes were blood loss ≥1000 mL, total blood loss, secondary uterotonic use, and a composite outcome related to PPH management (transfusion, vasopressor administration, and/or surgical procedures). A post hoc subgroup analysis compared nadir hematocrit, hematocrit reduction ≥10%, and difference between vBL or tBL and calculated blood loss (cBL) between VDs before and after introduction of the device. All outcome comparisons were performed using segmented regression with inverse probability of treatment weighting. RESULTS: The weighted odds ratio (wOR) of PPH detection post- versus preimplementation of the device was 2.74 (95% confidence interval [CI], 1.39-5.41; P = .004) for VDs versus 1.43 (95% CI, 0.72-2.85; P = .304) for CDs (P for interaction .190). No difference was detected in the secondary outcomes for VDs between time periods. In the subgroup of VD patients who had postdelivery hematocrits measured, the mean difference between vBL or tBL and cBL was smaller in the tBL (mean ± standard deviation [SD]: -237 ± 522 mL) versus vBL group (-600 ± 596 mL; weighted difference in means [95% CI]: 349 mL [13-684]; P = .042). CONCLUSIONS: In this interrupted time series analysis, the odds of PPH detection after VD increased after implementation of the tBL device. However, a statistical difference was not detected between the increase in PPH detection post- versus preimplementation of the device in VDs versus CDs.

Identifying Barriers to Implementation of the National Partnership for Maternal Safety Obstetric Hemorrhage Bundle at a Tertiary Center: Utilization of the Delphi Method.

BACKGROUND: In 2015, the National Partnership for Maternal Safety (NPMS) developed an obstetric hemorrhage consensus bundle to provide birthing facilities in the United States with consistent, validated practice guidelines for postpartum hemorrhage management. The process of implementing each bundle element at a large tertiary labor and delivery unit has not been described; we sought to identify practice deficiencies and perceived barriers to bundle implementation among multidisciplinary providers. METHODS: We conducted a prospective, cross-sectional, consensus-building study based on the Delphi method. A multidisciplinary expert panel comprised of anesthesiologists, obstetricians, nurses, and surgical technicians was assembled and participated in 4 sequential questionnaires. The first round identified bundle elements that experts determined as not currently adequate and perceived barriers to implementation. The second round established prioritization of elements within each professional group; and the third round ranked the elements with at least 60% agreement on feasibility of implementation and positive impact on patient care. The last round revealed responses across all 4 professional groups to derive a final consensus. Descriptive statistics were performed. RESULTS: A total of 38 experts completed the study (11 anesthesiologists, 11 obstetricians, 10 nurses, and 6 surgical technicians). While all 13 (100%) NPMS obstetric bundle elements were described as deficient in our labor and delivery unit by a provider in at least 1 discipline, consensus among at least 3 of the 4 disciplines was achieved for 6 element deficiencies. Barriers to implementation were determined. The initiatives that achieved consensus as possessing high patient impact and implementation feasibility were protocol-driven management, unit-based simulation drills, blood loss quantification, and team huddles and debriefings. CONCLUSIONS: The NPMS obstetric hemorrhage bundle was created to help guide practice and systems improvement for US birthing facilities. The Delphi method enabled identification of deficient elements and perceived barriers to element implementation, as well as group consensus on elements with highest patient impact and feasibility. Multidisciplinary group consensus can identify deficiencies and promote tangible, quality improvements in a large, tertiary-care labor and delivery unit. Institutions may utilize our described technique to guide implementation of future care bundles.

Neuraxial Anesthesia During Cesarean Delivery for Placenta Previa With Suspected Morbidly Adherent Placenta: A Retrospective Analysis.

BACKGROUND: General anesthesia (GA) is often selected for cesarean deliveries (CD) with placenta previa and suspected morbidly adherent placenta (MAP) due to increased risk of hemorrhage and hysterectomy. We reviewed maternal outcomes and risk factors for conversion to GA in a cohort of patients undergoing CD and hysterectomy under neuraxial anesthesia (NA). METHODS: We performed a single-center, retrospective cohort study of parturients undergoing nonemergent CD for placenta previa with suspected MAP from 1997 to 2015. Patients were classified according to whether they received GA, NA, or intraoperative conversion from NA to GA. The primary outcome measure was postoperative acuity, defined as the need for intensive care unit admission, arterial embolization, reoperation, or ongoing transfusion with ≥3 units packed red blood cells. We additionally identified variables positively associated with intraoperative conversion from NA to GA during hysterectomy. Confounding was controlled with logistic regression models. RESULTS: Of 129 patients undergoing nonemergent CD for placenta previa with suspected MAP, 122 (95%) received NA as the primary anesthetic. NA was selected in the majority of patients with a body mass index ≥40 kg/m (9 of 10, 90%), a history of ≥3 prior CDs (18 of 20, 90%), suspected placenta increta or percreta (29 of 35, 83%), and Mallampati classification ≥3 (19 of 21, 90%). Of 72 patients with NA at the time of delivery who required hysterectomy, 15 (21%) required conversion to GA intraoperatively. Converted patients had a higher rate of major packed red blood cell transfusion (60% vs 25%; P = .01), with similar rates of massive transfusion (9% vs 7%; P = 1.0). Converted patients also had a higher incidence of postoperative acuity (47% vs 4%; P < .0001), including 5 intensive care unit admissions for airway management after large-volume resuscitation. After adjusting for multiple confounders, the only independent predictors of conversion among hysterectomy patients were longer surgical duration (adjusted odds ratio 1.54, 95% CI, 1.01-2.42) and a history of ≥3 prior CDs (adjusted odds ratio, 6.45; 95% CI, 1.12-45.03). CONCLUSIONS: NA was applied to and successfully used in the majority of patients with suspected MAP. Our findings support selective conversion to GA during hysterectomy in these patients, focusing on those with the highest levels of surgical complexity.

The Placenta Accreta Spectrum: Epidemiology and Risk Factors.

The placenta accreta spectrum has become an important contributor to severe maternal morbidity. The true incidence is difficult to ascertain, but likely falls near 1/1000 deliveries. This number seems to have increased along with the rate of risk factors. These include placenta previa, previous cesarean section, use of assisted reproductive technologies, uterine surgeries, and advanced maternal age. With increased uterine conservation, previous retained placenta or placenta accreta have become significant risk factors. Understanding placenta accreta spectrum risk factors facilitates patient identification and safe delivery planning. Patients considering elective uterine procedures or delayed childbirth should consider the impact on peripartum morbidity.

Patient selection for later delivery timing with suspected previa-accreta.

INTRODUCTION: We identified patients with previa and suspected accreta who are at lowest risk of unscheduled delivery or major morbidity with planned delivery beyond 34 weeks' gestation. MATERIAL AND METHODS: This was a retrospective cohort study of patients who had reached 34.0 weeks' gestational age with a suspected previa-accreta. We evaluated rates of unscheduled and emergent delivery based on known risk factors for premature birth. In a second analysis, we stratified patients based on level of preoperative morbidity concern and evaluated rates of major transfusion and Intensive Care Unit admission by delivery week (34 weeks, 35 weeks or 36 weeks and beyond). RESULTS: Of 84 available patients, we classified 31 patients as low risk for unscheduled delivery and 52 as high risk. The low risk group was scheduled later (36.6 vs. 36.0 weeks; p < 0.01), but demonstrated lower rates of unscheduled delivery prior to 36 weeks (3% vs. 19%, p = 0.05). Of the patients with no prior cesarean section, only one (7%) experienced massive blood loss even though 36% had unscheduled deliveries. We observed no significant increase in major transfusion or massive blood loss with advancing gestational age, likely due to selection of the most concerning patients for early, scheduled delivery. CONCLUSION: Patients with suspected previa-accreta and no risk factors for preterm birth are at low risk for an unscheduled delivery prior to 36 weeks. Those with no concern for percreta or increta or no prior cesarean section may also be candidates for later delivery.

Outcome of cesarean scar pregnancies diagnosed sonographically in the first trimester.

OBJECTIVES: The purpose of this study was to determine the outcome of cesarean scar pregnancies diagnosed during the first trimester. METHODS: We retrospectively identified all cesarean scar implantation pregnancies diagnosed by sonography before 14 weeks' gestation between 2000 and 2012 at our institution. We reviewed the patients' sonograms and medical records and recorded sonographic findings and pregnancy outcomes. RESULTS: Thirty-four cases met study entry criteria. Ten patients presented with no embryonic cardiac activity, of whom 7 underwent interventions, and 3 were expectantly managed. One of the former 7 and none of the latter 3 required hysterectomy for bleeding. Among the 24 patients with embryonic cardiac activity, 8 were managed expectantly: 5 (62.5%) ultimately delivered a live-born neonate, 3 (60.0%) of whom required hysterectomy due to placenta accreta; and 3 had fetal demise. Sixteen of the 24 underwent interventions, 2 opting for gravid hysterectomy (10 and 11 weeks' gestation, respectively) and 14 treated by a minimally invasive method: intrasac potassium chloride injection (3 cases); intrasac potassium chloride injection plus intramuscular methotrexate (4 cases); sonographically guided dilation and curettage (6 cases); and laparascopic resection (1 case). None of the latter 14 subsequently required hysterectomy. CONCLUSIONS: If a woman has a first-trimester diagnosis of a cesarean scar implantation pregnancy and embryonic cardiac activity is present, expectant management offers the possibility of delivering a live-born neonate (62.5% in our study) but carries a substantial likelihood of hysterectomy at delivery due to placenta accreta (37.5% in our study), whereas minimally invasive therapy that interrupts the pregnancy largely eliminates the need for hysterectomy.

A risk factor profile for placenta accreta spectrum in pregnancies conceived with assisted reproductive technology.

Objective: To identify independent risk factors for placenta accreta spectrum among pregnancies conceived with assisted reproductive technology. Design: Retrospective cohort study. Setting: Tertiary hospital. Patients: Individuals who conceived with assisted reproductive technology and reached 20 weeks' gestation or later from 2011 to 2017. Interventions: Patient and cycle data was abstracted from hospital records and supplemented with state-level data. Poisson regression was used for multivariate analyses and reported as adjusted relative risks (aRR). Main Outcome Measures: Clinical or histologic placenta accreta spectrum. Results: Of 1,975 qualifying pregnancies, 44 (2.3%) met criteria for accreta spectrum at delivery. In the multivariate model, significant risk factors included low-lying placenta at delivery (aRR, 15.44; 95% CI 7.76-30.72), uterine factor infertility or prior uterine surgery (aRR, 4.68; 95% CI, 2.72-8.05), initial low-lying placentation that resolved (aRR, 3.83; 95% CI, 1.90-7.73), and use of frozen embryos (aRR, 3.02; 95% CI, 1.66-5.48). When the fresh vs frozen variable was replaced with controlled ovarian hyperstimulation, the final model did not change (aRR, 2.40 for unstimulated cycles, 95% CI, 1.32-4.38). With frozen transfers, the accreta rate was 16% when the endometrial thickness was < 6mm vs 3.8% with thicker endometrium (P=.02). Conclusions: Among pregnancies conceived with assisted reproductive technology, accreta spectrum is associated with low placental implantation (even when resolved), uterine factor infertility and prior uterine surgery, and the use of frozen embryo transfer or unstimulated cycles.

Circulating microparticle proteins predict pregnancies complicated by placenta accreta spectrum.

Placenta accreta spectrum (PAS) is characterized by abnormal attachment of the placenta to the uterus, and attempts at placental delivery can lead to catastrophic maternal hemorrhage and death. Multidisciplinary delivery planning can significantly improve outcomes; however, current diagnostics are lacking as approximately half of pregnancies with PAS are undiagnosed prior to delivery. This is a nested case-control study of 35 cases and 70 controls with the primary objective of identifying circulating microparticle (CMP) protein panels that identify pregnancies complicated by PAS. Size exclusion chromatography and liquid chromatography with tandem mass spectrometry were used for CMP protein isolation and identification, respectively. A two-step iterative workflow was used to establish putative panels. Using plasma sampled at a median of 26 weeks' gestation, five CMP proteins distinguished PAS from controls with a mean area under the curve (AUC) of 0.83. For a separate sample taken at a median of 35 weeks' gestation, the mean AUC was 0.78. In the second trimester, canonical pathway analyses demonstrate over-representation of processes related to iron homeostasis and erythropoietin signaling. In the third trimester, these analyses revealed abnormal immune function. CMP proteins classify PAS well prior to delivery and have potential to significantly reduce maternal morbidity and mortality.