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Quantitative Imaging in Medicine and... Mar 2024
PubMed: 38545048
DOI: 10.21037/qims-24-164 -
The Journal of Obstetrics and... Jun 2024The refinement of assisted reproductive technology, including the development of cryopreservation techniques (vitrification) and ovarian stimulation protocols, makes... (Review)
Review
AIM
The refinement of assisted reproductive technology, including the development of cryopreservation techniques (vitrification) and ovarian stimulation protocols, makes frozen embryo transfer (FET) an alternative to fresh ET and has contributed to the success of assisted reproductive technology. Compared with fresh ET cycles, FET cycles were associated with better in vitro fertilization outcomes; however, the occurrence of pregnancy-induced hypertension, preeclampsia, and placenta accreta spectrum (PAS) was higher in FET cycles. PAS has been increasing steadily in incidence as a life-threatening condition along with cesarean rates worldwide. In this review, we summarize the current understanding of the pathogenesis of PAS and discuss future research directions.
METHODS
A literature search was performed in the PubMed and Google Scholar databases.
RESULTS
Risk factors associated with PAS incidence include a primary defect of the decidua basalis or scar dehiscence, aberrant vascular remodeling, and abnormally invasive trophoblasts, or a combination thereof. Freezing, thawing, and hormone replacement manipulations have been shown to affect multiple cellular pathways, including cell proliferation, invasion, epithelial-to-mesenchymal transition (EMT), and mitochondrial function. Molecules involved in abnormal migration and EMT of extravillous trophoblast cells are beginning to be identified in PAS placentas. Many of these molecules were also found to be involved in mitochondrial biogenesis and dynamics.
CONCLUSION
The etiology of PAS may be a multifactorial genesis with intrinsic predisposition (e.g., placental abnormalities) and certain environmental factors (e.g., defective decidua) as triggers for its development. A distinctive feature of this review is its focus on the potential factors linking mitochondrial function to PAS development.
Topics: Humans; Placenta Accreta; Female; Pregnancy; Mitochondria
PubMed: 38544343
DOI: 10.1111/jog.15936 -
Journal of Assisted Reproduction and... Apr 2024In the first of two companion papers, we comprehensively reviewed the recent evidence in the primary literature, which addressed the increased prevalence of hypertensive... (Review)
Review
PURPOSE
In the first of two companion papers, we comprehensively reviewed the recent evidence in the primary literature, which addressed the increased prevalence of hypertensive disorders of pregnancy, late-onset or term preeclampsia, fetal overgrowth, postterm birth, and placenta accreta in women conceiving by in vitro fertilization. The preponderance of evidence implicated frozen embryo transfer cycles and, specifically, those employing programmed endometrial preparations, in the higher risk for these adverse maternal and neonatal pregnancy outcomes. Based upon this critical appraisal of the primary literature, we formulate potential etiologies and suggest strategies for prevention in the second article.
METHODS
Comprehensive review of primary literature.
RESULTS
Presupposing significant overlap of these apparently diverse pathological pregnancy outcomes within subjects who conceive by programmed autologous FET cycles, shared etiologies may be at play. One plausible but clearly provocative explanation is that aberrant decidualization arising from suboptimal endometrial preparation causes greater than normal trophoblast invasion and myometrial spiral artery remodeling. Thus, overly robust placentation produces larger placentas and fetuses that, in turn, lead to overcrowding of villi within the confines of the uterine cavity which encroach upon intervillous spaces precipitating placental ischemia, oxidative and syncytiotrophoblast stress, and, ultimately, late-onset or term preeclampsia. The absence of circulating corpus luteal factors like relaxin in most programmed cycles might further compromise decidualization and exacerbate the maternal endothelial response to deleterious circulating placental products like soluble fms-like tyrosine kinase-1 that mediate disease manifestations. An alternative, but not mutually exclusive, determinant might be a thinner endometrium frequently associated with programmed endometrial preparations, which could conspire with dysregulated decidualization to elicit greater than normal trophoblast invasion and myometrial spiral artery remodeling. In extreme cases, placenta accreta could conceivably arise. Though lower uterine artery resistance and pulsatility indices observed during early pregnancy in programmed embryo transfer cycles are consistent with this initiating event, quantitative analyses of trophoblast invasion and myometrial spiral artery remodeling required to validate the hypothesis have not yet been conducted.
CONCLUSIONS
Endometrial preparation that is not optimal, absent circulating corpus luteal factors, or a combination thereof are attractive etiologies; however, the requisite investigations to prove them have yet to be undertaken. Presuming that in ongoing RCTs, some or all adverse pregnancy outcomes associated with programmed autologous FET are circumvented or mitigated by employing natural or stimulated cycles instead, then for women who can conceive using these regimens, they would be preferable. For the 15% or so of women who require programmed FET, additional research as suggested in this review is needed to elucidate the responsible mechanisms and develop preventative strategies.
Topics: Humans; Female; Pregnancy; Embryo Transfer; Pregnancy Outcome; Fertilization in Vitro; Pre-Eclampsia; Infant, Newborn; Placenta Accreta; Placenta; Endometrium
PubMed: 38536596
DOI: 10.1007/s10815-024-03042-8 -
Journal of Assisted Reproduction and... Apr 2024In this first of two companion papers, we critically review the evidence recently published in the primary literature, which addresses adverse maternal and neonatal... (Review)
Review
PURPOSE
In this first of two companion papers, we critically review the evidence recently published in the primary literature, which addresses adverse maternal and neonatal pregnancy outcomes associated with programmed embryo transfer cycles. We next consider whether these pathological pregnancy outcomes might be attributable to traditional risk factors, unknown parental factors, embryo culture, culture duration, or cryopreservation. Finally, in the second companion article, we explore potential etiologies and suggest strategies for prevention.
METHODS
Comprehensive review of primary literature.
RESULTS
The preponderance of retrospective and prospective observational studies suggests that increased risk for hypertensive disorders of pregnancy (HDP) and preeclampsia in assisted reproduction involving autologous embryo transfer is associated with programmed cycles. For autologous frozen embryo transfer (FET) and singleton live births, the risk of developing HDP and preeclampsia, respectively, was less for true or modified natural and stimulated cycles relative to programmed cycles: OR 0.63 [95% CI (0.57-0.070)] and 0.44 [95% CI (0.40-0.50)]. Though data are limited, the classification of preeclampsia associated with programmed autologous FET was predominantly late-onset or term disease. Other adverse pregnancy outcomes associated with autologous FET, especially programmed cycles, included increased prevalence of large for gestational age infants and macrosomia, as well as higher birth weights. In one large registry study, FET was associated with fetal overgrowth of a symmetrical nature. Postterm birth and placenta accreta not associated with prior cesarean section, uterine surgery, or concurrent placenta previa were also associated with autologous FET, particularly programmed cycles. The heightened risk of these pathologic pregnancy outcomes in programmed autologous FET does not appear to be attributable to traditional risk factors, unknown parental factors, embryo culture, culture duration, or cryopreservation, although the latter may contribute a modest degree of increased risk for fetal overgrowth and perhaps HDP and preeclampsia in FET irrespective of the endometrial preparation.
CONCLUSIONS
Programmed autologous FET is associated with an increased risk of several, seemingly diverse, pathologic pregnancy outcomes including HDP, preeclampsia, fetal overgrowth, postterm birth, and placenta accreta. Though the greater risk for preeclampsia specifically associated with programmed autologous FET appears to be well established, further research is needed to substantiate the limited data currently available suggesting that the classification of preeclampsia involved is predominately late-onset or term. If substantiated, then this knowledge could provide insight into placental pathogenesis, which has been proposed to differ between early- and late-onset or term preeclampsia (see companion paper for a discussion of potential mechanisms). If a higher prevalence of preeclampsia with severe features as suggested by some studies is corroborated in future investigations, then the danger to maternal and fetal/neonatal health is considerably greater with severe disease, thus increasing the urgency to find preventative measures. Presupposing significant overlap of these diverse pathologic pregnancy outcomes within subjects who conceive by programmed embryo transfer, there may be common etiologies.
Topics: Humans; Female; Pregnancy; Embryo Transfer; Pregnancy Outcome; Pre-Eclampsia; Infant, Newborn; Fertilization in Vitro; Cryopreservation; Hypertension, Pregnancy-Induced; Risk Factors
PubMed: 38536594
DOI: 10.1007/s10815-024-03041-9 -
Assessment of obstetric characteristics and outcomes associated with pregnancy with Turner syndrome.Fertility and Sterility Mar 2024To assess national-level trends, characteristics, and outcomes of pregnancies with Turner syndrome in the United States.
OBJECTIVE
To assess national-level trends, characteristics, and outcomes of pregnancies with Turner syndrome in the United States.
DESIGN
Cross-sectional study.
SETTING
The Healthcare Cost and Utilization Project's National Inpatient Sample.
SUBJECTS
A total of 17,865,495 hospital deliveries from 2016-2020.
EXPOSURE
A diagnosis of Turner syndrome, identified according to the World Health Organization's International Classification of Disease 10th revision code of Q96.
MAIN OUTCOME MEASURES
Obstetrics outcomes related to Turner syndrome, assessed with inverse probability of treatment weighting cohort and multivariable binary logistic regression modeling.
RESULTS
The prevalence of pregnant patients with Turner syndrome was 7.0 per 100,000 deliveries (one in 14,235). The number of hospital deliveries with patients who have a diagnosis of Turner syndrome increased from 5.0 to 11.7 per 100,000 deliveries during the study period (adjusted-odds ratio [aOR] for 2020 vs. 2016; 2.18, 95% confidence interval [CI] 1.83-2.60). Pregnant patients with Turner syndrome were more likely to have a diagnosis of pregestational hypertension (4.8% vs. 2.8%; aOR 1.65; 95% CI 1.26-2.15), uterine anomaly (1.6% vs. 0.4%; aOR, 3.01; 95% CI 1.93-4.69), and prior pregnancy losses (1.6% vs. 0.3%; aOR 4.70; 95% CI 3.01-7.32) compared with those without Turner syndrome. For the index obstetric characteristics, Turner syndrome was associated with an increased risk of intrauterine fetal demise (10.9% vs. 0.7%; aOR 8.40; 95% CI 5.30-13.30), intrauterine growth restriction (8.5% vs. 3.5%; aOR 2.11; 95% CI 1.48-2.99), and placenta accreta spectrum (aOR 3.63; 95% CI 1.20-10.97). For delivery outcome, pregnant patients with Turner syndrome were more likely to undergo cesarean delivery (41.6% vs. 32.3%; aOR 1.53; 95% CI 1.26-1.87). Moreover, the odds of periviable delivery (22-25 weeks: 6.1% vs. 0.4%; aOR 5.88; 95% CI 3.47-9.98) and previable delivery (<22 weeks: 3.3% vs. 0.3%; aOR 2.87; 95% CI 1.45-5.69) were increased compared with those without Turner syndrome.
CONCLUSIONS
The results of contemporaneous, nationwide assessment in the United States suggest that although pregnancy with Turner syndrome is uncommon this may represent a high-risk group, particularly for intrauterine fetal demise and periviable delivery. Establishing a society-based approach for preconception counseling and antenatal follow-up would be clinically compelling.
PubMed: 38522502
DOI: 10.1016/j.fertnstert.2024.03.019 -
Acta Obstetricia Et Gynecologica... Jul 2024Pregnant women with a fibrinogen level <2 g/L represent a high-risk group that is associated with severe postpartum hemorrhage and other complications. Women who would...
INTRODUCTION
Pregnant women with a fibrinogen level <2 g/L represent a high-risk group that is associated with severe postpartum hemorrhage and other complications. Women who would qualify for fibrinogen therapy are not yet identified.
MATERIAL AND METHODS
A population-based cross-sectional study was conducted using the UK Obstetric Surveillance System between November 2017 and October 2018 in any UK hospital with a consultant-led maternity unit. Any woman pregnant or immediately postpartum with a fibrinogen <2 g/L was included. Our aims were to determine the incidence of fibrinogen <2 g/L in pregnancy, and to describe its causes, management and outcomes.
RESULTS
Over the study period 124 women with fibrinogen <2 g/L were identified (1.7 per 10 000 maternities; 95% confidence interval 1.4-2.0 per 10 000 maternities). Less than 5% of cases of low fibrinogen were due to preexisting inherited dysfibrinogenemia or hypofibrinogenemia. Sixty percent of cases were due to postpartum hemorrhage caused by placental abruption, atony, or trauma. Amniotic fluid embolism and placental causes other than abruption (previa, accreta, retention) were associated with the highest estimated blood loss (median 4400 mL) and lowest levels of fibrinogen. Mortality was high with two maternal deaths due to massive postpartum hemorrhage, 27 stillbirths, and two neonatal deaths.
CONCLUSIONS
Fibrinogen <2 g/L often, but not exclusively, affected women with postpartum hemorrhage due to placental abruption, atony, or trauma. Other more rare and catastrophic obstetrical events such as amniotic fluid embolism and placenta accreta also led to low levels of fibrinogen. Maternal and perinatal mortality was extremely high in our cohort.
Topics: Humans; Female; Pregnancy; United Kingdom; Adult; Cross-Sectional Studies; Postpartum Hemorrhage; Fibrinogen; Cohort Studies; Afibrinogenemia; Pregnancy Outcome; Infant, Newborn; Postpartum Period
PubMed: 38519441
DOI: 10.1111/aogs.14828 -
Paediatric and Perinatal Epidemiology Mar 2024The 10th revision of the International Classification of Diseases, Clinical Modification (ICD-10) includes diagnosis codes for placenta accreta spectrum for the first...
BACKGROUND
The 10th revision of the International Classification of Diseases, Clinical Modification (ICD-10) includes diagnosis codes for placenta accreta spectrum for the first time. These codes could enable valuable research and surveillance of placenta accreta spectrum, a life-threatening pregnancy complication that is increasing in incidence.
OBJECTIVE
We sought to evaluate the validity of placenta accreta spectrum diagnosis codes that were introduced in ICD-10 and assess contributing factors to incorrect code assignments.
METHODS
We calculated sensitivity, specificity, positive predictive value and negative predictive value of the ICD-10 placenta accreta spectrum code assignments after reviewing medical records from October 2015 to March 2020 at a quaternary obstetric centre. Histopathologic diagnosis was considered the gold standard.
RESULTS
Among 22,345 patients, 104 (0.46%) had an ICD-10 code for placenta accreta spectrum and 51 (0.23%) had a histopathologic diagnosis. ICD-10 codes had a sensitivity of 0.71 (95% CI 0.56, 0.83), specificity of 0.98 (95% CI 0.93, 1.00), positive predictive value of 0.61 (95% CI 0.48, 0.72) and negative predictive value of 1.00 (95% CI 0.96, 1.00). The sensitivities of the ICD-10 codes for placenta accreta spectrum subtypes- accreta, increta and percreta-were 0.55 (95% CI 0.31, 0.78), 0.33 (95% CI 0.12, 0.62) and 0.56 (95% CI 0.31, 0.78), respectively. Cases with incorrect code assignment were less morbid than cases with correct code assignment, with a lower incidence of hysterectomy at delivery (17% vs 100%), blood transfusion (26% vs 75%) and admission to the intensive care unit (0% vs 53%). Primary reasons for code misassignment included code assigned to cases of occult placenta accreta (35%) or to cases with clinical evidence of placental adherence without histopatholic diagnostic (35%) features.
CONCLUSION
These findings from a quaternary obstetric centre suggest that ICD-10 codes may be useful for research and surveillance of placenta accreta spectrum, but researchers should be aware of likely substantial false positive cases.
PubMed: 38514907
DOI: 10.1111/ppe.13076 -
Magnetic Resonance Imaging Jun 2024Increasing trend of PAS (placenta accreta spectrum disorders) incidence is a major health concern as PAS is associated with high maternal morbidity and mortality during...
Diffusion-derived vessel density (DDVD) computed from a simple diffusion MRI protocol as a biomarker of placental blood circulation in patients with placenta accreta spectrum disorders: A proof-of-concept study.
OBJECTIVES
Increasing trend of PAS (placenta accreta spectrum disorders) incidence is a major health concern as PAS is associated with high maternal morbidity and mortality during cesarean section. Prenatal identification of PAS is crucial for delivery planning and patients management. This study aims to explore whether diffusion-derived vessel density (DDVD) computed from a simple diffusion MRI protocol differs in PAS from normal placenta.
METHODS
We enrolled 86 patients with PAS disorders and 40 pregnant women without PAS disorders. Each patient underwent intravoxel incoherent motion (IVIM) MRI sequence with 11 b-values. Placenta diffusion-derived vessel density (DDVD-b0b50) was the signal difference between b = 0 and b = 50 s/mm images. DDVD(b0b50) A/N was calculated as [accreta lesion DDVD(b0b50)]/ [normal placenta DDVD(b0b50)]. The correlation between DDVD and gestational age was explored using Spearman rank correlation. Differences of DDVD(b0b50) A/N in patients with normal placentas and with PAS, and in patients with different subtypes of PAS were explored.
RESULTS
DDVD was negatively correlated with gestational age (p = 0.023, r = -0.359) in patients with normal placentas. DDVD(b0b50) A/N was significantly higher in patients with PAS (median:1.16, mean: 1.261) than normal placenta (median:1.02, mean: 1.032, p < 0.001) and especially higher in patients with placenta increta (median:1.14, mean: 1.278) and percreta (median: 1.20, mean: 1.396, p < 0.001).
CONCLUSION
As a higher DDVD indicates higher physiological volume of micro-vessels in PAS, this study suggests DDVD can be a potential biomarker to evaluate the placenta perfusion.
Topics: Pregnancy; Humans; Female; Placenta; Placenta Accreta; Cesarean Section; Diffusion Magnetic Resonance Imaging; Biomarkers; Retrospective Studies
PubMed: 38513786
DOI: 10.1016/j.mri.2024.03.028 -
Roadmap to safety: a single center study of evidence-informed approach to placenta accreta spectrum.Frontiers in Surgery 2024To assess the impact of an evidence-informed protocol for management of placenta accreta spectrum (PAS).
OBJECTIVE
To assess the impact of an evidence-informed protocol for management of placenta accreta spectrum (PAS).
METHODS
This was a retrospective cohort study of patients who underwent cesarean hysterectomy (c-hyst) for suspected PAS from 2012 to 2022 at a single tertiary care center. Perioperative outcomes were compared pre- and post-implementation of a standardized Multidisciplinary Approach to the Placenta Service (MAPS) protocol, which incorporates evidence-informed perioperative interventions including preoperative imaging and group case review. Intraoperatively, the MAPS protocol includes placement of ureteral stents, possible placental mapping with ultrasound, and uterine artery embolization by interventional radiology. Patients suspected to have PAS on prenatal imaging who underwent c-hyst were included in the analysis. Primary outcomes were intraoperative complications and postoperative complications. Secondary outcomes were blood loss, need for ICU, and length of stay. Proportions were compared using Fisher's exact test, and continuous variables were compared used -tests and Mood's Median test.
RESULTS
There were no differences in baseline demographics between the pre- ( = 38) and post-MAPS ( = 34) groups. The pre-MAPS group had more placenta previa (95% pre- vs. 74% post-MAPS, = 0.013) and prior cesarean sections (2 prior pre- vs. 1 prior post-MAPS, = 0.012). The post-MAPS group had more severe pathology (PAS Grade 3 8% pre- vs. 47% post-MAPS, = 0.001). There were fewer intraoperative complications (39% pre- vs.3% post-MAPS, < 0.001), postoperative complications (32% pre- vs.12% post-MAPS, = 0.043), hemorrhages >1l (95% pre- vs.65% post-MAPS, = 0.001), ICU admissions (59% pre- vs.35% post-MAPS, = 0.04) and shorter hospital stays (10 days pre- vs.7 days post-MAPS, = 0.02) in the post-MAPS compared to pre-MAPS patients. Neonatal length of stay was 8 days longer in the post-MAPS group (9 days pre- vs. 17 days post-MAPS, = 0.03). Subgroup analyses demonstrated that ureteral stent placement and uterine artery embolization (UAE) may be important steps to reduce complications and ICU admissions. When comparing just those who underwent UAE, patients in the post-MAPS group experienced fewer hemorrhages greater five liters (EBL >5l 43% pre- vs.4% post-MAPS, = 0.007).
CONCLUSION
An evidence-informed approach to management of PAS was associated with decreased complication rate, EBL >1l, ICU admission and length of hospitalization, particularly for patients with severe pathology.
PubMed: 38511075
DOI: 10.3389/fsurg.2024.1347549 -
International Journal of Gynaecology... Mar 2024The optimal management of placenta accreta spectrum (PAS) requires the participation of multidisciplinary teams that are often not locally available in low-resource...
OBJECTIVE
The optimal management of placenta accreta spectrum (PAS) requires the participation of multidisciplinary teams that are often not locally available in low-resource settings. Telehealth has been increasingly used to manage complex obstetric conditions. Few studies have explored the use of telehealth for PAS management, and we aimed evaluate the usage of telehealth in the management of PAS patients in low-resource settings.
METHODS
Between March and April 2023, an observational, survey-based study was conducted, and obstetricians-gynecologists with expertise in PAS management in low- and middle-income countries were contacted to share their opinion on the potential use of telehealth for the diagnosis and management of patients at high-risk of PAS at birth. Participants were identified based on their authorship of at least one published clinical study on PAS in the last 5 years and contacted by email. This is a secondary analysis of the results of that survey.
RESULTS
From 158 authors contacted we obtained 65 responses from participants in 27 middle-income countries. A third of the participants reported the use of telehealth during the management obstetric emergencies (38.5%, n = 25) and PAS (36.9%, n = 24). Over 70% of those surveyed indicated that they had used "informal" telemedicine (phone call, email, or text message) during PAS management. Fifty-nine participants (90.8%) reported that recommendations given remotely by expert colleagues were useful for management of patients with PAS in their setting.
CONCLUSION
Telehealth has been successfully used for the management of PAS in middle-income countries, and our survey indicates that it could support the development of specialist care in other low resource settings.
PubMed: 38509726
DOI: 10.1002/ijgo.15474