Maternal endothelial function, circulating endothelial cells, and endothelial progenitor cells in pregnancies conceived with or without in vitro fertilization.
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ABSTRACT:
SUBMITTER: Conrad KP
PROVIDER: S-EPMC7311682 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundIn vitro fertilization (IVF) as a fertility treatment is associated with adverse perinatal outcomes. Racial/ethnic disparity in severe maternal morbidity (SMM) in women who conceived by IVF is understudied.ObjectiveTo examine differences in the association between race/ethnicity and SMM between women who conceived spontaneously and those who conceived using IVF.MethodsWe included all singleton live births and stillbirths in the United States, 2016-2021; data were obtained from the National Center for Health Statistics. Maternal race/ethnicity included non-Hispanic White (NHW), non-Hispanic Black (NHB), American Indian and Alaska Native (AIAN), Asian, Pacific Islander (PI), Hispanic, and mixed-race categories. The SMM composite outcome included eclampsia, uterine rupture, peripartum hysterectomy, blood transfusion, and intensive care unit (ICU) admission. We used logistic regression to adjust for potential confounders (such as age, education, parity, prepregnancy body mass index, smoking during pregnancy, chronic hypertension, and preexisting diabetes) and to assess modification of the association between race/ethnicity and SMM by IVF.ResultsThe study population included 21,585,015 women: 52% were NHW, 15% NHB, 0.8% AIAN, 6% Asian, 0.2% PI, 24% Hispanic, and 2% were of mixed race. IVF was used by 183,662 (0.85%) women; the rate of the SMM composite outcome was 18.5 per 1000 deliveries and 7.9 per 1000 deliveries in the IVF and spontaneous conception groups, respectively (unadjusted rate ratio 2.34, 95% confidence interval [CI] 2.26-2.43). In women with spontaneous conception, NHB, Asian and mixed-race women had elevated odds of SMM compared with NHW women (adjusted odds ratio [aOR]=1.39, 95% CI 1.37-1.41; aOR=1.04, 95% CI 1.02-1.07; and aOR=1.42, 95% CI 1.38-1.46, respectively). Racial/ethnic disparities in SMM and its components were not different between the IVF and spontaneous conception groups for the mixed-race category. NHB and Hispanic women had significantly higher aORs for uterine rupture/intrapartum hysterectomy compared with NHW women in the IVF group, while Asian women had a higher aOR for ICU admission compared with NHW women in the IVF group.ConclusionWomen who conceived by IVF have a greater than two-fold higher risk of SMM and this higher risk is evident across all racial/ethnic groups. However, NHB and Hispanic women who conceived by IVF had a higher risk of uterine rupture/hysterectomy, and Asian women who conceived by IVF had a higher risk of ICU admission. Our results warrant further investigation examining pregnancy and postpartum care issues among racial/ethnic minority women who conceive using IVF.
| S-EPMC11296243 | biostudies-literature
Project description:OBJECTIVE:To evaluate whether in vitro fertilization (IVF) has an effect on the cardiovascular health of offspring. STUDY DESIGN:This was a cross-sectional pilot study. We performed vascular health assessment for 17 children aged 10-14 years who were conceived via IVF with autologous oocytes at Stanford University. Carotid artery ultrasound evaluated intima-media thickness and stiffness, carotid-femoral pulse wave velocity determined segmental arterial stiffness, and endothelial pulse amplitude testing assessed endothelial function. We compared IVF offspring with control adolescents assessed in the same laboratory, with all comparisons adjusted for age, sex, and race/ethnicity. RESULTS:All participants had normal body mass index and blood pressure. Compared with controls, IVF children had thicker common carotid artery intima-media thickness (0.44 ± 0.03 mm vs 0.38 ± 0.03 mm; P < .01), higher elastic modulus (395.29 ± 185.33 mm Hg vs 242.79 ± 37.69 mm Hg; P = .01), higher ?stiffness (2.65 ± 0.38 vs 2.28 ± 0.23; P < .01), and higher peak velocity (142.29 ± 31.62 cm/s vs 117.71 ± 32.69 cm/s; P = .04). The mean endothelial pulse amplitude testing reactive hyperemia index was not significantly different between IVF and controls. The mean pulse wave velocity was 4.69 ± 0.51 m/s compared with the controls 4.60 ± 0.57 m/s (P = .11), with 8 (47%) having abnormal values. CONCLUSION:In an assessment of endothelial function and arterial properties of children conceived via IVF, we found that children conceived via IVF seem to have evidence of abnormal vascular health. Further studies with larger sample size and long-term follow-up are warranted.
| S-EPMC6815705 | biostudies-literature
Project description:IntroductionIn pregnancy, the mother and fetus differ in HLA antigens, and yet the maternal immune system generally tolerates the fetus. KIR receptors expressed by maternal uterine NK cells at the maternal-fetal interface directly interact with HLA-C on extravillous trophoblast cells for optimal placental development. In this study, we aimed to determine whether there is a preferential selection for HLA compatibility and specific KIR/HLA-C combinations in uncomplicated and preeclamptic naturally conceived pregnancies compared to what would be expected by chance.MethodsGenotyping for maternal and fetal HLA-A, -B, -C, -DR, and -DQ, and maternal KIR was performed for 451 uncomplicated pregnancies and 77 pregnancies complicated with preeclampsia. The number of HLA antigen (mis)matches between mother and fetus was calculated and compared to expected values obtained by randomization of the HLA haplotype, inherited from the father, over the existing maternal haplotype of the fetuses. A similar methodology was executed for analysis of the KIR/HLA-C data (n=309).ResultsIn uncomplicated pregnancies, the degree of maternal-fetal HLA matching was not different than expected-by-chance values. In preeclamptic pregnancies, the degree of maternal-fetal HLA matching was different in observed compared to expected-by-chance values (p=0.012). More specifically, the degree of maternal-fetal matching of HLA-C was higher in the actual preeclamptic pregnancies than was expected-by-chance (p=0.007). Preeclamptic pregnancies showed an overall tendency towards higher maternal-fetal HLA compatibility, for total HLA matches (p=0.021), HLA class I (p=0.038) and HLA-C (p=0.025) compared to uncomplicated pregnancies.ConclusionThe data suggest that there is no preferential selection of maternal-fetal HLA compatibility in uncomplicated pregnancies. In contrast, increased total HLA, HLA class I and, especially, HLA-C compatibility is associated with preeclampsia, suggestive for a role of HLA mismatches in immune regulation leading to uncomplicated pregnancy.
| S-EPMC8155594 | biostudies-literature
Project description:IntroductionThere is no well-recognized biomarker for accurately predicting outcome in the presence of moyamoya disease (MMD), a progressive occlusive cerebrovascular disease of the internal carotid arteries or their branches. The aim of this study was to investigate the presence of endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) in MMD and correlate the findings with clinical features.MethodsPatients with MMD (n = 66) were compared with healthy controls (n = 81). Blood samples were obtained from an antecubital vein and analyzed using flow cytometry. EPCs were defined as CD31+ CD45dim CD34br CD133+ and CECs as CD31br CD45- CD34dim CD133- . Univariate and multivariate linear regression analyses were carried out.ResultsThe CEC counts were significantly higher in the patients than in the controls (p = 0.008). In multivariate analysis, EPC counts were independently associated with age of patients with MMD (p = 0.049) and CEC counts were independently negatively associated with concomitant disease such as hypertension, diabetes mellitus, and coronary heart disease (p = 0.034).ConclusionsThis is the first study to investigate the presence of CECs in the plasma of patients with MMD, and the amount of CECs was negatively correlated with concomitant disease in these patients.
| S-EPMC6160662 | biostudies-literature
Project description:ImportanceTwin pregnancy is a common occurrence in pregnancies conceived with in vitro fertilization (IVF), but the absolute risk of adverse obstetric outcomes stratified by IVF, twin or singleton pregnancy, and maternal age are unknown.ObjectiveTo estimate the absolute risk of adverse obstetric outcomes at each maternal age among twin pregnancies conceived with IVF.Design, setting, and participantsThis retrospective cohort study included pregnant women with infants born from January 1, 2013, to December 31, 2018, based on the Hospital Quality Monitoring System in China. Data were analyzed from September 1, 2020, to June 30, 2021.ExposuresTwin pregnancy with IVF (IVF-T), singleton pregnancy with IVF (IVF-S), twin pregnancy with non-IVF (nIVF-T), and singleton pregnancy with non-IVF (nIVF-S).Main outcomes and measuresSixteen obstetric outcomes, including 10 maternal complications (gestational hypertension, eclampsia and preeclampsia, gestational diabetes, placenta previa, placental abruption, placenta accreta, preterm birth, dystocia, cesarean delivery, and postpartum hemorrhage) and 6 neonatal complications (fetal growth restriction, low birth weight, very low birth weight, macrosomia, malformation, and stillbirth).ResultsAmong 16 879 728 pregnant women aged 20 to 49 years (mean [SD] age, 29.2 [4.7] years), the twin-pregnancy rates were 32.1% in the IVF group and 1.5% in the non-IVF group (relative risk, 20.8; 95% CI, 20.6-20.9). The most common adverse obstetric outcomes after pregnancy conceived with IVF were cesarean delivery (88.8%), low birth weight (43.8%), preterm birth (39.6%), gestational diabetes (20.5%), gestational hypertension and preeclampsia and eclampsia (17.5%), dystocia (16.8%), and postpartum hemorrhage (11.9%). The absolute risk of most adverse obstetric outcomes in each subgroup presented in 2 dominant patterns: Pattern A indicated the absolute risk ranging from IVF-T to nIVF-T to IVF-S to nIVF-S, and pattern B indicated the absolute risk ranging from IVF-T to IVF-S to nIVF-T to nIVF-S. Both patterns showed an elevated obstetric risk with increasing maternal age in each subgroup.Conclusions and relevanceIn this cohort study, twin pregnancy, IVF, and advanced maternal age were independently associated with adverse obstetric outcomes. Given these findings, promotion of the elective single embryo transfer strategy is needed to reduce multiple pregnancies following IVF technologies. Unnecessary cesarean delivery shouldh be avoided in all pregnant women.
| S-EPMC8433605 | biostudies-literature
Project description:BackgroundThe current understanding of the functional characteristics of circulating endothelial progenitor cells (EPC) is limited, especially in patients affected by cardiovascular diseases. In this study, we have analyzed the in vitro clonogenic capacity of circulating EPC, also known as endothelial colony-forming cells (ECFC), in patients with acute coronary syndrome (ACS), in comparison to the colony forming unit-endothelial-like cells (CFU-EC) of hematopoietic/monocytic origin.Methodology/principal findingsBy culturing peripheral blood mononuclear cells (PBMC) of patients with ACS (n?=?70), CFU-EC were frequently isolated (from 77% of ACS patients), while EPC/ECFC were obtained only in a small subset (13%) of PBMC samples, all harvested between 7-14 days after the acute cardiovascular event. Notably, ex-vivo generation of EPC/ECFC was correlated to a higher in vitro release of PDGF-AA by the corresponding ACS patient PBMC. By using specific endothelial culture media, EPC/ECFC displayed in vitro expansion capacity, allowing the phenotypic and functional characterization of the cells. Indeed, after expansion, EPC/ECFC exhibited a normal diploid chromosomal setting by FISH analysis and an immunophenotype characterized by: i) uniform positivity for the expression of CD105, CD31, CD146 and Factor VIII, i) variable expression of the CD34, CD106 and CD184 markers, and iii) negativity for CD45, CD90, CD117 and CD133. Of interest, in single-cell replanting assays EPC/ECFC exhibited clonogenic expansion capacity, forming secondary colonies characterized by variable proliferation capacities.Conclusion/significanceOur data indicate that a careful characterization of true EPC is needed in order to design future studies in the clinical autologous setting of patients with ACS.
| S-EPMC3569417 | biostudies-literature
Project description:BackgroundKidney transplantation (RTx) leads to amelioration of endothelial function in patients with advanced renal failure. Endothelial progenitor cells (EPCs) may play a key role in this repair process. The aim of this study was to determine the impact of RTx and immunosuppressive therapy on the number of circulating EPCs.MethodsWe analyzed 52 RTx patients (58±13 years; 33 males, mean ± SD) and 16 age- and gender-matched subjects with normal kidney function (57±17; 10 males). RTx patients received a calcineurin inhibitor (CNI)-based (65%) or a CNI-free therapy (35%) and steroids. EPC number was determined by double positive staining for CD133/VEGFR2 and CD34/VEGFR2 by flow cytometry. Stromal cell-derived factor 1 alpha (SDF-1) levels were assessed by ELISA. Experimentally, to dissociate the impact of RTx from the impact of immunosuppressants, we used the 5/6 nephrectomy model. The animals were treated with a CNI-based or a CNI-free therapy, and EPCs (Sca+cKit+) and CD26+ cells were determined by flow cytometry.ResultsCompared to controls, circulating number of CD34+/VEGFR2+ and CD133+/VEGFR2+ EPCs increased in RTx patients. There were no correlations between EPC levels and statin, erythropoietin or use of renin angiotensin system blockers in our study. Indeed, multivariate analysis showed that SDF-1--a cytokine responsible for EPC mobilization--is independently associated with the EPC number. 5/6 rats presented decreased EPC counts in comparison to control animals. Immunosuppressive therapy was able to restore normal EPC values in 5/6 rats. These effects on EPC number were associated with reduced number of CD26+ cells, which might be related to consequent accumulation of SDF-1.ConclusionsWe conclude that kidney transplantation and its associated use of immunosuppressive drugs increases the number of circulating EPCs via the manipulation of the CD26/SDF-1 axis. Increased EPC count may be associated to endothelial repair and function in these patients.
| S-EPMC3169568 | biostudies-literature
Project description:Colorectal cancer (CRC) is one of the common malignancies worldwide, accounting for a significant percentage of cancer mortality. Concurrent chemoradiation (CCRT) is now a standard treatment for unresectable malignancies of anorectum. To improve quality of life, CCRT is also commonly applied in treatment of lower rectal and anal canal cancer to preserve anal sphincter function. The most commonly used chemotherapeutic drugs combined with radiation as radiosensitizers is 5-fluorouracil (5-FU). Circulating endothelial progenitor cells (EPC), which contribute to the tumor vessel formation, reflect the response to chemotherapy both in animal model and clinical trial. Thus, circulating EPC can be used as a marker for optimizing and monitoring the anti-angiogenesis therapy including angiogenesis inhibitors and chemotherapy. Whether circulating EPC can be served as a marker of CCRT efficacy or not remains undetermined. Since CCRT is now a standard treatment of locally advanced and high-risk CRC, the development of a surrogate marker for monitoring CCRT response and optimize treatment intensity is very important.
In this grant we intent to monitor the levels of circulating EPC in locally advanced and high-risk CRC patients before, during and after CCRT. To further characterize the changes in function and biology of EPC caused by CCRT, a syngeneic animal model will be also used to evaluate the clonogenecity and specific gene expression of EPC in tumor-bearing mice receiving CCRT.
| 2028928 | ecrin-mdr-crc
Project description:Study questionDoes IVF independently increase the risk of gestational diabetes mellitus (GDM) and is this increase in risk modified by maternal body mass index?Summary answerIVF appears to be an independent risk factor for GDM and elevated blood glucose levels in overweight women (BMI > 25 kg/m2).What is known alreadyIVF has been associated with increased risk of GDM, but most previous studies did not adequately assess confounding or effect modification by other risk factors.Study design, size, durationCross-sectional study using data from 1089 women with singleton pregnancies who participated in a Singaporean birth cohort study (GUSTO) and received a 75 g oral glucose tolerance test (OGTT) at 26-28 weeks gestation.Participants/materials, setting, methodsA total of 1089 women (n = 1013 conceived spontaneously, n = 76 conceived through IVF) with singleton pregnancies received a 75 g OGTT at 26-28 weeks gestation. Fasting and 2 h postprandial blood glucose levels were assayed. World Health Organization criteria (1999) standard criteria were used to classify GDM: ≥7.0 mmol/L for fasting and/or ≥7.8 mmol/L for 2-h postprandial plasma glucose levels, which was the clinical guideline in use during the study.Main results and the role of chanceIVF pregnancies had nearly double the odds of GDM (OR = 1.83, 95% CI: 1.03-3.26) and elevated fasting (mean difference = 0.12 mmol/L, 95% CI: 0.00-0.24) and OGTT 2-h blood glucose levels (mean difference = 0.64 mmol/L, 95% CI: 0.27-1.01), after adjusting for commonly recognized risk factors for GDM. After stratification by first-trimester BMI, these increased risks of GDM (OR = 3.54, 95% CI: 1.44-8.72) and elevated fasting (mean difference = 0.39 mmol/L, 95% CI: 0.13-0.65) and 2-h blood (mean difference = 1.24 mmol/L, 95% CI: 0.56-1.91) glucose levels were significant only in the IVF group who is also overweight or obese (BMI > 25 kg/m2).Limitations reasons for cautionOne limitation of our study is the absence of a 1 h post-OGTT plasma glucose sample, as we were using the 1999 WHO diagnostic criteria (the clinical guideline in Singapore) at the time of our study, instead of the revised 2013 WHO diagnostic criteria. Our cohort may not be representative of the general Singapore obstetric population, although participants were recruited from the two largest maternity hospitals in the country and include both private and subsidized patients.Wider implications of the findingsIVF appears to be an independent risk factor for GDM and elevated blood glucose levels in overweight women. Our findings reinforce the need to advise overweight or obese women contemplating IVF to lose weight before the procedure to reduce their risk of GDM and hyperglycemia-related adverse outcomes arising therefrom. In settings where universal GDM screening is not routine, overweight or obese women who conceive by IVF should be screened.Study funding/competing interest(s)This research was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Program and administered by the Singapore Ministry of Health's National Medical Research Council (NMRC), Singapore (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding was provided by the Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR). K.M.G. and Y.S.C. have received lecture fees from Nestle Nutrition Institute and Danone, respectively. K.M.G., Y.S.C. and S.Y.C. are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. The other authors have nothing to disclose. The other authors have nothing to disclose.Trial registration numberN/A.
| S-EPMC5638004 | biostudies-literature
Project description:BackgroundEndothelial progenitor cells (EPCs) have been shown to increase during physiological pregnancy and are believed to play a fundamental role in the process of placentation. Reduced levels of EPCs during pregnancy have been associated with preeclampsia and miscarriage. Women with multiple sclerosis (MS) are not at increased risk of preeclampsia nor of general adverse obstetric outcome, in contrast with some other autoimmune diseases.ObjectiveThe aim of this study was to evaluate circulating EPCs levels in pregnant patients with MS.MethodsCD34+ and CD133+ were longitudinally detected by flow cytometry in the maternal plasma of 29 healthy controls and 9 MS patients and in the cord blood of their newborns.ResultsEPCs were affected by pregnancy with the same trend in both groups (CD34+ p = 0.0342; CD133+ p = 0.0347). EPCs during pregnancy were increased in MS (mean ± SD: CD34+ cells 0.038 ± 0.010; CD133+ 0.024 ± 0.009) with respect to healthy controls (mean ± SD: CD34+ cells 0.022 ± 0.006; CD133+ 0.016 ± 0.004), CD34+ p = 0.0004; CD133+ p = 0.0109. EPCs levels of the cord blood of MS patients' newborns mild correlated with maternal EPC levels at delivery (CD34+: spearman's Rho 0.658, p = 0.054; CD133+: spearman's Rho 0.758, p = 0.018).ConclusionsThis work identified increased circulating EPC levels during pregnancy, following the same trend both in MS patients and healthy controls. Despite the similar trend, the levels of circulating EPCs were significantly higher in MS patients with respect to the control population. A correlation was also found in MS patients between cord blood EPCs and circulating EPCs at delivery.
| S-EPMC7956006 | biostudies-literature