High Uterine Artery Resistance Research Articles

Role of soluble fms-like tyrosine kinase-1/placental growth factor ratio along with uterine artery Doppler for the prediction of pre-eclampsia – A case–control study

Role of soluble fms-like tyrosine kinase-1/placental growth factor ratio along with uterine artery Doppler for the prediction of pre-eclampsia – A case–control study

Investigation of the relationship between diastolic notching in uterine artery Doppler and serum salusin alpha and beta concentrations in the first trimester

Objective Studies have shown that members of the salusin family regulate the migration and proliferation of arterial smooth muscle cells and increase the tendency to atherosclerosis through fibrosis and calcification in the vascular wall. However, the effect of salusins on the uterine artery has not yet been investigated. This study was conducted to investigate whether serum salusin alpha and beta concentrations in the first trimester are associated with diastolic notching in uterine artery Doppler. Methods This non-interventional cohort study was conducted on 88 pregnant women, 44 of whom had diastolic notching on unilateral or bilateral uterine artery Doppler, and 44 of whom did not have diastolic notching on uterine artery Doppler. The uterine artery notch positive and negative groups were compared in terms of serum salusin alpha and beta concentrations. Results The two groups were similar in terms of demographic characteristics (p < 0.05). The median salusin alpha concentration was found to be 689.4 pg/ml in the uterine artery notch positive group, while it was 734.6 pg/ml in the uterine artery notch negative group (p = 0.608). The median salusin beta concentration was found to be 674.5 pg/ml in the uterine artery notch positive group, while it was 693.8 pg/ml in the uterine artery notch negative group (p = 0.453). Participants were regrouped into normal and high uterine artery resistance and compared in terms of serum salusin alpha and beta concentrations. The median salusin alpha concentration was found to be 994.5 pg/ml in the high uterine artery PI group, while it was 685.2 pg/ml in the normal uterine artery PI group (p = 0.698). The median salusin beta concentration was found to be 1,100.8 pg/ml in the high uterine artery PI group, while it was 669.1 pg/ml in the normal uterine artery PI group (p = 0.584). Conclusion Although the sample size was too small to draw a definitive conclusion, our results indicate that uterine artery diastolic notching or increased resistance in the uterine artery does not appear to be associated with serum salusin alpha or beta concentrations.

Gebeliğin birinci trimesterinde sistemik inflamatuar belirteçler ile yüksek uterin arter pulsatilite indeksi ilişkisi

Introduction: Preeclampsia is a serious complication of pregnancy leading to maternal and perinatal morbidity and mortality. The etiopathogenesis still remains unsolved, however, various theories currently become well-proved. The leading etiopathogenetic mechanisms are impaired placentation, and placental hypoxia, immune mechanisms, systemic inflammatory reaction, endothelial damage and maternal cardiovascular maladaptation. These mechanisms overlap and induce each other. There are some preventive interventions only if the patients at high-risk are identified timely. This study aimed to investigate the relationship between the inflammatory pathway and placental insufficiency in the first trimester, utilizing the clinical markers of both. It also aims to find out a cheap and easy test to identify those who absolutely need to undergo a comprehensive risk assessment. Methods: This retrospective observational study included 28 patients with high uterine artery resistance (pulsatility index &amp;gt;90th centile) in the first trimester as study group and 67 patients with normal uterine artery resistance in the first trimester as control group. The two groups were compared in terms of risk factors for preeclampsia. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio as systemic inflammatory markers were compared between the groups. ROC analysis was performed to obtain a cut-off value for predicting high uterine artery pulsatility index. Results: Demographic data, anamnestic and examination risk factors for preeclampsia did not differ between the groups. However, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were significantly higher in the patients with uterine artery pulsatility index above 90th centile. A cut off value of 3.58 and 136.9 of Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio, respectively were determined for predicting first trimester uterine artery pulsatility index above 90th centile. Conclusions: Neutrophil/lymphocyte and platelet/lymphocyte ratio can simply be used to identify the patients who need referral for uterine artery doppler assessment. Keywords: preeclampsia, uterine artery, pulsatil flow, neutrophil, lymphocyte, placenta

Progress Toward Reversed Uterine Diastolic Flow in the Third Trimester - An Inauspicious Sign.

Increased uteroplacental resistance is associated with high uterine artery pulsatility and resistance indices and early diastolic notching. Evolution toward reversed diastolic uterine flow in the third trimester was scarcely reported previously. The feature was related to severe complications for both mother and fetus. Data were collected from 3638 pregnancies undergoing prenatal care in our hospital. In this study, we aimed to identify those pregnancies with development of a reversed diastolic flow at the spectral Doppler interrogation of uterine arteries later than 24 weeks of gestation. A secondary aim was to follow up and actively manage these pregnancies. Previously, reversed uterine diastolic flow was reported during the third trimester in four cases only. In our study three pregnancies only developed reversed uterine arteries diastolic flow, none being associated with preeclampsia. All cases evolved with complications at birth. Progressive deterioration of uterine arteries flow is possible during pregnancy. Reversed diastolic flow is a rare occurrence in the third trimester of pregnancy. Based on current knowledge, it may be considered an ominous sign and should trigger a close follow-up. Future studies using routine investigation of uterine arteries flow late in pregnancy may prove informative.

Diagnostic utility of serial circulating placental growth factor levels and uterine artery Doppler waveforms in diagnosing underlying placental diseases in pregnancies at high risk of placental dysfunction

Placental pathology assessment following delivery in pregnancies complicated by preeclampsia, fetal growth restriction, abruption, and stillbirth reveals a range of underlying diseases. The most common pathology is maternal vascular malperfusion, characterized by high-resistance uterine artery Doppler waveforms and abnormal expression of circulating maternal angiogenic growth factors. Rare placental diseases (massive perivillous fibrinoid deposition and chronic histiocytic intervillositis) are reported to have high recurrence risks, but their associations with uterine artery Doppler waveforms and angiogenic growth factors are presently ill-defined. To characterize the patterns of serial placental growth factor measurements and uterine artery Doppler waveform assessments in pregnancies that develop specific types of placental pathology to gain insight into their relationships with the timing of disease onset and pregnancy outcomes. A retrospective cohort study conducted between January 2017 and November 2021 included all singleton pregnancies with at least 1 measurement of maternal circulating placental growth factor between 16 and 36 weeks' gestation, delivery at our institution, and placental pathology analysis demonstrating diagnostic features of maternal vascular malperfusion, fetal vascular malperfusion, villitis of unknown etiology, chronic histiocytic intervillositis, or massive perivillous fibrinoid deposition. Profiles of circulating placental growth factor as gestational age advanced were compared between these placental pathologies. Maternal and perinatal outcomes were recorded. A total of 337 pregnancies from 329 individuals met our inclusion criteria. These comprised placental pathology diagnoses of maternal vascular malperfusion (n=109), fetal vascular malperfusion (n=87), villitis of unknown etiology (n=96), chronic histiocytic intervillositis (n=16), and massive perivillous fibrinoid deposition (n=29). Among patients who developed maternal vascular malperfusion, placental growth factor levels gradually declined as pregnancy progressed (placental growth factor <10th percentile at 16-20 weeks' gestation in 42.9%; 20-24 weeks in 61.9%; 24-28 weeks in 77%; and 28-32 weeks in 81.4%) accompanied by mean uterine artery Doppler pulsatility index >95th percentile in 71.6% cases. Patients who developed either fetal vascular malperfusion or villitis of unknown etiology mostly exhibited normal circulating placental growth factor values in association with normal uterine artery Doppler waveforms (mean [standard deviation] pulsatility index values: fetal vascular malperfusion, 1.14 [0.49]; villitis of unknown etiology, 1.13 [0.45]). Patients who developed either chronic histiocytic intervillositis or massive perivillous fibrinoid deposition exhibited persistently low placental growth factor levels from the early second trimester (placental growth factor <10th centile at 16-20 weeks' gestation in 80% and 77.8%, respectively; 20-24 weeks in 88.9% and 63.6%; 24-28 weeks in 85.7% and 75%), all in combination with normal uterine artery Doppler waveforms (mean pulsatility index >95th centile: chronic histiocytic intervillositis, 25%; massive perivillous fibrinoid deposition, 37.9%). Preeclampsia developed in 83 of 337 (24.6%) patients and was most common in those developing maternal vascular malperfusion (54/109, 49.5%) followed by chronic histiocytic intervillositis (7/16, 43.8%). There were 29 stillbirths in the cohort (maternal vascular malperfusion, n=10 [9.2%]; fetal vascular malperfusion, n=5 [5.7%]; villitis of unknown etiology, n=1 [1.0%]; chronic histiocytic intervillositis, n=7 [43.8%]; massive perivillous fibrinoid deposition, n=6 [20.7%]). Most patients experiencing stillbirth exhibited normal uterine artery Doppler waveforms (21/29, 72.4%) and had nonmaternal vascular malperfusion pathologies (19/29, 65.5%). By contrast, 28 of 29 (96.5%) patients experiencing stillbirth had ≥1 low placental growth factor values before fetal death. Serial circulating maternal placental growth factor tests, in combination with uterine artery Doppler waveform assessments in the second trimester, may indicate the likely underlying type of placental pathology mediating severe adverse perinatal events. This approach has the potential to test disease-specific therapeutic strategies to improve clinical outcomes. Serial placental growth factor testing, compared with uterine artery Doppler studies, identifies a greater proportion of patients destined to have a poor perinatal outcome because diseases other than maternal vascular malperfusion are characterized by normal uteroplacental circulation.

Nitric Oxide Donor Administration For improvement of Uterine Blood Flow in Unexplained Recurrent Pregnancy Loss

Background: Recurrent pregnancy loss is still a challenging obstetric condition. It linked to impaired uterine blood, and vasodilators seem to prevent recurrent pregnancy loss. The aim of the work: The current study aimed to compare between investigate the Doppler uterine artery indices in females with recurrent pregnancy loss [unexplained]. It also aimed to study the effect of intravaginal isosorbide mononitrate, on the pattern of uterine blood flow. Materials and Methods: This observational, nested case control study had been completed at Al-Azhar University Hospitals. Two groups of females [each 50 females] were studied. The control group [females with no previous pregnancy loss and have a viable child or more]. The study group [females with history of unexplained recurrent pregnancy loss]. Vaginal color Doppler ultrasound was done to assess pulsation and resistance indices of uterine arteries in the mid-luteal phase of the cycle. Then, 20 mg of isosorbide mononitrate was applied vaginally and measurement of the vascular indices were registered after two hours again. Both groups were compared and the effect of isosorbide mononitrate on the uterine artery vascular indices the study group was documented. Results: Higher uterine artery resistance and pulsation indices are noticed in females with recurrent pregnancy. A significant reduction in these indices was found after vaginal application of Isosorbide mononitrate. Both groups were comparable regarding patient demographics. Doppler indices were significantly lower in control than study group. The endometrial thickness was negatively correlated with right RI and left PI (r = -0.328, -0.342, p = 0.039 and 0.031, respectively). Conclusion: Poor uterine perfusion is associated with spontaneous abortion. The vaginal application of isosorbide mononitrate, nitric oxide donor could be an effective treatment for the correction of uterine vasculature in patients with recurrent pregnancy loss.

Maternal Angiotensin Increases Placental Leptin in Early Gestation via an Alternative Renin-Angiotensin System Pathway: Suggesting a Link to Preeclampsia.

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Study of placental laterality with uterine artery Doppler in the prediction of preeclampsia

Objective To demonst rate if placental laterality combined with uterine artery Doppler can be used as a predictor for the development of preeclampsia. Background The uteroplacental blood flow may be deficient in cases with lateral placenta, and this may facilitate development of preeclampsia. Placenta is considered lateral when 75% or more of the placental mass is located at one side of the midline of uterine cavity. Uterine artery Doppler was done to all cases to find out high resistance index and abnormal protodiastolic notch in Doppler waveform. Patients and methods Ultrasonography was done for all participants at 18–22 weeks of pregnancy to determine the placenta location. Uterine artery Doppler was done for all cases at 18–24 weeks of gestation to find out the presence of protodiastolic notch and high resistance index. Results Of 73 cases with lateral placenta and high uterine artery resistance index, 56 (76.7%) cases developed preeclampsia (P = 0.026). Moreover, among 77 cases with lateral and presented protodiastolic notch, 57 (74%) cases developed preeclampsia (P = 0.050). Conclusion The risk of developing preeclampsia is significantly increased when lateral placentas are associated with uterine artery Doppler abnormality.

Placental histopathology in sickle cell disease: A descriptive and hypothesis-generating study

IntroductionAbnormal placental development is a unifying factor amongst many adverse pregnancy outcomes (APOs) in Sickle Cell Disease (SCD). Our aim was to describe placental histopathologic findings in women with SCD and their relationship with APOs, and to explore the association between antenatal sonographic findings and placental pathology. MethodsRetrospective single-centre case series of all pregnant women with SCD (January 2000–December 2017), pregnancy beyond 20 weeks’ gestation, and available placenta histopathology. APOs included intrauterine fetal death, early neonatal death, preterm birth, small for gestational age, and hypertensive disorders of pregnancy. Review of images for mid-pregnancy ultrasound and one proximal to delivery was completed, blinded to clinical outcomes and histopathology results. Gross and histopathologic findings were reviewed and characterized per published classification. ResultsOf 72 placentas, abnormalities were present in 69%, with Maternal Vascular Malperfusion (MVM) noted in 40%. APOs were encountered in 61% overall and in 79% of those with MVM. Neither SCD genotype nor severe maternal anemia had an influence on histopathologic placental features. Presence of high-resistance uterine artery waveforms at mid-trimester ultrasound was strongly associated with APOs and with abnormal findings on placental histopathology, most notably MVM. MVM was strongly associated with small for gestational age infants, preterm birth, and stillbirth. DiscussionMVM is the predominant lesion in placentas of women with SCD and is strongly associated with APOs. Mid-trimester ultrasound can identify a subset of women at risk. Future research into advanced imaging modalities to aid in antenatal diagnosis alongside investigations of potentially beneficial therapies is needed.

The predictive capacity of uterine artery Doppler for preterm birth-A cohort study.

IntroductionMid‐trimester uterine artery resistance measured with Doppler sonography is predictive for iatrogenic preterm birth. In view of the emerging association between hypertensive disease in pregnancy and spontaneous preterm birth, we hypothesized that uterine artery resistance could also predict spontaneous preterm birth.Material and methodsWe performed a cohort study of women with singleton pregnancies. Uterine artery resistance was routinely measured at the 18‐22 weeks anomaly scan. Pregnancies complicated by congenital anomalies or intrauterine fetal death were excluded. We analyzed if the waveform of the uterine artery (no notch, unilateral notch or bilateral notch) was predictive for spontaneous and iatrogenic preterm birth, defined as delivery before 37 weeks of gestation. Furthermore, we assessed whether the uterine artery pulsatility index was associated with the risk of preterm birth.ResultsBetween January 2009 and December 2016 we collected uterine Doppler indices and relevant outcome data in 4521 women. Mean gestational age at measurement was 19+6 weeks. There were 137 (3.0%) women with a bilateral and 213 (4.7%) with a unilateral notch. Mean gestational age at birth was 38+6 weeks. Spontaneous and iatrogenic preterm birth rates were 5.7% and 4.9%, respectively. Mean uterine artery resistance was 1.12 in the spontaneous preterm birth group compared with 1.04 in the term group (P = 0.004) The risk of preterm birth was increased with high uterine artery resistance (OR 2.9 per unit; 95% CI 2.4‐3.9). Prevalence of spontaneous preterm birth increased from 5.5% in women without a notch in the uterine arteries to 8.0% in women with a unilateral notch and 8.0% in women with a bilateral notch. For iatrogenic preterm birth, these rates were 3.9%, 13.6% and 23.4%, respectively. Likelihood ratios for the prediction of spontaneous preterm birth were 1.6 (95% CI 1.0‐2.6) and 1.9 (95% CI 1.0‐3.5) for unilateral and bilateral notches, respectively, and for iatrogenic preterm birth they were 3.6 (95% CI 2.5‐5.2) and 6.8 (95% CI 4.7‐9.9) for unilateral and bilateral notches, respectively. Of all women with bilateral notching, 31.4% delivered preterm.ConclusionsMid‐trimester uterine artery resistance measured at 18‐22 weeks of gestation is a weak predictor of spontaneous preterm birth.

Maternal cardiac function, uterine artery hemodynamics and natriuretic peptides at 22-24weeks of gestation and subsequent development of hypertensive disorders of pregnancy.

Maternal cardiac dysfunction as well as abnormal uterine artery (UtA) Doppler are associated with hypertensive disorders of pregnancy (HDP), but their relation is unclear. We investigated the correlation between maternal cardiac function, UtA hemodynamics and natriuretic peptides, and explored differences between women who subsequently developed HDP and those who did not. This wasa prospective cross-sectional cohort study of 347 pregnant women at 22-24weeks. Maternal cardiac function and systemic hemodynamics were investigated at baseline and after 90seconds of passive leg raising using impedance cardiography. Preload reserve was defined as percent change (Δ%) in stroke volume and cardiac output from baseline to passive leg raising. UtA hemodynamics was studied using Doppler ultrasonography. UtA blood flow, resistance and pulsatility index were calculated. Fasting venous blood samples were analyzed for natriuretic peptides (pro atrial natriuretic peptide [proANP], N-terminal pro brain natriuretic peptide [Nt-proBNP] and C-type natriuretic peptide [CNP]). The course and outcome of pregnancy were recorded. At baseline, ProANP correlated significantly with cardiac output (r=-0.122; P= .023) and left cardiac work index (r=-0.112; P= .037), whereas Nt-ProBNP correlated significantly with acceleration index (r= .127; P= .018) and velocity index (r=-0.111; P= .039. CNP correlated significantly with UtA blood flow (r= .118; P= .028) and resistance (r=-0.112; P= .037) but not with UtA pulsatility index (r= .034; P= .523). None of the natriuretic peptides correlated with preload reserve. At 22-24weeks, women who subsequently developed HDP had lower UtA blood flow (552 vs 692mL/min; P= .028), higher UtA resistance (0.28 vs .17mmHg/mL/min; P= .004) and higher mean UtA pulsatility index (1.12 vs .84; P< .001) compared with those who did not; however, the natriuretic peptide levels were similar in the two groups. Women developing HDP had a significantly higher increase in stroke volume and cardiac output and more reduction in systemic vascular resistance following passive leg raising compared with the reference group. Left cardiac work index, acceleration index and velocity index decreased following passive leg raising in the reference group but increased in women who later developed HDP. ProANP correlated with cardiac output and cardiac work, Nt-proBNP with indices of cardiac contractility, and CNP with UtA blood flow and resistance. None of these natriuretic peptides measured at 22-24weeks of gestation reflected cardiac preload reserve or predicted development of HDP.

Prenatal air pollution exposure, smoking, and uterine vascular resistance.

Prenatal exposure to air pollution and smoking increases the risk of pregnancy complications and adverse birth outcomes, but pathophysiologic mechanisms are still debated. Few studies to date have examined the influence of air pollution on uterine vascular resistance and no studies have examined the independent impact of these exposures. We aimed to assess the impact of prenatal exposure to traffic-related air pollution and smoking on uterine vascular resistance. Our study included 566 pregnant women recruited between 1993 and 1996 in Los Angeles who completed visits at three gestational ages. Information on smoking was collected and uterine vascular resistance was measured at each visit by Doppler ultrasound. We calculated three resistance indices: the resistance index (RI), the pulsatility index (PI), and the systolic/diastolic (S/D) ratio. We estimated exposure to NO2 at the home address of the mother using a land use regression (LUR) model and to NOx using CALINE4 air dispersion modeling. We used generalized linear mixed models to estimate the effects of air pollution and smoking on uterine vascular resistance indices. LUR-derived NO2 and CALINE4-derived NOx exposure increased the risk of high uterine artery resistance in late pregnancy. Smoking during pregnancy also increased the risk of higher uterine resistance and contributed to bilateral notching in mid-pregnancy. Our results suggest that uterine vascular resistance is a mechanism underlying the association between smoking and air pollution, and adverse birth outcomes.

Uterine artery Doppler: Changing Concepts in Prediction and Prevention of PE and FGR

AbstractOne of the most promising screening tools in detection of PE and FGR is uterine artery Doppler velocimetry. The underlying pathology for the development of PE is thought to be due to defective trophoblastic invasion of uterine spiral arteries. Increased impedance during mid-trimester is known to be associated with a high incidence of adverse pregnancy outcomes. High resistance in uterine arteries can be observed as early in the first trimester in cases with impaired placentation. The predictive efficacy of first trimester UtA Doppler has improved after the development of risk specific algorithm by including maternal characteristics, biophysical and biochemical parameters. With the understanding of late onset FGR and PE, it was realised that first trimester UtA Doppler may not serve as an efficient marker to identify this group which led to the evolution of its assessment in third trimester. The importance of UtA Doppler in third trimester is its ability to differentiate a physiologically small baby from a pathologically small fetus, which is growth restricted. PE and FGR remains an important cause of maternal and fetal mortality and its prediction is a challenging task which needs to be done early in gestation. Low dose aspirin when started before 16 weeks in the truly high risk population has proven to significantly reduce PE and FGR. To initiate aspirin therapy, the development of first trimester risk prediction model remains the key component. This paper is a review of the predictive efficacy of UtA Doppler in detecting uteroplacental insufficiency in each of the three trimesters.

12: The predictive capacity of Uterine artery Doppler for preterm birth - a prospective cohort study

Mid-trimester Uterine Artery (UtA) resistance measured with Doppler sonography is known to be predictive for preeclampsia and thus iatrogenic preterm birth (iPTB). In view of the emerging association between hypertensive disease in pregnancy and spontaneous preterm birth (sPTB), we hypothesized that UtA resistance could predict sPTB. We performed a prospective cohort study. During the 18-22 week routine fetal anomaly scan we measured UtA resistance in singleton pregnancies. Pregnancies complicated by major congenital anomalies were excluded. We classified the resistance in the uterine artery (no notch, unilateral notch or bilateral notch) and related it to sPTB and iPTB, defined as delivery before 37 weeks, using likelihood ratios. Furthermore, we assessed whether the UtA Pulsatility Index (PI) was associated with the risk of sPTB. Between January 2009 and December 2016, we included 2,987 women. Mean gestational age at measurement was 19+6 weeks. There were 79 (2.6%) women with a bilateral notch and 134 (4.5%) with a unilateral notch. Mean gestational age at birth was 39+0 weeks, 6.3 % had sPTB while 4.0 % had iPTB. Mean UtA resistance was 1.11 in the sPTB group compared to 1.05 in the term group (p <0.001). The risk of PTB was increased with high UtA resistance (OR 2.6 per unit ; 95% CI 2.0-3.4). Figure 1 shows the time to delivery. The prevalence of spontaneous preterm birth increased from 6.1% in women with normal uterine arteries to 9.0% in women with a unilateral notch and 10.1% in women with a bilateral notch (Table 1). For iPTB, these rates were 3.4%, 9.0% and 19.0% respectively. Likelihood ratios for the prediction of sPTB were 1.5 (95% CI 0.8-2.7) and 1.7 (95% CI 0.8-3.6) for unilateral and bilateral notches respectively, and 2.6 (95% CI 1.4-4.6) and 6.0 (95% CI 3.3-10.3) for iPTB. Of all women with bilateral notching 29.1% delivered preterm. Mid-Trimester UtA resistance measured at 19 weeks gestation predicts sPTB.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The effect of vitamin E and aspirin on the uterine artery blood flow in women with recurrent abortion: A single-blind randomized controlled trial

Recurrent spontaneous abortion has high incidence rate. The etiology is unknown in 30-40%. However high uterine artery resistance is accounted as one of the recurrent abortion reasons. The objective of the current study was to determine the impacts of vitamin E and aspirin on the uterine artery blood flow in women having recurrent abortions due to impaired uterine blood flow. This randomized clinical trial was conducted on 99 women having uterine pulsatility index (PI) more than 2.5 and the history of more than two times abortions. The candidates were categorized into three groups; receiving aspirin, only vitamin E, and aspirin+vitamin E. After 2 months, uterine PIs were compared with each other. All drug regimens caused an enhancement in uterine perfusion with a significant decline in uterine artery PI value. The women receiving vitamin E in accompanied with aspirin had the least mean PI of the uterine artery (p<0.001). The total average PI score of the right and left uterine arteries in groups receiving vitamin E in accompanied with aspirin was lower than the two counterparts significantly (p<0.001). Vitamin E, aspirin and especially their combination are effective in improving uterine artery blood flow in women with recurrent abortion due to impaired uterine blood flow. More well-designed studies are needed to find out whether the enhancement of uterine perfusion may lead to a better pregnancy outcome.

Emerging role for dysregulated decidualization in the genesis of preeclampsia

In normal human placentation, uterine invasion by trophoblast cells and subsequent spiral artery remodeling depend on cooperation among fetal trophoblasts and maternal decidual, myometrial, immune and vascular cells in the uterine wall. Therefore, aberrant function of anyone or several of these cell-types could theoretically impair placentation leading to the development of preeclampsia. Because trophoblast invasion and spiral artery remodeling occur during the first half of pregnancy, the molecular pathology of fetal placental and maternal decidual tissues following delivery may not be informative about the genesis of impaired placentation, which transpired months earlier. Therefore, in this review, we focus on the emerging prospective evidence supporting the concept that deficient or defective endometrial maturation in the late secretory phase and during early pregnancy, i.e., pre-decidualization and decidualization, respectively, may contribute to the genesis of preeclampsia. The first prospectively-acquired data directly supporting this concept were unexpectedly revealed in transcriptomic analyses of chorionic villous samples (CVS) obtained during the first trimester of women who developed preeclampsia 5 months later. Additional supportive evidence arose from investigations of Natural Killer cells in first trimester decidua from elective terminations of women with high resistance uterine artery indices, a surrogate for deficient trophoblast invasion. Last, circulating insulin growth factor binding protein-1, which is secreted by decidual stromal cells was decreased during early pregnancy in women who developed preeclampsia. We conclude this review by making recommendations for further prospectively-designed studies to corroborate the concept of endometrial antecedents of preeclampsia. These studies could also enable identification of women at increased risk for developing preeclampsia, unveil the molecular mechanisms of deficient or defective (pre)decidualization, and lead to preventative strategies designed to improve (pre)decidualization, thereby reducing risk for preeclampsia development.

Sonoendocrinology and Monitoring Assisted Reproduction Technology

ABSTRACT Reproductive function in a human being consists of continuous hormonal changes in the female. These hormonal changes are responsible for dynamic changes occurring in the ovarian and uterine morphology and vascularity. Ultrasound and Doppler are very useful modalities for assessing these changes, and therefore, very effective for diagnosis of hormonal derangements and monitoring the assisted reproductive technology (ART) treated cycles. Among the common hormones that need to be assessed, androgen can be correlated with high antral follicle count (AFC) and high uterine artery resistance and anti-Müllerian hormone (AMH) also has a positive correlation with AFC. Follicle-stimulating hormone (FSH) is reflected as follicular growth, and luteinizing hormone (LH) by ovarian stromal echogenicity and vascularity and endometrial hyperechogenicity. Estrogen adequacy can be judged by follicular and endometrial flow in preovulatory phase whereas progesterone adequacy can be judged by corpus luteal and endometrial flow in mid luteal phase. Day-to-day hormonal assessment can therefore be replaced by ultrasound and Doppler during ART. How to cite this article Panchal S, Nagori C. Sonoendocrinology and Monitoring Assisted Reproduction Technology. Donald School J Ultrasound Obstet Gynecol 2016;10(4):376-386.

Increased Apoptosis, Altered Oxygen Signaling, and Antioxidant Defenses in First-Trimester Pregnancies with High-Resistance Uterine Artery Blood Flow

The mechanisms of deficient placentation in the first trimester remain poorly understood, although apoptosis, hypoxia, and oxidative stress have been implicated. High uterine artery Doppler resistance indexes (RIs) are predictive of placental complications of pregnancy, such as preeclampsia, fetal growth restriction, and stillbirth. We provide evidence that even in the first trimester, pregnancies with high uterine artery Doppler RI demonstrate alterations in placental gene and protein expression. Apoptosis was significantly higher in high RI placental tissue, as determined by Western blot analysis of cleaved poly (ADP-ribose) polymerase and caspase 3. Protein expression of the trophoblast survival factor insulin-like growth factor-2 was significantly lower. Both high and normal RI placentas showed evidence of hypoxia and oxidative stress with expression of hypoxia-inducible factors 1α and 2α, heat shock protein 70, presence of nitrotyrosine residues, and lipid peroxidation. We observed no exaggerated placental hypoxia or oxidative stress associated with high RI pregnancies. High RI placental tissue demonstrated an altered balance of antioxidant enzyme activity. Hypoxia and oxidative stress appear to be a physiological state in early pregnancy; our data did not support the hypothesis that they are associated with deficient placentation in the first trimester. Higher levels of apoptosis, reduced insulin-like growth factor-2 expression, and altered antioxidant defenses may contribute to abnormal placentation and the later development of pregnancy complications, such as preeclampsia, fetal growth restriction, and stillbirth.

Decidual natural killer cells regulate vessel stability: implications for impaired spiral artery remodelling

Decidual NK (dNK) cells are present during uterine spiral artery remodelling, an event that is crucial for successful placentation and the provision of an adequate blood supply to the developing fetus. Spiral artery remodelling is impaired in the pregnancy complication pre-eclampsia. Although dNK cells are known to play active roles at the maternal–fetal interface, little is known about their effect on endothelial integrity, an important component of vessel stability. We present a study in which we have modelled dNK–endothelium interactions, using first-trimester dNK cells isolated from both normal pregnancies and those with impaired spiral artery remodelling. dNK cells were isolated from first-trimester pregnancies, screened by uterine artery Doppler ultrasound to determine resistance indices (RI) that relate to the extent of spiral artery remodelling. dNK culture supernatant from normal-RI pregnancies (but not high-RI pregnancies) destabilised endothelial tube-like structures in Matrigel, and normal-RI dNK cells induced endothelial intercellular adhesion molecule-1 and tumour necrosis factor-α expression to a greater extent than high-RI dNK cells. We have established a functional role for dNK cells in the disruption of endothelial structures and have suggested how impairment of this process may be contributing to the reduced vessel remodelling in pregnancies with a high uterine artery resistance index. These findings have implications for our understanding of the pathology of pre-eclampsia and other pregnancy disorders where remodelling is impaired.

OC01.01: High resistance uterine artery indices in the first trimester predispose to increased trophoblast apoptosis, altered oxygen signalling and antioxidant defenses

<scp>OC</scp>01.01: High resistance uterine artery indices in the first trimester predispose to increased trophoblast apoptosis, altered oxygen signalling and antioxidant defenses