Uterine Artery Resistance Index Research Articles

Mid-luteal uterine artery Doppler indices in the prediction of pregnancy outcome in nulliparous women undergoing assisted reproduction

Traditionally, the assessment of endometrial receptivity at transvaginal ultrasound scan has been based on the thickness and the morphological appearance of the endometrium. The objective of this study was to prospectively evaluate endometrial thickness (ET), endometrial morphology and uterine artery Doppler parameters prior to assisted reproduction treatment (ART) in the prediction of pregnancy outcome. This was a prospective cohort study. ET, morphology and uterine artery Doppler (UtAD) pulsatility index (PI) and resistance index (RI) were measured in the mid-luteal stage of the menstrual cycle ultrasonographically, timed with urinary luteinizing hormone testing. A total of 50 women were included in the analysis. The clinical pregnancy rate (CPR) per embryo transfer was 42.0% (n = 21/50). Twenty nine women (58.0%) had an unsuccessful outcome. There were no differences in mean ± SD endometrial thickness (ET) (10.0 ± 1.8 mm vs. 10.5 ± 2.4; p = 0.43), or endometrial morphology (100% (n = 21) vs 100% (n = 29); p = 1.00) between the pregnant and not pregnant groups. Similarly, there were no differences in mean ± SD UtAD PI (2.17 ± 0.83 vs. 2.07 ± 0.81; p = 0.67 or mean ± SD UtAD RI (0.84 ± 0.10 vs. 0.81 ± 0.10; p = 0.30). Ultrasonographic endometrial assessment did not differentiate between those who would have a subsequent clinical pregnancy.

Relationship between temporal changes of endometrial blood flow impedance during natural and hormone replacement cycles and prediction of pregnancy during vitrified-warmed embryo transfer.

This study aimed to examine the relationship between the temporal changes in endometrial blood flow impedance during natural and hormone replacement therapy (HRT) cycles and clinical outcomes of vitrified-warmed embryo transfer (ET). This retrospective observational cohort study included 60 women, 28 with natural, and 32 with HRT cycles, who underwent vitrified-warmed ET. Uterine radial artery resistance index (RA-RI) was measured during the natural and HRT cycles at the following time points: early follicular phase, day of the human chorionic gonadotropin injection during a natural cycle or day of progesterone administration during an HRT cycle, and day of ET. The clinical pregnancy rates of the natural and HRT cycles were 32.1% and 34.4%, respectively. The RA-RI at the early follicular phase was significantly lower in the pregnant group than in the nonpregnant group with natural but not HRT cycles (p = 0.04). The odds ratio for pregnancy was 0.70 (95% confidence interval [CI], 0.52-0.95) when the RA-RI value at the early follicular phase was increased by 0.01 in the natural cycle. With the natural cycle, the area under the receiver-operating characteristic curves for the RA-RI at the early follicular phase with a threshold of 0.68 was 0.75 (95% CI, 0.57-0.93), and the positive and negative predictive values were 0.53 (95% CI, 0.37-0.59) and 0.92 (0.74-0.99), respectively. RA-RI at the early follicular phase might be an effective and useful tool for deciding between natural or HRT cycles for vitrified-warmed ET.

The impact of major uterine wall resection and reconstruction of the uterus (MURU) on uterine hemodynamics and ovarian function in patients with adenomyosis: a clinical study

Background: Previous studies had shown that major uterine wall resection and reconstruction of the uterus (MURU) was safe and effective in the treatment of adenomyosis. However, MURU results in loss of a significant amount of myometrial and some endometrial tissues, which may have an impact on uterine hemodynamics and ovarian function. Therefore, it is necessary to study the changes of uterine hemodynamics and ovarian function in patients after MURU, in order to provide an evidence-base for its clinical application. Objective: To explore the effects of major uterine wall resection and reconstruction of the uterus (MURU) on uterine hemodynamics and ovarian function in patients with adenomyosis. Study design: The maximum thickness of unilateral uterine muscle wall or the maximum diameters of adenomyosis focus were measured by ultrasonography. Patients with adenomyosis were divided into three groups: mild, moderate or severe. Fifty cases of adenomyosis without fertility requirement were treated with MURU (observation group), and levonorgestrel-releasing system (LNG-IUS) was placed in uterine cavity during the operation. Fifty patients with intramural myoma of the uterus were selected for hysteromyomectomy (control group). The changes of arterial pulsation index (PI) and resistance index (RI) of uterine artery, as well as antral follicle count (AFC) and serum antimullerian hormone (AMH) were observed before operation and 1 month, 3 months, 6 months, 12 months and 18 months post-operation. Results: No complications were observed in both groups, no significant difference in uterine hemodynamics and ovarian function were found between the two groups (P > 0.05). During intragroup comparison, there were no significant changes in PI and RI before and after operation in the two groups, and no significant changes in AFC and AMH were detected in both groups before and after operation (P > 0.05). Conclusions: MURU did not significantly affect the uterine hemodynamics and ovarian function in patients with adenomyosis, but the long-term effects need to be further investigated.

Adoptive transfer of placental ischemia-stimulated natural killer cells causes a preeclampsia-like phenotype in pregnant rats.

The Reduced Uterine Perfusion Pressure (RUPP) rat model of placental ischemia recapitulates many characteristics of preeclampsia including maternal hypertension, intrauterine growth restriction (IUGR), and increased cytolytic natural killer cells (cNKs). While we have previously shown a 5-fold higher cytotoxicity of RUPP NKs versus normal pregnant NKs, their role in RUPP pathophysiology remains unclear. In this study, we tested the hypotheses that (1) adoptive transfer of RUPP-stimulated NKs will induce maternal hypertension and IUGR in normal pregnant control (Sham) rats and (2) adoptive transfer of Sham NKs will attenuate maternal hypertension and IUGR in RUPP rats. On gestation day (GD)14, vehicle or 5×106 RUPP NKs were infused i.v. into a subset of Sham rats (Sham+RUPP NK), and vehicle or 5×106 Sham NKs were infused i.v. into a subset of RUPP rats (RUPP+Sham NK; n=12/group). On GD18, Uterine Artery Resistance Index (UARI) was measured. On GD19, mean arterial pressure (MAP) was measured, animals were sacrificed, and blood and tissues were collected for analysis. Adoptive transfer of RUPP NKs into Sham rats resulted in elevated NK activation, UARI, placental oxidative stress, and preproendothelin expression as well as reduced circulating nitrate/nitrite. This led to maternal hypertension and IUGR. RUPP recipients of Sham NKs demonstrated normalized NK activation, sFlt-1, circulating and placental VEGF, and UARI, which led to improved maternal blood pressure and normal fetal growth. These data suggest a direct role for cNKs in causing preeclampsia pathophysiology and a role for normal NKs to improve maternal outcomes and IUGR during late gestation.

Associations of DASH Diet in Pregnancy With Blood Pressure Patterns, Placental Hemodynamics, and Gestational Hypertensive Disorders.

BackgroundThe Dietary Approaches to Stop Hypertension (DASH) diet improves blood pressure in nonpregnant populations. We hypothesized that adherence to the DASH diet during pregnancy improves hemodynamic adaptations, leading to a lower risk of gestational hypertensive disorders.Methods and ResultsWe examined whether the DASH diet score was associated with blood pressure, placental hemodynamics, and gestational hypertensive disorders in a population‐based cohort study among 3414 Dutch women. We assessed DASH score using food‐frequency questionnaires. We measured blood pressure in early‐, mid‐, and late pregnancy (medians, 95% range: 12.9 [9.8–17.9], 20.4 [16.6–23.2], 30.2 [28.6–32.6] weeks gestation, respectively), and placental hemodynamics in mid‐ and late pregnancy (medians, 95% range: 20.5 [18.7–23.1], 30.4 [28.5–32.8] weeks gestation, respectively). Information on gestational hypertensive disorders was obtained from medical records. Lower DASH score quartiles were associated with a higher mid pregnancy diastolic blood pressure, compared with the highest quartile (P<0.05). No associations were present for early‐ and late pregnancy diastolic blood pressure and systolic blood pressure throughout pregnancy. Compared with the highest DASH score quartile, the lower DASH score quartiles were associated with a higher mid‐ and late pregnancy umbilical artery pulsatility index (P≤0.05) but not with uterine artery resistance index. No associations with gestational hypertensive disorders were present.ConclusionsA higher DASH diet score is associated with lower mid pregnancy diastolic blood pressure and mid‐ and late pregnancy fetoplacental vascular function but not with uteroplacental vascular function or gestational hypertensive disorders within a low‐risk population. Further studies need to assess whether the effects of the DASH diet on gestational hemodynamic adaptations are more pronounced among higher‐risk populations.

The role of uterine artery Doppler index and nuchal translucency measurement in predicting perinatal problems and the gestational age in patients diagnosed with hyperemesis gravidarum

Objective:&#x0D; We aimed to investigate the effectiveness of uterine artery Doppler index and nuchal translucency (NT) measurement in determining perinatal problems in patients diagnosed with hyperemesis gravidarum (HEG).&#x0D; Material and methods:&#x0D; We included 80 pregnant women between the ages of 19–40 years with a singleton, noncomplicated pregnancy, no systemic disease, and no structural and chromosomal disorders in the fetus, who were admitted to our hospital which is a tertiary center with a large patient population in the region, between October 2015 and October 2016 in this study. Further, two group were formed as 40 pregnant women with the diagnosis of HEG (group 1) and 40 pregnant women for control group (group 2). Age, body mass index (BMI), educational status,pregnancy history (live birth, miscarriages), smoking, alcohol consumption, substance&#x0D; use, last menstrual period, serum pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotropin, (free ß-hCG), thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4) levels, nuchal translucency (NT), and uterine artery Doppler measurement values were recorded. The data between two groups were compared.&#x0D; Results:&#x0D; The education level of the group 1 was found higher (p = 0.001). The frequency of smoking in group 1 (n = 18; 45%) was found significantly higher than group 2 (n = 3; 7.5%) (p = 0.001). In group 1, uterine artery Doppler pulsatility index (PI) and resistance index (RI) values were found higher than group 2 (p = 0.026 and 0.024, respectively).&#x0D; Conclusion:&#x0D; The uterine artery Doppler PI, RI values measured at 20–24 weeks in patients with HEG were statistically significantly higher than those without HEG.

Combined hereditary thrombophilias are responsible for poor placental vascularization development and low molecular weight heparins (LMWH) prevent adverse pregnancy outcomes in these patients

Background Even though thrombophilias are associated with negative pregnancy outcomes (PO), there is not a consensus of when thrombophilias should be screened for, or how they affect placental vascularization during pregnancy. Therefore, the main aim of this study was to discover inherited thrombophilias (IHT) in the first trimester in women with otherwise no indications for thrombophilia screening, based on their vascularization parameters. LMWH treatment in improvement of placental vascularization and PO was also assessed. Finally, the classification of thrombophilias based on observed obstetric risks was proposed. Methods Women were included in study based on their poor gestational sac and later utero-placental juncture vascularization signal and screening for inherited thrombophilias. LMWH were then initiated and Resistance index of Uterine artery (RIAU) was followed alongside PO (preterm birth, preeclampsia, placental abruption, intrauterine growth reduction). Study group consisted of women with combined inherited thrombophilias. Control group consisted of patients with inherited thrombophilias who have received LMWH therapy since pregnancy beginning. Findings Out of 219 women, 93 had IHT, and 43 had combined IHT. All pregnancies both in both groups ended up with live births. Vaginal birth was more present in the control group (p < .001), and all women in study group delivered by CS. Premature birth was present in 8.4% of patients in control group, and in 32.55% of the patients in the study (p < .001). PE wasn’t noted, and only 1 case of PA in control group. In the control group, 6.5% patients had IUGR, and 32.55% in the study group (p < .05). Based on RIAU and PO, thrombophilia categories were established: S (severe), MO (moderate), MI (mild) and L (low). Higher risk thrombophilias had higher RIAU later in the pregnancy, earlier pregnancy termination and Intrauterine Growth Reduction (IUGR). Conclusions Thrombophilias should be considered and screened when poor vascularization is noted early in the pregnancy with Doppler sonography. Intervention with LMWH prevents adverse PO in these patients.

Stimulation of soluble guanylate cyclase diminishes intrauterine growth restriction in a rat model of placental ischemia.

Placental ischemia in preeclampsia (PE) results in hypertension and intrauterine growth restriction (IUGR). Stimulation of soluble guanylate cyclase (sGC) reduces blood pressure in the clinically relevant reduced uterine perfusion pressure (RUPP) rat model of PE, implicating involvement in RUPP-induced hypertension. However, the contribution of sGC in the development of IUGR in PE is not known. Thus, this study demonstrated the efficacy of Riociguat, an sGC stimulator, in IUGR reversion in the RUPP rat model of PE, and tested the hypothesis that improvement in fetal weight occurs in association with improvement in placental perfusion, placental morphology, and placental nutrient transport protein expression. Sham or RUPP surgery was performed at gestational day 14 (G14) with administration of vehicle (Sham or RUPP) or the sGC stimulator (Riociguat, 10 mg/kg/day sc; sGC-treated) until G20. Fetal weight was reduced (P = 0.004) at G20 in RUPP but not in sGC-treated RUPP compared with Sham, the control group. At G20, uterine artery resistance index (UARI) was increased (P = 0.010) in RUPP, indicating poor placental perfusion; proportional junctional zone surface area was elevated (P = 0.035), indicating impaired placental development. These effects were ameliorated in sGC-treated RUPP. Placental protein expression of nutrient transporter heart fatty acid-binding protein (hFABP) was increased (P = 0.008) in RUPP but not in sGC-treated RUPP, suggesting a compensatory mechanism to maintain normal neurodevelopment. Yet, UARI (P < 0.001), proportional junctional zone surface area (P = 0.013), and placental hFABP protein expression (P = 0.008) were increased in sGC-treated Sham, suggesting a potential adverse effect of Riociguat. Collectively, these results suggest sGC contributes to IUGR in PE.

Non-invasive cardiovascular assessment of pregnancy in healthy female cats

IntroductionThe aim of this study was to evaluate cardiac morphology, indices of systolic and diastolic function, systolic blood pressure (SBP), and uterine artery resistance index (RI) during normal feline pregnancy. Animals; Materials and MethodsTwenty domestic short-hair pregnant queens, weighing 2.4–3.9 kg. Animals were assessed by two-dimensional, M-mode, and Doppler echocardiography, non-invasive SBP measurement, and uterine Doppler ultrasound every 10 days from mating to parturition. ResultsInterventricular septal thickness at end-diastole and end-systole, left ventricular internal dimension at end-diastole, left ventricular free wall thickness at end-diastole and end-systole, fractional shortening, stroke volume, cardiac output (CO), heart rate, and peak velocities of early and late diastolic transmitral flow increased during the second half of gestation, while SBP and RI decreased during the same period (p < 0.01). Discussion and ConclusionsCardiac structure and function varied during normal pregnancy in these queens. Eccentric hypertrophy, increased indices of systolic function, and increased measurements of CO seem to be the consequences of the hemodynamic modifications occurring during pregnancy. The assessment of maternal cardiovascular function may prove a useful screening tool to detect pregnancy complications in feline species.

Early Gestational Exposure to Inhaled Ozone Impairs Maternal Uterine Artery and Cardiac Function.

Exposure to air pollutants such as ozone (O3) is associated with adverse pregnancy outcomes, including higher incidence of gestational hypertension, preeclampsia, and peripartum cardiomyopathy; however, the underlying mechanisms of this association remain unclear. We hypothesized that O3 exposures during early placental formation would lead to more adverse cardiovascular effects at term for exposed dams, as compared with late-term exposures. Pregnant Sprague Dawley rats were exposed (4 h) to either filtered air (FA) or O3 (0.3 or 1.0 ppm) at either gestational day (GD)10 or GD20, with longitudinal functional assessments and molecular endpoints conducted at term. Exposure at GD10 led to placental transcriptional changes at term that were consistent with markers in human preeclampsia, including reduced mmp10 and increased cd36, fzd1, and col1a1. O3 exposure, at both early and late gestation, induced a significant increase in maternal circulating soluble FMS-like tyrosine kinase-1 (sFlt-1), a known driver of preeclampsia. Otherwise, exposure to 0.3 ppm O3 at GD10 led to several late-stage cardiovascular outcomes in dams that were not evident in GD20-exposed dams, including elevated uterine artery resistance index and reduced cardiac output and stroke volume. GD10 O3 exposure proteomic profile in maternal hearts characterized by a reduction in proteins with essential roles in metabolism and mitochondrial function, whereas phosphoproteomic changes were consistent with pathways involved in cardiomyopathic responses. Thus, the developing placenta is an indirect target of inhaled O3 and systemic maternal cardiovascular abnormalities may be induced by O3 exposure at a specific window of gestation.

Comparative Study of Color Doppler Imaging in Normal and Abnormal First Trimester Pregnancy

Background: Color Doppler ultrasonography enables the non-invasive study of physiologic and pathophysiologic changes in the uterine and ovarian circulation in pregnant and non-pregnant women.Aim of the work: To evaluate the potential value of color Doppler of the uterine artery, corpus luteum blood flow, and subchorionic blood vessels in abnormal first-trimester pregnancy.Patients and methods: The study included 200 pregnant women in the first trimester in the antenatal care clinic of the Department of Obstetrics and Gynecology AL Azhar University [Assiut], divided into two groups; control group [100 cases] with normal pregnancy and study group [100 cases] which was further subdivided into threatened abortion [60 cases], blighted ovum [20 cases] and vesicular mole [20 cases].Results:The uterine artery resistance index [RI] of the study groups was lower than the control group. The decrease was highly significant in the uterine artery RI of both threatened abortion and blighted ovum groups and significant in the vesicular mole group. Uterine artery pulsatility index [PI] showed a significant decrease in the study group compared with the control cases. There was a highly significant negative correlation between gestational age and both RI and PI of the study group's uterine artery. There was a higher prevalence of abortion in a group of threatened abortion compared to the control group.Conclusion: The prevalence of pregnancy complications is increased in association with abnormal blood flow patterns of the early uteroplacental circulation. Doppler indices of the early gestation uteroplacental circulation have an important value in the threatened abortion follow up.

Resistance Index of Uterine and Spiral Arteries as a Predictor of Threatened Miscarriage Outcome

Background: Miscarriage is a common event in the first half of pregnancy. Improvements in Ultrasound and Doppler technology, have led to a better understanding of early pregnancy development. Such a facility may be used in turn to predict pregnancy outcome in threatened miscarriage. Objective: To assess the ability of the Uterine artery RI and Spiral artery RI to predict outcome in cases of Threatened miscarriage Patients and methods: Prospective observational study was conducted in the Department of Obstetrics and Gynecology at Menoufia University Hospital. The study included 90 women with gestational age between 5 – 13 w. divided into three groups; Group (A): involved (30) women diagnosed with threatened miscarriage and was followed up and got aborted before pregnancy completed 24weeks. Group (B): (30) women diagnosed with threatened miscarriage and were followed up and the pregnancy continued till 24weeks. Group (C): 30 women having singleton normal ongoing pregnancy till 24 weeks of gestation as a control group. Results: In this study, the Doppler study of uterine arteries the subchorionic blood flow revealed that (RI) was significantly higher in the miscarried group than both continued and control groups. Conclusion: Uterine artery RI and Subchorionic blood flow RI can predict the fate of pregnancy in cases with threatened miscarriage with high accuracy.

Resistance Index of Uterine and Spiral Arteries as a Predictor of Threatened Miscarriage Outcome

Background: Miscarriage is a common event in the first half of pregnancy. Improvements in Ultrasound and Doppler technology, have led to a better understanding of early pregnancy development. Such a facility may be used in turn to predict pregnancy outcome in threatened miscarriage. Objective: To assess the ability of the Uterine artery RI and Spiral artery RI to predict outcome in cases of Threatened miscarriage Patients and methods: Prospective observational study was conducted in the Department of Obstetrics and Gynecology at Menoufia University Hospital. The study included 90 women with gestational age between 5 – 13 w. divided into three groups; Group (A): involved (30) women diagnosed with threatened miscarriage and was followed up and got aborted before pregnancy completed 24weeks. Group (B): (30) women diagnosed with threatened miscarriage and were followed up and the pregnancy continued till 24weeks. Group (C): 30 women having singleton normal ongoing pregnancy till 24 weeks of gestation as a control group. Results: In this study, the Doppler study of uterine arteries the subchorionic blood flow revealed that (RI) was significantly higher in the miscarried group than both continued and control groups. Conclusion: Uterine artery RI and Subchorionic blood flow RI can predict the fate of pregnancy in cases with threatened miscarriage with high accuracy.

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.

Abstract P213: Placental Ischemia-Stimulated Natural Killer Cells Contribute To Hypertension, Vascular Dysfunction, And Intrauterine Growth Restriction In Pregnant Rats

The Reduced Uterine Perfusion Pressure (RUPP) rat model of placental ischemia mimics many characteristics of preeclampsia (PE) such as hypertension (HTN), intrauterine growth restriction (IUGR), and increased cytolytic natural killer cells (cNKs). We have previously shown that natural killer (NK) cell depletion in RUPP rats improves PE pathophysiology and that RUPP NKs have a 5-fold increase in cytotoxicity vs normal pregnant NKs. In this study, we tested the hypotheses that (1) RUPP stimulated NKs play a direct role in causing HTN and IUGR in pregnant rats and (2) normal pregnant control (Sham) NKs attenuate HTN and IUGR in RUPP rats. NKs were isolated from the placentas of Sham and RUPP rats on gestation day (GD) 19. On GD14, vehicle or 5x10 6 RUPP NKs were infused i.v. into a subset of Sham rats, and vehicle or 5x10 6 Sham NKs were infused i.v. into a subset of RUPP rats. On GD18, Uterine Artery Resistance Index (UARI) was measured via Doppler Ultrasound; GD19, cNKs were quantified via flow cytometry and MAP, fetal weight, and blood were acquired. Plasma VEGF and sFlt-1 were measured via ELISA. Placental cNKs (% gated) increased from 3±1% in Sham to 19±5% in RUPP and 21±4% in Sham+RUPP NK (p&lt;0.05 vs Sham), and decreased to 3±1% in RUPP+Sham NK (p&lt;0.05 vs RUPP). Circulating cNKs also followed this trend. MAP increased from 102±1 mmHg in Sham to 130±2 mmHg in RUPP and 121±2 mmHg in Sham+RUPP NK (p&lt;0.05 vs Sham), and was blunted to 113±1 mmHg in RUPP+Sham NK (p&lt;0.05 vs RUPP). Fetal weight decreased from 2.4±0.04 g in Sham to 2.1±0.07 g in RUPP and 2.1±0.03 g in Sham+RUPP NK (p&lt;0.05 vs Sham), and this was normalized to 2.3±0.03 g in RUPP+Sham NK (p&lt;0.05 vs RUPP). UARI increased from 0.56±0.05 in Sham to 0.75±0.06 in RUPP and 0.76±0.05 in Sham+RUPP NK (p&lt;0.05 vs Sham), and decreased to 0.64±0.05 in RUPP+Sham NK (p&lt;0.05 vs RUPP). Circulating sFlt-1 increased from 76±15 pg/mL in Sham to 1391±424 pg/mL in RUPP (p&lt;0.05 vs Sham), 780±256 pg/mL in Sham+RUPP NK, and decreased to 67±8 pg/mL in RUPP+Sham NK (p&lt;0.05 vs RUPP). Furthermore, circulating VEGF decreased in RUPP and Sham+RUPP NK compared to Sham (p&lt;0.05), and increased in RUPP+Sham NK (p&lt;0.05 vs RUPP). These data demonstrate a direct role for cNKs to mediate vascular dysfunction in PE and for normal NKs to promote positive maternal and fetal outcomes.

Abstract MP20: Prepartum 1,3-butanediol Treatment Improves Placental Perfusion In The Preeclamptic Dahl Salt-sensitive Rat

Chronic hypertension increases the risk of developing superimposed preeclampsia (PE). Previous reports showed that 1,3-Butanediol (BD) lowers blood pressure (BP) in male Dahl salt-sensitive (S) rats and female congenic S.SHR(11) rats which exhibit increased kidney injury over Dahl S rats. The goal of this study was to test if attenuating hypertension before pregnancy through the placentation period via BD prevents the onset of PE. Female Dahl S rats (a spontaneous model of superimposed PE, 11-16 weeks old) were divided into two groups: BD treated (20% via drinking water) and control (ad libitum water). Animals received BD for 7 weeks, baseline BP measurements (telemetry) were taken, and both groups were then mated. On gestation day (GD) 12, treatment was stopped because pilot studies showed that treatment reduced water intake during late pregnancy. Both groups were maintained on low-salt rodent chow (Teklad 7034, 0.3% NaCl; n=8/group). At GD18 (late pregnancy), uterine artery resistance index (UARI) was measured via Doppler ultrasound, 24h urine was collected on GD19, and tissues were harvested on GD20. Mean arterial pressure was lower in the treated group at baseline (141.9 ± 4.1 vs. 165.7 ± 4.5 mmHg, p= 0.008), early (135.9 ± 3.4 vs. 168.9 ± 4.6 mmHg, p= 0.0003), mid (142.0 ± 5.2 vs. 170.8 ± 4.61, p= 0.0048) but not late pregnancy (144.9 ± 5.9 vs. 161.9 ± 4.5 mmHg, p= 0.165). Late pregnancy maternal body weight was similar between groups (299.3 ± 5.6 vs. 311.3 ±7.0 g, p=0.201). Treated dams had a lower UARI (0.71 ± 0.02 vs. 0.81 ± 0.02, p=0.008) and less fetal resorptions (1.12 ± 0.29 vs. 2.25 ± 0.41, p= 0.043). No harm to the fetus was noted as no differences in pup weight (2.20 ±0.05 vs. 2.20 ± 0.09, p= 0.994) and pup length (30.19 ±0.24 vs. 29.45 ± 0.28 cm, p=0.072) were observed. Placentas from treated dams had decreased VEGF levels via ELISA (276.2 ± 33.4 vs. 498.9 ± 16.8 pg/mL, p= 0.001), suggesting reduced placental ischemia. In this study, we observed slightly improved placental perfusion and lower fetal demise following prepartum BD treatment; however, the antihypertensive effects of BD were not sustained through late pregnancy when supplementation was stopped at mid-pregnancy.

Abstract P218: Tumor Necrosis Factor Alpha Improves Placental Perfusion And Attenuates Intrauterine Growth Restriction In A Rodent Model Of Preeclampsia

Preeclampsia ( PE ) is not only detrimental to the mother and her fetus during pregnancy, but it is also associated with increased cardiovascular ( CV ) risk in the mother and her intrauterine growth restricted ( IUGR ) offspring in later life. Currently there are no known treatment options for PE beyond early delivery. Thus, there is a critical need to identify therapeutic treatments for PE. The inflammatory cytokine TNF-α is increased in women with PE. In the clinically relevant Reduced Uterine Perfusion Pressure ( RUPP ) model of PE in the rat, TNF-α is also increased and importantly, etanercept abolishes maternal hypertension. Etanercept is a soluble receptor that binds TNF-alpha to inhibit the inflammatory response. Although not yet prescribed for PE, etanercept is non-contraindicated during pregnancy. Therefore, this study tested the hypothesis that maternal administration of etanercept will mitigate IUGR in the RUPP model of PE and that improvement in fetal growth occurs in association with improved uteroplacental perfusion, placental morphology, and placental nutrient transporter protein expression. Sham or RUPP was performed at gestational day 14 ( G14 ). Dams were administered vehicle or the TNF-α inhibitor (etanercept, 0.4 mg/kg, s.c.) at G18. At G20 uterine artery resistance index ( UARI ) was significantly increased in vehicle RUPP (0.69±0.02 mm/s) vs. vehicle Sham (0.60±0.02mm/s)( p &lt;0.05), indicative of reduced uteroplacental perfusion, but UARI was no longer increased in treated RUPP (0.65±0.03 mm/s)( p &lt;0.05). At G20, fetal weight was significantly reduced in vehicle RUPP (3.52g±0.10) vs. vehicle Sham (3.82 g±0.09)( p &lt;0.05). Yet, fetal weight was significantly increased in treated RUPP (3.82g±0.12) vs. vehicle RUPP ( p &lt;0.05). Fetal brain weight did not differ in Sham or RUPP, regardless of maternal treatment. However, fetal liver weight was significantly increased in treated RUPP (0.29g ±0.02) vs. vehicle RUPP (0.24g±0.01)( p &lt;0.05) suggesting attenuation of asymmetric growth restriction. These findings indicate that maternal administration of a TNF-α inhibitor during PE improves fetal growth in association with improved uteroplacental blood flow. Future studies are warranted to investigate the long-term benefit in IUGR offspring.

Abstract MP21: Suppression Of Reactive Oxygen Species Protects The Dahl Salt-sensitive Rat From Developing Maternal Syndrome

The Dahl Salt-Sensitive (SS) rat maintained on a low salt diet exhibits a differential response to pregnancy; approximately half develop maternal syndrome (hypertension and proteinuria) while the other half are protected. The exact mechanisms of maternal syndrome are unclear, but it is proposed that reactive oxygen species (ROS) are involved. Previous studies from our laboratory demonstrated the importance of NADPH oxidase (NOX) 2-derived ROS produced by immune cells in the development of salt-sensitive hypertension and renal disease. Given the role of NOX2-derived ROS in the Dahl SS rat, we tested the hypothesis that genetic deletion of the p67phox subunit of NOX2 (SS Ncf2-/- ) will result in the protection from developing maternal syndrome. To test this hypothesis, 8 week old female Dahl SS and SS Ncf2-/- were instrumented with radio-telemeters for continuous measurement of mean arterial pressure (MAP). After a recovery period, baseline MAP was measured as well as an overnight urine collection for markers of renal damage before females were mated with males of the same strain and age. Virgin litter-mate controls were run in parallel. As expected, MAP and protein excretion levels were comparable at baseline between virgin and mated SS Ncf2-/- rats. These parameters remained comparable at the late pregnancy time point (108±3 vs 112±1mmHg, 9±3 vs 16±5mg/day, p &gt;0.05). In contrast to the SS preeclamptic pregnancy, the SS Ncf2-/- mated rats are protected from the development of maternal syndrome (141±8 vs 112±1mmHg, p &lt;0.001; and 98±16 vs 16±5mg/day, p &lt;0.001; in the SS vs SS Ncf2-/- , respectively). This protection is accompanied with a significant reduction in uterine artery resistance index which is a marker of impaired blood flow, in the SS Ncf2-/- (0.85±0.03 vs 0.59±0.02, p &lt;0.01). Despite these phenotypic differences, the number of infiltrating immune cells into kidneys or placentas do not differ between these two groups. These results suggest that NOX2-derived ROS contribute to the pathogenesis of maternal syndrome in the Dahl SS rat, and further investigations are necessary to clarify the source of the ROS within key organs such as the kidney and placenta.

RELATIONSHIP BETWEEN TEMPORAL CHANGES OF ENDOMETRIAL BLOOD FLOW IMPEDANCE IN A NATURAL AND HORMONE REPLACEMENT CYCLE AND PREDICTION OF PREGNANCY DURING VITRIFIED-WARMED EMBRYO TRANSFER

Frozen-thawed embryo transfer (ET) is performed in a natural or hormone replacement therapy (HRT) cycle for endometrial preparations. However, how to determine which endometrial preparation method is suitable for the individual is unknown.This study was to examine the relationship between the temporal changes in endometrial blood flow impedance during natural and HRT cycles and clinical outcomes in vitrified-warmed ET. A single-center retrospective observational cohort study. This study was approved by the institutional review board of the Fukushima Medical University. This study included a total of 60 women, 28 with natural and 32 with HRT cycles, who underwent vitrified-warmed ET. Uterine radial artery resistance index (RA-RI) was measured during the natural and HRT cycles at the early follicular phase, days of the human chorionic gonadotropin trigger during a natural cycle or start of progesterone administration during the HRT cycle, and the day of ET. The association between the RA-RI at the different measurement point and the pregnancy were examined in the natural and HRT cycles by univariate analysis and multivariate logistic analysis. Receiver-operating characteristic analysis was used to determine the cut-off value of the RI with respect to pregnancy in natural and HRT cycles. The area under the curves (AUC) and their 95% confidence intervals (CI) were calculated. The clinical pregnancy rates of the natural and HRT cycles were 32.1% and 34.4%, respectively. In the univariate analysis, the RA-RI at the early follicular phase was significantly lower in the pregnant group than that in the non-pregnant group in the natural but not HRT cycle (P=0.04). In the multivariate logistic analysis, the RA-RI at the early follicular phase was an independent predictive factor for pregnancy in the natural but not HRT cycle (P=0.02). The odds ratio for pregnancy was 0.7 (95% CI, 0.52–0.95) when the levels of RA-RI at the early follicular phase was increased by 0.01 in the natural cycle. With the natural cycle, the area under the receiver-operating characteristic curves for the RA-RI at the early follicular phase with a threshold of 0.68 was 0.75 (95% CI, 0.57–0.93). The positive predictive and negative predictive values were 0.53 (95% CI, 0.37–0.59) and 0.92 (0.74–0.99), respectively. With the natural cycle, the RA-RI at the early follicular phase was associated with pregnancy, and this might have a potential in predicting pregnancy in vitrified-warmed ET cycles. Our findings suggest that RA-RI at the early follicular phase might be an effective and useful tool in choosing natural or HRT cycles for vitrified-warmed ET. This provides a clue to the individualization of the choice of an endometrial preparation method during the frozen-thawed ET.

Correlation of Uterine Artery Resistive Index with Endometrial Thickness among the Patients of Primary Infertility

Infertility is a worldwide social, economic, and psychological problem. It can be caused by various factors including age, mental health, polycystic ovarian syndrome, ovarian failure, and defective endometrial receptivity. Endometrial receptivity is the preparation and thickening of the endometrium.