Uterine Artery Blood Flow Research Articles

Levonorgestrel Intrauterine System Effects versus Copper Intrauterine Device on Changing Of Menstruation and Uterine Artery Doppler

Background: The most effective methods for birth control are the long-acting reversible contraceptives LARCs include Paragard IUD in silver, Mirena IUD in hormonal (progesterone) and hormonal contraceptive implant. The intrauterine levonorgestrel-releasing system (LNG-IUS) and the intrauterine copper unit (Cu-IUD) influenced changing of menstruation and uterine artery Doppler indices Aim of the work: Comparison of the effects of copper intrauterine device (Cu-IUD) and an intrauterine levonorgestrel releasing system (LNG-IUS) on changing of menstruation and Doppler indices of uterine arteries. Methods: This was RCT was completed between February 2017 to January 2020 at the Obstetrics and Gynecology department, Tanta University hospitals. There were two group first group A :LNG-IUS (N=200) and second group B CuIUD (N=200), they were randomly assigned to 400 multiparous women preferring intrauterine contraception., the UA pulsatility index (PI) and the resistant index (RI) were determined at the beginning, and the associations with irregular bleeding were evaluated three and six months after insertion. Results: In group A: LNG-IUS, some women registered irregular bleeding (28 percent) than in the Cu-IUD group (52 percent) at the beginning of the study (P<0.001). There was bleeding irregularity (73 percent) in the group (A): LNG-IUS and severe menstrual bleeding (68 percent) in the Cu-IUD group. The uterine artery PI was associated with bleeding irregularity at value of 1.40, with a curve area (AUC) of 0.91, 90 percent sensitivity, and 100 percent specificity. Uterine artery RI was associated with 0.65 with 0.22 AUC bleeding irregularity, 95 percent sensitivity and accuracy 100 percent. Conclusion: LNG - IUS related irregular bleeding was linked to changes in the blood flow of uterine arteries that were not evident among Cu - IUD users.

Melatoninin kaynağı triptofanın IVF hastalarının sonuçlarına ve Doppler parametrelerine etkisi

Aims: Melatonin is the most powerful antioxidant and protects sperm, oocyte and embryo against oxidative stress. The effect of tryptophan, which is the building block of melatonin, on follicular melatonin levels and IVF outcomes is unknown. The objective of this study was to investigate the effect of tryptophan administration, a precursor for melatonin, on the levels of intrafollicular melatonin with the aim to reveal the correlation between tryptophan and the total number and quality of oocytes as well as clinical pregnancy rates. In addition, we aimed to examine the effect of melatonin increased by tryptophan on uterine and ovarian blood flow. Methods: Out of 103 patients who applied to Ondokuzmayis University IVF clinic for IVF treatment, 51 patients were administered a 100 mg dose of tryptophan orally (Group A) and 50 control patients who were randomly selected did not receive tryptophan (Group B). Firstly, follicular melatonin levels were compared between Group A receiving tryptophan and Group B without tryptophan. Both groups were also compared according to the oocyte count, oocyte count, fertilized oocyte count, embryo count and pregnancy rates, ultimately. In addition, all patients were measured for uterine and ovarian artery blood flow by vaginal ultrasound on the day of OPU.. Results: There were no differences in age (32.16 ± 3.82 years vs 33.06 ± 4.44 years) (p = 0.276), BMI (28.45 ± 2.82 kg/m)2 vs 28.15 ± 3.03kg/m2 (p = 0.602) and peak estradiol levels (2451.69 ± 469.75 pg/ml vs 2420.26 ± 443.71 pg / ml) (p = 0.73) between the groups. Group A exhibited high levels of melatonin in the follicular fluid with a mean value of 259.8 pg/ml, whereas Group B had 91.3 pg/ml (p <0.001). There were found significant differences in the oocyte count (9.08 ± 3.22 vs 7.66 ± 1.89) (p = 0,008), mature oocyte count (7.2 ± 2.8 vs 6.1 ± 1.8) (p = 0,021) and fertilized oocyte count (6.35 ± 2.44 vs 5.28 ± 1.69) between group A and group B. Pregnancy rates were higher in group A (35.3%). The pregnancy rate (30%) was lower in Group B, which did not receive tryptophan and had low melatonin levels in follicular fluid. However, there was no statistically significant difference. Uterine, ovarian artery systolic and diastolic blood flows of Group A were significantly lower than Group B (P <0.001). Conclusions: Administration of tryptophan to IVF patients significantly increases the level of melatonin in follicular fluid. The results demonstrate that high levels of melatonin in follicular fluid may increase oocyte count and quality although they do not significantly improve clinical pregnancy rates.

RETRACTED: Effects of low-dose aspirin on the prevention of preeclampsia and pregnancy outcomes: A randomized controlled trial from Shanghai, China

ObjectivesTo evaluate the preventive effects of low-dose aspirin on the incidence of preeclampsia and pregnancy outcomes of women at high-risk for preeclampsia. Study designThis prospective randomized clinical trial was conducted at the Obstetrics Department of The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, China. It analyzed data from 1105 high-risk women who were divided into the control group (placebo group) and the aspirin group (including three subgroups: 25 mg, 50 mg and 75 mg). The aspirin group in this study was instructed to take aspirin daily before bedtime beginning in the 12th week of pregnancy. Main outcome measures: The primary outcome is the occurrence of preeclampsia. The secondary outcomes included maternal and neonatal outcomes (such as premature delivery, FGR etc.), maternal serum biomarkers (including d-dimers, platelet aggregation rates, etc.) and uterine arterial blood flow resistance. The onset of preeclampsia and pregnancy outcomes were recorded after all participants delivered. ResultsLow-dose aspirin significantly reduced the incidence of preeclampsia and early-onset preeclampsia. Aspirin also showed significant dose dependence in preeclampsia prevention. The results of Mantel-Haenszel trend test showed that there was a linear relationship between the dosage and the incidence of preeclampsia and early preeclampsia (P < 0.05). Pearson's results showed that the incidence of preeclampsia and early preeclampsia was negatively correlated with aspirin dosage. There was also a linear relationship between the dosage and the rates of postpartum hemorrhage, fetal growth restriction, premature births and cesarean section (P < 0.05). There was no evidence to suggest differences in the incidence of fetal distress, miscarriage and placental abruption among the four groups. The blood resistance S/D value of uterine artery in early pregnancy was the only independent factor affecting the efficacy of aspirin (OR = 1.405; 95 %CI,1.058–1.867; P = 0.019). ConclusionLow-dose aspirin can prevent preeclampsia and early-preeclampsia. Its efficacy is dose-dependent. It can reduce the rates of postpartum hemorrhage, fetal growth restriction, premature births and cesarean section. The prophylactic effect of aspirin on preeclampsia seemed to be greater in patients with higher blood resistance S/D value of uterine artery during early pregnancy.

Effects of low-dose aspirin combined with letrozole on serum visfatin, monocyte chemoattractant protein-1 and pregnancy rate in patients with polycystic ovary syndrome

Objective To study the effect of low-dose aspirin combined with letrozole on serum visfatin, monocyte chemoattractant protein-1(MCP-1) and pregnancy rate in patients with polycystic ovary syndrome(PCOS). Methods From November 2016 to November 2018, 110 patients with PCOS in the Third People's Hospital of Datong were selected.According to the random number table, they were divided into the observation group(60 cases) and the control group(50 cases). The control group was treated with letrozole, while the observation group was given letrozole combined with low-dose aspirin.The patients were continuously treated for 3 menstrual cycles.The changes of the serum visfatin, MCP-1, sex hormones, uterine artery blood flow before and after treatment, pregnancy and adverse reactions were compared between the two groups. Results After treatment, the serum visfatin, MCP-1, testosterone (T), luteinizing hormone (LH), LH/follicular estrogen (FSH), uterine arterial pulsation index (PI) and resistance index (RI) in the observation group were (11.03±2.17)ng/mL, (99.31±14.50)ng/L, (1.57±0.29)mmol/L, (6.57±1.30)U/L, (1.16±0.22), (1.07±0.24), (0.41±0.08), respectively, which were significantly lower than those in the control group[(15.57±2.56)ng/mL, (121.29±20.37)ng/L, (1.78±0.32)mmol/L, (8.40±1.88)U/L, (1.50±0.27), (1.45±0.29), (0.57±0.11)], the differences were statistically significant(t=10.068, 6.593, 3.608, 6.012, 7.278, 7.521, 8.815, all P 0.05). Conclusion Low-dose aspirin combined with letrozole in the treatment of PCOS can effectively reduce the serum visfatin and MCP-1, regulate the sex hormones levels, improve uterine artery blood flow, improve pregnancy rate, and without increasing adverse drug reactions, so it's worthy of popularizing. Key words: Polycystic ovary syndrome; Aspirin; Letrozole; Drug therapy, combination; Visfatin; Monocyte chemoattractant proteins; Gonadal hormones; Uterine artery; Pregnancy

Sonographic Association of Uterine Artery Pulsatility Index with Hypertension During Third Trimester of Pregnancy

Background: Hypertension (HTN) in pregnancy is the second most basic reason for maternal death and cause obstetric complications in 5-10% of all pregnancies. HTN directly affects the blood flow of uterine artery. Doppler screening test is a valuable method to do safe and non-invasive detection and has high reliability in the detection of uterine artery blood flow characteristics. Objective: The purpose of the present study is to find association between predictive value of uterine artery pulsatility index in normal and hypertensive pregnancy during third trimester. Methods: A descriptive cross-sectional study was conducted with the sample size of 138 patients by selecting the convenient sampling from Ghurki Trust Teaching Hospital, Lahore. The pulsatility index of uterine artery of all the women with normal singleton pregnancy and hypertensive during third trimester of pregnancy were obtained using Doppler ultrasound. Data was analyzed with the help of Anova .The results were derived by mean, frequency and standard deviation . Results: The significance between groups was 0.002. The mean values of right and left uterine artery pulsatility index of 36 hypertensive patients were 1.40 and 1.41 and standard deviation 0.4 and 0.5 respectively whereas the mean values of right and left uterine artery pulsatility index of 102 normal patients were 0.739 and 0.77 and standard deviation 0.23 and 0.5 respectively Conclusion: Our study concluded that there was an association between uterine atery pulsatility index and hypertension during pregnancy. The uterine artery pulsatiltiy index has increased with hypertension in third trimester of pregnancy. Keywords: Hypertension, Pulsatility Index, Doppler Ultrasound DOI: 10.7176/JHMN/72-07 Publication date: March 31 st 2020

Predictive Factors of Response to Selective Progesterone Receptor Modulator (Ulipristal Acetate) in the Pharmacological Treatment of Uterine Fibroids.

Background: Selective progesterone receptor modulator ulipristal acetate (UPA) is a drug used in management of symptomatic myomas. It was observed that the response to UPA treatment in uterine myomas varied amongst patients. An attempt was thus made at establishing predictive factors conducive to better reaction to treatment with UPA. The aim of this study was to assess the efficacy of UPA treatment in women with myomas, depending on pretreatment myomas’ volume, number of myomas, age of patients, estrogenic status of women, and pretreatment blood flow in uterine arteries. Materials and methods: The study included patients with one to four myomas. The UPA treatment was a preparation stage for surgical treatment in all patients. The study group was divided into the subgroups according to pretreatment myomas’ volume, number of myomas, age of patients, estrogenic status of women, and pretreatment blood flow in uterine arteries. Results: A better effect of reduction in size of myomas after UPA treatment was noted when pretreatment myomas’ volume was lower than 30 cm3. A significant reduction in fibroids’ size was observed after UPA therapy independently of the number of myomas and age of patients. A good response after the UPA therapy was observed when pretreatment estradiol concentration was below 50 pg/mL and when uterine artery resistance index (RI) was above 0.8. Conclusions: Our research demonstrates that treatment with ulipristal acetate is an efficient method in preoperative preparation of patients with uterine fibroids. The most important factor of positive response to UPA therapy is myoma volume. The number of myomas and patient’s age do not interfere with effects of UPA therapy. Pretreatment estradiol concentration is significant, yet secondary for the effects of therapy. The UPA therapy has no impact on blood flow in the uterine arteries and no adverse influence on estradiol concentrations.

Uteroplacental Ischemia Is Associated with Increased PAPP-A2.

Residence at high altitude (> 2500m) has been associated with an increased frequency of preeclampsia. Pappalysin-2 (PAPP-A2) is an insulin-like growth factor binding protein-5 (IGFBP-5) protease that is elevated in preeclampsia, and up-regulated by hypoxia in placental explants. The relationships between PAPP-A2, altitude, and indices of uteroplacental ischemia are unknown. We aimed to evaluate the association of altitude, preeclampsia, and uterine artery flow or vascular resistance with PAPP-A2 levels. PAPP-A2, uterine artery diameter, volumetric blood flow, and pulsatility indices were measured longitudinally in normotensive Andean women residing at low or high altitudes in Bolivia and in a separate Andean high-altitude cohort with or without preeclampsia. PAPP-A2 levels increased with advancing gestation, with the rise tending to be greater at high compared to low altitude, and higher in early-onset preeclamptic compared to normotensive women at high altitude. Uterine artery blood flow was markedly lower and pulsatility index higher in early-onset preeclamptic normotensive women compared to normotensive women. PAPP-A2 was unrelated to uterine artery pulsatility index in normotensive women but positively correlated in the early-onset preeclampsia cases. We concluded that PAPP-A2 is elevated at high altitude and especially in cases of early-onset preeclampsia with Doppler indices of uteroplacental ischemia.

Comparison of the immediate analgesic effect of perpendicular needling and transverse needling at SP6 in patients with primary dysmenorrhea

Background:Acupuncture has been widely used to treat primary dysmenorrhea (PD) with satisfactory outcomes. Sanyinjiao (SP6) is the most commonly used acupoint for PD. Different needling techniques may influence the effect of SP6, and its underlying mechanism needs to be explored. This randomized controlled parallel trial is designed to evaluate the immediate analgesic effect and hemodynamic responses in uterine arterial blood flow of perpendicular needling and transverse needling at SP6 in patients with PD of cold-dampness stagnation pattern using color doppler ultrasonography.Methods:Forty-eight patients who meet inclusion criteria will be randomized in a ratio of 1:1 to either perpendicular needling or transverse needling groups. Every participant will receive 1 session of acupuncture treatment for 10 minutes at bilateral SP6. In the perpendicular needling group, needles will be inserted vertically 1 to 1.2 cun and will be manipulated to achieve needling sensation. In transverse needling group, the needles will be inserted transversely 1 to 1.2 cun toward the abdomen without any manipulation to avoid needling sensation. Color doppler ultrasonography will be performed before, during, and after needling. The primary outcome measure is visual analog scale for pain. The secondary outcome measures include the uterine artery blood flow changes by measuring pulsatility index, resistance index values, and ratio of systolic peak and diastolic peak, the Hamilton anxiety scale, blood pressure, and heart rate. Adverse events in both groups also will be recorded.Discussion:This trial will be the first study protocol designed to explore the influence of needling techniques on the analgesia effect of solo acupoint and its hemodynamic responses for PD. It will promote more widespread awareness of the benefits of using suitable needling techniques in acupuncture clinical setting and provide a further explanation of the underlying hemodynamic mechanism.Trial registration:This study protocol was registered at the Chinese clinical trial registry (ChiCTR1900026051).

Color Doppler Ultrasound Assessment of the Uterine and Intraovarian Arteries Blood Flow in Cases of Menorrhagia

Color Doppler Ultrasound Assessment of the Uterine and Intraovarian Arteries Blood Flow in Cases of Menorrhagia

Uterine and umbilical resistance index and fetal heart rate in pregnant bitches of different body weight

The aim of this study was to compare uterine and umbilical artery blood flow and fetal heart rate (FHR) in small, medium and large body weight (BW) dogs during the second half of pregnancy. Purebred pregnant bitches were assigned to one of the following groups according to their BW: small (S; ≤10 kg), medium (M; 11−25 kg) and large (L; >25−45 kg). Uterine and umbilical Doppler and M-mode ultrasonography was conducted every 10 days from Day 30–60 (Day 0 = first day of gestation). From Day 40, uterine and umbilical artery resistance index (RI) progressively and differentially decreased in the three groups (P < 0.01) being less in L than S bitches (P < 0.01). Litter size but not maternal BW (P > 0.1) affected uterine RI on Days 40 (r = 0.39; P < 0.01) and 50 (r = 0.41; P < 0.01). Conversely, on Day 60, maternal BW (r = 0.61; P < 0.01) had an effect on uterine RI while litter size did not (P > 0.1). Fetal heart rate increased from Day 30–50 and decreased to the time of parturition (P < 0.01) without differences among groups at any time point (P > 0.1). Uterine and umbilical blood flow differentially increased throughout mid- and late-pregnancy in breeds with large and small BW. These differences were affected by litter size on Days 40 and 50, and by maternal BW on Day 60. Conversely, during this same period, FHR did not vary among BW groups. Physiological variations should be considered when gestational ultrasonic examination is interpreted in different BW bitches.

298 Effects of parity on late gestational uterine blood flow and hemodynamics in beef cattle

Abstract To determine parity effects on late gestational uteroplacental blood flow, uterine artery hemodynamics were measured in 13 primiparous and 11 multiparous (parity 3 and 4) non-lactating, fall-calving crossbred females beginning 109 d prepartum. Females were nutritionally managed as one group to meet or exceed nutrient requirements. Transrectal color Doppler ultrasonography of the both uterine arteries was conducted 3 to 6 times per female across late gestation, ending at approximately 20 d prepartum. Data were analyzed with parity (primiparous vs. multiparous), day prior to calving, and their interaction in the model; day was a repeated effect. Dam BW was greater (P &amp;lt; 0.001) for multiparous than primiparous females, and increased (P = 0.004) as gestation progressed. Calf birth weight was unaffected (P = 0.87) by parity. The parity x day interaction tended to affect (P = 0.06) ipsilateral uterine artery blood flow (L/min), where multiparous cows had a greater increase per day. Total and contralateral uterine artery blood flow were unaffected (P ≥ 0.11) by parity, but increased (P &amp;lt; 0.001) with day of gestation. When expressed relative to dam BW, total and contralateral blood flow were greater (P ≤ 0.04) in primiparous than multiparous females; ipsilateral blood flow was unaffected (P ≥ 0.13) by parity, however. Ipsilateral pulsatility index and both resistance indices were unaffected (P ≥ 0.28) by parity and day, but day tended to affect (P = 0.07) contralateral pulsatility index. Parity did not affect (P ≥ 0.11) cross-sectional area, mean velocity, peak systolic velocity, and end diastolic velocity of either uterine artery, but all increased (P &amp;lt; 0.001) as gestation progressed. Heart rate was greater (P = 0.03) in primiparous than multiparous females. Data suggest that uterine artery blood flow and heart rate may be altered in primiparous females, even when birth weight is unaffected by parity.

PSII-7 Uterine artery hemodynamics and placentome quantification during maternal nutrient restriction in beef cattle

Abstract Proper fetal nutrition via adequate uteroplacental blood flow is critical for maximizing fetal development and reducing mortality. However, our understanding of adaptations during maternal nutrient restriction is incomplete. The purpose of this study was to determine the effect of nutrient restriction during mid to late gestation on utero-placental hemodynamics and placentome morphometrics in gestating beef cattle. Animals (n = 10) were randomly assigned one of 2 treatments: Control (CON; 100% NRC Requirements) vs Restricted Feed (NR; 60% of NRC Requirements) from 140 to 240 days of gestation. Hemodynamic parameters were collected by Doppler ultrasonography 1 week prior to slaughter from the ipsilateral and contralateral uterine arteries, after which, total uterine artery blood flow was calculated. Six animals (n = 3 per treatment) were slaughtered on day 240 of gestation (Group 1) and the remaining 4 animals were slaughtered on 265 ± 15 days (Group 2). Placentome tissues were harvested for weight and number determination. Placentome number decreased (P = 0.01) in nutrient restricted (49 ± 6) versus control (83 ± 6) fed dams. There was an interaction between treatment and group in which ipsilateral diameter increased (P &amp;lt; 0.05) in group 2 NR animals versus group 2 CON animals while there was no difference between NR and CON in group 1. There was no difference (P = 0.30) in total uterine artery blood flow in fetal weight, which averaged 212 ± 37 mL/min*kg in nutrient restricted versus 153 ± 34 mL/min*kg in control fed dams. In summary, these data indicate limited alterations in uterine artery blood flow and fetal weight in nutrient restricted dams during the last half of gestation. The decrease in placentome number with no difference in placentome weight could indicate larger placentomes in nutrient restricted dams were able to compensate for the reduction in total number.

Can increased resistance to uterine artery flow be a risk factor for adverse neurodevelopmental outcomes in childhood? A prospective cohort study

A prospective cohort study was conducted to determine whether an increased uterine artery pulsatility index (UtA-PI) in the second trimester of pregnancy is a risk factor for neurodevelopmental outcomes in children 2–3 years of age. A group of pregnant women with a UtA-PI below the 90th percentile (P90) and a second group with a UtA-PI ≥ P90 in the second trimester were included in this study. The children of these women were evaluated during their second or third year of life using the Bayley III Screening Test. A total of 858 pregnancies with UtA-PI < P90 and 96 pregnancies with UtA-PI ≥ 90 were studied. The differences between the groups related to UtA-PI ≥ 90 were detected in relation to the variables of the Caucasian ethnicity, hypertension, newborn weight and stay in the intensive care unit after birth. However, adjusted neurodevelopmental outcomes did not differ between the groups: OR 0.53 (95% CI 0.27–1.04%). This study failed to demonstrate that the UtA-PI is a risk factor for adverse neurodevelopment in children.Impact statementWhat is already known on this subject? Early interventions in children at high risk for neurodevelopmental deficiency have proved to be beneficial. The complications associated with gestation and delivery negatively influence neurodevelopment. Several studies have shown that some adverse pregnancy outcomes such as preeclampsia, foetal growth restriction and foetal death can be predicted by increased resistance to flow in the uterine artery in the second trimester. However, there are no studies evaluating the association of the uterine artery with neurodevelopmental results.What do the results of this study add? This study concludes that neurodevelopment is influenced by multiple environmental and intrinsic factors and cannot be predicted by only one variable, such as the uterine artery blood flow. The brain has repair mechanisms to attenuate insults that occur during gestation and delivery.What are the implications of these findings for clinical practice and/or further research? This study was unable to demonstrate that blood flow in the uterine artery is a risk factor for neurodevelopment. Different, larger studies should be conducted by combining other factors with the uterine artery in an algorithm to allow the early identification of children at risk for neurodevelopmental impairment.

Trophoblast-induced spiral artery remodelling and uteroplacental haemodynamics in pregnant rats with increased blood pressure induced by heme oxygenase inhibition

IntroductionThe aim of the present study was to determine the contribution of the heme oxygenase (HO) system to the adaptation of the uteroplacental circulation to pregnancy in the rat, and its relationship with the maintenance of blood pressure during late gestation. MethodsThe HO inhibitor, stannous mesoporphyrin (SnMP), or vehicle were administered intraperitoneally to virgin and midpregnant rats. Mean arterial pressure (MAP) was measured before and after the treatment, in the conscious rats. Uterine and radial arteries blood flow velocities were obtained from pregnant rats at days 14 and 19 of gestation using high frequency ultrasonography. Trophoblast invasion and spiral arteries remodelling were analyzed in the mesometrial triangle of pregnant rats by immunohistochemistry. ResultsHO activity inhibition during late gestation induced a significantly increase in the MAP of pregnant rats (114 ± 1 mmHg vs 100 ± 2 mmHg, p < 0.05) but it did not affect this parameter in virgin rats (121 ± 2 mmHg vs 124 ± 3 mmHg). MAP elevation was associated with marked (p < 0.05) decreases in the systolic and diastolic flow velocities in uterine and radial arteries, as compared with pregnant control rats. Furthermore, spiral arteries of pregnant rats treated with SnMP showed lower (p < 0.001) proportion of lumen circumference covered by trophoblast (21 ± 3%) and a higher (p < 0.05) proportion of vascular smooth muscle (33 ± 5%) than control pregnant rats (59 ± 5% and 16 ± 5%, respectively) DiscussionThese data indicate that HO system play an important role in the adaptation of the uteroplacental circulation to pregnancy and in the blood pressure regulation during late gestation.

Increased uterine artery blood flow in hypoxic murine pregnancy is not sufficient to prevent fetal growth restriction†.

Incomplete maternal vascular responses to pregnancy contribute to pregnancy complications including intrauterine growth restriction (IUGR) and preeclampsia. We aimed to characterize maternal vascular dysfunction in a murine model of fetal growth restriction as an approach toward identifying targetable pathways for improving pregnancy outcomes. We utilized a murine model of late-gestation hypoxia-induced IUGR that reduced E18.5 fetal weight by 34%. Contrary to our hypothesis, uterine artery blood flow as measured in vivo by Doppler ultrasound was increased in mice housed under hypobaric hypoxia (385mmHg; 5500m) vs normoxia (760mmHg; 0m). Using wire myography, uterine arteries isolated from hypoxic mice had similar vasodilator responses to the two activators A769662 and acetylcholine as those from normoxic mice, although the contribution of an increase in nitric oxide production to uterine artery vasodilation was reduced in the hypoxic vs normoxic groups. Vasoconstrictor responses to phenylephrine and potassium chloride were unaltered by hypoxia. The levels of activated adenosine monophosphate-activated protein kinase (AMPK) were reduced with hypoxia in both the uterine artery and placenta as measured by western blot and immunohistochemistry. We concluded that the rise in uterine artery blood flow may be compensatory to hypoxia but was not sufficient to prevent fetal growth restriction. Although AMPK signaling was reduced by hypoxia, AMPK was still receptive to pharmacologic activation in the uterine arteries in which it was a potent vasodilator. Thus, AMPK activation may represent a new therapy for pregnancy complications involving reduced uteroplacental perfusion.

Effect of Omega-3 Fatty Acids on Hormonal Profile and Ovarian Stromal Blood Flow in Patients with Polycystic Ovary Syndrome

Background: In Polycystic ovary syndrome (PCOS) life style and dietary changes are recommended as the first line of management; however, the optimal nutritional management is not certain yet. Polyunsaturated fatty acids (PUFAs), particularly long-chain (omega-3) PUFAs, is known to improve overall human health and its widely used in managing infertility, but its role in PCOS management is still uncertain. Objective: The purpose of this study was to assess if omega-3 fatty acids supplementation for Polycystic ovary syndrome patients will have a positive effect on body weight, Hirsutism score, Menstrual cyclicity, hormonal status and Doppler flow to the Uterine and Ovarian stromal arteries.Study Design: A randomized prospective trial.Patients and Methods: A total of 67 patients with Polycystic ovary syndrome were randomized into two groups. Group I patients who received omega-3 fatty acid 1 gram daily capsules and group II patients who received no treatment for 3 months. Changes in weight, BMI, menstrual cycle length, modified Ferriman Gallway score, serum FSH, LH ,free Testosterone levels and Doppler of ovarian stromal and uterine arteries between baseline and the 3 months study period were compared between the 2 groups. Results: After 3 months supplementation with omega-3 fatty acid capsules, there was a statistically significant decrease in menstrual cycle length in the study group in comparison to the control group. Also, there was a statistically significant decrease in the pulsatility index (PI) of the uterine artery Doppler in the study group, but there was no change in the weight, BMI, ovarian stromal blood flow. Also, measures of FSH, LH and free testosterone did not show statistically significant changes for either group. Conclusion: Omega-3 fatty acids supplementation is effective in improving menstrual cyclicity and uterine artery blood flow in patients with PCOS and may be an helpful option for some patients with PCOS especially those who have defective endometrial receptivity and subsequent infertility or repeated miscarriages because of increased uterine artery resistance.

Maternal Blood Concentration of Tadalafil and Uterine Blood Flow in Pregnancy.

Background and Objectives: Tadalafil for treatment of fetal growth restriction (FGR) or preeclampsia is given once a day orally. The drug kinetics of tadalafil were investigated to determine the ideal dosage to promote uterine blood flow. Materials and Methods: We recruited five pregnant women with FGR or preeclampsia before administration of tadalafil, all of which were administered tadalafil (20 mg/day, once-daily dosing). The blood concentration of tadalafil was measured 1, 2, 4, 6, 8, and 24 h after administration, and uterine blood flow was measured before tadalafil administration and 2–4 and 20–24 h after. We then analyzed the correlation between tadalafil blood concentration and uterine artery blood flow. Results: The blood concentration of tadalafil correlated with uterine artery blood flow in pregnant women. The blood concentration of tadalafil and uterine artery blood flow decreased 5 h after administration of tadalafil. Conclusions: The blood concentration of tadalafil and uterine artery blood flow fluctuate in parallel, the latter was decreased by reduced blood concentration. Thus, a study of tadalafil administered twice a day in pregnant women will be needed to stabilize uterine artery blood flow.

Effects of tadalafil on the uterine artery of fetal growth restriction

Fetal growth restriction (FGR) is the most important cause of perinatal morbidity and mortality during the perinatal period. However, there is no established standard regarding the appropriate delivery time or treatment methods for fetuses with FGR. Reduced uterine arterial blood flow has been reported with FGR; however, if this is improved, then FGR may also be improved. Phosphodiesterase 5 inhibitors have vasodilating actions. When administered to the mother, they may improve FGR by improving fetal placental blood flow through improvements in uterine arterial blood flow.

Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth.

Substrate restriction during critical developmental windows of gestation programmes offspring for a predisposition towards cardiovascular disease in adult life. This study aimed to determine the effect of maternal resveratrol (RSV) treatment in an animal model in which chronic fetal catheterisation is possible and the timing of organ maturation reflects that of the human. Maternal RSV treatment increased uterine artery blood flow, fetal oxygenation and fetal weight. RSV was not detectable in the fetal circulation, indicating that it may not cross the sheep placenta. This study highlights RSV as a possible intervention to restore fetal substrate supply in pregnancies affected by placental insufficiency. Suboptimal in utero environments with reduced substrate supply during critical developmental windows of gestation predispose offspring to non-communicable diseases such as cardiovascular disease (CVD). Improving fetal substrate supply in these pregnancies may ameliorate the predisposition these offspring have toward adult-onset CVD. This study aimed to determine the effect of maternal resveratrol (RSV) supplementation on uterine artery blood flow and the direct effects of RSV on the fetal heart in a chronically catheterised sheep model of human pregnancy. Maternal RSV treatment significantly increased uterine artery blood flow as measured by phase contrast magnetic resonance imaging, mean gestational fetal and as well as fetal weight. RSV was not detectable in the fetal circulation, and mRNA and protein expression of the histone/protein deacetylase SIRT1 did not differ between treatment groups. No effect of maternal RSV supplementation on AKT/mTOR or CAMKII signalling in the fetal left ventricle was observed. Maternal RSV supplementation is capable of increasing fetal oxygenation and growth in an animal model in which cardiac development parallels that of the human.

Mechanotransduction and Uterine Blood Flow in Preeclampsia: The Role of Mechanosensing Piezo 1 Ion Channels.

There is a large increase in uterine arterial blood flow during normal pregnancy. Structural and cellular adjustments occur in the uterine vasculature during pregnancy to accommodate this increased blood flow through a complex adaptive process that is dependent on multiple coordinated and interactive influences and this process is known as "vascular remodeling." The etiology of preeclampsia involves aberrant placentation and vascular remodeling leading to reduced uteroplacental perfusion. The placental ischemia leads to development of hypertension and proteinuria in the mother, intrauterine growth restriction, and perinatal death in the fetus. However, the underlying source of the deficient vascular remodeling and the subsequent development of preeclampsia remain to be fully understood. Mechanoreceptors in the vascular system convert mechanical force (shear stress) to biochemical signals and feedback mechanisms. This review focuses on the Piezo 1 channel, a mechanosensitive channel that is sensitive to shear stress in the endothelium; it induces Ca2+ entry which is linked to endothelial nitric oxide synthase (eNOS) activation as the mechanoreceptor responsible for uterine vascular dilatation during pregnancy. Here we describe the downstream signaling pathways involved in this process and the possibility of a deficiency in expression of Piezo 1 in preeclampsia leading to the abnormal vascular dysfunction responsible for the pathophysiology of the disease. The Piezo 1 ion channel is expressed in the endothelium and vascular smooth muscle cells (VSMCs) of small-diameter arteries. It plays a role in the structural remodeling of arteries and is involved in mechanotransduction of hemodynamic shear stress by endothelial cells (ECs).