Adverse outcome in women with thrombophilia and bilateral uterine artery notches

Discrepancies about a possible relationship between prothrombotic mutations and a decreased uteroplacental blood flow are present in literature. We prospectively evaluated a cohort of pregnant women (n = 41) with bilateral uterine artery notches and found that women with inherited thrombophilia showed a sixfold higher risk to have an adverse outcome than women without.     

Maternal serum placental isoferritin levels in pregnant women with abnormal uterine artery Doppler velocemitry

High levels of placental isoferritin (PLF), which is an immunosuppressive cytokine, have been demonstrated in the sera of pregnant women. In the current study, 41 pregnant patients at high risk for placento-vascular complications, such as preeclamptic toxemia (PET) and/or intrauterine growth retardation (IUGR) were preselected if abnormal uterine artery Doppler measurements appeared at the time of the 20th-22nd gestational week scan. Concomitantly, venous blood was collected from each patient. PLF serum concentrations were determined by specific enzyme-linked immunoadsorbent assay (ELISA). The PLF levels were compared to 44 healthy pregnant women at midgestation with uneventful pregnancy outcomes. The aim of the current study was to evaluate the contribution of PLF measurement in this preselected group. Following delivery, two subgroups of abnormal uterine artery Doppler waveforms were retrospectively defined. Twenty-one (51%) patients had normal outcomes, whereas 20 (49%) had pathological outcomes mainly complicated by PET and/or IUGR. Significant differences in PLF serum levels were observed between the control group (84+/-64 U/mL; median 84 U/mL) compared with those of the study subgroup with normal outcome (31+/-19 U/mL; median 23 U/mL) and with the pathological outcome subgroup (19+/-8 U/mL; median 17 U/mL) (p<0.05). Nineteen percent of the normal subgroup compared with 45% of the pathological subgroup were found to have a serum PLF concentration <19 U/mL. This cutoff level was achieved based on receiver operating characteristic (ROC) curve. The combination of abnormal uterine artery waveforms followed by low serum PLF <19 U/mL increased the positive predictive value to 63%, as compared with up to 30% positive predictive value only for the abnormal Doppler waveforms. The current preliminary results concur with previous studies suggesting that low PLF levels may reflect abnormal placentation. The exact contribution of PLF and uterine artery Doppler waveforms in monitoring patients for placento-vascular complications should be the design of a future, larger, prospective study.     

Uterine artery Doppler velocimetry in pregnant women with hypertension

Uterine and umbilical artery velocimetry was carried out on 71 women with hypertensive disorders in pregnancy. Three categories of hypertensive disease were diagnosed: chronic hypertension, preeclampsia, and chronic hypertension with superimposed preeclampsia. Clinical classifications describe the severity of disease effectively, primarily because the classification is based on the appearance of abnormal physical or laboratory findings. Doppler velocimetry of the uterine arteries shows that normal pregnancy occurs when the systolic/diastolic ratio is less than or equal to 2.6. When the ratio exceeds this level and there is a notch in the waveform, the pregnancy is complicated by stillbirth, premature birth, intrauterine growth retardation, and maternal preeclampsia. The positive and negative predictive value of the examination is 93% and 91%, respectively. It appears that this new technology will be an essential ingredient of optimum pregnancy surveillance.     

Association between uterine artery Doppler blood flow changes and arterial wall elasticity in pregnant women

Introduction: Uterine artery (UtA) Doppler velocimetry changes and increased arterial stiffness are associated with preeclampsia. We aimed to investigate the relation between UtA velocimetry changes and arterial stiffness in pregnant women.

Methods: Doppler velocimetry and photoplethysmographic digital pulse wave analysis (DPA) were performed in 173 pregnant women in the second or the third trimester, where UtA Doppler pulsatility index (PI), diastolic notching, and UtA score (UAS) combining notching and high PI were calculated. DPA stiffness parameters representing large arteries were ejection elasticity index (EEI) and b/a, small arteries dicrotic index (DI) and d/a, and global stiffness the aging index (AI).

Results: One hundred and thirty women had normal Doppler and 43 had diastolic notching, of whom nine had high PI. DI indicated increased stiffness in small arteries when notching was present (p?=?0.044) and showed a significant but weak correlation to UAS (p?=?0.025, tau 0.12). EEI and b/a indicated increased large artery stiffness (p?≤0.014), d/a small artery stiffness (p = 0.023), and AI a systemic stiffness (p = 0.040) when high PI.

Conclusion: High UtA PI was associated with increased systemic arterial stiffness, whereas notching was related to increased stiffness in small arteries only. This indicates pathophysiological differences between the two Doppler parameters.     

Low-molecular-weight heparin for thrombophilia in pregnant women.

OBJECTIVE: Low-molecular-weight heparin (LMWH) is the anticoagulant of choice during pregnancy because it is associated with a low incidence of osteoporosis and thrombocytopenia. Antithrombotic therapy has recently been used to prevent pregnancy loss in high-risk patients with evidence of acquired or congenital thrombophilia. The aim of the present study was to gain further information on the teratogenic potential of LMWH in this patient group. METHODS: The study population included 46 patients with a history of recurrent abortions, intrauterine fetal death or intrauterine growth restriction (IUGR) and severe early-onset preeclampsia. Patients with a history of thromboembolism or positive findings for thrombophilia were prescribed LMWH (enoxaparin sodium, 40 mg daily) in combination with low-dose aspirin (100 mg daily) in the first trimester (group 1, n=14) or the second trimester (group 2, n=17); the remaining 15 patients received low-dose aspirin alone (group 3). RESULTS: No significant differences were noted between the groups in the incidence of congenital malformations or abortions, IUGR or preterm deliveries. One infant in group 1 had familial bilateral postaxial polydactyly of the hands and one in group 3 had patent ductus arteriosus. CONCLUSION: Despite the small size of the study groups, our results support the assumption that the use of LMWH is safe, at least as a teratogenic agent, in patients with thrombophilia throughout pregnancy.     

Altered vascular function in healthy normotensive pregnant women with bilateral uterine artery notches

Objectives To assess endothelial function and vascular mechanical properties in normotensive pregnant women with high resistance in the uteroplacental circulation.
Design Cross-sectional prospective study.
Setting Doppler ultrasound laboratory at university department of obstetrics and gynaecology referral centre for high risk pregnancies.
Participants Forty-two caucasian normotensive pregnant women: 23 with uncomplicated pregnancies and 19 with bilateral uterine artery notches.
Methods Flow-mediated dilatation of the brachial artery was measured by ultrasonography at 25 gestational weeks. Concentrations of nitrite and nitrate in the plasma were established at 25 and 32 gestational weeks. The elastic properties of the common carotid artery, abdominal aorta and popliteal artery were measured with an ultrasonic echo-tracking system.
Results Flow-mediated dilatation at two minutes after cuff deflation was significantly lower in the bilateral notch group compared with the control group, 8.3% and 13.7%, respectively (   P = 0.0007  ). The ability to sustain vasodilatation was reduced in the bilateral notch group (   P = 0.02  ). Lower values of nitrite and nitrate in the plasma were found at 32 gestational weeks in the bilateral notch group than in the control group (mean 24.76 μM/L (SD 5.6) and 30.93 μM/L (8.2), respectively;   P = 0.008  ). Nitrite and nitrate levels tended to be lower in the bilateral notch group even at 25 gestational weeks (29.45 μM/L (8.3) and 35.73 μM/L (11.0) in the bilateral notch and control group, respectively;   P = 0.09  ). There was no difference in aortic, carotid or popliteal elasticity between the two groups.
Conclusions Healthy normotensive pregnant women with bilateral uterine artery notches show impaired endothelial function, but no differences in vascular mechanical properties.     

Assessment of cerebral hemodynamics in pregnant women by internal carotid artery pulsed Doppler velocimetry

To date, no studies have been done of serial changes in maternal cerebral hemodynamics during pregnancy. We used the noninvasive method of Doppler velocimetry to assess cerebral hemodynamics in pregnant women. Velocimetry measurements of the internal carotid artery were performed in 17 normal nonpregnant women and 77 women with uncomplicated pregnancies with a 4 MHz pulsed Doppler ultrasound system. Peak systolic and mean velocities in the first and second trimesters were almost the same as those in nonpregnant women, whereas they became slower in the third trimester. Pulsatility index from 4 to 31 weeks' gestation was significantly higher than in nonpregnant women, but fell to the nonpregnant value after 32 weeks. Doppler velocimetry was found to be an extremely useful method of cerebrohemodynamic evaluation in pregnant women.     

Prediction of superimposed preeclampsia using uterine artery Doppler velocimetry in women with chronic hypertension

OBJECTIVE: To assess the role of uterine artery (UtA) Doppler to predict superimposed preeclampsia in women with chronic hypertension. METHODS: In a cohort of 182 women with chronic hypertension, UtA Doppler studies were performed before 25 weeks (mean 19.7 +/- 2.1 weeks) and repeated later in pregnancy (mean 28.5 +/- 3.7 weeks). RESULTS: The incidence of preeclampsia was 13% (24/182). Rates of preeclampsia increased with advancing gestation of abnormal UtA Doppler: 7% when UtA Doppler were normal at early exam, 18% when abnormal at early exam, and 28% when abnormal at late exam (Chi-square for trend: P < 0.001). The rate of preeclampsia among 40 women with abnormal early but normal late UtA Doppler was similar to that of women with normal findings at early exam (8 vs 7%; P = 1.00). Logistic regression analysis showed that the ability of UtA Doppler to predict preeclampsia was independent from other variables [Odds Ratio (OR) 7.1, 95% Confidence Interval (CI) 2.6-18.9). Receiver operating characteristic (ROC) curve identified a UtA value of 0.58 as the optimal threshold for the prediction of preeclampsia. CONCLUSION: The later in pregnancy the abnormal UtA Doppler findings are observed, the greater the risk of preeclampsia. Normalization of UtA Doppler after 25 weeks reduces the risk of preeclampsia to 8%.     

早发型重度子(癎)前期母体子宫动脉及胎儿血流动力学的研究

目的通过观察分析早发型重度子痢前期母儿血液动力学变化特点，结合其母儿预后，进一步探讨母儿血流动力学监测在早发型重度子痢前期的临床诊治及预后估计中的应用价值。方法采用前瞻性病例一对照研究方法，应用彩色多普勒超声对36例早发型重度子痢前期和72例正常同期孕妇进行血液动力学有关参数测定（包括UA-S／D、UA—PI、MCA—S／D、MCA-PI、UtA—S／D、UtA-PI），并结合其预后进行统计分析。结果在早发型重度子痢前期组和正常妊娠组，胎儿UA、MCA血流及孕妇UtA血流的S／D、PI值均随着妊娠的进展，呈逐渐下降的趋势，早发型重度子痢前期的UA—S／D，UA-PI，UtA-S／D，UtA-PI比正常妊娠时明显增高（P〈0．05），而MCA-S／D和MCA—PI在妊娠33周前则比正常妊娠组降低，妊娠33周后有显著性差异。当早发型重度子痢前期出现母胎血流动学变化时，围产儿不良结局的发生率高于正常妊娠组。本研究中有7例胎儿产前出现脐动脉舒张末期血流缺如（AEDV），全部合并FGR，围产儿死亡6例。结论母胎血流动学参数在早发型重度子痢前期时常发生明显的改变，并与不良的围产儿结局有关，AEDV的出现意味着胎儿循环已出现或临近失代偿阶段，警示预后不良。     

Exercise-induced changes in uterine artery blood flow, as measured by Doppler ultrasound, in pregnant subjects

Eleven healthy women with singleton pregnancies between 16 and 28 weeks gestation were continuously exercised, in a graded fashion, by stationary bicycle to a predetermined target heart rate. Before and within 3 minutes after exercise, uterine artery waveforms were identified from a semirecumbent position using a 3.5 MHz continuous-wave Doppler transducer coupled to an Angioscan spectrum analyzer. The ratio of peak systolic to end-diastolic frequency (A/B ratio) was utilized to assess qualitative differences in flow before and after exercise. No statistically significant changes in A/B ratios were noted. This study suggests that nonexhaustive maternal exercise does not compromise uterine artery blood flow in healthy, low-risk pregnant subjects.     

Serum relaxin levels are reduced in pregnant women with a history of recurrent miscarriage, and correlate with maternal uterine artery Doppler indices in first trimester

Objectives

Defective implantation is a mechanism for recurrent pregnancy loss (RPL). We sought to determine whether the serum expression of human relaxin-2 (RLX) is impaired in women with a history of RPL.

Study design

Employing a prospective case-controlled design we studied 20 pregnant women with a history of RPL and 20 age-matched women with no history of RPL (NRPL). We measured serum relaxin-2 levels by ELISA at 6–8, 10–12, 20, and 34 weeks gestation and in cord blood, and maternal uterine artery Doppler resistance index (RI) at ≥10 weeks gestation.

Results

Relaxin rose to a peak at 12 weeks, and gradually declined towards term. At all gestations, women with a history of RPL had lower RLX levels than women without. At 10–12 weeks gestation, uterine artery RI correlated with serum RLX for both RPL and NRPL. In the NRPL group at 10–12 weeks the presence of a notched waveform was associated with higher RLX levels than the absence of a notch (mean 2.1 ng/ml vs. 1.3 ng/ml, P < 0.05) and also at 20 weeks (2.1 ng/ml vs. 0.95 ng/ml, P < 0.05) but no such difference was seen in the RPL group. Umbilical venous RLX was 4-fold higher in the RPL group than the NRPL group.

Conclusion

Women with a history of RPL demonstrate attenuated levels of serum RLX across all pregnancy trimesters. How dysregulated RLX metabolism may contribute to adverse pregnancy outcome in RPL requires further investigation.     

Etiology and diagnostic problems in pregnant women with uterine myomas

OBJECTIVES: Authors present different aspects of coexistence of uterine myomas with pregnancy. In the article special attention was given to etiology, complications and practical methods of treating pregnant women. DESIGN: The occurrence of uterine myomas is connected with the period of hormonal activity of the ovaries, so with the female reproductive age. Uterine myomas are tumors whose actions are dependent on hormonal action of estrogens which are often characterized by acceleration of growth especially in the first trimester of pregnancy. The dynamics of uterine myomas is specifically different and independent of neither the original size nor localisation of the myomas. During the antenatal period together with the involutional changes of the uterine muscle there is an observed decrease in the size of the myomas. MATERIALS: Based on literature, the effect of uterine myomas on fertility of women, pregnancy follow-up, development of foetus and occurrence of perinatal complications was analysed. The diagnostic methods as well as procedures underwent analysis depending on the localisation of the changes. The effect of nonpharmacological and surgical therapy were compared in pregnant women and those planning to conceive. CONCLUSION: In modern obstetrics, pregnancy complications as a result of uterine myomas is still actual and there is a lot of controversy on this topic. This is because up until now, there is no generalised opinion on therapeutic procedures and ways of resolving pregnancy complicated by the presence of uterine myomas.     

Frequency cesarean section in pregnant women with uterine myoma

We were investigated in the connection of the frequency of cesarean sections at pregnant women with uterus myomatous and physiological pregnancies. 189 pregnant patients with myomas have been analyzed retrospectively 72 women with physiological pregnancies belong to the controlled group. Our results didn't confirm the higher risk of cesarean sections in analyzed group.     

彩色多普勒超声评价反复种植失败患者子宫动脉血流特点研究

目的 探讨反复种植失败（recurrent implantation failure,RIF）患者子宫动脉血流及其相关因素的特点。方法 选取2012年3月至2013 年8月于烟台毓璜顶医院生殖医学科因输卵管因素行体外受精-胚胎移植（in vitro fertilization- embryo transfer,IVF－ET）治疗的RIF患者（RIF组,n=40）为研究对象;同期IVF－ET治疗首次助孕成功的患者（首次IVF助孕成功组,n=40）,首次IVF－ET助孕治疗失败患者（首次IVF助孕失败组,n=40）为对照组,进行回顾性分析。于注射人绒毛膜促性腺激素（human chorionic gonadotropin,HCG）日行经阴道彩色多普勒超声检查,测量子宫动脉搏动指数（uterine artery pulsatility index,UAPI）、子宫内膜厚度,并同时测定血雌二醇及孕酮值。比较三组间相关指标的差异。结果 RIF组患者UAPI 3.3±0.4,显著高于同期IVF-ET治疗首次助孕成功组2.3±0.5及失败组UAPI 2.4±0.4,差异有统计学意义（P<0.05）,而IVF-ET治疗首次助孕成功组与失败组相比,差异无统计学意义（P＞0.05）。3组间的子宫内膜厚度、雌二醇及孕酮值差异无统计学意义（P>0.05）。结论 HCG日测定UAPI有助于评价子宫内膜容受性,预测种植率。