Israel Thaler

Changes in uterine blood flow during human pregnancy.

A transvaginal duplex Doppler ultrasonography system was used to measure blood flow characteristics in the ascending uterine artery before and during pregnancy. The system uses a 5 MHz Doppler transducer coupled to a 6.5 MHz imaging probe. There was a steady increase in volume flow rate in the left ascending uterine artery from a mean of 94.5 ml/min before pregnancy to a mean of 342 ml/min in late gestation (reflecting a 3.5-fold increase). With the assumption of equal flow on both uterine arteries, the fraction of the cardiac output that is distributed to these vessels was calculated to be 3.5% in early pregnancy and to reach 12% near term. The mean diameter of this vessel in the nonpregnant state was 1.6 mm, increasing to 3.7 mm toward term. The resistance to flow, expressed as the peak systolic to end-diastolic flow velocity ratio, declined from a mean of 5.3 in the nonpregnant state to a mean of 2.3 near term. These changes reflect the perpetual growth and development of the uteroplacental circulation, which provides the metabolic demands of the growing fetus throughout gestation.

Assessment of ovarian and uterine blood flow by transvaginal color Doppler in ovarian-stimulated women: correlation with the number of follicles and steroid hormone levels.

OBJECTIVE To study the changes that occur in vascular resistance to flow in the utero-ovarian circulation and their correlation with the number of follicles and steroid hormone levels in patients undergoing ovarian stimulation with gonadotropin. DESIGN In a prospective study, the impedance to flow in the intraovarian and uterine vessels was measured by means of transvaginal color flow Doppler imaging throughout the cycle. SETTING University-based IVF program. PATIENTS Eleven infertile patients undergoing ovarian stimulation with gonadotropin in preparation for IVF and ET. MAIN OUTCOME MEASURES Intraovarian, uterine, and arcuate artery blood flow velocity waveforms, follicular growth, and serum E2 and P concentrations throughout the cycle. RESULTS Pulsatility index (PI) of the intraovarian blood vessels and uterine artery decreased gradually during the follicular and luteal phase. The PI of the arcuate artery did not change significantly. The PI of the intraovarian blood vessels correlated with the number of follicles (> 15 mm; day of hCG). Serum E2 concentrations but not P demonstrated negative linear correlation with the PI of the intraovarian vessels and uterine artery. CONCLUSIONS Induced cycles are associated with decreased impedance to blood flow in the utero-ovarian circulation. Intraovarian PI correlates negatively at each stage of the cycle with the eventual number of preovulatory follicles. Little or no changes are observed when the response to ovarian stimulation is poor.

Uterine artery flow velocity waveforms and color flow imaging in women with perimenopausal and postmenopausal bleeding. Correlation to endometrial histopathology.

We performed Doppler studies of the uterine artery in 85 women with postmenopausal and perimenopausal bleeding. Sixty‐six women had non‐malignant changes and 19 women had malignant changes on histologic examination of the endometrium. Uterine fibroids were detected in 30 women. When malignant changes were detected in the endometrium, uterine artery resistance index was always below 0.83. The mean uterine artery resistance index was significantly lower in the group of women with pathologic changes of the endometrium (RI = 0.77±0.03) compared to the group with non pathologic changes (RI=0.85±0.08 p<0.01), excluding the women with uterine fibroids. The lowest mean resistance index in the uterine artery was observed in the group of women with uterine fibroids (RI = 0.60 ± 0.09 p< 0.001). In five of six patients with endometrial carcinoma blood vessels were detected around the myometrium by using color flow imaging. Their RI was always less than 0.5. In five patients, blood vessels were detected in uterine fibroids but their RI was always more than 0.5. All six women with endometrial carcinoma but only seven of 13 women with endometrial hyperplasia, had endometrial thickness greater than 5 mm. Doppler velocimetry of the uterine artery carries a high sensitivity (100%) in detecting pathological changes of the endometrium in patients presenting with postmenopausal or perimenopausal bleeding. The presence of high resistance in this vessel, may allow a more conservative approach in this group of patients.

Treatment of Ovarian Hyperstimulation Syndrome: the Physiologic Basis for a Modified Approach

A case of severe ovarian hyperstimulation syndrome (OHSS) secondary to human menopausal gonadotropin-human chorionic gonadotropin therapy is presented. Draining 4000 ml of exudate by abdominal paracentesis under real-time B-scan imaging induced a marked improvement in the patients condition. Fluids from the third space were rapidly excreted, renal function improved, and the patients weight decreased substantially. The underlying physiologic factors responsible for these changes are discussed. Other modes of treatment, including salt and water restriction and the use of volume expanders and diuretics, had no significant effect on the course of the syndrome. Paracentesis has a definite therapeutic value and is recommended in cases of OHSS with tense ascites.

Transvaginal embryo aspiration—a safe method for selective reduction in multiple pregnancies

OBJECTIVE To evaluate pregnancy outcome after transvaginal selective embryo aspiration and to compare the results with those reported previously with other techniques for selective abortion. DESIGN Retrospective case series. SETTING University-based in vitro fertilization (IVF) program. PATIENTS Nineteen women with multiple pregnancy who conceived after ovulation induction or IVF/gamete intrafallopian transfer. INTERVENTION Transvaginal ultrasound-guided aspiration of the embryo(s) was performed at 7 to 8 weeks of gestation. MAIN OUTCOME MEASURES Early and late complications related to the procedure, outcome of pregnancy, and birth weight. RESULTS In 18 cases, the initial number of embryos (3 to 7) was reduced to two. In 1 case, the number of embryos was reduced from 4 to 3. None of the remaining fetuses vanished after the procedure. One patient delivered at 25 weeks and all other patients delivered healthy, viable infants (a pregnancy loss rate of 5.3%). CONCLUSIONS Transvaginal embryo aspiration in early gestation appears to be a simple and relatively safe procedure for selective termination in patients with high-order multiple pregnancy. The cumulative loss rate of selective termination procedures previously reported by others is three times higher than the loss encountered in our series. This earlier procedure may be more acceptable to patients from emotional and religious points of view.

Maternal cerebral blood flow during normal pregnancy: a cross-sectional study.

OBJECTIVE Pregnancy is associated with substantial changes in the maternal circulatory physiology. Our aim was to investigate maternal cerebral blood flow (CBF) during normal pregnancies. STUDY DESIGN We prospectively measured maternal CBF in 210 low-risk pregnant women at different gestational ages, and in 15 nonpregnant women. CBF was assessed by measuring blood flow volume in the internal carotid artery (ICA) by dual-beam angle-independent digital Doppler ultrasound. RESULTS ICA blood flow volume increased during pregnancy from 318 mL/min ± 40.6 mL/min in the first trimester to 382.1 mL/min ± 50.0 mL/min during the third trimester, corresponding to CBF values of 44.4 and 51.8 mL/min(-1)/100 g(-1), respectively (P < .0001). CBF changes were associated with progressive decrease in cerebral vascular resistance and moderate increase in ICA diameter. CONCLUSION Maternal CBF is gradually increasing during normal pregnancy. Vasorelaxing impact of estrogens and other factors on cerebral vessels may explain the changes in CBF during pregnancy.

The effect of isosorbide dinitrate on placental blood flow and maternal blood pressure in women with pregnancy induced hypertension

The effect of isosorbide dinitrate (ISDN) on maternal and fetal circulation was assessed in 23 women with pregnancy induced hypertension (PIH). A double-blind randomized design was employed. Each woman was given a sublingual tablet of ISDN (5 mg) or placebo. Maternal blood pressure (BP) and heart rate (HR) were measured before and every 2 min after the medication or placebo, for a total of 20 min. Flow velocity waveforms in the uterine and umbilical arteries were recorded at the same time periods, using pulsed Doppler ultrasound. The ratio of peak systolic to end-diastolic flow velocity (S/D) in those vessels was calculated. After ISDN mean maternal BP fell from 103 +/- 1.8 mm Hg to 90.5 +/- 2.9 mm Hg at 14 min (P < .0001) and mean maternal HR increased from 97.3 +/- 3.8 beats/min to 115.7 +/- 3.5 beats/min at 12 min (P < .0001). The mean S/D in the umbilical artery fell from 3.07 +/- 0.33 to 2.58 +/- 0.23 at 8 min (P < .0007). The mean S/D in the uterine artery fell from 3.27 +/- 0.6 to 2.38 +/- 0.28 at 10 min (P < .0001). In seven of 12 women with an early diastolic notch in the uterine artery flow velocity waveform the notch diminished or disappeared within the first 6 min after the medication. No significant change in any of the measured parameters was observed in the placebo group. Our finding that ISDN altered maternal and fetal hemodynamics in PIH lends support to the further exploration of nitric oxide donors in the treatment and prevention of pregnancy induced hypertension.

N-acetyl-cysteine (NAC) attenuates LPS-induced maternal and amniotic fluid oxidative stress and inflammatory responses in the preterm gestation

OBJECTIVE Maternal infection is associated with oxidative stress and inflammation. We sought to determine whether N-acetyl-cysteine can decrease maternal oxidative stress and the inflammatory response in preterm gestation. STUDY DESIGN Pregnant rats 16 days, were treated with (1) lipopolysaccharide, (2) N-acetyl-cysteine 120 minutes after lipopolysaccharide, or (3) saline solution (intraperitoneal). Six hours after lipopolysaccharide administration, serum lipid peroxide formation (LPO), tumor necrosis factor-α, interleukin-6, and interleukin-1β levels in maternal serum and amniotic fluid were determined. RESULTS Lipopolysaccharide significantly increased maternal serum lipid peroxide formation (24-118.5 nmol/mL; P < .05), and maternal serum and amniotic fluid tumor necrosis factor-α, interleukin-6, and interleukin-1β. N-acetyl-cysteine treatment after lipopolysaccharide significantly attenuated lipid peroxide formation (47.5 nmol/mL) and proinflammatory cytokines response in maternal serum and amniotic fluid. CONCLUSION Maternal and amniotic fluid oxidative stress and inflammatory stimulation are attenuated by N-acetyl-cysteine even when administered after lipopolysaccharide. These results suggest that N-acetyl-cysteine may protect the fetus from adverse sequelae associated with inflammatory stimulation.

Real-time spectral analysis of the fetal EEG: a new approach to monitoring sleep states and fetal condition during labor.

Adverse perinatal events affecting cerebral functions are a major cause of neonatal mortality, morbidity, and long-term neurologic deficit. Intrapartum fetal EEG, which records fetal brain electrical activity, provides a monitoring modality for evaluating the fetal CNS during labor. In this study, we describe a new approach to such monitoring that is based on real-time spectral analysis of the fetal EEG during labor. Fourteen pregnant women with uncomplicated term pregnancies who went into labor participated in the study. Two suction-cup electrodes were applied to the fetal scalp at the occipitoparietal or parietal region after rupture of membranes. Real-time spectral analysis was used to determine the frequency and amplitude of the fetal EEG signal. The spectral edge frequency (SEF) was calculated as the frequency below which 90% of the power in the power spectrum resides. The average EEG amplitude and the SEF were displayed using the density spectral array technique. Fetal heart rate and intrauterine pressure were also measured. Two fundamental EEG patterns were identified: high-voltage slow activity and low-voltage fast activity. The SEF was found to be an excellent index of cyclic EEG activity. Fetal heart rate demonstrated increased variability and an elevated baseline during low-voltage fast activity, whereas both parameters decreased during high-voltage slow activity. During episodes of variable decelerations in the fetal heart rate, a decrease in the SEF was observed, accompanied by an increased EEG voltage. The results obtained substantiate the presence of sleep cycles in the human fetus. This kind of cortical activity monitoring may enable rapid alertness to cerebral hypoxia and allow for prompt intervention, thereby decreasing the risk for birth asphyxia and subsequent brain damage.

Basic principles and clinical applications of the transvaginal Doppler duplex system in reproductive medicine

ConclusionNew technological advances in the field of ultrasound imaging and in Doppler signal acquisition and analysis help to open new fields of investigation in reproductive medicine. One such example is the recent introduction of the transvaginal Doppler duplex system, which can be applied as a sensitive, noninvasive “flow probe” to evaluate hemodynamic changes in pregnant and nonpregnant patients. Another important development is the application of Doppler color flow mappping, which facilitates vessel recognition and localization. Such instruments are expensive at present and are mostly limited for research purposes. Further developments are likely to emerge once new instruments and new methods of data analysis become available. Further increases in image resolution and improved Doppler signal generation and processing will enable more accurate flow measurements. Another important field is invasive flow measurement, which could be developed for intraoperative and intravascular investigations, based on specialized probes and catheter-mounted transducers. At present further investigations are required for defining the normal ranges in the population and for establishing abnormal patterns. Once causative mechanisms are defined, various treatments may be offered, while monitoring the changes using the techniques described here.