Assessment of sub-endometrial blood flow parameters following dydrogesterone and micronized vaginal progesterone administration in women with idiopathic recurrent miscarriage: a pilot study.

AIM: To evaluate differences in uteroplacental blood flow and pregnancy outcome in women with idiopathic recurrent spontaneous miscarriage (IRSM) following administration of micronized vaginal progesterone and oral dydrogesterone. METHODS: One hundred and thirty-three women (aged 23-40 years) who had had early miscarriages and spontaneous conception participated. Oral dydrogesterone (group A, n = 51) and micronized vaginal progesterone (group B, n = 50) were administrated for luteal support and compared. Pregnant women without history of recurrent miscarriage served as controls (group C, n = 32). The outcome measures consisted of endometrial blood flow parameters by Doppler indices and ongoing pregnancy rate. RESULTS: Before progesterone supplementation, resistivity index (RI) and pulsatility index (PI) were found to be significantly higher in groups A and B as compared to controls. Although statistically not significant, end diastolic velocity (EDV) and systolic/diastolic (S/D) ratio was found to be superior in controls than IRSM women. Peak systolic velocity (PSV) was comparable between IRSM and non-IRSM groups. Following progesterone supplementation, groups A and B showed a highly significant reduction in RI, PI and an increase in EDV. A relative increase in the value of PSV was observed in group A as compared to group B. There was remarkable difference in S/D in both groups. Although not statistically significant, group C showed reduction in RI, PI, PSV, EDV and S/D ratio. Pregnancy salvage rates were higher in group A (92.0%) as compared to group B (82.3%). CONCLUSION: Progesterone supplementation appears to lower vascular resistance in women with IRSM. Oral dydrogesterone appears to be equally effective in improving endometrial blood flow as compared with micronized progesterone.

Stereological assessment of placental morphology in intrahepatic cholestasis of pregnancy.

OBJECTIVE: To apply stereology for the detection of possibly morphological abnormalities in placentas of women with intrahepatic cholestasis of pregnancy (ICP). STUDY DESIGN: Prospective case-control study of placentas from untreated and UDCA-treated ICP, respectively, and normal pregnancies, examined for morphological differences by systematic random sampling generated by computerized stereology methodology. MAIN OUTCOME MEASURES: Volume of placenta, surface area of terminal villi and capillaries, volume fraction of collagen, number of syncytial knots, and chorangiosis. RESULTS: Surface area of terminal villi and capillaries, and number of syncytial knots were higher in placentas from all ICP, as compared to controls (p < 0.01). A reduction of collagen was found in placentas from UDCA-treated ICP, both in comparison to placentas from untreated ICP and controls (p < 0.05). CONCLUSION: ICP affects the placenta morphologically as shown by increased terminal villous and capillary surface area, and number of syncytial knots.

Folic acid is positively associated with uteroplacental vascular resistance: the Generation R study.

BACKGROUND AND AIMS: Periconception folic acid supplementation may influence early placentation processes and thereby the occurrence of hypertensive pregnancy disorders. For this reason we examined the associations between periconception folic acid supplementation and uteroplacental vascular resistance, blood pressure, and the risks of gestational hypertension and preeclampsia, in 5993 pregnant women, participating in a population-based cohort study. METHODS AND RESULTS: Folic acid supplementation was assessed by questionnaire. Mean pulsatility index (PI) and resistance index (RI) of the uterine (UtA) and umbilical arteries (UmA) were measured by Doppler ultrasound in mid- and late pregnancy. Systolic and diastolic blood pressures (SBP, DBP) were measured in early, mid- and late pregnancy. Compared to women who did not use folic acid, preconception folic acid users had a slightly lower UtA-RI in mid-pregnancy [ß -0.02, 95% confidence interval (CI) -0.03, -0.01] and late pregnancy [ß -0.02, 95% CI -0.03, -0.001], a lower UtA-PI in mid-pregnancy [ß -0.06, 95% CI -0.1, -0.03] and late pregnancy [ß -0.03, 95% CI -0.05, -0.01], as well as tendencies towards a lower UmA-PI in mid-pregnancy [ß -0.02, 95% CI -0.04, -0.001] and late pregnancy [ß -0.01, 95% CI -0.02, 0.01]. Additionally, these women had slightly higher SBP and DBP throughout pregnancy. Neither the patterns of blood-pressure change during pregnancy, nor the risk of gestational hypertension and preeclampsia differed between the folic acid categories. CONCLUSION: Periconception folic acid supplementation is associated with lower uteroplacental vascular resistance and higher blood pressures during pregnancy. The effects are small and within physiologic ranges and seem not associated with the risk of hypertensive pregnancy disorders.

Uterine and fetal blood flow indexes and fetal growth assessment after chronic estrogen suppression in the second half of baboon pregnancy.

Although estrogen regulates important aspects of maternal cardiovascular physiology, the role of estrogen on uteroplacental and fetal blood flow is incompletely understood. This study tested the hypothesis that chronically suppressing endogenous estrogen production during the second half of baboon pregnancy alters uterine and fetal blood flow dynamics assessed by ultrasonography. Pregnant baboons were untreated or treated daily with the aromatase inhibitor letrozole or letrozole plus estradiol on days 100-160 of gestation (term = 184 days). Blood flow dynamics were determined by Doppler ultrasonography on day 60 and longitudinally between days 110 and 160 of gestation. Letrozole decreased maternal serum estradiol and estrone concentrations by 95% (P < 0.001). Fetal growth biometrical parameters increased (P < 0.001) between days 110 and 160 of gestation and were similar in untreated and letrozole-treated animals. Uterine, umbilical, and fetal middle cerebral artery pulsatility index and resistance index declined (P < 0.01) by 30-50% and uterine artery volume flow increased sixfold (P < 0.001) between days 60 and 160, but values were similar in untreated, letrozole-treated, and letrozole plus estradiol-treated baboons. Thus uterine and fetal artery blood flow indexes, uterine artery volume flow, and fetal growth were maintained at normal levels despite chronic estrogen suppression in the second half of baboon pregnancy. This suggests that elevated levels of endogenous estrogen are not required to maintain low impedance blood flow within the uteroplacental vascular bed during the second half of nonhuman primate pregnancy.

Acute effect of cigarette smoking on placental circulation - a study by carbon-monoxide measurement and Doppler assessment.

OBJECTIVE: Carbon-monoxide (CO) decreases placental vascular impedance. We assessed the consequences of smoking-induced temporary maternal CO-increase on fetal and placental circulation. STUDY DESIGN: In a prospective study twenty-nine smoking pregnant women and their fetuses were evaluated. We determined the changes in maternal blood CO levels after smoking, and the concomitant changes in maternal and fetal circulation. Changes in fetal heart rate, uterine artery (UTA), middle cerebral artery (MCA), and descending aorta (DA) flow were measured by Doppler velocimetry. Changes in maternal CO level and umbilical flow value were assessed by paired t-test. The correlation between CO level and placental flow was assessed by partial correlation test. RESULTS: CO level increased (mean +/-SD 1.7 +/- 0.065% vs. 2.36 +/- 0.89, p<0.0001). Nicotine-related maternal circulatory parameters changed significantly, but uterine flow values remained unchanged. Fetal heart rate increased, while flow in MCA and DA showed no change. CO-dependent umbilical artery impedance remained unchanged (Pulsatility Index: 0.956 +/- 0.18 vs. 0.948 +/- 0.21). Partial correlation between CO level and umbilical arterial impedance showed no significance (r:-0.324). CONCLUSION: Despite significant CO elevation, the mainly CO-regulated placental flow remained unchanged.

Assessment of volume preload on uteroplacental blood flow during epidural anaesthesia for Caesarean section.

BACKGROUND AND OBJECTIVE: Epidural and spinal anaesthesia are the preferred mode of anaesthesia for Caesarean section. Volume preloading is recommended to prevent maternal hypotension and a reduction in uteroplacental blood flow, although positive effects of volume preloading on maternal cardiac output and arterial pressure are debatable. Doppler measurements of the umbilical artery beyond deriving pulsatility indices are not routinely performed. METHODS: After Institutional Review Board approval and written informed consent, 14 consecutiVe women with epidural anaesthesia for Caesarean section received either hydroxyethyl starch 500 mL or gelatine 500 mL. Haemodynamic variables monitored were maternal arterial pressure, maximal blood flow velocity and pulsatility indices of the uterine artery derived from Doppler measurements. CONCLUSIONS: Maternal arterial pressure and pulsatility indices in both groups did not change from baseline after intravenous colloid infusion. However, uterine blood flow increased significantly in both groups. The effectiveness of volume preloading may therefore be better described by changes in maximum uterine blood flow velocity than by pulsatility indices or maternal arterial pressure.