Estetrol-Drospirenone combination oral contraceptive: a clinical study of contraceptive efficacy, bleeding pattern and safety in Europe and Russia.

OBJECTIVES: To assess the contraceptive efficacy, bleeding pattern and safety of a combined oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg. DESIGN: Multicenter, open-label, phase 3 trial. SETTING: Sixty-nine sites in Europe and Russia. POPULATION: Sexually active women aged 18-50 years with regular menstrual cycles and body mass index ≤35 kg/m2 . METHODS: E4/DRSP was administered in a 24 active/4 placebo regimen for up to 13 cycles. Visits were scheduled during Cycles 2, 4, 7 and 10 and after completing treatment during which adverse events (AEs) were collected. Participants recorded medication intake, vaginal bleeding/spotting, use of other contraceptive methods and sexual intercourse on a daily diary. MAIN OUTCOME MEASURES: Pearl Index (PI) for women 18-35 years (overall and method-failure), bleeding pattern and AEs. RESULTS: A total of 1553 women aged 18-50 years, including 1353 from 18 to 35 years old, received the study medication. PI was 0.47 pregnancies/100 woman-years (95% CI 0.15-1.11); method failure PI was 0.29 pregnancies/100 woman-years (95% CI 0.06-0.83). Scheduled bleeding/spotting occurred in 91.9-94.4% of women over Cycles 1 to 12 and lasted a median of 4-5 days per cycle. The percentage of women with unscheduled bleeding/spotting episodes decreased from 23.5% in Cycle 1 to <16% from Cycle 6 onwards. The most common AEs were headache (7.7%), metrorrhagia (5.5%), vaginal haemorrhage (4.8%) and acne (4.2%). One treatment-related serious AE was reported, a lower extremity venous thromboembolism. One-hundred and forty-one (9.1%) women discontinued study participation because of treatment-related adverse events. CONCLUSION: E4/DRSP provides effective contraception, a predictable bleeding pattern and a favourable safety profile. TWEETABLE ABSTRACT: A phase 3 trial with E4/DRSP shows high contraceptive efficacy, a predictable bleeding pattern and favourable safety profile.

Breath holding test in preeclampsia: lack of evidence for altered cerebral vascular reactivity.

Twenty-five healthy and thirty-one preeclamptic pregnant women were assessed by means of transcranial Doppler sonography. Resting cerebral blood flow velocities in the middle cerebral arteries were measured followed by a repeat measurement 30 s after breath holding. Absolute blood flow velocities and per cent changes after breath holding procedure were compared between the groups. Absolute blood flow velocities were higher in preeclamptic pregnant women both at rest and after breath holding. The percent increase in cerebral blood flow velocity after breath holding (cerebral vascular reactivity) was similar in the two groups. Our data suggest that cerebral vascular reactivity is preserved in pregnant women with preeclampsia.

[Doppler evaluation of the fetal arterial circulation: reference values of the Resistance Index and Pulsatility Index between the 28th and 41st weeks of gestation]. / A magzat artériás vérkeringésének ultrahangvizsgálata: a rezisztenciaindex és a pulzatilitási index referenciaértékei a terhesség 28. és 41. hete között.

The authors established reference ranges for the Resistance Index and the Pulsatility Index of the umbilical artery, the fetal descending aorta and the middle cerebral artery in order to facilitate the uniform evaluation of the Doppler ultrasound examination in obstetrics. 164 patients with uncomplicated pregnancies between the 28th and 41st weeks of gestation were recruited for the longitudinal assessment of Doppler Resistance Indices and Pulsatility Indices in the fetal and umbilical arteries. Data were retrospectively analysed in order to establish the weekly mean values and standard deviations. The mean values of the indices in three periods (I.: 28-31, II.: 32-36, III.: 37-41 weeks) were compared. The normal haemodynamic resistance is reflected by the Doppler indices within the weekly mean +/- 2SD range. The results designate decreasing haemodynamic impedance in the umbilical and in the middle cerebral arteries while the resistance to the blood flow in the abdominal aorta is constant throughout the third trimester of gestation. The introduction and the clinical application of the reference values provides appropriate interpretation of the physiologic fetal blood flow patterns which is the prerequisite of the diagnostic accuracy of the Doppler ultrasound in obstetrics.

[Open heart surgery with extracorporeal circulation during pregnancy]. / Szívmútét extracorporalis keringéssel és terhesség.

The incidence of heart disease in pregnancy has been gradually falling during the last three decades. Cardiopathy still remains a prominent cause of maternal and fetal morbidity and mortality. Most patients know about their heart disease long before conception, even though the potential risk factors of deteriorating cardiac function during pregnancy are generally not emphasized. These women when pregnant may develop heart failure due to the increased cardiorespiratory requirements. When medical therapy proves insufficient heart surgery becomes mandatory to save the patient's life. The pregnant state is not optimal for cardiac surgery as the principle interest of the mother and the fetus is different. We report on two pregnant patients who underwent unavoidable heart surgery with cardiopulmonary bypass and review the literature regarding the optimal management of open-heart operation in pregnancy aiming to decrease the feto-maternal mortality. The successful outcome of the cardiac surgery on pregnant women is determined by the severity of the preexisting disease, the surgical techniques, and the circumstances of the cardiopulmonary bypass. The best possible results can be achieved by providing preconceptional counseling for the cardiopathic patients regarding the relation between the preexisting risk factors and the adverse maternal and neonatal outcome. When heart surgery is mandatory in pregnancy the careful technical precautions and the continuous cardiotocography help to minimize fetal complications during the cardiopulmonary bypass (CPB).

Comparison of cerebral blood flow velocity as measured in preeclamptic, healthy pregnant, and nonpregnant women by transcranial Doppler sonography.

AIM: To test the hypothesis that the middle cerebral artery blood flow velocity (MCAV) is altered in preeclamptic pregnant women as compared with healthy pregnant and nonpregnant women. METHODS: Preeclamptic (n = 21) and healthy pregnant (n = 17) as well as healthy nonpregnant (n = 29) women underwent transcranial Doppler MCAV measurements. The mean MCAV values were compared between the different groups. Anova combined with Bonferroni correction was used for statistical analysis. RESULTS: The MCAV was significantly higher in nonpregnant women (mean +/- SE 73.0 +/- 2.12 cm/s) as compared with healthy pregnant women (67.0 +/- 1.8 cm/s, p = 0.0356). Preeclamptic women showed significantly higher MCAV values (83.5 +/- 2.1 cm/s) as compared with nonpregnant females (73.0 +/- 2.12 cm/s, p = 0.0014). Similar to nonpregnant women, healthy pregnant women showed lower MCAV values (67.0 +/- 1.8 cm/s) as compared with preeclamptic women (83.5 +/- 2.1 cm/s, p = 0.001). After Bonferroni correction the MCAV values in patients suffering from preeclampsia were still statistically significantly higher as compared with the two other groups. CONCLUSIONS: We detected increased resting MCAV values in pregnant women with preeclampsia. In our opinion, this finding refers to arteriolar dilation of the resistance vessels of the brain. Further studies are needed to prove altered vasoreactivity responses of the brain resistance arterioles in preeclampsia.

[The role of uterine and umbilical artery Doppler velocimetry for the early detection of pathologic pregnancy]. / Az arteria uterina és az arteria umbilicalis Doppler-ultrahangvizsgálatának szerepe a kóros terhesség korai felismerésében.

Pregnancy induced hypertension remains the most frequent reason of maternal and fetal complications. Recent studies of the entire pathophysiology of the abnormal implantation proved association between the impaired placental performance and the reduced uteroplacental circulation. Therefore the Doppler examination of uterine and umbilical blood flow may provide the early recognition of high-risk pregnancies complicated by maternal hypertension and fetal intrauterine growth retardation. The authors endeavor to describe the details and characteristics of uteroplacental haemodynamic changes during the course of physiologic and defective implantation. On the basis of the currently available scientific publications they summarize the role of the uterine and umbilical artery Doppler velocimetry as a screening tool in the detection of the consequences of the impaired uteroplacental perfusion. They conclude that abnormal velocity waveforms obtained from the uterine and umbilical arteries may help to improve the efficacy of the prenatal care and the perinatal outcome as well. The clinical benefits of this screening method will be precisely defined on the basis of further multicenter studies in Hungary.

Assessment of cerebral hemodynamics during roll over test in healthy pregnant women and those with pre-eclampsia.

OBJECTIVE: To compare cerebral autoregulatory responses obtained during roll over tests in healthy pregnant women and those with pre-eclampsia in order to assess the middle cerebral artery velocity changes in relation to the roll over test in normotensive and pre-eclamptic women. PARTICIPANTS: Twenty-two healthy pregnant women and 26 with pre-eclampsia underwent transcranial Doppler measurements of the middle cerebral artery. METHODS: Systolic, mean and diastolic blood flow velocities and mean arterial blood pressures were recorded in the left lateral position and five minutes after turning to the supine position. Absolute values of mean blood flow velocities, mean arterial blood pressure values and calculated cerebral blood flow indices as well as cerebrovascular resistance area products were compared at different positions among the groups. RESULTS: Mean arterial blood pressure increased in both groups while turning from the left lateral to the supine position. In women with pre-eclampsia both mean arterial blood pressure and absolute values of mean blood flow velocity values were higher in both positions, compared with healthy pregnant women. In both groups, changing the position resulted in a decrease of absolute values of mean blood flow velocities. Calculated cerebral blood flow indices did not change, while cerebrovascular resistance area products increased significantly in the groups during roll over testing. In women with pre-eclampsia, the increase of cerebrovascular resistance area products was more pronounced as compared with healthy pregnant women. CONCLUSIONS: In women with pre-eclampsia roll over test results in an increase of the mean arterial blood pressure, which is accompanied by a decreased mean blood flow velocity in the middle cerebral artery. Further studies are needed to clarify the pathophysiological background of cerebral haemodynamic changes in pre-eclampsia.

Effect of hyperventilation on cerebral blood flow velocity in preeclamptic pregnancies: is there evidence for an altered cerebral vasoreactivity?

The purpose of this study was to investigate cerebral arteriolar vasoreactivity function in preeclampsia. Preeclamptic (n = 26) and healthy pregnant (n = 22) women underwent transcranial Doppler sonography of the middle cerebral artery at rest and after 60 seconds of hyperventilation (HV). Systolic, diastolic, and mean blood flow velocities were recorded. The percentage change of the blood flow velocities after HV was calculated. Mean blood flow velocity of the middle cerebral artery was higher in preeclamptic women as compared with healthy pregnant women. No difference could be detected in percentage change of middle cerebral artery blood flow velocities after HV between the two groups. There is no evidence of a small-vessel vasoconstriction among preeclamptic patients. The role of vasoconstriction of the large cerebral arteries and vasodilation of the resistance arterioles, as well as a combination of these 2 pathomechanisms, in determining cerebral blood flow in preeclampsia and eclampsia should be investigated in further studies.

[Alterations of cerebral hemodynamics in pre-eclampsia and eclampsia]. / Az agyi hemodinamika változása praeeclampsiában és eclampsiában.

Clinical and pathophysiological aspects of preeclampsia and eclampsia have been found to be responsible for the majority of maternal mortality, but the exact role of them is still unknown. It is conceivable that altered cerebral hemodynamics and autoregulation is responsible for the neurological complications. The background of the cerebral processes is still not clarified. Authors summarize the changes of cerebral circulation which develop during preeclampsia and explanations for cerebral hemodynamic alterations during normal, preeclamptic and exclamptic pregnancies are discussed. They conclude that there is no accurate method for predicting eclampsia. Cerebral hemodynamical studies are only helpful in better understanding the pathophysiological background of preeclampsia-eclampsia syndrome at present.