L. Cabero

Predictive value of angiogenic factors and uterine artery Doppler for early- versus late-onset pre-eclampsia and intrauterine growth restriction

To investigate potential differences in the prediction of early‐ vs. late‐onset pre‐eclampsia and/or intrauterine growth restriction (PE/IUGR) by second‐trimester uterine artery Doppler examination, and measurement of maternal serum placental growth factor (PlGF) and soluble fms‐like tyrosine kinase 1 (sFlt1).

A modified myocardial performance (Tei) index based on the use of valve clicks improves reproducibility of fetal left cardiac function assessment

To determine whether a modified myocardial performance index (Mod‐MPI) involving assessment of the movements (clicks) of the mitral valve (MV) and aortic valve (AV), improves intra‐ and interobserver agreement as compared to the previously reported method for MPI estimation.

Prevalence of neurological damage in monochorionic twins with selective intrauterine growth restriction and intermittent absent or reversed end-diastolic umbilical artery flow

To assess the incidence of parenchymal lesions on early and late neonatal brain scans and its association with the presence or absence of intermittent absent or reversed end‐diastolic umbilical artery flow velocity (A/REDV) in monochorionic twins complicated by selective intrauterine growth restriction (IUGR), as compared to dichorionic twins and monochorionic twins without selective IUGR.

Female-specific features of recombinational double-stranded DNA repair in relation to synapsis and telomere dynamics in human oocytes

Chromosome segregation errors are a significant cause of aneuploidy among human neonates and often result from errors in female meiosis that occur during fetal life. For the latter reason, little is known about chromosome dynamics during female prophase I. Here, we analyzed chromosome reorganization, and centromere and telomere dynamics in meiosis in the human female by immunofluorescent staining of the SYCP3 and SYCP1 synaptonemal complex proteins and the course of recombinational DNA repair by IF of phospho-histone H2A.X (γ-H2AX), RPA and MLH1 recombination proteins. We found that SYCP3, but not SYCP1, aggregates appear in the preleptotene nucleus and some persist up to pachytene. Telomere clustering (bouquet stage) in oocytes lasted from late-leptotene to early pachytene—significantly longer than in the male. Leptotene and zygotene oocytes and spermatocytes showed strong γ-H2AX labeling, while γ-H2AX patches, which colocalized with RPA, were present on SYCP1-tagged pachytene SCs. This was rarely seen in the male and may suggest that synapsis installs faster with respect to progression of recombinational double-strand break repair or that the latter is slower in the female. It is speculated that the presence of γ-H2AX into pachytene highlights female-specific peculiarities of recombination, chromosome behavior and checkpoint control that may contribute to female susceptibility for aneuploidy.

Incidence and characteristics of umbilical artery intermittent absent and/or reversed end-diastolic flow in complicated and uncomplicated monochorionic twin pregnancies.

To evaluate the incidence and clinical relevance of intermittent absent and/or reversed diastolic flow on umbilical artery Doppler in different groups of monochorionic twin pregnancies.

Dynamics of cohesin proteins REC8, STAG3, SMC1β and SMC3 are consistent with a role in sister chromatid cohesion during meiosis in human oocytes

BACKGROUND Sister chromatid cohesion is essential for ordered chromosome segregation at mitosis and meiosis. This is carried out by cohesin complexes, comprising four proteins, which seem to form a ring-like complex. Data from animal models suggest that loss of sister chromatid cohesion may be involved in age-related non-disjunction in human oocytes. Here, we describe the distribution of cohesins throughout meiosis in human oocytes. METHODS We used immunofluorescence in human oocytes at different meiotic stages to detect cohesin subunits REC8, STAG3, SMC1 beta and SMC3, [also synaptonemal complex (SC) protein 3 and shugoshin 1]. Samples from euploid fetuses and adult women were collected, and 51 metaphase I (MI) and 113 metaphase II (MII) oocytes analyzed. SMC1 beta transcript levels were quantified in 85 maturing germinal vesicle (GV) oocytes from 34 women aged 19-43 years by real-time PCR. RESULTS At prophase I, cohesin subunits REC8, STAG3, SMC1 beta and SMC3 overlapped with the lateral element of the SC. Short cohesin fibers are observed in the oocyte nucleus during dictyate arrest. All four subunits are observed at centromeres and along chromosomal arms, except at chiasmata, at MI and are present at centromeric domains from anaphase I to MII. SMC1 beta transcripts were detected (with high inter-sample variability) in GV oocytes but no correlation between SMC1 beta mRNA levels and age was found. CONCLUSIONS The dynamics of cohesins REC8, STAG3, SMC1 beta and SMC3 suggest their participation in sister chromatid cohesion throughout the whole meiotic process in human oocytes. Our data do not support the view that decreased levels of SMC1 beta gene expression in older women are involved in age-related non-disjunction.

Monochorionic twins with selective intrauterine growth restriction and intermittent absent or reversed end-diastolic flow (Type III): feasibility and perinatal outcome of fetoscopic placental laser coagulation

To assess the feasibility and impact on perinatal outcome of fetoscopic laser coagulation of placental anastomoses in monochorionic twins with selective intrauterine growth restriction (sIUGR) and intermittent absent or reversed end‐diastolic flow (iAREDF) in the umbilical artery (Type III), in comparison with expectant management.

Doppler changes in the main fetal brain arteries at different stages of hemodynamic adaptation in severe intrauterine growth restriction

To evaluate changes in the temporal evolution and regional distribution of arterial brain Doppler parameters in relation to different stages of hemodynamic adaptation in fetuses with severe intrauterine growth restriction (IUGR).

Maternal history and uterine artery Doppler in the assessment of risk for development of early- and late-onset preeclampsia and intrauterine growth restriction.

Objective. To examine the value of one-step uterine artery Doppler at 20 weeks of gestation in the prediction pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR). Methods. A prospective multicentre study that included all women with singleton pregnancies at 19–22 weeks of gestation (w). The mean pulsatility index (mPI) of both uterine arteries was calculated. Receiver-operating characteristics curves (ROC) were drawn to compare uterine artery Doppler and maternal risk factors for the prediction of early-onset PE and/or IUGR (before 32 w) and late-onset PE and/or IUGR. Results. 6,586 women were included in the study. Complete outcome data was recorded for 6,035 of these women (91.6%). PE developed in 75 (1.2%) and IUGR in 69 (1.1%) cases. Uterine Doppler mPI was 0.99 and the 90th centile was 1.40. For 10% false-positive rate, uterine Doppler mPI identified 70.6% of pregnancies that subsequently developed early-onset PE and 73.3% of pregnancies that developed early-onset IUGR. The test had a lower detection rate for the late-onset forms of the disease (23.5% for PE and 30% for IUGR). Maternal history has a low sensitivity in the detection of early-onset cases, although it is better at detecting late-onset PE. Conclusion. Uterine artery Doppler and maternal risk factors seem to select two different populations - early and late-onset PE which might suggest a different pathogenesis.

Tissue factor levels and high ratio of fibrinopeptide A:D-dimer as a measure of endothelial procoagulant disorder in pre-eclampsia

To assess coagulation activation and endothelial cell injury in normotensive and pre‐eclamptic pregnant women, a comparision was made of plama levels of tissue factor, fibronectin, fibrinopeptide A and D‐dimer. Samples were taken from 50 nonpregnant women, 40 normotensive pregnant women in the third trimester and 27 women with pre‐eclampsia after diagnosis and before treatment. High levels of fibrinopeptide A and D‐dimer were found in pre‐eclampsia women. Moreover, the ratio fibrinopeptide A:D‐dimer was much greater in the pre‐eclampsia group than in normotensive pregnant women. The levels of fibronectin and tissue factor were also higher in the pre‐eclampsia group. The increase of tissue factor levels suggests an alteration of the extrinsir coagulation pathway in pre‐eclampsia. The increase of fibrinopeptide A:D dimer ratio shows that the activation of coagulation is associated with a relative hypofibrinolysis in pre‐eclampsia.