Patients with placenta-mediated adverse pregnancy outcomes (PVP) showed higher median TFPI activity values than patients without (No PVP) both during pregnancy and in the postpartum period.

<p>The lower and upper limits of the box represent the first and third quartiles respectively and the heavy line inside the box the median. The horizontal line at the bottom and at the top of each plot represent the value of the lower and upper quartiles respectively. The circles represent the points that fall outside the nominal range of the data inferred from the upper and lower quartiles. * p<0.05, Wilcoxon Mann-Whitney test. PVP for Placental Vascular Pathology.</p

No difference between TFPI resistance (median normalized ratio) during pregnancy and postpartum for patients with placenta-mediated adverse pregnancy outcomes (PVP) and patients without (No PVP).

<p>The lower and upper limits of the box represent the first and third quartiles respectively and the heavy line inside the box the median. The horizontal line at the bottom and at the top of each plot represent the value of the lower and upper quartiles respectively. The circles represent the points that fall outside the nominal range of the data inferred from the upper and lower quartiles.</p

Placental volumes were smaller in cases of PVP.

<p>Summary with box plots of the distribution of values according to gestational age and the occurrence or not of a PVP. (A) Placental volume at 12, 16 and 20 WG and comparison of data based on the occurrence or not of a PVP. (B) D-dimer concentrations at 12, 16 and 20 WG and comparison of data based on the occurrence or not of a PVP. (C) sEPCR concentrations at 12, 16 and 20 WG and comparison of data based on the occurrence or not of a PVP.</p

Plasma D-dimer level was positively correlated with placental volume.

<p>Regression graphs obtained from Spearman's rank-order correlation in order to elucidate linkage between placental volume and D-dimer. A. All patients and all measurements. B. Only patients with no PVP. C. Only patients with PVP.</p

Comparison of TFPI activity during pregnancy in patients with placenta-mediated adverse pregnancy outcomes and without.

<p>Comparison of TFPI activity during pregnancy in patients with placenta-mediated adverse pregnancy outcomes and without.</p

Median normalised ratio was below 0.70 during pregnancy and higher in postpartum.

<p>The lower and upper limits of the box represent the first and third quartiles respectively and the heavy line inside the box the median. The horizontal line at the bottom and at the top of each plot represent the value of the lower and upper quartiles respectively. The circles represent the points that fall outside the nominal range of the data inferred from the upper and lower quartiles.</p

Patient characteristics at inclusion^a.

<p>Patient characteristics at inclusion<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0173596#t001fn001" target="_blank">^a</a>.</p

No relation between sEPCR and placental volume was found.

<p>Regression graphs obtained from Spearman's rank-order correlation in order to elucidate linkage between placental volume and sEPCR.</p

Novel genes and mutations in patients affected by recurrent pregnancy loss

<div><p>Recurrent pregnancy loss is a frequently occurring human infertility-related disease affecting ~1% of women. It has been estimated that the cause remains unexplained in >50% cases which strongly suggests that genetic factors may contribute towards the phenotype. Concerning its molecular aetiology numerous studies have had limited success in identifying the disease’s genetic causes. This might have been due to the fact that hundreds of genes are involved in each physiological step necessary for guaranteeing reproductive success in mammals. In such scenario, next generation sequencing provides a potentially interesting tool for research into recurrent pregnancy loss causative mutations.</p><p>The present study involved whole-exome sequencing and an innovative bioinformatics analysis, for the first time, in 49 unrelated women affected by recurrent pregnancy loss. We identified 27 coding variants (22 genes) potentially related to the phenotype (41% of patients). The affected genes, which were enriched by potentially deleterious sequence variants, belonged to distinct molecular cascades playing key roles in implantation/pregnancy biology.</p><p>Using a quantum chemical approach method we established that mutations in MMP-10 and FGA proteins led to substantial energetic modifications suggesting an impact on their functions and/or stability.</p><p>The next generation sequencing and bioinformatics approaches presented here represent an efficient way to find mutations, having potentially moderate/strong functional effects, associated with recurrent pregnancy loss aetiology. We consider that some of these variants (and genes) represent probable future biomarkers for recurrent pregnancy loss.</p></div

Sequence variants identified in RPL patients.

<p>Sequence variants identified in RPL patients.</p