Soluble Fms Like Tyrosine Kinase 1 And Vascular Endothelial Growth Factor:

2768 words - 12 pages

Objective: To evaluate the role of soluble fms-like tyrosine kinase-1 (sFlt-1) and vascular
endothelial growth factor (VEGF) for prediction of pregnancy loss in patients with history of
unexplained early recurrent pregnancy loss (RPL). Methods: A prospective case control study
was conducted in 42 women with history of unexplained early RPL, and 170 pregnant controls
with history of uncomplicated pregnancy. We measured maternal serum sFlt-1 and VEGF at
gestational age 6-9 weeks as predictor for pregnancy loss. Results: Mean serum levels of sFlt-1
and VEGF were significantly higher in RPL group than controls (10439.7±385.4 vs 3304.5±104.8;
P<0.0001, for sFlt-1, and 1885.0±98.3 vs 709.8±24.8; P<0.0001, for VEGF). Receiver operating
characteristic (ROC) curves analyses established that sFlt-1 and VEGF were able to discriminate
women at risk of developing pregnancy loss with area under ROC curve 0.970 for sFlt-1 and 0.953
for VEGF. Cutoff value of 5159.5 pg/mL for sFlt-1 was predictor for early pregnancy loss with
95.2% sensitivity, 91.2% specificity, and odds ratio (OR) 206 [95%confidence interval (CI), 45.4-
941]. Cutoff value of 915.5 pg/mL for VEGF was predictor for early pregnancy loss with 92.9%
sensitivity, 90.6% specificity, and OR 125 [95% CI: 34.7-451]. Conclusion: These data advocate a
relationship between sFlt-1, VEGF, and RPL suggesting that the high levels of sFlt-1 and VEGF
might be associated with the pathogenesis of RPL.
1. Introduction
Pregnancy loss is the most common complication of
pregnancy which affects up to 15% of the reproducing
couples and recurs in 2% to 3% of them [1]. Recurrent
pregnancy loss (RPL) is defined as two or more unsuccessful
pregnancies, in which the pregnancy is defined as a
clinical pregnancy documented by ultrasonography or
histopathological test [2]. The pathophysiology of RPL is
complex with many unknown contributing factors and
mechanisms. Despite a wide range of investigations, no
obvious reason can be established in more than 50% of
The success of the implantation of an embryo depends
on the formation of its own blood vessels. Therefore, the
successful establishment of fetoplacental circulation is
essential for the continuation of pregnancy[4]. A defective
maternal hemostatic response leading to hypoxia secondary
to thrombosis of the utero-placental vasculature has
been hypothesized to subsequently lead to miscarriage.
This may comprise impairment of trophoblast invasion,
villitis, thrombosis in decidual vessels, and placental
microthrombi [5]. Recent studies reported that high
expression levels of the soluble fms-like tyrosine kinase-1
(sFlt-1) mRNA and the vascular endothelial growth factor
(VEGF) mRNA are found in the chorionic villus tissue of
women with RPL [6]. VEGF, which has a mitogenic effect on
endothelial cells and increases their migratory capacity, is
secreted from many tissues, including the placenta. VEGF
controls physiological and pathophysiological vascular
development [7]....

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