Soluble fms-like tyrosine kinase-1 and vascular endothelial growth factor: Novel markers for unexplained early recurrent pregnancy loss

Abstract

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.

Keywords

• Recurrent miscarriage
• Soluble fms-like tyrosine kinase-1
• Vascular endothelial growth factor