Soluble fms-Like Tyrosine Kinase-1 (sFlt-1) and Serum Placental Growth Factor (PlGF) as Biomarkers for Ectopic Pregnancy and Missed Abortion

Abstract

Context: Diagnosis of early pregnancy failure is hampered by the lack of reliable serological markers. Objective: We assessed whether a single serum measurement of placental growth factor (PlGF) and the soluble Flt-1 (sFlt-1) receptor of vascular endothelial growth factor at 6-8 wk gestation could differentiate failed pregnancies, whether ectopic pregnancies (EP) or missed abortions (MA), from healthy intrauterine pregnancies (IUP). Design and Setting: We conducted a prospective clinical study at a tertiary university hospital between January 2009 and February 2011. Patients: A total of 78 consecutive patients (38 EP, 40 MA) with failed early pregnancy and 50 IUP (control group) participated in the study. Intervention(s): Determination of serum PlGF and sFlt-1 has been carried out by ELISA. Gene expression of PlGF and Flt-1 in trophoblasts was performed by RT-PCR. Main Outcome Measure(s): We investigated whether a single, combined serum measurement of the above markers could contribute to the differential diagnosis. Results: PlGF and sFlt-1 concentration was lower in both EP (mean, 14.60 +/- 3.42/178.16 +/- 76.03 pg/ml) and MA (mean, 16.25 +/- 4.73/399.42 +/- 337.54 pg/ml) compared to IUP (mean, 21.64 +/- 5.68/1390.32 +/- 655.37 pg/ml). sFlt-1 (P = 0.033) and sFlt-1/PlGF ratio (P = 0.029) but not PlGF had the ability to discriminate MA from EP. Compared to women with viable IUP, mRNA gene expression levels of PlGF and Flt-1 were considerably lower in women with MA and in women with EP. Conclusions: Combined measurement of sFlt-1 and PlGF levels can differentiate normal from failed pregnancies, whereas sFlt-1 as well as sFlt-1/PlGF ratio can also discriminate EP from MA. PlGF and Flt-1 gene expression in trophoblasts from women with EP and MA appears impaired. (J Clin Endocrinol Metab 96: E1444-E1451, 2011)