Soluble FMS-like tyrosine kinase-1 (sFlt-1) and serum placental growth factor (PlGF) as biomarkers for ectopic pregnancy and missed abortion

J Clin Endocrinol Metab. 2011 Sep;96(9):E1444-51. doi: 10.1210/jc.2011-0037. Epub 2011 Jun 29.

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.

MeSH terms

  • Abortion, Missed / blood
  • Abortion, Missed / diagnosis*
  • Adult
  • Biomarkers / blood
  • Diagnosis, Differential
  • Female
  • Humans
  • Placenta Growth Factor
  • Pregnancy
  • Pregnancy Proteins / blood*
  • Pregnancy, Ectopic / blood
  • Pregnancy, Ectopic / diagnosis*
  • Prospective Studies
  • Vascular Endothelial Growth Factor Receptor-1 / blood*

Substances

  • Biomarkers
  • PGF protein, human
  • Pregnancy Proteins
  • Placenta Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1