Placental growth factor, soluble fms-like tyrosine kinase 1 and progesterone as diagnostic biomarkers for ectopic pregnancy and missed abortion.
OBJECTIVE
The aim of this study is to investigate if progesterone, placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt1) serum levels are useful markers to differentiate between ectopic pregnancy (EP), missed abortion (MA) and viable intrauterine implantation pregnancy (IUP).


METHODS
We designed a retrospective case-control study which included 100 pregnant women (50 EP and 50 MA) at 6-8 weeks of gestation with βhCG serum levels between 800 and 3500 UI/L and a viable IUP group. Progesterone, PlGF and sFlt-1 levels were measured with an electrochemiluminescence assay (Roche Diagnostics, Manheim, Alemania). A non parametric test was used to compare the markers in the different groups and we used receiver operating characteristic (ROC) curve analysis to calculate the area under the curve (AUC).


RESULTS
When we compared the EP group with the MA group, we didn't find significant differences for PlGF (15.1[13.2-17.4]/16.7[12.8-18.7] pg/mL) (p=0.275). We only obtained significant differences for progesterone (9.1[3.1-16.8]/2.6[1.3-6.1] ng/mL) (p<0.001) and sFlt-1 (84[65-96]/126[94-256] pg/mL) (p<0.001). The AUC for progesterone was 0.756 and the cutoff point with better sensitivity and lower false positive rate was 6 ng/mL (sensitivity=60%, specificity=72.7%). The AUC for sFlt-1 was 0.842 and the cutoff point was 93 pg/mL (sensitivity=84.5%, specificity=86.3%). The combination of both markers allowed us to increase the AUC to 0.910.


CONCLUSIONS
In conclusion, the present study suggests that sFlt-1 could be a useful marker to differentiate between an EP or a MA when βhCG levels are similar in both groups. The combination of sFlt-1 with progesterone helps to increase the diagnostic performance.
Clinical Analysis Department, Virgen de la Arrixaca University Hospital, Murcia, Spain. Electronic address: anamr82@gmail.com.
Ana
A
Martínez-Ruiz
Clinical Analysis Department, Virgen de la Arrixaca University Hospital, Murcia, Spain.
María Desamparados
MD
Sarabia-Meseguer
Clinical Analysis Department, Virgen de la Arrixaca University Hospital, Murcia, Spain.
Joaquín
J
Pérez-Fornieles
Clinical Analysis Department, Virgen de la Arrixaca University Hospital, Murcia, Spain.
Juan Antonio
JA
Vílchez
Clinical Analysis Department, Virgen de la Arrixaca University Hospital, Murcia, Spain.
Isabel
I
Tovar-Zapata
Clinical Analysis Department, Virgen de la Arrixaca University Hospital, Murcia, Spain.
Jose Antonio
JA
Noguera-Velasco
D000030:Abortion, Missed / Q000097:blood* / Q000175:diagnosis; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011271:Pregnancy, Ectopic / Q000097:blood* / Q000175:diagnosis; D011374:Progesterone / Q000097:blood*; D012372:ROC Curve; D012189:Retrospective Studies; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D055815:Young Adult
D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D011374:Progesterone; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
Ectopic pregnancy; Missed abortion; Progesterone; Soluble fms-like tyrosine kinase 1