Activin A and Follistatin as Biomarkers for Ectopic Pregnancy and Missed Abortion

Abstract

Activin A as a predictor of pregnancy failure has been the focus of heated debate, but the value of a combined activin A and follistatin (FS) measurement in serum to predict pregnancy failure has not been reported yet. We assessed whether a single serum measurement of the two physiological antagonists at 6–8 weeks gestation could differentiate ectopic pregnancies (EP) or missed abortions (MA) from healthy intrauterine pregnancies (IUP). activin A concentrations were significantly lower in women with EP (n = 30, median value of 264 pg/mL) and women with MA (n = 30, median value of 350 pg/mL) compared to IUP (n = 33, median value of 788 pg/mL); P < 0.001. At a threshold value of 505 pg/mL, activin A had 87.9% sensitivity and 100% specificity and negative predictive value of 0.974 for discriminating an ectopic pregnancy from viable pregnancies. FS was able to discriminate IUP from EP (ROC curve P < 0.001) as was their ratio (ROC curve P = 0.008), but was unable to discriminate a MA from an EP. In EP, activin A did not correlate with beta HCG levels. The present findings support the thesis that activin A or FS could be considered promising biomarkers for the discrimination between an IUP and a failed pregnancy (MA or EP).

The Role of Activin a and Follistatin in the Differentiation Between Viable Intrauterine Pregnancy From Missed Miscarriage and Ectopic Pregnancy

“…In our study serum level of activin A, FS and activin A/FS ratio were significantly higher in normal pregnancy compared to failed pregnancy; these findings were in agreement with the results of several studies Rausch et al, Florio et al,and Johns et al [13,15,16]. Activin A had good ability to differentiate a normal IUP from failed pregnancy with a sensitivity of 65.0% and 100% specificity with a cutoff value ≤284 pg/ml, while Daponte et al reported excellent ability with 87.9% sensitivity, 85.0% specificity, and ≤504.66 pg/ml as a cutoff value [17]. Activin A had fair ability to differentiate a normal IUP from missed miscarriage, while Muttukrishna et al [18].…”

Fetal Sex‐Based Differences in Maternal Hormones, Angiogenic Factors, and Immune Mediators During Pregnancy and the Postpartum Period

“…Since none of the women followed in our study had preeclampsia,, our data suggests that endoglin plays a supportive, tightly regulated role in pregnancy, especially considering the relative lack of longitudinal variability observed with male fetuses.. Finally, follistatin has been suggested as a predictor of ectopic pregnancies or missed abortions 50 . Although our cohort is fairly small, the differences were statistically significant, and future research involving these factors and pregnancy outcomes should consider the possibility of differences based on the sex of the fetus.…”

“…Finally, follistatin has been suggested as a predictor of ectopic pregnancies or missed abortions. 49 Although our cohort is fairly small, the differences were statistically significant, and future research involving these factors and pregnancy outcomes should consider the possibility of differences based on the sex of the fetus.…”

Plasma metabolomic profile and potential biomarkers for missed abortion

“…It would be of great clinical value to find a satisfactory biomarker of MA to dispel the patient's doubt and avoid further unnecessary damage. At present, several plasma factors have been extensively investigated, and these mainly consist of certain enzymes and hormones (Daponte et al, ; Martinez‐Ruiz et al, ). However, none of these studies have systematically analyzed the role of plasma metabolites as promising biomarkers of MA.…”