Single Serum Activin A Testing to Predict Ectopic Pregnancy

Abstract

Most fatal cases of maternal deaths in early pregnancy from ectopic pregnancy (EP) result from delayed diagnosis. Transvaginal sonography (TVS), the method of choice for initial diagnosis, fails to identify 8–31% of women with EP. For these women, either surgical or biochemical assessment (usually by measurement of serum levels of human chorionic gonadotropin (β-hCG) and/or progesterone) is used to make the correct diagnosis. None of these methods, however, has the accuracy, reproducibility, and simplicity to become a universal predictive marker for EP. Levels of activin A, a placental glycoprotein, increase in the maternal circulation throughout pregnancy until delivery. Addition of activin A to primary human placental cell cultures stimulates progesterone production and the release of β-hCG. This prospective observational study assessed the possible role of activin A as a diagnostic marker among 535 pregnant women with unknown pregnancy location (UPL) presenting at a tertiary referral center between 2004 and 2005. Following clinical examination, the women were evaluated with TVS, β-hCG, and progesterone, and blood levels of activin A were measured. The sensitivity and specificity of activin A as a diagnostic test for the detection of EP in women with UPL was assessed with the receiver operating curve (ROC) test. Pregnancy outcomes were evaluated in 155 (28.9%) viable intrauterine pregnancies (IUP), 305 (56.9%) first-trimester spontaneous abortions (SAB), and 76 (14.2%) EP. SAB had lower β-hCG and progesterone concentrations compared to both EP or IUP (P < 0.001 for each). Among women with EP, both β-hCG and progesterone levels were significantly lower than those with IUP or SAB (P < 0.001 for both). In contrast, levels of activin A were lowest among women with EP, being significantly lower in comparison to either SAB or IUP (P < 0.001 for each). Activin A levels were significantly lower in women with IUP than those with SAB (P < 0.001). ROC analysis showed that activin A had the highest accuracy for prediction of EP in women with UPL at the cutoff of 0.37 ng/ml; the sensitivity was 100% with a specificity of 99.6%. These findings suggest that measurement of activin A may be a useful biochemical marker to identify EP in women with UPL.