Diagnosis of hydatidiform mole and persistent trophoblastic disease:: diagnostic accuracy of total human chorionic gonadotropin (hCG), free hCG α- and β-subunits, and their ratios

Objective: Human chorionic gonadotropin (hCG) is widely used in the management of hydatidiform mole and persistent trophoblastic disease (PTD). Predicting PTD after molar pregnancy might be beneficial since prophylactic chemotherapy reduces the incidence of PTD. Design: A retrospective study based on blood specimens collected in the Dutch Registry for Hydatidiform Moles. A group of 165 patients with complete moles (of which 43 had PTD) and 39 patients with partial moles (of which 7 had PTD) were compared with 27 pregnant women with uneventful pregnancy. Methods: Serum samples from patients with hydatidiform mole with or without PTD were assayed using specific (radio)immunoassays for free alpha-subunit (hCG alpha), free beta-subunit (hCG beta) and 'total' hCG (hCG + hCG beta). In addition, we calculated the ratios hCG alpha/hCG + hCG beta, hCG beta/hCG + hCG beta, and hCG alpha/hCG beta. Specificity and sensitivity were calculated and paired in receiver-operating characteristic (ROC) curve analysis, resulting in areas under the curves (AUCs). Results: hCG beta, hCG beta/hCG + hCG beta and hCG alpha/hCG beta show AUCs ranging between 0.922 and 0.999 and, therefore, are excellent diagnostic tests to distinguish complete and partial moles from normal pregnancy. To distinguish partial from complete moles the analytes hCG beta, hCG + hCG beta and the ratio hCG alpha/hCG beta have AUCs between 0.7 and 0.8. Although hCG alpha, hCG beta and hCG + hCGP concentrations are significantly elevated in patients who will develop PTD compared with patients with spontaneous regression after evacuation of their moles, in predicting PTD, these analytes and parameters have AUCs < 0.7. Conclusions: Distinction between hydatidiform mole and normal pregnancy is best shown by a single blood specimen with hCG beta, but hCG beta/hCG + hCG beta and hCG alpha/hCG beta are also excellent diagnostic parameters. To predict PTD, hCG alpha, hCG beta, hCG + hCG beta and hCG alpha/hCG beta are moderately accurate tests, although they are not accurate enough to justify prophylactic chemotherapy treatment for prevention of PTD.