Positive serum β-human chorionic gonadotropin (β-hCG) testing in reproductive-age women generally indicates a pregnancy and to a lesser extent gestational trophoblastic disease (GTD) or a germ cell tumor (GCT). Other non-pregnant or false-positive causes of serum β-hCG testing include pituitary hormone production in perimenopausal or postmenopausal women, heterophilic antibody interference, chronic renal disease, familial β-hCG, and exogenous hCG administration for assisted reproductive technology. Non-gynecologic cancer can be associated with positive β-hCG results. We review the general physiology of the β-hCG molecule and typical approaches to β-hCG testing. We present an algorithm to help guide clinicians in evaluating the non-pregnant or false-positive causes of positive β-hCG test results.

Gestational trophoblastic disease (GTD) incorporates a spectrum of placental related disorders, with both benign and malignant (Gestational trophoblastic neoplasia (GTN)) subtypes. Upon initial presentation, one should establish diagnosis (GTD versus GTN), the requirement for chemotherapy and whether monitoring has been concluded by a specialist trophoblastic centre. Women with a prior history of GTD or GTN that have completed monitoring, or early pregnant GTD patients, do not require specialist pregnancy management. Dissimilarly, early pregnant GTN patients, particularly those treated for high-risk disease, or women with a twin pregnancy involving a complete hydatidiform mole and viable co-existent foetus should receive detailed antenatal counselling and be managed under consultant-led care. Patients with a twin mole and viable co-existent foetus have a high risk of antenatal, intrapartum and post-partum complications. Fortunately, in women with a prior history of trophoblastic disease, live birth rates equal the general population, with no increased risk of disease relapse.