Measurement of Human Chorionic Gonadotrophin (hCG) in the management of Trophoblastic disease

Human Chorionic Gonadotrophin (hCG) is mainly a product of the syncytiotropoblastic cells of the placenta although it is also secreted, in lesser quantities, by cytotrophoblastic cells and several nonplacental tissues. It is produced in gestational trophoblastic neoplasms (GTN) and maybe seen in nontrophoblastic neoplasms (Stenman, 2006). hCG is essential in pregnancy as it promotes transformation of cyclic ovary corpus luteum to gravid corpus luteum allowing continued ovarian production of progesterone and oestrogens in the first 6-7 weeks of pregnancy until the luteo-placental shift in progesterone production occurs (Tulchinsky, 1973). The hormone was discovered in 1920 by observing the stimulatory effect of placental extracts on corpus luteal formation and progesterone production in rabbits (Hirose, 1920). The first assay for hCG was developed several years later and was based on the ability of hCG to activate receptors in the gonads of mice (Ascheim and Zondek, 1927). Despite their many drawbacks such animal based bioassays remained the only pregnancy tests until the ‘60s. It was a quantitative variant of a mouse bioassay that enabled Li et al to discover the sensitivity of trophoblastic neoplasms to treatment with methotrexate (MTX) when they observed a decline in urine hCG potency following its administration (Li, 1956). However, it was not until the advent of radioimmunoassays in the early ‘60s that the first sensitive and truly quantitative tests for determination of hCG became available (Berson & Yallow, 1960). Presently, effective management of trophoblastic disease is heavily reliant on immunoassay determinations of serum hCG which are used at all stages of trophoblastic disease management including diagnosis, treatment planning, monitoring response to therapy and relapse detection (Stenman, 2004, 2006; Muller & Cole 2009; Seckl, 2013; Mangili, 2014). Due partly to clinical reliance and partly the nature of hCG immunoassays, false or inaccurate determinations of hCG have had serious adverse consequences (Rotmensch & Cole, 2000; Stenman 2006, 2013). Hence, mitigating these risks has been a topic of debate and interest to clinicians responsible for the treatment of trophoblastic neoplasms.