Novel biochemical markers in the diagnosis and management of early pregnancy problem

Abstract

Background and purpose: Early pregnancy problems, including miscarriage, ectopic pregnancy and pregnancy of unknown location, occur commonly and have significant medical, psychological and economic consequences. Biochemical markers are increasingly being used as an adjunct to ultrasonography and this thesis describes three studies exploring the use of novel biochemical markers in the diagnosis and management of early pregnancy problems. Materials and methods: These are observational studies of women in early pregnancy recruited at Sunderland Royal Hospital and King’s College Hospital. Serum samples were taken from women in early pregnancy and lectin affinity chromatography used to characterise the glycosylation of hCG by gestational age and by pregnancy outcome. Women with a diagnosis of a miscarriage, ectopic pregnancy or pregnancy of unknown location had serum levels of hCG, progesterone, inhibin A, IGFBP-1 and inhibin proαC quantified, and statistical analysis was used to see if spontaneous resolution of the pregnancies could be predicted. Results: Lectin-affinity chromatography reveals five major glyco-isoforms of hCG in early pregnancy, the expression of which changes with gestational age and by pregnancy outcome. The novel markers of the luteo-trophoblastic axis inhibin A, IGFBP-1 and inhibin proαC are found not to be clinically useful in the prediction of spontaneously resolving PULs although when used in the decision trees developed by Elson in 2005, they are useful for predicting spontaneous resolution of miscarriages and failed pregnancies. Conclusions: Novel biochemical markers have the potential to be a useful addition in the management of early pregnancy problems. Further studies are required to explore the physiological basis of these findings and the clinical applicability of these tools.