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Title: Evaluation of hyperglycosylated hCG as a predictor of adverse pregnancy outcome
Author: Kazim, Nahla
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2010
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Hyperglycosylated human chorionic gonadotrophin (HhCG) is a glycoprotein hormone that reportedly has biological functions different from those of hCG. It is produced by invasive cytotrophoblast cells at the time of implantation and in gestational trophoblastic disease. The invasion of cytotrophoblasts and their regulated proliferation are major determinants of pregnancy outcome: a shift of these controlling mechanisms has been associated with adverse pregnancy complications. Altered levels of HhCG may mirror placental dysfunction or impaired placental differentiation. This observational cohort study was undertaken to correlate various pregnancy outcomes with serum and urinary concentrations of HhCG and other hCG molecular forms, in order to determine whether HhCG is a helpful predictor of adverse pregnancy outcome. The first cohort included 287 women with spontaneous conceptions who attended the Obstetrics and Gynaecology Department of Mafraq Hospital in the United Arab Emirates. Paired serum and urine samples were collected on a single occasion from singleton pregnancies between 6 and 24 weeks of gestation. Patients were followed up until the pregnancy outcome was available. HhCG levels in pregnancies with uneventful outcomes and those with pregnancy complications were compared. Significantly lower HhCG levels were observed for pregnancies resulting in miscarriage as compared with late pregnancy complications. In the second cohort of 128 patients undergoing in vitro fertilisation or intracytoplasmic sperm injection at the Assisted Conception Unit in Edinburgh, the usefulness of serum HhCG levels on Day 14 of oocyte retrieval was assessed. HhCG levels were found to be significantly lower in pregnancies ending in spontaneous miscarriages and biochemical pregnancies. The potential diagnostic and prognostic utility of HhCG was confirmed by a receiver operating characteristic curve plot. The sugar chain heterogeneity of hCG from various sources was also investigated by SDS-PAGE and immunoblot analyses of pregnancy urine samples to assess their potential value as new diagnostic tools for predicting pregnancy outcome. Using monoclonal antibodies and a panel of lectins that can separate N- from O-linked sugar chains, variations in the hCG glycosylation patterns during different stages of pregnancy and pregnancy complication were studied. While the differences in the hCG glycosylation profiles reported here are interesting, whether they can helpfully contribute to the prediction of pregnancy outcome requires further study.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available