 Research Focus
Laboratory-based studies to further understanding, diagnosis and treatment of ectopic pregnancy.
Background to the Research
Ectopic pregnancy: the clinical problem
An ectopic, or extra-uterine, pregnancy is defined as a pregnancy implanted outside of the uterine cavity with over 98% implanting in the Fallopian tube. Approximately 1-2% of all pregnancies in Europe and the USA are ectopic and in the Western world ectopic pregnancy remains the most common cause of maternal mortality in the first trimester of pregnancy. In the developing world, the incidence is much higher and one in ten women admitted with a diagnosis of ectopic pregnancy ultimately die from the condition. The major risk factors for ectopic pregnancy include: tubal damage as a result of surgery or infection (particularly Chlamydia trachomatis), smoking, and in-vitro fertilization (IVF).
Understanding what causes an ectopic pregnancy
Studies on the aetiology of ectopic pregancy to date have been largely descriptive and focused on dysregulated gene or protein expression, comparing Fallopian tube collected from women with tubal pregnancy and Fallopian tubes collected from non-pregnant women or women with a ‘pseudo-pregnancy’. There has been very limited analysis of the functional consequences of the observed changes in gene or protein expression reported in these studies. Furthermore, although the epidemiological risk factors for ectopic pregnancy have been well documented, the exact mechanism by which infection, or smoking, leads to tubal implantation remains unexplained. Data thus far have been largely descriptive and mechanistically speculative. Thus, our studies are focusing on investigating the functional consequences of smoking and infection on Fallopian tube physiology and pathobiology. We believe that a greater understanding of the aetiology of ectopic pregnancy is critical for the development of improved preventative measures, the advancement of diagnostic screening methods and the development of novel treatments.
Diagnosing ectopic pregnancy
The diagnosis of an ectopic pregnancy (currently a combination of ultrasound and serum hCG measurement) remains problematic often resulting in treatment delays. Fewer than 50% of tubal ectopic pregnancies are diagnosed at the patient’s initial presentation. Despite clinical advances in imaging, ultrasound is non-conclusive in up to 20% of women for whom measurement of serial hCG concentrations is necessary to guide management. The inevitable multiple visits and tests currently necessary are a sizeable expense for health services. Thus, it is clear that a diagnostic serum biomarker would at the very least be cost effective in the UK. However, to have significant impact on the case mortality and morbidity rate associated with tubal ectopic pregnancy in developing countries, it would need to be one that would be accurately and quickly assayed, preferably in an emergency department setting. Furthermore, such a test would have to be low cost to measure to have true clinical utility.
Schematic summary of candidate biomarkers identified in the literature to date
Recent Progress
We have shown that health services in Scotland are spending up to £1.5 million per year diagnosing and excluding ectopic pregnancy (an estimated £9 million in direct costs alone to health services per year throughout the UK) (Wedderburn et al., 2009).
We have identified new candidate biomarkers using genomic technology (Horne et al., 2008: Horne et al., 2009). This approach raises the possibility of using multiple serum biomarker analysis in order to diagnose ectopic pregnancy.
This work was highlighted by the BBC http://news.bbc.co.uk/1/hi/health/8379433.stm.
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