Gonadotrophin releasing hormone receptor antagonists: a novel treatment for ectopic pregnancy (360G-Wellcome-108766_Z_15_Z)

£237,155

Ectopic pregnancies (EP) represent 1-2% of pregnancies and are a leading cause of maternal morbidity and mortality. 60% of EP currently require surgical management but progressively earlier diagnosis is allowing more women to choose medical management with systemic methotrexate. However, methotrexate treatment requires prolonged follow-up, has significant side effects and fails in 30%, which then necessitates surgery. I propose that gonadotrophin releasing hormone receptor antagonists (GnRHR-ant ), drugs currently licensed for infertility treatment in women with few side effects, may offer an alternative EP treatment for the following reasons. GnRH and its receptor (GnRHR) are expressed by placenta-forming trophoblast cells. My pilot data confirms EP trophoblast GnRHR expression and shows that GnRHR-ant inhibit trophoblast proliferation in culture. Moreover, GnRH controls trophoblast human chorionic gonadotrophin (hCG) production, the critical endocrine support of an early pregnancy. Th us, I plan to investigate the effect of GnRHR-ant on trophoblast proliferation, invasion and hCG production in-vitro; using human and immortalised trophoblast cells and a novel trophoblast-oviduct co-culture; and in-vivo using a human trophoblast xenograft model and a fetal resorption mouse model. I will increase our knowledge of trophoblast biology and aim to provide sufficient evidence to support a clinical trial using GnRHR-ant to treat EP.

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Grant Details

Amount Awarded 237155
Applicant Surname Campbell
Approval Committee Clinical Interview Committee
Award Date 2015-06-24T00:00:00+00:00
Financial Year 2014/15
Grant Programme: Title Research Training Fellowship
Internal ID 108766/Z/15/Z
Lead Applicant Dr Lisa Campbell
Partnership Value 237155
Planned Dates: End Date 2018-10-31T00:00:00+00:00
Planned Dates: Start Date 2015-11-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Scotland
Sponsor(s) Prof Jeffrey Pollard