title: Molecular diagnostics and therapeutics for ectopic pregnancy.
abstract: Ectopic pregnancies are a serious gynaecological emergency that can be fatal. As such, prompt diagnosis and safe timely treatment is essential. Here, we review the literature on the development of molecularly targeted diagnostics and therapeutics for ectopic pregnancy. A blood-based biomarker that accurately identifies an ectopic pregnancy could be used to offer early diagnostic certainty in cases where ultrasound cannot determine the location of the embryo ('a pregnancy of unknown location'). Molecules examined so far can be broadly grouped into biological themes of relevance to reproduction: (i) Fallopian tube (dys)function, (ii) embryo/trophoblast growth, (iii) corpus luteum function, (iv) inflammation, (v) uterine function and (vi) angiogenesis. While a sensitive and specific biomarker for ectopic pregnancy has yet to be identified, it is possible that improvements in platform technologies or a multi-modal biomarker approach may yield an accurate diagnostic biomarker test. Furthermore, with the advent of better imaging technology, the need for a blood-based biomarker test may be superseded by improvements in ultrasound or magnetic resonance imaging technology. There have been some recent preclinical studies describing molecularly targeted therapeutic approaches for ectopic pregnancy. Notably, bench-to-bedside studies have examined the use of combination gefitinib (orally available epidermal growth factor receptor inhibitor) and methotrexate. Preclinical studies suggest that combination gefitinib and methotrexate is highly effective in inducing placental cell death, and is significantly more effective than methotrexate alone. In early human trials, encouraging preliminary efficacy data have shown that combination gefitinib and methotrexate can rapidly resolve tubal ectopic pregnancies, and large extra-tubal ectopic pregnancies. If a large clinical randomized controlled trial confirms these findings, combination gefitinib and methotrexate could become a new medical treatment option for ectopic pregnancy.
authors.affiliation: Translational Obstetrics Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Rd, Heidelberg 3084, Australia stong@unimelb.edu.au.
authors.forename: Stephen
authors.initials: S
authors.lastname: Tong
authors.affiliation: Translational Obstetrics Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Rd, Heidelberg 3084, Australia.
authors.forename: Monika M
authors.initials: MM
authors.lastname: Skubisz
authors.affiliation: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Horne
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D011799:Quinazolines / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D011799:Quinazolines; D000077156:Gefitinib; D008727:Methotrexate
keywords: biomarker; ectopic pregnancy; gefitinib; methotrexate; treatment