Research project
Testing The Health And Therapeutic Potential Of In Vitro Derived Oocytes For The Restoration Of Female Fertility
- Start date: 1 October 2020
- End date: 30 August 2026
- Value: £1,618,740
- Partners and collaborators: School of Biological Sciences and Deanery of Clinical Sciences, University of Edinburgh
- Primary investigator: Helen M Picton
- Co-investigators: John Huntriss
- External co-investigators: Professor Evelyn Telfer and Professor Colin Duncan
Description
Premature ovarian insufficiency (POI) or total sterility can occur in girls & young women as a result of genetic defects, surgery, abdominal trauma, or as a side effect of radiation or chemotherapy treatment for cancers or haematological disease. POI has adverse clinical & psychological effects on women's health. Ovarian cryopreservation can now be used to safeguard the fertility of girls & young women at high risk of sterility or POI. Primordial follicles, containing primordial oocytes, can be cryopreserved within ovarian cortex & stored long-term at -196C. When the patient wishes to start her family, stored tissue is autografted back at an orthotopic or heterotopic site to restore fertility. However, for girls & women with blood-born leukaemias or cancers with a high risk of ovarian metastasis, ovarian autografting risks reseeding the cancer through the transplant. For these individuals fertility restoration can only be safely achieved in the laboratory by the complete in vitro growth & maturation (IVGM) of cryopreserved primordial oocytes into fertile metaphase II (MII) oocytes. Following in vitro fertilisation, a healthy embryo can be transferred to the patient to produce a pregnancy. The therapeutic potential of IVGM is huge but the technology is extremely challenging. Never-the-less significant advances in IVGM have recently been made by the applicants' laboratories. We now aim to: (i) complete IVGM optimization by testing the health, fertility & developmental competence of oocytes & embryos derived using slow vs. fast growth IVGM systems; (ii) conduct a pilot study to test the implantation & pregnancy potential of embryos derived from IVGM oocytes in (i) & (iii) conduct an embryo transfer trial to confirm the safety & hence therapeutic potential of IVGM oocytes for fertility restoration. These studies will be conducted in sheep as a proven, physiologically and clinically relevant model for fertility preservation & restoration in women.
Impact
The research project will have a direct impact on key STAKEHOLDERS that include patients who suffer from POI. The legacy of this project will also impact on academics, reproductive and developmental scientists and clinicians as well as the wider scientific community including biomedical scientists, computational biologists, and healthcare professionals. The team of applicants have established, extensive communication networks in these areas that will be used to discuss and distribute the findings of the proposed studies to both the scientific and clinical communities and to the public. The unique collaborative network established for this project will impact on the MRC through realization of the potential of past, publicly funded research investments, as well as additional analyses of existing research tissue and data banks. THE UK GOVERNMENT and NHS will benefit in the medium to long-term from the proposed research through: improved health and wellbeing of cancer survivors; the development of new infertility therapies; and expansion of its research base. HEALTH POLICY MAKERS in the UK and beyond will benefit from this research in the median term through the generation of increased understanding of the ramifications of- and treatment options for- ovarian dysfunction and its contribution to lifelong health. In the long term this will positively impact on the health and wealth of the UK in terms of better health and fertility for subsequent generations, and has the potential to lessen the burden of infertility treatment costs upon the healthcare services. THE GENERAL PUBLIC will benefit in the medium term, as we aim to disseminate our findings beyond the academic community to increase awareness of ovarian dysfunction and the need for fertility preservation for key groups of patients. By interfacing with the clinical community the project will impact directly upon health professionals through the development of new therapeutic paradigms. We will disseminate our findings beyond the academic community to increase awareness of fertility preservation strategies and by interfacing with the clinical community this knowledge will impact directly upon health professionals. THE COMMERCIAL SECTOR will benefit in the medium term as a key driver in this application is realization of the potential of a novel therapeutic pathway as well as core and platform culture technologies and associated intellectual property. In addition to patient treatment, the core IVGM technology underpinning this application may impact on animal breeding and conservation programmes.