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Title: Optimising ovarian tissue transplantation by improving graft revasacularisation
Author: Getreu, Natalie Rebecca
ISNI:       0000 0004 7965 0574
Awarding Body: University College London (UCL)
Current Institution: University College London (University of London)
Date of Award: 2019
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In recent years the demand for fertility preservation (FP) for oncologic and benign pathologies has increased dramatically. Cancer, haematological diseases, autoimmune disorders and other ovarian pathologies often require treatment that may impair future fertility. These treatments whilst curative, are highly toxic to the gonads, diminish the primordial follicle pool and can cause ovarian atrophy. Consequently, the number of women likely to suffer from premature ovarian insufficiency or early menopause is exponentially increasing as the population of adult cancer survivors continues to grow. With more than 130 live births reported to date, there is now sufficient evidence to support the feasibility and efficacy of ovarian tissue cryopreservation and transplantation for both fertility preservation and endocrine restoration purposes. However, there are still a number of issues regarding the grafting procedure. Of primary concern is the massive follicular loss which occurs in the early post grafting period. The ovarian tissue is currently grafted without vascular anastomosis causing the graft to experience a period of hypoxia and ischemia lasting up to five days while angiogenesis occurs. In this work approaches which have been successful in other transplanted tissues were implemented in an attempt to reduce the hypoxic conditions, increase vascularisation to the tissue and maintain the ovarian reserve. Using in vitro, in ovo and in vivo experimental procedures, encapsulation of ovarian cortical tissue in an alginate matrix and/or the addition of an angiogenic growth factor, VEGF, was explored. The optimal way for delivering VEGF and in-situ measurement of vascularisation using novel biomedical photonics was also evaluated. Outcomes were determined using histology, immunohistochemistry and multi spectral imaging analysis. Results: Overall a significant reduction in apoptosis and increased follicle survival was found when cortical ovarian tissue was encapsulated in alginate prior to cryopreservation in all models. In both the in vitro and in ovo experiments exogenous VEGF was also found to effective in improving the ovarian angiogenesis. The results suggest that both alginate and VEGF are promising applications to lessen post transplantation ischemic damage subsequent follicle loss. Although this work is preliminary, the data should be further developed and optimised for translational application. In doing so, the data may contribute to overall improved outcomes following OTC-TP, an extremely beneficial procedure providing female cancer survivors with an opportunity to conceive following their recovery.
Supervisor: Hardiman, P. ; Fuller, B. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available