Fertility Preservation in Young Women at Risk of Ovarian Insufficiency due to Malignancy or Endometriosis

Advances in science have afforded women the opportunity to avail of resources which has the potential to prolong their reproductive lifespan. Unfortunately predicting those who may need fertility preservation most, is not always feasible. We identified two cohorts of women, potentially at high risk of impaired ovarian reserve and therefore could benefit most from availing of assisted reproductive therapy (ART), including fertility preservation, with the potential to mitigate the negative fertility consequences of their underlying conditions and prevent unintended childlessness. The research presented in this study takes us firstly through the implementation and development of the first National Program for fertility preservation services for female adolescents and young adults with cancer, and for female survivors of childhood cancer in Ireland. We describe the processes navigated to provide an essential fertility counselling, surveillance and assessment service for this vulnerable cohort of survivors. A service which should be provided as standard by the Health Service Executive in Ireland, to match the standards of care available across Europe and in the U.K. We then present our work which explored doctors attitudes and practices in the management and optimisation of fertility in women with moderate to severe endometriosis and endometriomas, and our findings on how these patients described their experienced of the care and counselling they received as part of the surgical management of endometrioma, moving on to the assessment of ovarian reserve in women who have undergone surgery for endometrioma. Finally through the analysis of RNA sequencing studies, we sought to further the knowledge of potential biomarkers of oocyte quality and competence in women with endometriosis. The identification of such biomarkers, in either the form of differentially expressed genes or enriched biological pathways aims to provide potential therapeutic targets in the treatment of endometriosis related sub-fertility, and aid in providing a personalised and individual approach to their care, specifically those undergoing ART. The findings presented in this thesis have built upon the growing body of evidence that fertility preservation resources should be available, and discussed with women who are at risk of impaired fertility due to current or prior history of malignancy, or benign diseases such as diagnosis of moderate to severe endometriosis, and in particular endometrioma which are known to negatively impact upon fertility. An individualised approach to fertility assessment, optimisation and prioritization should be strongly considered as the standard of care for women with endometriosis, particularly with endometriomas. For endometriosis, and other diseases which we know can negatively impact future reproductive capacity, such as treatment with gonadotoxic therapies, fertility preservation should be considered and included in pre-treatment counseling for those who have not yet completed their family, and for young girls undergoing gonadotoxic therapies who can be afforded a short window of time to avail of this. We believe the education of doctors working with young women with cancer, and those caring for women with moderate to severe endometriosis, will lead to an improvement in the dissemination of knowledge of, and uptake in and accessibility of these specialised services in those who need them most. Going forward, the identification of a clinical biomarker for oocyte quality and oocyte developmental competence, particularly in women with endometriosis will further streamline the approach to and counselling for fertility preservation procedures for this cohort of women. The mechanisms leading to poor oocyte quality remain largely unknown and multifactorial, as such, the identification of pathways or genes that might shed further light on this topic is hugely beneficial, and will facilitate essential advances in the world of ART.