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The Reproductive Decision-Making of Women with Mitochondrial Disease

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The Reproductive Decision-Making of Women with Mitochondrial Disease Julia Tonge Uncertain Existence: The reproductive decision-making of women with Mitochondrial Disease. Thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy Institute of Neuroscience, Newcastle University October 2017 Abstract The aim of this thesis was to understand the process of reproductive decision- making in women with maternally inherited mitochondrial disease. It demonstrates the uncertainty fundamental to the experiences of women with mitochondrial DNA mutations (a subsection of women with mitochondrial disease). This uncertainty manifests in the personal accounts of their condition, as well as in relation to their reproductive decision-making. Twenty semi-structured qualitative interviews were conducted with eighteen women with mitochondrial DNA mutations, sampled via their connection to a mitochondrial disease specialist service in North East England. Retrospective, prospective and hypothetical questions were utilised in data collection. The data generated from the study, which was informed by constructivist grounded theory, can be organised into two central areas, both of which can be related back to uncertainty. The first area relates to how women harbour the desire for a healthy biologically related child. The second area features decision-making, which within the context of maternally inherited mitochondrial disease, is essentially the process by which women consolidate their desires for healthy children, and how they negotiate risk. The women’s accounts highlight social aspects of uncertainty that features in their reproductive decision-making, in contrast to the current literature that focuses on more clinical aspects of uncertainty. In addition, they also demonstrate how educational and employment institutions struggle to manage the uncertainty inherent in mitochondrial disease. An important outcome of this thesis, therefore, has been the adaptation of a sociological conceptual model to address this inconsistency. The model can be utilised by clinicians in discussions with women to comprehensively explore the process of decision-making in the face of uncertainty. This thesis demonstrates how the decision-making process is necessarily social, and highlights the importance of sociological understanding of uncertainty in the mitochondrial disease reproductive advice clinic. i Dedication This thesis is dedicated to my husband Dan, my parents Lilian and Gary and my little study companion Toby. ii Acknowledgements I would like to first thank the women and their partners who took part in this study. I am not only grateful for their time to sit with me but for sharing their experiences and viewpoints that have made this research possible. This research and its outcomes would not have been imaginable had Prof Sir Doug Turnbull not gifted me this opportunity to study alongside my professional role within the mitochondrial team. I would like to thank him for the support with the design, implementation and supervision of this study, along with providing generous resources that have allowed me to engage and participate in the national academic community. I would like to thank Dr Jane Stewart for providing invaluable expertise in the design of the study and helping me to understand the varied experiences of women on their reproductive journeys. I would like to express my gratitude to my progression panel Prof Robert McFarland, Prof Rita Horvath and Dr Judy Richards for their continued words of support and positivity during the lifetime of this project. Thanks are also due to Dr Gráinne Gorman as an inspiration and trusted mentor throughout my time in the group. My most special thanks are given to Prof Tim Rapley, who has taken a previously trained bench scientist and transformed me into a researcher that now sees the tremendous benefit of qualitative research and its exceptional importance in health research. I am forever indebted to him for the many years of support and guidance that made this thesis a reality. I am endlessly grateful for the new perspective on life this work has given me. Finally, I would like to thank my friends and family who have lived this project and all the highs and lows with me. To my friends Alexandra Bright and Catherine Feeney who provided not only practical support to complete this study, but were always on hand to provide words of encouragement and to help me process the strong emotions that circled during data analysis. To everyone who has shared in the little office, past and present, who have listened with interest to my project chatter. To my fellow Ph.D. researchers, Jen and Becca for providing a sounding board for all my frustrations. To Jen especially for all her support in the final write iii up of this thesis. You are both already exceptional researchers and I wish you both fulfilled careers and happiness in the future. To my parents, to whom I owe all my achievements to, your constant love and support throughout my entire lifetime has allowed me to reach out and follow all my dreams. This work is a testament to your endless faith in my abilities. Lastly, to my husband Dan, who had known me only 6 months before this project started, you have lived ‘my PhD' and I share this with you the most. Our journey together so far has included this project, its completion is down to your endless encouragement and support in every way possible. I love you. iv Contents Abstract ........................................................................................................................ i Dedication .................................................................................................................... ii Acknowledgements ..................................................................................................... iii List of Figures ............................................................................................................ xii List of Tables ............................................................................................................ xiii Chapter 1. Introduction ............................................................................................... 1 1.1 Mitochondria, Mitochondrial Function .......................................................... 1 1.2 Mitochondrial Genetics ................................................................................ 3 1.2.1 Mitochondrial Genome .......................................................................... 3 1.2.2 Heteroplasmy ........................................................................................ 4 1.2.3 Threshold Effect .................................................................................... 5 1.2.4 Genetic Bottleneck ................................................................................ 6 1.3 Medical Implications of Mitochondrial Disease ............................................ 7 1.3.1 Mitochondrial Mutations......................................................................... 8 1.3.2 Nuclear Mutations ............................................................................... 13 1.3.3 Pregnancy in Mitochondrial Disease ................................................... 13 1.3.4 Treatments in Mitochondrial Disease .................................................. 14 1.4 Social Implications of Mitochondrial Disease ............................................. 15 1.4.1 Work and Education ............................................................................ 15 1.4.2 Family Relationships ........................................................................... 16 1.4.3 Social Relationships ............................................................................ 17 1.5 Reproductive Options in Maternally Inherited Mitochondrial Disease ........ 17 1.6 Research Aims .......................................................................................... 18 1.6.1 Primary Objective ................................................................................ 18 1.6.2 Primary Outcome ................................................................................ 18 1.7 Contribution of Study ................................................................................. 18 1.8 Chapter Summaries ................................................................................... 21 Chapter 2 Literature Review ......................................................................... 21 v Chapter 3 Reproductive Options................................................................... 21 Chapter 4 Methodology and Methods ........................................................... 21 Chapter 5 Diagnostic Pathways: Women’s Practical Experiences................ 22 Chapter 6 Social Implications of Diagnosis ................................................... 23 Chapter 7 Reproductive Options: Searching for the Healthy and Biologically Authentic Child.............................................................................................. 23 Chapter 8 Reproductive Decision Making in Maternally Inherited Mitochondrial Disease: Conceptual Model .................................................... 23 Chapter 9 Discussion, Recommendations and Conclusion .......................... 24 Chapter 2. Literature Review ..................................................................................... 25 2.1 Introduction ................................................................................................ 25 2.2 Perspectives of Decision Making in the Clinic ...........................................
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