The investigation of the relationships between pre-treatment mood, lifestyle, cortisol, and outcomes of assisted reproductive treatment
Publication Date
December 15, 2022
Creator
Abstract
Patients seeking fertility treatment often experience considerable stress. Whether this stress influences treatment outcomes is one of the most frequently asked questions by patients undergoing in vitro fertilisation (IVF) treatment. However, the answer to this question is still the subject of much debate. One salient issue with current studies is that they have primarily focused on self-reported measures of stress while evidence on the physiological mechanisms that might give rise to a relationship between psychological stress and treatment outcomes is relatively absent. A candidate biomarker exists to explore precisely this relationship. The hypothalamic-pituitary-adrenal (HPA) axis has been identified as being central to the body’s physiological response to stress, particularly in the context of chronic stress. The final hormonal product of the HPA axis, cortisol, is considered an appropriate ‘biomarker of stress’ and appropriate for use in studies investigating the effect of stress on pregnancy outcomes. However evidence is again inconclusive about the association between cortisol and IVF treatment outcomes. One outstanding methodological limitation of the previous evidence was the reliance on short-term measures of cortisol which, by their very nature, only provide information about cortisol levels over minutes (e.g., in saliva/blood) to hours (e.g., in urine/follicular fluid). The development of methods to measure systemic levels of cortisol over longer periods in hair has been an important innovation in the attempts to examine the relationship between stress and IVF treatment outcomes. Compared with other acute measures of cortisol, hair cortisol sampling is less invasive, less affected by compliance, and reflects the cumulative cortisol exposure over extended periods of up to six months. Recent studies have indicated an inverse relationship between higher hair cortisol levels and the likelihood of achieving pregnancy following IVF treatment. Such studies, however, are limited by small sample sizes and lack of inclusion of lifestyle factors (e.g., physical activity and sleep) which may influence both cortisol and IVF treatment outcomes.
This thesis presents findings from a prospective cohort study which aimed to build upon previous work by: (1) examining the relationship between hair cortisol levels before commencing IVF treatment, and clinical pregnancy; but also examining the relationship across two important treatment outcomes: biochemical pregnancy and discontinued treatment; (2) examining the relationship between lifestyle and mood factors and the three treatment outcomes both directly, and indirectly through the hair cortisol before commencing IVF treatment.
This study included 234 women undergoing IVF or intracytoplasmic sperm injection (ICSI) from a fertility clinic in the United Kingdom (January 2018 – August 2019), with an average age of 34.4 years (SD = 4.6). This study found no significant association between hair cortisol prior to commencing IVF/ICSI treatment and clinical pregnancy, biochemical pregnancy, or discontinued treatment. Lifestyle and mood factors were not significantly associated with any of the three treatment outcomes either directly or indirectly through pre-treatment hair cortisol. However, it was observed that women undergoing IVF/ICSI treatment were likely to report poor sleep quality and high levels of depression before treatment. Poor sleep quality was significantly correlated with greater anxiety, depression, negative mood, and lower positive mood. A positive association between hair cortisol levels and depression was also observed.
Implications of this study are three fold. Firstly, the null associations indicated that cortisol may not be a major pathway for chronic stress to influence treatment outcomes of IVF/ICSI treatment. Other pathways such as the sympathetic and parasympathetic systems could be focus of future studies. Secondly, although this study did not find significant associations between lifestyle and mood factors and treatment outcomes either directly or indirectly through hair cortisol, it suggested that women were likely to experience poor sleep quality before treatment, which might be relevant to their experience of stress. Thirdly, this study supported an association between hair cortisol and depression among women undergoing IVF/ICSI treatment. This study added to the evidence base that hair cortisol might be a useful tool to monitor long-term psychological distress. Under the current environment of a global pandemic which has been ongoing for more than two years at the time of writing, utilising hair cortisol as a tool to measure stress is valuable for understanding the long-term health consequences of chronic stress.
The unique contributions of this study lie in its methodological and theoretical considerations: (1) use of hair cortisol to reflect chronic levels of stress; (2) inclusion of lifestyle and mood factors and use of mediation analysis to examine the possible indirect associations between these factors and treatment outcomes; (3) exploration of the association of lifestyle and mood factors and long-term cortisol levels to extend the literature that focused on acute measures of cortisol. Based on the findings of this thesis, future studies are encouraged to investigate how sleep quality and depression are associated and how they influence patients undergoing IVF treatment. Tools such as hair cortisol might be helpful to explore the underlying mechanism of these possible associations.
Item Type
ethesis
Thesis Type
PhD
Supervisors
Subjects (LC)
Associated Schools / Departments
School of Medicine
eprints ID
69862
UoN Repository URI
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