Stressful Life Events Are Associated With a Poor IVF Outcome
Stressful Life Events Are Associated With a Poor IVF Outcome
Background: There is preliminary evidence to suggest an impact of stress on chances of achieving a pregnancy with in-vitro fertilization (IVF). The majority of the available research has focused on stress related to infertility and going through IVF-treatment, and it is still unclear whether non-fertility-related, naturally occurring stressors may influence IVF pregnancy chances. Our aim was to explore the association between IVF-outcome and negative, i.e. stressful, life-events during the previous 12 months.
Methods: Prior to IVF, 809 women (mean age: 31.2 years) completed the List of Recent Events (LRE) and questionnaires measuring perceived stress and depressive symptoms.
Results: Women who became pregnant reported fewer non-fertility-related negative life-events prior to IVF (Mean: 2.5; SD: 2.5) than women who did not obtain a pregnancy (Mean: 3.0; SD: 3.0) (t(465.28) = 2.390, P = 0.017). Logistic regression analyses revealed that the number of negative life-events remained a significant predictor of pregnancy (OR: 0.889; P = 0.02), when controlling for age, total number of life-events, perceived stress within the previous month, depressive symptoms, and relevant medical factors related to the patient or treatment procedure, including duration of infertility, number of oocytes retrieved and infertility etiology. Mediation analyses indicated that the association between negative life events and IVF pregnancy was partly mediated by the number of oocytes harvested during oocyte retrieval.
Conclusion: A large number of life-events perceived as having a negative impact on quality of life may indicate chronic stress, and the results of our study indicate that stress may reduce the chances of a successful outcome following IVF, possibly through psychobiological mechanisms affecting medical end-points such as oocyte retrieval outcome.
Between 10 and 15% of all couples experience fertility problems due to a variety of causes (Schmidt et al., 1995; Eugster and Vingerhoets, 1999; Juul et al., 1999), and infertility is increasing in the industrialized countries, possibly due to social and behavioural factors along with environmental exposures (Skakkebaek et al., 2006). Infertility is commonly defined as failure to conceive after at least 1 year of attempting to achieve a pregnancy with unprotected intercourse (Schmidt, 2006; Dansk Fertilitetsselskab, 2007). Couples suffering fertility problems frequently turn to artificial reproductive technology (ART), and it is assumed that ~50% of all Danish couples experiencing infertility seek ART treatment (Schmidt et al., 1995). In Denmark, the number of initiated treatments with in-vitro fertilization (IVF) and intra cytoplasmatic sperm injection (ICSI) performed at public and private fertility clinics has increased by 83%, from approximately 6000 per year to more than 11 000 per year, within the last 10 years (National Board of Health D, 2006; The Danish Fertility Society, 2009).
There is evidence to suggest that psychological factors may influence the chances of obtaining a pregnancy with IVF (Eugster and Vingerhoets, 1999; Klonoff-Cohen, 2005; Boivin and Schmidt, 2005). A number of studies have shown associations between distress, mostly anxiety and depression, and IVF-outcome, although a few studies have been unable to confirm this link (Milad et al., 1998; Lovely et al., 2003; de Klerk et al., 2008). Such findings are often reported as studies on effects of 'stress' on IVF-outcome (Harlow et al., 1996; Csemiczky et al., 2000; Lovely et al., 2003; Smeenk et al., 2005). However, the instruments used in these studies are generally measures of various types of distress which may be unrelated to external factors. The majority of the available studies therefore do not qualify as studies of stress.
The term 'stress' is, in fact, often confused with distress, which, although considered part of the same process, is a different phenomenon. The stress process is generally considered to consist of three aspects: (1) a stressor, i.e. an environmental demand, e.g. a life event or a series of life events, followed by (2) a set of appraisals and the perception of stress, which then may lead to (3) affective, behavioural and/or biological stress responses (i.e. distress) (Cohen et al., 1995). Perception of stress results when the individual finds the environmental demands taxing and/or threatening, and at the same time feels insufficiently able to cope with the demands due to lack of personal or environmental resources (Cohen et al., 1995). According to the original conceptualization of a stressor, it is defined as 'that which produces stress' (Selye, 1976).
However, there is a challenge in assessing stressors in terms of life events, as the interpretation of and capacity to handle an experienced event both emotionally and practically is highly individual (Cohen et al., 1995).
For our purpose of examining the possible association between stress and reproductive outcomes, stress is defined as events or environmental demands (i.e. stressors), rated by the individual as having had a negative influence on her quality of life. These events will from here on be referred to as 'negative life events'. The psychobiological effects of stress may potentially be long-lasting and persist even after the stressor has ceased to act (Selye, 1976).
Only very few studies of stress in the strict sense of the term and IVF-outcome have been conducted, focusing primarily on perceived marital stress and perceived stress caused by infertility and IVF-treatment. Infertility can indeed be very stressful for the affected couples (Berg et al., 1991; Eugster and Vingerhoets, 1999; Oddens et al., 1999; Webb and Daniluk, 1999; Peterson et al., 2003, 2006; Throsby and Gill, 2004; Schmidt et al., 2005a, b), and two large studies conducted with IVF-populations have found some support for infertility-related stress as a predictor of IVF-outcome (Klonoff-Cohen et al., 2001; Boivin and Schmidt, 2005). Another study, however, found the opposite result, i.e. higher infertility-related stress in the group that subsequently achieved a pregnancy (Cooper et al., 2007). One study measured IVF-treatment related stress (Klonoff-Cohen and Natarajan, 2004) and found this source of stress to be a predictor of the number of retrieved and fertilized oocytes. Women who prior to treatment had severe concerns about the medical aspects of the procedure, about missing work, or about finances, had up to 20% fewer oocytes retrieved and fertilized, which affected their pregnancy chances negatively. The third type of stressor studied in relation to IVF-treatment outcome, perceived marital stress, has also been associated with treatment outcome, in that the number of cycles-to-pregnancy was higher in women reporting high-marital stress compared with women reporting low-marital stress (Boivin and Schmidt, 2005). Preliminary evidence for an association between perceived marital stress and IVF outcome has also found partial support in two other studies (Stoleru et al., 1997; Verhaak et al., 2001). Finally, two studies (Facchinetti et al., 1997; Gallinelli et al., 2001) have provided evidence for an effect of experimentally induced stress on IVF-outcome using the Stroop Color Word Test (Stroop, 1935).
Taken together the available evidence is limited, yet suggestive of a stress effect on IVF-outcome. The majority of the available research has focused on perceived stress in relation to infertility and IVF-treatment, which may be confounded by the couples' knowledge about their prognosis, and it is still unclear whether naturally occurring stressors, which are unrelated to infertility, may influence pregnancy chances following IVF. The aim of our study was therefore to investigate the possible association between negative life events and pregnancy chances in a sample of women in IVF-treatment at a large regional university hospital fertility clinic. We hypothesized that an increase in the number of negative life events would be associated with reduced chances of obtaining IVF-induced pregnancy. Stress may impact fertility possibly by interrupting menstrual cycles (Chrousos and Gold, 1992; Ferin, 1999) or through a poorer ovarian functional response to IVF-treatment (Klonoff-Cohen and Natarajan, 2004). We therefore planned to explore the possible role of the number of retrieved oocytes as a possible mediator of this association, if an association between negative life events and pregnancy chances was found.
Abstract and Introduction
Abstract
Background: There is preliminary evidence to suggest an impact of stress on chances of achieving a pregnancy with in-vitro fertilization (IVF). The majority of the available research has focused on stress related to infertility and going through IVF-treatment, and it is still unclear whether non-fertility-related, naturally occurring stressors may influence IVF pregnancy chances. Our aim was to explore the association between IVF-outcome and negative, i.e. stressful, life-events during the previous 12 months.
Methods: Prior to IVF, 809 women (mean age: 31.2 years) completed the List of Recent Events (LRE) and questionnaires measuring perceived stress and depressive symptoms.
Results: Women who became pregnant reported fewer non-fertility-related negative life-events prior to IVF (Mean: 2.5; SD: 2.5) than women who did not obtain a pregnancy (Mean: 3.0; SD: 3.0) (t(465.28) = 2.390, P = 0.017). Logistic regression analyses revealed that the number of negative life-events remained a significant predictor of pregnancy (OR: 0.889; P = 0.02), when controlling for age, total number of life-events, perceived stress within the previous month, depressive symptoms, and relevant medical factors related to the patient or treatment procedure, including duration of infertility, number of oocytes retrieved and infertility etiology. Mediation analyses indicated that the association between negative life events and IVF pregnancy was partly mediated by the number of oocytes harvested during oocyte retrieval.
Conclusion: A large number of life-events perceived as having a negative impact on quality of life may indicate chronic stress, and the results of our study indicate that stress may reduce the chances of a successful outcome following IVF, possibly through psychobiological mechanisms affecting medical end-points such as oocyte retrieval outcome.
Introduction
Between 10 and 15% of all couples experience fertility problems due to a variety of causes (Schmidt et al., 1995; Eugster and Vingerhoets, 1999; Juul et al., 1999), and infertility is increasing in the industrialized countries, possibly due to social and behavioural factors along with environmental exposures (Skakkebaek et al., 2006). Infertility is commonly defined as failure to conceive after at least 1 year of attempting to achieve a pregnancy with unprotected intercourse (Schmidt, 2006; Dansk Fertilitetsselskab, 2007). Couples suffering fertility problems frequently turn to artificial reproductive technology (ART), and it is assumed that ~50% of all Danish couples experiencing infertility seek ART treatment (Schmidt et al., 1995). In Denmark, the number of initiated treatments with in-vitro fertilization (IVF) and intra cytoplasmatic sperm injection (ICSI) performed at public and private fertility clinics has increased by 83%, from approximately 6000 per year to more than 11 000 per year, within the last 10 years (National Board of Health D, 2006; The Danish Fertility Society, 2009).
There is evidence to suggest that psychological factors may influence the chances of obtaining a pregnancy with IVF (Eugster and Vingerhoets, 1999; Klonoff-Cohen, 2005; Boivin and Schmidt, 2005). A number of studies have shown associations between distress, mostly anxiety and depression, and IVF-outcome, although a few studies have been unable to confirm this link (Milad et al., 1998; Lovely et al., 2003; de Klerk et al., 2008). Such findings are often reported as studies on effects of 'stress' on IVF-outcome (Harlow et al., 1996; Csemiczky et al., 2000; Lovely et al., 2003; Smeenk et al., 2005). However, the instruments used in these studies are generally measures of various types of distress which may be unrelated to external factors. The majority of the available studies therefore do not qualify as studies of stress.
The term 'stress' is, in fact, often confused with distress, which, although considered part of the same process, is a different phenomenon. The stress process is generally considered to consist of three aspects: (1) a stressor, i.e. an environmental demand, e.g. a life event or a series of life events, followed by (2) a set of appraisals and the perception of stress, which then may lead to (3) affective, behavioural and/or biological stress responses (i.e. distress) (Cohen et al., 1995). Perception of stress results when the individual finds the environmental demands taxing and/or threatening, and at the same time feels insufficiently able to cope with the demands due to lack of personal or environmental resources (Cohen et al., 1995). According to the original conceptualization of a stressor, it is defined as 'that which produces stress' (Selye, 1976).
However, there is a challenge in assessing stressors in terms of life events, as the interpretation of and capacity to handle an experienced event both emotionally and practically is highly individual (Cohen et al., 1995).
For our purpose of examining the possible association between stress and reproductive outcomes, stress is defined as events or environmental demands (i.e. stressors), rated by the individual as having had a negative influence on her quality of life. These events will from here on be referred to as 'negative life events'. The psychobiological effects of stress may potentially be long-lasting and persist even after the stressor has ceased to act (Selye, 1976).
Only very few studies of stress in the strict sense of the term and IVF-outcome have been conducted, focusing primarily on perceived marital stress and perceived stress caused by infertility and IVF-treatment. Infertility can indeed be very stressful for the affected couples (Berg et al., 1991; Eugster and Vingerhoets, 1999; Oddens et al., 1999; Webb and Daniluk, 1999; Peterson et al., 2003, 2006; Throsby and Gill, 2004; Schmidt et al., 2005a, b), and two large studies conducted with IVF-populations have found some support for infertility-related stress as a predictor of IVF-outcome (Klonoff-Cohen et al., 2001; Boivin and Schmidt, 2005). Another study, however, found the opposite result, i.e. higher infertility-related stress in the group that subsequently achieved a pregnancy (Cooper et al., 2007). One study measured IVF-treatment related stress (Klonoff-Cohen and Natarajan, 2004) and found this source of stress to be a predictor of the number of retrieved and fertilized oocytes. Women who prior to treatment had severe concerns about the medical aspects of the procedure, about missing work, or about finances, had up to 20% fewer oocytes retrieved and fertilized, which affected their pregnancy chances negatively. The third type of stressor studied in relation to IVF-treatment outcome, perceived marital stress, has also been associated with treatment outcome, in that the number of cycles-to-pregnancy was higher in women reporting high-marital stress compared with women reporting low-marital stress (Boivin and Schmidt, 2005). Preliminary evidence for an association between perceived marital stress and IVF outcome has also found partial support in two other studies (Stoleru et al., 1997; Verhaak et al., 2001). Finally, two studies (Facchinetti et al., 1997; Gallinelli et al., 2001) have provided evidence for an effect of experimentally induced stress on IVF-outcome using the Stroop Color Word Test (Stroop, 1935).
Taken together the available evidence is limited, yet suggestive of a stress effect on IVF-outcome. The majority of the available research has focused on perceived stress in relation to infertility and IVF-treatment, which may be confounded by the couples' knowledge about their prognosis, and it is still unclear whether naturally occurring stressors, which are unrelated to infertility, may influence pregnancy chances following IVF. The aim of our study was therefore to investigate the possible association between negative life events and pregnancy chances in a sample of women in IVF-treatment at a large regional university hospital fertility clinic. We hypothesized that an increase in the number of negative life events would be associated with reduced chances of obtaining IVF-induced pregnancy. Stress may impact fertility possibly by interrupting menstrual cycles (Chrousos and Gold, 1992; Ferin, 1999) or through a poorer ovarian functional response to IVF-treatment (Klonoff-Cohen and Natarajan, 2004). We therefore planned to explore the possible role of the number of retrieved oocytes as a possible mediator of this association, if an association between negative life events and pregnancy chances was found.
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