Stress and Fertility – What’s the real scoop?!


July 20th, 2016

Sooooo…. I have applied to Adler School of Psychology to do my MPsy.  I have my interview coming up and am hoping to get in! As the first order of business, applicants took a “Thrive and Survive in Graduate School” course which entailed writing an essay.

I chose to write about stress and fertility, as it is very relevant in my life right now.  I have attached it here for your reading pleasure!  Sorry it’s lengthly, but I believe it’s well worth the read.  In the interest of space, I am not including the list of references here, but if you would like to see it, just shoot me an email.

Be Well,
Melissa  :)

 

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Exploring the Relationship between Stress and Fertility in Women: Implications for Clinical Intervention

 
“Just relax, and it will happen!” Well meaning friends and family, as well as various health and helping professionals have said this to me over the past six years that my husband and I have been trying to have a baby. However, is this an old wives’ tale or is there actual empirical evidence in support of this? If a woman has various stressors in her life, such as a highly demanding job or a sudden move or a sick parent or a death in the family or looking at advancements in her career, could this impede upon her ability to get pregnant? The purpose of this paper is to explore the complex relationship between stress and fertility in women.

 
Impact of stress on fertility
From a biological and chemical and perspective, it does seem feasible that stress hormones could interfere with reproductive hormones. Several researchers have noted the role of the stress hormone system called the hypothalamic-pituitary-adrenal (HPA) axis (Coubrough, 1985; Harrison et al., 2005; Negro-Villar, 1993; Sanders and Bruce, 1997). When stressed, the hypothalamus releases corticotropin-releasing factor (CRF), which then stimulates the pituitary gland to release adrenocorticotropin hormone (ACTH), which in turn stimulates the adrenal glands to secrete stress hormones including: cortisol, adrenaline and noradrenaline (Coubrough, 1985; Harrison et al., 2005; Negro-Villar, 1993).

 
When the adrenal gland releases adrenaline and noradrenaline, part of the flight or flight response is activated and this may interfere with transporting gametes through the fallopian tubes or by altering uterine blood flow (Sanders and Bruce, 1997). Increased CRF and cortisol may also lead to suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are the hormones responsible for ovulation (Coubrough, 1985; Harrison et al., 2005; Negro-Villar, 1993). Without ovulation, there is no egg for the sperm to fertilize. Disruption of ovulation also affects progesterone and estrogen levels, which are partially responsible for the regulation of fallopian tube motility (Harrison et al. 2005). When a stressor takes place, it immediately activates changes in these various hormones, and the body may adapt and distribute metabolic activity away from digestion and reproduction, in order to maintain other vital functions (Harrison et al., 2005; Negro-Villar, 1993).

 
In animal research, stress can be brought on in various ways, including environmental temperature, light, prolonged noise, isolation, confined spaces and moving locations (Coubrough, 1985). For example, with moving comes the stress of transport and the strangeness of the new environment which alters adrenal function, and was found to ultimately reduce fertility in cattle for up to two months (Coubrough 1985). Coubrough (1985) indicated that “Because of the clear influence of stressors on signal hormones of reproduction, some effect of stress on fertility is inescapable” (p. 155). The degree of the effect of stress would be determined by the intensity and duration of the stress (Coubrough, 1985) as well as the individual’s tolerance of stress (Bethea et al., 2005). Bethea et al. (2005) found in a study of 13 female cynomolgus monkeys that the combination of mild psychosocial stress (moving to unfamiliar surroundings), decreased food and increased activity level lead to a significantly greater release of cortisol, thus decreasing fertility, for stress-sensitive animals compared to high stress-resilient animals.

 
Cortisol can also impact upon fertility through suppressing the immune system (Sanders and Bruce, 1997), which then causes inflammation in the reproductive organs (Harrison et al., 2005). Immunological changes can impact on the ability of the body to accept foreign substances, such as an embryo (Gallinelli et al., 2001). For example, in a study with 40 women undergoing In Vitro Fertilization (IVF) fertility treatment, Gallinelli et al. (2001) found that prolonged stress was associated with high amounts of activated T cells in peripheral blood (T cells are a lymphocyte that is a subtype of white blood cells that attack infected cells) and a lower implantation rate of the embryo. It could be that the T cells mistakenly saw the embryo as an intruder. Thus, the chain reaction from the stressful event through to the various hormonal and immune system reactions can interfere with fertility.

 
Excessive stress may cause various reproductive issues in women, namely psychologic amenorrhea (no menses when stressed), pseudocyesis (phantom pregnancy), menstrual dysfunction, early pregnancy failure, (Negro-Villar, 1993), chronic anovulation (ovary not releasing egg) (Coubrough, 1985; Negro-Villar, 1993), delayed ovulation, cystic ovarian degeneration, (Coubrough, 1985), reduced fertilization/ conception rates, spontaneous abortions, (Coubrough, 1985 and Klonoff-Cohen, 2009), no live birth deliveries, low birth infants, multiple gestations, (Klonoff-Cohen, 2009), endometriosis (Harrison et al., 2005), longer natural cycles and poorer response to fertility treatment (Boivin and Schmidt, 2005). For example, Negro-Villar (1993) noted that changes in cortisol levels were found in women who had psychologic amenorrhea, which was more common for women who had stressful lives and occupations, were underweight, single and had a history of drug use.

 
From a behavioural perspective, stress can influence lifestyle habits and unhealthy coping strategies which can also have an impact on infertility. For example, eating disorders (under-eating or over-eating), overly intense exercise, (Negro-Vilar, 1993), caffeine intake, alcohol consumption (Klonoff-Cohen, 2009; Louis et al., 2011) and cigarette smoking (Louis et al., 2011). Louis et al. (2011) found that the highest mean caffeine (coffee, tea, pop, chocolate) consumption was in women who experienced pregnancy losses and Klonoff-Cohen (2009) found that caffeine had an impact on miscarriages, not achieving pregnancy and infant gestational age. It appears important, then, to use effective healthy coping strategies to manage stress and achieve well-being, to improve the chances of having full term healthy baby.

 
From a psychological perspective, stress can affect general mood which can in turn impact upon infertility. Psychologic distress has generally been recognized as a contributing factor to infertility (Negro-Vilar, 1993). For example, Barry et al. (2011) found that women with polycystic ovarian syndrome (PCOS) had significantly more difficulty coping with stress, were more neurotic, had more anger symptoms, withheld feelings of anger, and experienced more anxiety and depression than a control group of women with infertility problems that were not related to PCOS. Even when controlling for symptoms of PCOS with matched group comparisons, neuroticism and anger still remained higher in the PCOS group.

 
There was also a prospective study done by Sanders and Bruce (1997) that examined stress level and mood over several months for 13 women in the general community who were trying to conceive. The researchers collected samples to measure hormone levels (noradrenaline, adrenaline, and cortisol) and administered various questionnaires to assess psychosocial stress (State-Trait Anxiety Inventory and Bi-polar Profile of Mood States [POMS]) and lifestyle (sleep, work satisfaction, tiredness with work, time pressure, leisure time, and feelings of being hassled). Hassles were defined as irritants from minor annoyances to fairly major problems, pressures or difficulties.

 

 

The women reported significantly better mood states (more composed, agreeable, elated, confident, energetic, clear-headed), less anxiety and felt significantly less hassled during the month of conception compared to their previous non-conception (infertile) cycles. However, there was no significant difference in hormone secretions between the conception and non-conception cycles. There was also little relationship found between psychological mood and hormones during infertile cycles, aside from a negative association between noradrenaline and composed-anxious and clear-headed- confused scales of the POMS. In other words, during the infertile months, the higher the noradrenaline level, the less composed and clear-headed they were. During the conception cycle, there was a significant negative association between noradrenaline and the composed-anxious, agreeable-hostile and energetic-tired POMS scales. In other words, the month that women were successful in conceiving a baby, the higher the noradrenaline level, the less composed, agreeable and energetic they were.

 
There was also a trend for the women to find their work less mentally tiring and to get more adequate sleep during the conception cycle, although this relationship was not significant. Stress does appear to influence fertility in women, and the mechanism by which this occurs could be due to biological effects of stress on the quality or production of gametes, or on the subsequent fertilization, implantation or maintenance the pregnancy (Sanders and Bruce, 1997). It is important to capture data on not only hormones or the immune system, but also on psychological levels of distress.

 
There is inconsistent evidence in the literature of the impact of distress on fertility. Boivin et al. (2011) found that women’s emotional distress did not impact upon fertility. They performed a meta-analysis which included 14 studies of women who had undergone one cycle of a fertility treatment. Those 14 studies sampled a total of 3583 women in 10 different countries. The pretreatment emotional distress level, including depression and anxiety, before fertility treatment was not found to have an impact on achieving pregnancy. They only included studies that tested for anxiety and depression as a measure of emotional distress because they were reliably related to stress induced activation of the HPA axis. Boivin et al. (2011) pointed out that fertility rates are often highest in countries with harsh conditions such as war, famine and poverty, and so the hypothalamic-pituitary-gonadotrophin axis has likely evolved to guard against activation of the stress response in the HPA axis. They concluded that women and doctors should be reassured that emotional distress, whether caused by fertility issues or whether caused by other life events, would not compromise the chance of achieving pregnancy.

 
Impact of infertility on stress
It appears that stress could potentially have an impact on infertility through chemistry, biology, behaviour and/or psychology/mood, although the results are inconsistent. Alternatively, could infertility itself actually cause the stress? For women who experience more social pressure for motherhood, they viewed an infertility diagnosis as more stressful (Miles et al., 2009). In their study examining predictors of distress in infertile women, Miles et al. (2009) received personal statements from 56 participants, where they wrote about their experiences with infertility. They found that 55% of those women reported stress, anxiety and depression, and 27% wrote that infertility was “the most painful experience in their life” (p. 249). In addition, 12% expressed frustration with the lack of appropriate counselling services for those experiencing infertility treatment.

 
Not only is the diagnosis of infertility in and of itself stressful, but so are invasive infertility procedures such as IVF (Klonoff-Cohen, 2009). Greil et al. (2011) conducted a two wave national study comparing 266 infertile women who did and did not receive fertility treatments, in an effort to disentangle the effects of infertility treatment versus experiencing infertility on fertility-specific distress. The group with the highest increase in fertility-specific distress was the group that had fertility treatment at both waves and still did not have a child. The researchers found that infertility treatment itself is associated with levels of distress that are over and above those associated with the state of being infertile (Greil et al., 2011).

 
Eugster and Vingerhoets (1999) conducted a review of IVF research in the context of psychological state. They found that couples who entered into IVF treatment were generally well adjusted. The experience of waiting for the outcome of the treatment and the news of an unsuccessful IVF treatment were the most stressful for both men and women. During the IVF treatment, patients were commonly anxious and depressed, and after an unsuccessful IVF treatment, they were often sad, depressed and angry. Psychosocial factors, such as ineffective coping strategies, depression and/ or anxiety were associated with lower pregnancy rates with IVF treatment (Eugster and Vingerhoets, 1999).

 
Personally, I know first hand that the IVF treatment experience is stressful. It involves daily hormone injections of potent fertility drugs to stimulate the production of eggs making my ovaries feel like two uncomfortable tennis balls in your abdomen, painful progesterone oil needles administered into muscle, frequent visits to the infertility clinic for blood work and external and invasive internal ultrasounds, surgical transvaginal ultrasonography procedure (Boivin et al., 2011) to extract the eggs, fertilization of the eggs in the laboratory with the sperm, waiting impatiently for the embryos to develop, seeing embryos dying every day and hoping that the rest survive to the blastocyst stage (day 5 of development), another procedure to transfer the embryo(s) into the uterus, and finally the dreaded waiting for two to three weeks to find out whether our prayers have been answered. This is a stressful series of events which would all be absolutely worth it if the result is in our favour, but is devastating when it is not. Indeed, Boivin et al. (2011) found in a meta-analysis that there was significantly more distress in women who found out that they did not get pregnant compared to women who did get pregnant.

 
Klonoff-Cohen (2009) found that women who were concerned about the medical aspects of the IVF procedure by itself, such as side effects, surgery, anesthesia or pain, had 20% fewer oocytes (eggs) retrieved and 19% fewer oocytes fertilized. Further, women who were very concerned about missing work for the procedure had 30% fewer oocytes fertilized and those even moderately concerned about missing work had 2.83 times the risk of not achieving a pregnancy at all.

 

Another very recent study by Gana and Jakubowski (2016) found that infertility-related stress significantly predicted both emotional distress and, interestingly, marital distress. The effect was stronger for emotional distress, particularly life domains which included social, marital and sexual areas of the person’s life that are affected by infertility (Gana and Jakubowski, 2016).  It is plausible, therefore, that the diagnosis and subsequent treatment can itself contribute to the stress endured during the fertility journey.

 
Interaction of stress and fertility
Another alternative is that perhaps there is a reciprocal causation/ reciprocal determinism (Bandura, 1978) interaction, where daily chronic stress impacts upon infertility but also infertility increases daily chronic stress. According to Bandura’s (1978) model of reciprocal determinism, behaviour, cognitions and the external environment all interact with each other in such a way that each of these components interact with each other and influence each other. In applying this model, stress does not independently cause infertility and infertility does not independently cause stress. Rather, Bandura (1978) argues that personal and environmental factors do not function independently, but indeed determine each other. It is through actions that people produce environmental conditions that affect their behaviour in a reciprocal way. The experiences generated by behaviour also in part determine what people think, expect and do, which then affect their subsequent behaviour (Bandura 1978).

 
In application to fertility, the actions or behaviours can be over-working or under-eating or moving locations or drinking coffee that affects stress levels in a reciprocal fashion. The experience of infertility generated by the behaviour then determine self-perceptions, such as ruminating over the personal failure of being infertile (Gana and Jakubowski, 2016), and affect subsequent behaviour, which could look like seeking out fertility treatment. The experience of seeking out fertility treatment then has an interactive relationship that makes the person more stressed, which further impacts upon the infertility issues.

 
Wright et al. (1989) conducted a review of the research on psychosocial distress and infertility. In the 30 publications that they examined, they found that overall, patients diagnosed and treated in infertility clinics showed significantly higher psychosocial distress compared to control groups. However, it was difficult for them to conclude the exact nature of the relationship, namely whether psychosocial issues trigger infertility or infertility triggers psychosocial distress or whether there was an interactive causal relationship between infertility and psychosocial distress. More longitudinal research is required in order to make definitive conclusions (Wright et al., 1989).

 
The interactive causal relation can also include the couples’ marital relationship in the fertility process, as an external factor. Gana and Jakubowska (2016) found that there was an interaction between emotional distress and marital dissatisfaction in fertility. The more emotional distress people experience, the more dissatisfied in their marriage they were, and the more marital dissatisfaction they experience, the more emotionally distressed they were. This is in line with Bandura’s (1978) model of reciprocal determinism.

 
Further research is required in order to fully understand the exact relationship between stress and fertility. It is difficult to draw definitive conclusions due to the wide variation in study methods and measures of outcome, for example, in measures of emotional distress. The Spielberger State-Trait Anxiety Inventory has been the most commonly used tool (Boivin et al., 2011), but perhaps that is not specific enough to assess problems of infertility (Greil et al., 2011). In fact, there have been tools designed to measure infertility distress, such as the Fertility Problem Inventory (Newton et al., 1999). The Fertility Problem Inventory encompasses five dimensions: social concern, sexual concern, relationship concern, rejection of a childfree lifestyle, and need for parenthood.

 
It would also be helpful for future studies to include more data on men (Boivin and Schmidt, 2005; Negro-Vilar, 1993) and couples (Gana and Jakubowska, 2016). Limited research on men shows that stress for men is also related to infertility issues, namely poor semen quality (count, motility, morphology) (Boivin and Schmidt, 2005; Negro-Vilar, 1993), impotence, ejaculatory disorders and decreased serum lutinizing hormone and testosterone (Negro-Vilar, 1993). Men’s lifestyle habits can also have an impact on fertility. For instance, Klonoff-Cohen (2009) found that men’s alcohol use was associated with spontaneous miscarriages and not achieving a live birth.

 
Clinical Interventions
Although there is no conclusive empirical evidence as yet to demonstrate that reducing stress leads to higher take home baby rates (Boivin, 2003), there is mounting evidence to show that less stress is conducive to better fertility (Campagne, 2006). Given this information, it may be worth it to make attempts to reduce stress or learn to cope better with stress before even starting fertility treatments (Campagne, 2006). Doing so may make the fertility treatment no longer necessary or reduce the number of treatment cycles required before pregnancy is achieved, or it may prepare the couple for an initial failure of treatment if it comes to that (Campagne, 2006).

 

There are numerous infertility interventions available which have shown very positive results in lowering stress, such as acupuncture (Balk et al., 2010), Integrative Body-Mind-Spirit (I-BMS) therapy (Chan et al., 2012), art therapy (Hughes, 2010), expressive writing (Matthiesen et al., 2012), group therapy (Domar et al., 2000), hypnosis (Levitas et al., 2006) and even clown therapy (medical clown visits after an embryo transfer) (Friedler et al., 2011). Some of these have demonstrated success in improving pregnancy rates. For example, acupuncture for 57 women undergoing IVF treatment resulted in a 64.7% pregnancy rate compared to 42.5% who achieved pregnancy without acupuncture (Balk et al., 2010).

 

Chan et al. (2012) outlines a full I-BMS program for women in their first IVF treatment. They have four group sessions for I-BMS that involve education on the interconnectedness of body, mind and spirit, along with acceptance, forgiveness, self-love, letting go of high IVF expectations and growing through pain and personal transformation. Using a randomized controlled study of 339 women, they taught treatment participants mindfulness (living in the moment) and relaxation skills such as guided imagery and meditation. Although there was no significant difference found in biological outcomes (pregnancy) between the intervention group and control group, they did find that compared to baseline for the treatment group, they had significant decreases in trait anxiety, lower levels of physical distress, and disorientation. They reported being more tranquil and had significant increases in marital satisfaction. They also saw childbearing as less important compared to the control group. In other words, they were more accepting of the outcome in the event that no pregnancy was achieved. Disorientation (lack of vitality and loss of direction) could occur in women who see having a child as their next life goal and may feel blocked and incapable of moving forward if they are not able to conceive (Chan et al., 2012). To address this, the intervention group was encouraged to re-evaluate their life goals, focusing on personal fulfillment and broadening their perspectives, regardless of whether or not they become pregnant.  These types of programs would be helpful for women and couples going through fertility treatment, even if the result is better overall well-being and not achieving pregnancy.

 

Boivin (2003) compared psychosocial interventions in infertility, and found that when compared to counselling interventions, educational interventions resulted in twice as many positive changes across various measures including negative affect, interpersonal functioning and pregnancy. The most successful interventions lasted for six to 12 weeks, had a follow-up period of at least six months, and had strong educational and skills training and/or group format that emphasized medical knowledge and learning stress management and coping techniques (Boivin, 2003). Infertility education may increase understanding of the implications of infertility for the couples’ psychological health and help to eliminate the social stigma attached to childless families (Ridenour et al., 2009).

 
It would be helpful for clinical interventions to include the couple. Boivin and Schmidt (2005) found that higher marital stress, higher personal stress, older age and more years struggling with infertility were each associated with poorer fertility treatment outcome. Thus, strains on the marital relationship that are caused by fertility issues, could interfere with the success of the fertility treatment, and could actually make couples discontinue with treatment (Boivin and Schmidt, 2005). Boivin and Schmidt (2005) found that women who had more marital distress required more treatment cycles to conceive a child than women who had less marital distress.
Women require a supportive marital relationship to help them adjust to infertility diagnosis and to infertility treatment, especially if the treatment fails (Boivin and Schmidt, 2005). Experiencing the infertility journey together can either strengthen the couple or create a strain in the relationship. Peterson et al. (2003) found that couples who perceived an equal level of social infertility stress reported greater marital adjustment in comparison to couples who perceived the stress differently. High congruence, or agreement, between partners in relation to the stresses that they experience help them to successfully manage the impact of those stressful life events (Peterson et al., 2003). Thus, if couples view the infertility journey in the same way, then they are more likely to be stronger as a couple as a result.
Ridenour et al. (2009) developed an Infertility Resilience Model (IRM) that encompasses the individual, the couple, and external factors that influence resilience to infertility-related stress. The model provides research-based guidelines for assessing a couples’ level of resilience in relation to infertility. In the IRM, external or environmental influences (such as duration of infertility, culture, social support, etc.) affect each person, which forms the individual perception, and the collective perception or the congruence within the couple creates the couples’ resiliency. Protective factors for the couple could include the quality of the relationship that the couple had before infertility, communication skills, access to information and access to infertility treatments. Individual protective factors could include mental health and religion or spirituality. Ultimately resilience results in acceptance of infertility regardless of infertility treatment outcomes or external influences (Ridenour et al., 2009).
Ridenour et al. (2009) created a sample assessment questionnaire based on the IRM, that would be helpful for clinicians in working with couples. Sample items from this questionnaire include: “Do you feel pressure when friends and acquaintances become pregnant?”, “Is it wise to make a decision if your partner still has reservations?” and “How do you see your relationship if you were unable to have children?” (Appendix A, p. 47-48). A thorough assessment would allow the therapist to understand the individual circumstances and how these may affect couple interactions.
In closing, I feel blessed to have what I call “My Preconception Dream Team”, working with us to help us to achieve our goal of parenthood. We have a nutritionist, bio-energetic practitioner, naturopathic doctor who uses acupuncture, a massage therapist who is also a doula, a psychologist who is familiar with fertility issues and of course our fertility doctor. They do mainly work with me, but they have helped my husband as well. They help to make sure that my hormone levels are in their proper balance, we are taking the appropriate vitamins and supplements, we’re taking time to de-stress, we’re eating healthy foods that help with fertility, we have an open space to talk about our fertility journey and we are taking the appropriate medical measures. Reflecting upon all of the above research, I feel very lucky to have a husband who I feel congruent with as we continue to proceed along this fertility journey. I feel ever hopeful, that despite my highly demanding job, pending move, sick parent, recent death in the family and applying to an incredible graduate school, that we are resilient, and our dreams of being parents will come true. Together, we continue to remain hopeful, and whatever the outcome, we will accept it and embrace it.

 


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