Stress and Fertility

Intervention #20 Stress
 
Fact Check

  • People with infertility often experience emotional distress.
  • Stress predisposes people to have less sex and is the main reason for people to stop fertility treatment.
  • Professional guidance in a cognitive-behavioural group approach may be the most efficient approach to manage stress.

Does Infertility Cause Stress?

Patients with infertility experience a significant amount of emotional distress as the result of their diagnosis. The inability to reproduce can cause feelings of shame, guilt, and low self-esteem. These negative feelings may lead to varying degrees of depression, anxiety, distress, and a poor quality of life.

  • In a study, 40% of women were diagnosed as having anxiety, depression, or both.
  • Another study showed a 31% prevalence of psychiatric symptoms, the most common of which was major depression.
  • In a large Danish study of 42 000 women who underwent ART treatment and were screened for depression prior to treatment, 35% screened positive.
  • In another recent study of 174 women undergoing infertility treatment, 39% met the criteria for major depressive disorder.
  • A recent literature review on the prevalence of psychological symptoms in infertility concluded that 25% to 60% of infertile individuals report psychiatric symptoms and that their levels of anxiety and depression are significantly higher than in fertile controls.
  • The medications used to treat infertility, including clomiphene, leuprolide, and gonadotropins, are associated with psychological symptoms such as anxiety, depression, and irritability. Thus, when assessing symptoms of women mid-treatment, it is difficult to differentiate between the psychological impact of infertility versus the side effects of the medication.

Does Stress Cause Infertility?

Whilst it is clear that infertility causes emotional distress, it is not so clear if stress causes infertility. We know however that people behave differently when stressed, and some of those stress induced behaviours can impact fertility:

  • Stress makes people eat a high fat diet (obesity is associated with poor ART outcomes).
  • Stress makes people who smoke, smoke more (also associated with poor outcomes ART).
  • Stress makes people less likely to start treatment.
  • Stress makes people more likely to stop treatment.
  • Stress makes relationships breakdown or be disrupted.
  • Stress makes people avoid making decisions.

We also know that the physiological response to stress (through the HPA and HPT axis) can impact reproductive hormones.

The HPA Axis

The hypothalamic-pituitary-adrenal axis (HPA) refers to the relationship between the hypothalamus, the pituitary gland and the adrenal glands. It plays a key role in basal homeostasis and in the body's response to stress.
When faced with a stressful situation (either physical, immunological or psychological), the brain initiates a cascade of events involving the HPA axis. The hypothalamus signals the pituitary gland to produce a hormone, which in turn signals the adrenal glands (located above the kidneys), to increase the production of glucocorticoids, including cortisol (known as the stress hormone). Cortisol increases the level of energy to help us cope with the stressful situation.


Glucocorticoids are important for regulating the immune system and reducing inflammation. While this is valuable during stressful or threatening situations where injury might result in increased immune system activation, chronic stress can result in impaired communication between the immune system and the HPA axis. This impaired communication has been linked to the future development of numerous physical and mental health conditions, including chronic fatigue, metabolic disorders (e.g., diabetes, obesity), depression and immune disorders.


The HPT Axis

A different pathway, called hypothalamic-pituitary-thyroid (HPT) axis is also responsible for some stress response. It refers to the relationship between the hypothalamus, pituitary gland and thyroid gland.

The hypothalamus produces thyrotropin-releasing hormone (TRH). The TRH stimulates the anterior pituitary to produce thyroid-stimulating hormone (TSH). The TSH, in turn, stimulates the thyroid to produce thyroid hormone T3 and T4 until levels in the blood return to normal.


This axis is largely genetically determined but may also be malleable to environmental demands such as psychosocial stress. HPA production of CRH and cortisol, suppresses HPT production of TSH and prevents the conversion of T4 to T3.


Relationship between HPA, HPG and HPT axis

The hypothalamic-pituitary-gonadal axis (HPG) is an important part of the reproductive system. It regards the relationship between the hypothalamus, pituitary gland, and gonads (ovaries and testicles). The hypothalamus produces Gonadotropin-releasing hormone (GnRH). This induces the synthesis and release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland, which trigger testosterone release from the testis and estradiol and progesterone release from the ovaries. A feedback loop exists whereby gonadal hormones communicate and impact with hypothalamus and pituitary hormones.


There exists a reciprocal relationship between the hypothalamic-pituitary-adrenal (HPA) and the hypothalamic-pituitary-gonadal (HPG) axes wherein the activation of one affects the function of the other and vice versa. Increased levels of glucocorticoids (like cortisol) promote gluconeogenesis, mobilization of amino acids, and stimulation of fat breakdown to maintain circulating levels of glucose necessary to mount a stress response. In addition glucocorticoids affect gonadal function at multiple levels in the hypothalamo-pituitary-gonadal axis:

  1. The hypothalamus (to decrease the synthesis and release of GnRH);
  2. the pituitary gland (to inhibit the synthesis and release of LH and FSH);
  3. the testis/ovary (to modulate steroidogenesis and/or gametogenesis directly).



It is believed this happens in consequence of the HPA production of glucocorticoids which upregulate Gonadotropin-inhibitory hormone (GnIH) release in the hypothalamus. GnIH is thought to reduce pituitary gland production of LH and FSH which in turn impact gonadal production of oestrogen and testosterone.

There is also a relationship between the hypothalamic-pituitary-thyroid (HPT) axis and the hypothalamic-pituitary-gonadal (HPG) axis. High concentrations of thyroid hormones (hyperthyroidism) decrease expression of GnIH, whilst lower level of thyroid hormones (hypothyroidism) increases GnIH expression.
Increased GnIH expression caused by hypothyroidism, reduces circulating levels of gonadotropins (LH and FSH) and gonadal hormones. In clinical practice, a TSH level of 5mU/l or greater is indicative of hypothyroidism. A TSH level less than 5 mUl but greater than 2.5mUl is associated with implantation failure and early pregnancy loss.

Impact of Stress on Trying To Conceive

The impact of stress is not only physical as shown above. Psychological symptoms have a negative impact on fertility and on couples' experience of trying to conceive. Research shows that:
  • Despite a good prognosis and having the finances available to pay for treatment, discontinuation is most often due to psychological reasons.
  • The more depressed a woman is, the less likely she is to start fertility treatment and the more likely she is to drop out after only one cycle.
  • Couples also showed decreased desire to have sexual intercourse as a result of stress.


What interventions can help manage stress

Evidence indicates that cognitive behavioral therapy, acceptance and commitment therapy, education interventions, and mind-and-body interventions are the most frequently used psychosocial interventions for infertile individuals.

Research has documented the efficacy of psychological interventions in lowering psychological distress as well as being associated with an increase in pregnancy rates. Self-administered cognitive coping mindset exercises, relaxation intervention, yoga, meditation, some forms of mindfulness, expressive writing and keeping a gratitude diary can be helpful.

Professional guidance in a cognitive-behavioral group approach may be the most efficient approach. This must include an emphasis on education, skills training and relaxation training. Men and women benefit equally from these interventions.