Everyone hears that stress can have a negative impact on your fertility and reproductive health, but have you ever wondered exactly how? Stress seems like such an abstract term, and not long ago the entire medical profession underestimated its effect on our health. We now know so much about the profound effects stress can have on our physiology and reproductive health. In fact, stress is one of the leading causes of all disease. It is likely that it has a major role to play in cases of unexplained infertility and can aggravate nearly any other reproductive health diagnosis.
Stress and Stress Hormones can Cause Infertility in the Following Major Ways:
- Impairs follicle health and development. Stress reduces the secretion of estrogen from the follicle which reduces the thickness of the endometrium and the fertile mucous
- Reduces the secretion of progesterone from the corpus luteum in the luteal phase, and thus affects implantation. Stress can cause luteal phase defects.
- Affects the surge of luteinizing hormone (LH) from the pituitary gland which is responsible for stimulating ovulation.
- Increases prolactin secretion by the pituitary gland, which inhibits ovarian function
- Affects the part of the immune system responsible for preventing miscarriage in early pregnancy
- Negatively impacts many other health concerns which may impair fertility, such as thyroid health, autoimmune conditions, allergic conditions, PCOS, endometriosis, and gastrointestinal concerns
What Happens in the Body During Stress?
During stress, the adrenal glands which sit on top of the kidneys are stimulated to produce stress hormones including cortisol and adrenalin. This process happens due to a mechanism which begins in the brain, specifically, in the hypothalamus. Activation of the sympathetic nervous system (the flight or fight aspect of the nervous system) occurs. The hypothalamus, pituitary gland, and adrenal gland work together through feedback mechanisms to perceive stressors in the environment and produce stress hormones that enhance survival in challenging times. Though these hormones allow our bodies to successfully overcome major stresses and threats, they are often counterproductive when trying to conceive.
Mechanisms Through Which Stress Reduces Fertility
Cortisol, a major stress hormone has been shown to affect reproduction in multiple ways. It interferes with the surge of luteinizing hormone(LH) from the pituitary, delaying it and making the surge less powerful. LH is responsible for the final development of the follicle into the corpus luteum and the release of the egg. This has many negative impacts on healthy ovulation and on the hormones required to sustain implantation. Formation of a healthy corpus luteum is required to produce progesterone which allows for full development of the endometrial lining and hence, implantation .
High levels of glucocorticoids (stress hormones) are also known to reduce estrogen secretion by the follicle. Low estrogen levels will reduce fertile mucous and the development of the endometrial lining. The reduced estrogen output by the follicle also indicates that its development may not be normal or adequate.
A study on a rural Mayan population found that women who had the highest stress (measured by urinary cortisol levels), had lower levels of progesterone between 4 and 10 days after ovulation. A drop in progesterone at this time interferes with implantation and full development of the endometrial lining.
How Stress is Related to Early Miscarriage
It has also been more recently discovered that adequate progesterone levels are required for immune tolerance during early pregnancy. There are significant changes which occur in the immune system during early pregnancy to prevent the mother’s immune system from rejecting the newly implanted embryo. The effect of stress on progesterone levels can interfere with this natural immune process, leading to early pregnancy loss.
A 1995 study found that women who had significant work related stresses were more likely to have experience miscarriages. This was especially significant in women over 32, and in women carrying their first child. Elevated urinary cortisol (a marker of stress) has been found in several studies to be associated with a higher rate of miscarriage.
Effects on IVF and ART
A 2005 study found that women who had lower adrenaline levels at the day of retrieval and lower adrenaline levels at the day of transfer had a higher success rate in IVF cycles. A study on Swedish women undergoing IVF found that those who did not conceive had an overall higher level of stress hormones including prolactin and cortisol in the luteal phase of their cycles, indicating that stress negatively affects implantation. An Italian study in 1996 showed that women who were more vulnerable to stress had a poorer result in IVF.
Conclusion
Evidence is growing for a new condition known as “pregnancy stress syndrome”. This syndrome indicates that women with heightened levels of stress and anxiety are more at risk for early pregnancy loss. This syndrome also states that women with stress and anxiety have lower rates of success in assisted reproductive technology procedures. This “syndrome” may seem to be common sense to many of us. We must consider though how important this really is. The idea of pregnancy stress syndrome comes from a very large body of evidence which has found stress to have a major impact on female fertility through multiple pathways. If medicine is to achieve the best outcome for all infertility patients, patients and doctors alike should view the diagnosis of stress as important as other reproductive health related diagnoses.
References
- Arck P, Hansen PJ, Jericevic BM, Piccinni MP, Szekeres-Bartho J. Progesterone during pregnancy: endocrine-immune cross talk in mammalian species and the role of stress. Am J Reprod Immunol 2007;58:268–79.
- Csemiczky et al. The influence of stress and state anxiety on the outcome of IVF-treatment: Psychological and endocrinological assessment of Swedish women entering IVF-treatment. Acta Obstetricia et Gynecologica Scandinavica Volume 79 Issue 2: 113 – 118 Dec 2001.
- Facchinetti et al. An increased vulnerability to stress is associated with a poor outcome of in vitro fertilization-embryo transfer treatment .Fertility and Sterility Volume 67, Issue 2, February 1997, Pages 309-314
- Magiakou MA, Mastorakos G, Webster E, Chrousos GP. The hypothalamic–pituitary–adrenal axis and the female reproductive system. Ann NY Acad Sci 1997;816:42–56.
- Nepomnaschy PA, Welch K, McConnell DS, Strassman BI, England BG. Stress and female reproductive function: a study of daily variations in cortisol, gonadotrophins, and gonadal steroids in a rural Mayan population. Am J Human Biol 2004;16:523–32.
- Smeenk et al. Stress and outcome success in IVF: the role of self-reports and endocrine variables Human Reproduction 2005 20(4):991-996
- Wagenmaker et al. Cortisol Interferes with the Estradiol-Induced Surge of Luteinizing Hormone in the Ewe. Biology of Reproduction March 1, 2009 vol. 80 no. 3 458-463.
