In your quest for conception you have most likely come across the word ‘inflammation’, so what is it? Inflammation is an essential process in the body. It helps us repair damaged tissues and is important for immune protection. In response to stress, which may take the form of injury, illness, an unhealthy diet, sleep deprivation, or other physiological stress or emotional stress, the body’s immune system responds by releasing various chemical regulators to restore the normal environment, or ‘homeostasis’. These chemical regulators may be released from the white blood cells of the body which communicate with other cells and tissues.
Some of these chemical messengers are small proteins called cytokines which can be measured and therefore used to quantify the severity of the inflammation or the activation of the immune system. Delving into our immune system is incredibly complex though so measuring one protein will not provide you with the entire picture. We have spent a lot of time in clincial research understanding these processes of inflammation and oxidative stress and we love translating this knowledge into practice!
Inflammation, and the resolution of inflammation, is usually a tightly regulated process and controlled inflammation is essential for the process of embryo implantation.
While acute inflammation is a normal, healthy response to short-term stress or injury, chronic low-grade inflammation is implicated in several diseases such as cardiovascular disease, diabetes and most importantly infertility .
The cause of higher than normal levels of inflammation is multifactorial. These include a diet missing key micronutrients, carrying excess body fat, hormone imbalances, infections, stress, imablances in exercise and being sedentary.
What is Oxidative Stress?
With increased inflammation, oxidative stress is also elevated. This is also true for increased oxidative stress promoting inflammation, so it is a bit of the chicken and egg scenario.
Oxidative stress is happening within the body all the time. Reactive oxygen species that cause oxidative stress are necessary for many biological processes but just as the name suggests, these reactive oxygen species are unstable. If their levels rise too much, or there is a reduction in the defence systems used to combat reactive oxygen species (eg. antioxidants), they cause considerable damage to DNA and cell membranes, leading to cell death. Inflammation and oxidative stress are inextricably linked.
The main source of reactive oxygen species are mitochondria, a little organelle that sits within most cells. As oxygen is broken down (metabolised) to produce energy, electrons can escape from the energy production chain and these transform oxygen from a stable molecule to one that loses some electrons to become unstable. If your mitochondria are not functioning properly this will generate considerably more reactive oxygen species, leading to greater oxidative stress.
While most reactive oxygen species are produced from processes in the body, they can also come from outside sources including smoke, pollutants, tobacco, certain drugs and radiation.
Electromagnetic fields from mobile phones, laptops, and other electric devices have been shown to increase the production of reactive oxygen species with negative consequences for both male and female reproductive health (Santini, Cordone et al. 2018).
What Conditions are Associated with Elevated Infammation and Oxidative Stress?
Inflammation and oxidative stress underlie the pathology of many conditions including metabolic syndrome, cardiovascular disease, rheumatoid arthritis, diabetes, neurological conditions and importantly our reproductive health.
Unexplained Infertility: Over 70% of females with unexplained infertility have high levels of inflammation and oxidative stress . Antioxidant levels that protect against oxidative stress are lower in females with unexplained infertility (Alam, Khan et al. 2020). Total antioxidant capacity of follicular fluid is lower in infertile women while DNA oxidative damage was dramatically higher than those found in fertile women (Espino, Macedo et al. 2019).
PCOS: Women with PCOS show chronic low-grade inflammation, characterized by increased circulating levels of inflammatory proteins, which leads to insulin resistance. Levels of oxidative stress are also increased in PCOS (Mohammadi 2019). Our defences against oxidative stress include circulating levels of antioxidants (Vitamin C and E) and other antioxidant enzymes. These defences are lower in women with PCOS (Fatima, Amin et al. 2019).
Endometriosis: For 20% of people seeking fertility treatment it is the sole reason they require assisted reproductive technologies. Endometriosis is an estrogen driven inflammatory condition and women with endometriosis have elevated levels of inflammation and circulating immune toxins (such as lipopolysaccharide). Oxidaitve stress and inflammation are associated with the progression of endometriosis (Yun, Chon et al. 2016).
Recurrent Pregnancy Loss: Levels of inflammatory proteins and circulating immune toxins (such as lipopolysaccharide) are higher in women with recurrent pregnancy loss (Tersigni, D'Ippolito et al. 2018).
Male Factor: Increases in circulating markers of inflammation and oxidative stress play a significant role in male infertility (Haervig, Kierkegaard et al. 2018). It is estimated that oxidative stress may be present in about 56 million males presenting with infertility (Dutta, Majzoub et al. 2019). Inflammation and oxidative stress underlie sperm damage, which has been implicated in recurrent pregnancy loss .
How Can I Dampen Inflammation and Oxidative Stress?
The good news is that there are strategies you can adopt to dampen inflammation and oxidative stress! This then translates to enhanced fertility, and increased pregnancy success.
Diets rich in antioxidant whole foods that nurture your gut diversity can dampen inflammatory markers by more than 50%. Exercise is also a powerful anti-inflammatory and this in part is attributed to the beneficial changes at the level of the gut microbiota.
Understanding the cellular processes of inflammation and oxidative stress, and how to address these enables us to tailor evidenced based support for better outcomes.
Take a listen to us on the Beat Infertility Podcast if you would like to find out more.
Alam, F., T. A. Khan, R. Ali, F. Tariq and R. Rehman (2020). "SIRTI and cortisol in unexplained infertile females; a cross sectional study, in Karachi Pakistan." Taiwan J Obstet Gynecol 59(2): 189-194.
Dutta, S., A. Majzoub and A. Agarwal (2019). "Oxidative stress and sperm function: A systematic review on evaluation and management." Arab J Urol 17(2): 87-97.
Espino, J., M. Macedo, G. Lozano, A. Ortiz, C. Rodriguez, A. B. Rodriguez and I. Bejarano (2019). "Impact of Melatonin Supplementation in Women with Unexplained Infertility Undergoing Fertility Treatment." Antioxidants (Basel) 8(9).
Fatima, Q., S. Amin, I. A. Kawa, H. Jeelani, S. Manzoor, S. M. Rizvi and F. Rashid (2019). "Evaluation of antioxidant defense markers in relation to hormonal and insulin parameters in women with polycystic ovary syndrome (PCOS): A case-control study." Diabetes Metab Syndr 13(3): 1957-1961.
Haervig, K. K., L. Kierkegaard, R. Lund, H. Bruunsgaard, M. Osler and L. Schmidt (2018). "Is male factor infertility associated with midlife low-grade inflammation? A population based study." Hum Fertil (Camb) 21(2): 146-154.
Mohammadi, M. (2019). "Oxidative Stress and Polycystic Ovary Syndrome: A Brief Review." Int J Prev Med 10: 86.
Santini, S. J., V. Cordone, S. Falone, M. Mijit, C. Tatone, F. Amicarelli and G. Di Emidio (2018). "Role of Mitochondria in the Oxidative Stress Induced by Electromagnetic Fields: Focus on Reproductive Systems." Oxid Med Cell Longev 2018: 5076271.
Tersigni, C., S. D'Ippolito, F. Di Nicuolo, R. Marana, V. Valenza, V. Masciullo, F. Scaldaferri, F. Malatacca, C. de Waure, A. Gasbarrini, G. Scambia and N. Di Simone (2018). "Recurrent pregnancy loss is associated to leaky gut: a novel pathogenic model of endometrium inflammation?" J Transl Med 16(1): 102.
Yun, B. H., S. J. Chon, Y. S. Choi, S. Cho, B. S. Lee and S. K. Seo (2016). "Pathophysiology of Endometriosis: Role of High Mobility Group Box-1 and Toll-Like Receptor 4 Developing Inflammation in Endometrium." PLoS One 11(2): e0148165.