The Impact of COVID-19 on Fertility and IVF Treatments
The COVID-19 virus utilizes the angiotensin-converting enzyme 2 (ACE2) receptor to enter in to cells and infect them. The ACE2 receptors are found in various organs of the body, from the ovaries, fallopian tubes, uterine lining, the testes, as well as other organs. The possibility for infection through sexual transmission is still unknown, however, there is a higher expression of the ACE2 receptor in the uterus during the secretory phase of the cycle (luteal phase) raising concerns for increased risk for infection during this time.
Can COVID-19 infect other organs?
There is concern for the virus infection various organs as some case reports have detected the presence of the virus in the blood, stools, urine, and saliva. As mentioned above, there is an abundance of the ACE2 receptors on the ovaries, the endometrium during the luteal phase and in the testes as well.
How does COVID-19 affect Female Fertility?
One of the results of the COVID-19 virus is that it may reduce the expression of the ACE2 receptors, and this impacts the levels of Angiotensin 2 in the body. In the diagram below you can see that reducing the activity of the ACE2 enzyme increases the levels of Angiotensin 2 (as a part of the renin angiotensin system) and may decrease levels of angiotensin 1-7.
Ang ---Renin---> Ang 1 ---ACE1---> Ang 2 ---ACE2---> Ang 1-7
*Ang = angiotensin
This may be problematic as Angiotensin 2 tends to have a pro-inflammatory effect, as well as stimulates fibrosis and may induce cell death. Conversely, Ang 1-7 have an anti-inflammatory and anti-fibrotic effect. The increase in Angiotensin 2 levels as a result of infection with COVID-19 may negatively impact fertility. In normal levels Angiotensin 2 impacts maturation of eggs, regulates follicle growth, and ovulation. However, Angiotensin 1-7 also have been correlated with improved egg maturation during ovarian stimulation in assisted reproductive technologies (ARTs), and therefore a decrease in angiotensin 1-7 may negatively impact egg maturation. Increases in Ang 2 also contributes to increase oxidative stress, which has been associated with negative impacts on egg quality.
In the uterus and Fallopian tubes Ang 2 and Ang 1-7 balance each other out. The pro-inflammatory effect of Ang 2 is important in regular menses and facilitating growth of blood vessels during the follicular phase of the cycle and Ang 1-7 inhibits this. An imbalance in the levels of Ang 1-7 compared to Ang 2 may negatively impact endometrium health and may theoretically impact implantation.
Does COVID-19 impact IVF results?
It is not known whether infection may negatively impact IVF success, but it definitely cannot be ruled out at the time either. Not enough research is available to determine if the quality of eggs, the number of follicles, hormone levels, and inflammation in the body are affected after recovering from infection.
How does COVID-19 affect the Testes, Sperm Health, and Androgen Hormone Levels?
The ACE2 receptor is found on the two main cells of the testes: Leydig and Sertoli cells. Leydig cells are responsible for testosterone production and Sertoli cells are responsible for sperm growth. The reduction of ACE2 receptors in these cells may negatively impact sperm health, however, animal studies where the ACE2 receptors are knocked out do not support this. A decrease in Ang 2, ACE2, and Ang 1-7 have been associated with various sperm infertility disorders.
Increases in Angiotensin 2 levels, however, have been shown to decrease the production of testosterone by negatively affecting the Leydig cells.
Limited studies have found that patients who were infected with severe COVID-19 infections had lower sperm concentration, lower ejaculate volume, and decreased sperm motility compared to patients with mild infection.
Is COVID-19 present in Sperm or Seminal Fluid?
Various small studies have found presence of the virus in semen of patients during acute infection and some patients may still have the virus in their semen during the recovery phase. This is suggested to potentially have a negative impact on fertility rates, assisted reproduction outcomes and fetal development.
Postmortem reports from patients that passed away from complications associated with COVID-19 also found inflammation of the testes (known as orchitis). It was found that there was a higher presence of immune cells, damaged seminiferous tubules, and reduced number of Leydig cells. It is unclear if this was a result of the virus infecting the testes of blood clots.
With SARS-CoV-1 it was well known that the virus could infect the testes, so more research is needed to help determine if this is truly the case for COVID-19 as well. Studies have found, however, that Males infected with COVID-19 displayed an increase in prolactin levels and a decrease in testosterone levels.
Does Fever Impact Fertility?
Fever in itself has been shown to negatively impact sperm growth and health for up to 50-70 days following the fever. In female patients fever has been associated with decreased estrogen levels and follicle growth.
Fertility treatments need to be considered in the context of this pandemic and patients who may have had past infection should be evaluated to determine if treatment should be postponed until hormone panels, sperm health, and cycle regularity return to normal.
Lee, W., Mok, A., & Chung, J. P. (2021). Potential effects of covid-19 on reproductive systems and fertility; assisted reproductive technology guidelines and considerations: A review. Hong Kong Medical Journal.
*1. This blog post and video are not intended to give any kind of advice or opinion on COVID-19 vaccines.
2. Notice that there’s still limited research about the impact that COVID-19 might have on Fertility and IVF treatments. This blog post is intended to educate viewers on the existing preliminary results of small studies on the topic, and it does not represent a personal opinion about it. It does not give any medical diagnosis.
3. For more information on COVID-19, and if you have any questions or concerns regarding the Impact of COVID-19 on your health, please contact Canada Public Health or the Public Health representatives in your country.