Discussion
Many predisposing and prognostic factors for COVID-19 have been identified. Higher age [4], male gender, hypertension, diabetes, cardiovascular disease, chronic lung disease, cancer [5-8], acute cardiac injury, and acute kidney injury [9] have all been described as effective factors on COVID-19. Despite the increasing knowledge on COVID-19, the uncertainty around special illness or treatments, like immunosuppressors or modulator agents, still continues. There has been conjecture whether or not Inflammatory Bowel Disease (IBD), which is a type of chronic immune-inflammatory disease, has any effect on, or relation with, COVID-19. There have been no reports to suggest that Covid-19 occurs more frequently in IBD patients than in the general population [10], and while there are no current data on immune modulators for psoriasis [11] or the prolonged immunosuppressor treatments for organ transplant recipients [12], these conditions could cause a higher risk for this viral illness.
Gonadotropin-releasing hormone antagonist or agonists, clomiphene citrate, gonadotropins, progesterone, and human chorionic gonadotropin are the type of agents that are used in ART modalities. While these agents have been used for making a controlled ovarian hyperstimulation, promoting the development of the follicles, improving embryo implantation and pregnancy, they could cause supraphysiologic hormone levels that may be related with new clinical effects on a woman body. The high hormone levels during ART could cause some rare side effects in a long term period. It has been concluded that a women who applied to ART at any time should be closely monitored for the possibility of the complications of ART.
All new fertility treatments, except some cases, were postponed due to the key recommendations of the fertility societies since the middle of March 2020 [1,2]. After the prolonged lockdown of ART, it has been advised that fertility treatments for infertile couples can restart [3]. To provide fertility care in safe conditions, new recommendations have also been published [13]. According to our knowledge, only one patient pregnant after ART has been reported as testing positive for COVID-19 [14]. Although it was reported that 7 pregnant women died due to severe COVID-19 disease and one of these cases achieved pregnancy with ART due to the age-related infertility [14], another report showed that pregnant women are not at higher risk of COVID-19 compared with the general population [15]. It is still unknown whether or not ART could be a potential risk or prognostic factor for COVID-19. It has been shown that women are less likely to be positive for COVID 19 and that their mortality rate is less than men’s [16, 17]. It has also been hypothesized that this statistically significant difference has been caused by the role of the protective effect of estrogen (18). Furthermore, the use of conjugated equine estrogens [18] has been proposed to regulate the immune response to COVID-19 by activating the estrogen receptors. These receptors are known as transcription factors regulating the development of immune cells and the pathways of the immune system [19]. Despite the recommendation concerning the use of estrogen for the treatment of COVID-19, the beneficial or harmful estrogen level is undetermined. The estrogen and progesterone levels in a stimulated cycle could be 10 times greater than the hormone levels in natural menstrual cycles [20]. It is doubtful that such a high level of hormones may still have an immunomodulatory role. To evaluate this relationship, the patients, who had been treated with ART recently, could provide a great opportunity to gain insight about the association between ART and COVID-19. In our study, the 17 infertile couples who applied for infertility treatment between March 1, 2020 and March 10, 2020 were evaluated, contacted and asked if they were positive for COVID-19 or had any symptoms of the virus. While we were talking to all cases, none of them were suspected as having, or diagnosed with, COVID-19. This result cannot show whether ART treatment may be a predisposing or prognostic factor for COVID-19. In addition, the patients who achieved pregnancy by ART treatment did not have any medical problem related with COVID-19. Almost all patients were below 40 years old, and it is well known that COVID-19 especially affects people who are older. It may be speculated that the women did not show any significant signs of COVID-19 due to the young ages in our study. All pregnancies were almost in the first trimester, so it could not be said whether pregnant women may or may not be at a higher risk of COVID 19 at different stages of the pregnancy period.
The main limitations of this study were that these results are only from a single fertility center, the number of participants is very low and there were no COVID-19 positive case to compare any findings between COVID-19 positive and negative patients. The other limitation was that at the time when we reached the patient, she may have been in the incubation period of COVID-19, so the case of a positive COVID-19 diagnosis would have been after the interview.
In conclusion, we want to bring attention to the potential risk of COVID-19 infection in patients who have been treated with ART. With the return to normal practice life, all fertility societies’ guidelines should be followed carefully, all patients should be evaluated for COVID-19 during pre, per and post-treatment time for continuing ART treatments and protecting the patients from the side effects of ART, especially with the possible, but undefined, predisposition factor to COVID-19