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