Discussion
Discontinuation of IVF cycles has been part of the radical
transformation of healthcare provision to enable the reallocation of
staff and resources to deal with the COVID-19 pandemic. At the best of
our knowledge, this is the first study investigating the changes in the
psychological status of infertile patients whose IVF treatments have
been interrupted or postponed due to the COVID-19 pandemic. This survey
revealed that the COVID-19 epidemic caused a sharp increase in the
prevalence of anxiety and depression among infertile patients undergoing
IVF. More specifically, our analysis demonstrated that more than
one-third of patients referring to our IVF center had evidence of
anxiety or depression. Furthermore, a higher proportion of patients were
anxious than depressed (21.8% vs. 17.7%), although the mean anxiety
severity was lower than that of depression (mild severity score: 11.1%
vs. 5.0%; moderate severity score: 10.1% vs. 12.0%); however, only
about 1% of patients with evidence of these phycological disorders
showed severe symptoms (Table 2).
These results are in line with the existing literature on the topic
according to which depression and anxiety are frequently associated with
infertility, and they may worsen during assisted reproduction treatments
(6). In this regard, in a recent study on women undergoing infertility
treatments, 65.9% scored in the clinical range for depression and
75.9% for anxiety; these psychological disorders were higher for women
who did not have a successful ART procedure (13). Moreover,
approximately 13% of infertile women reported taking antidepressant
medications (14). Haimovici et al. found psychopathological symptoms in
72% of the couples and more commonly in females. Female and male stress
was associated with stress, anxiety, and depression in the respective
partner. Notably, a lower concentration of serum transforming growth
factor-beta (TGF-β) and a higher level of cervicovaginal interleukin
(IL) -6 and IL-1β correlated with the presence of stress (15).
Interestingly, Gourounti et al. underlined that low perception of
personal control and avoidant coping style may be positively associated
with fertility-related stress and state anxiety. In contrast, a
problem-appraisal coping style may be negatively related to
fertility-related stress and depressive symptomatology scores (16).
COVID-19 disease is an unprecedented global situation that is
drastically changing everyone’s daily life and perspective. The stress
caused by the COVID-19 pandemic is unprecedented in modern history.
Indeed, it was an unexpected event whose consequences continue to
threaten everyone’s present life and future, including the loss of
normal life due to the lockdown, financial insecurity, and social
isolation. In this regard, recent studies on this topic confirmed the
severe psychological repercussions of the emergency linked to the spread
of COVID-19 in many sections of the population such as healthcare
professionals and students (8, 17-19).
In this scenario, it is reasonable to hypothesize that the feelings of
stress, anxiety, and depression related to the COVID-19 pandemic can
have had a significant impact on the emotional well-being of couples who
should have undergone IVF treatment during the emergency. In this
regard, a short communication published during the COVID-19 pandemic
presented data about an anonymous cross-sectional online survey sent to
10,481 patients who attended a large university-affiliated infertility
practice in the USA. At three different time-points, respondents
indicated infertility as the most frequent top stressor, causing anxiety
and depression. COVID-19 was the third most common stressor among the
respondents in the early stages of the pandemic (first days of March);
nevertheless, in the latest period (first days of June), COVID-19 caused
stress with an incidence similar to infertility (63% and 66%,
respectively). In this study, only 6% of patients stated that
infertility treatment, including IVF, should not be offered during the
COVID-19 pandemic. In agreement with this data, our study showed that
the occurrence of anxiety and/or depression was significantly associated
with time spent on COVID-19 related news per day.
The impact of the IVF interruption due to the COVID-19 pandemic has been
evaluated on 271,438 ovarian stimulation cycles in the UK by estimating
the effect of age as a continuous, yet non-linear, function on the
cumulative live birth rate. This model was recalibrated to cumulative
live birth rates reported for the 135,673 stimulation cycles undertaken
in the USA in 2016, with live birth follow-up to October 2018. The
authors reported that discontinuation of fertility treatment for even
one month in the USA could result in 369 fewer women having live birth,
due to the increase in patients’ age during the shutdown (20). On the
opposite, another study preliminary reported that in women with
diminished ovarian reserve (AMH <1.1 ng/ml) there was no
difference in the live birth rate among women who initiated their IVF
cycle within 90 days of their first visit due to COVID-19 pandemic
compared to women who did procedures 91–180 days after initial
consultation (21). Although the psychological impact of ART delayed was
not evaluated in the study, these latter results may be reassuring to
women with poor ovarian reserve, who may feel particularly anxious and
depressed to begin their treatment and become frustrated when unexpected
delays occur, as demonstrated by the logistic regression analysis of our
data.
In the current study, women reported a higher rate of anxiety and/or
depression when compared with men (41.5 vs. 30.6%). It has been well
documented that infertility is commonly linked with depression,
particularly in women. Infertility diagnosis and the subsequent stress
of treatments have been linked with increased infertility distress (22).
Moreover, a large Spanish study population explored the psychological
impact of the COVID-19 pandemic in the general adult population; women
demonstrated to have a significant psychological impact, with not a
negligible rate of stress, anxiety, and depression (23). However, men
undergoing fertility treatment may also experience anxiety and stress
(24). To this purpose, in our study, 30.6% of men experienced anxiety
and/or depression. During COVID-19 lockdown, the health and
psychological consequences of not offering andrological services should
be considered. Indeed, the lockdown of andrological services may have a
devastating psychological impact on men undergoing ART treatment.
Psychological interventions may have a critical role in lowering
psychological distress in patients referring to IVF centers (25), in
particular, during the COVID-19 pandemic. A cognitive-behavioral may be
the most efficient way to achieve both goals. Even more so, during the
COVID-19 epidemic, IVF center must strengthen the psychological
counseling for couples to improve their quality of life and mental
health. To this purpose, specific strategies may support multiple times
across the treatment trajectory by various methods (i.e., website,
handouts, personal referral) and by multiple providers (i.e.,
psychologists, medical assistants, nurses, physicians).
Our study has some important strengths. As already underlined, it is one
of the first studies investigating the psychological impact of the
COVID-19 emergency on the infertile patients whose IVF treatments have
been interrupted or postponed. Furthermore, our sample is relatively
large, and consequently, our results can be considered significant.
However, there are also some limitations. First, this is a
cross-sectional study, and we did not analyze the prevalence of anxiety
and/or depression in patients undergoing IVF at our institution before
the COVID-19 pandemic. Therefore, we cannot establish an exact causal
relationship between the investigated variables. Secondly, we used an
internet-based questionnaire with self-reported measures, so it was not
possible to exclude a potential influence of self-report bias on our
results. Finally, despite a large number of respondents, it is possible
that this is not a general representative sample, as the survey was
distributed in our local population; thus, the responses may not be
generalizable in all the Italian regions or different countries. In the
next months, a longitudinal follow-up would help track the changes in
anxiety and depression levels at various stages of the epidemic.