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.