Introduction
The struggle to conceive with a history of infertility can be psychologically and physically demanding due to both the extensive scheduling and execution of medical testing and treatments (
1), and lack of insurance transparency or absence of insurance itself (
2). Infertility is also associated with immense psychological stress due to its inability to accomplish a desired social role (
3). It presents both as a chronic stressor from the potential loss of a personal ideal as well as an acute stressor which results from both the anticipation and the undergoing of a timely workup and the treatment itself. Trouble conceiving challenges men and women’s hopes of being a parent, expectations for their futures and confidence in one’s body and health (
4). The Covid-19 pandemic that began in early 2020 compounded the situation even further by adding more hurdles and delays in fertility treatment. Others have commented on the lack of knowledge about the psychological health of infertile couples during the pandemic (
5‐
7).
Resiliency involves employing strategies that allow one to succeed when faced with adversity, as in the case of a global pandemic, and successfully coping with stress (
8). Resilience has been found to be a protective factor that reduces the impact of a myriad of stressors. Importantly, resilience has also been shown to decrease the tendency to experience anxiety in infertility patients (
1), as it is well established that anxiety disorders are common in this patient population (
9). Other research has demonstrated that resilience is a moderator between infertility related stress and fertility quality of life among Chinese women with infertility (
10). We presumed that patients with greater resiliency would have less anxiety and greater coping skills, allowing them to better manage the uncertainty brought on by the impact of COVID-19 on their fertility care. While others have evaluated patient reactions to the suspension of services during the pandemic, most did not employ standardized measures of anxiety and none we found evaluated resiliency with a well validated instrument.
On March 17, 2020, an expert ASRM task force composed of physicians, embryologists and mental health professionals released recommendations for the temporary suspension of new, non-urgent fertility treatments during an ongoing world-wide pandemic. This suspension included new treatment cycles, embryo transfers and elective surgeries. Such recommendations were unprecedented in dealing with an extraordinary crisis which was, at the time, poorly defined, life threatening and ever changing. The lack of warning as well as the ambiguity of such a serious situation led to extreme anxiety on behalf of all involved. From our patients’ perspective the pandemic was disruptive in every aspect of their lives and was perceived as an uncontrollable, poorly understood and unanticipated stressful event. Going forward the issued ASRM recommendations were reviewed and revised by the ASRM task force in two-week intervals based on real time acquired information. This eventually resulted in the recommendation of incrementally reopening clinics as of April 24, 2020.
The purpose of this study was to assess the psychological experience as well as the coping strategies of patients pausing their workup and/or treatment due to the Covid-19 pandemic when fertility services were resumed. Furthermore, we were interested in determining which characteristics were associated with and may be predictive of specific psychological outcomes including anxiety, resilience, stress and hopefulness. This knowledge can be useful for providers who care for fertility patients as the pandemic continues. While fertility clinic closures were a unique event, they are likely to recur or alter the way in which fertility care is delivered in the future (
7).
Materials and methods
This was a cross sectional cohort survey study using an anonymous, self-reported, single time, online, web-based, HIPPA compliant platform (REDCap). The survey sampled two Northeast academic infertility practices (Yale Medicine Fertility Center in New Haven and Greenwich, CT and Montefiore’s Institute for Reproductive Medicine and Health in Hartsdale, NY). Patients who were asked to pause their workup and/or fertility treatment during a period from March 2020 until resumption of care were eligible to participate. Non-English speaking patients were excluded from the study. Upon resumption of care patients received an explanation of the study by either an Epic My Chart message or an email and elected to participate or not by taking an online REDcap survey. Patients received one My Chart or email reminder 3 days from the initial request. No further attempts were made to send additional reminders to avoid disturbing anyone’s intended sense of privacy or reluctance to participate. Data from multiple choice and open response questions collected demographic, reproductive history, experience and attitudes about Covid-19, infertility treatment, sense of hopefulness, sense of stress, coping strategies for mitigating stress, and to two validated psychological surveys to assess anxiety (six-item short-form State Trait Anxiety Inventory (STAl-6)) and resilience 10-item Connor-Davidson Resilience Scale (CD-RISC-10) with respect to an individual’s delay or pause in evaluation and/or treatment during Covid-19. When appropriate, question responses were answered on a 5-point Likert Scale. Survey questions were created through an iterative process and revised to incorporate changes following a pilot delivery to 3 patients and 5 physicians. Data was collected over a three-month period between 5.22.20 and 8.21.20 after IRB exempt status was granted at both institutions.
Psychological surveys
Speilberger’s State – Trait Anxiety Inventory (STAI) is a sensitive and reliable measure of anxiety but its 40-item length is a barrier to its use. Developed for these circumstances, the STAI-6 has been shown to produce reliable scores comparable to those obtained with the 40-question full-form. It was specifically developed for those situations where the use of the complete form may be contraindicated (
11). Other 6-item versions of the STAI have been developed (
12) but a comparison study found the Marteau and Bekker version had the best correlation with the original STAI (
13). Therefore, the present study employed the Marteau and Bekker version, most recently used with infertility patients being treated with preimplantation genetic testing for aneuploidy (PGT-A) (
14).
The STAI questions asked participants to choose the most appropriate statement indicating how they felt, at that moment. Directions indicated that there were no right or wrong answers. Participants were advised not to spend too much time on any one statement but to give the answer that best seemed to describe their present feelings. Each question took the form “I feel …” and respondents could choose “not at all” “somewhat” “moderately so” or “very much so.” Items are scored between 1 and 4. Higher scores on the STAI-6 indicate greater anxiety levels.
CD-RISC 10
The Connor Davidson Resilience Scale was initially developed to study posttraumatic stress disorder (PTSD) and the impact of resilience on its treatment. A wide range of studies have developed norms for many populations since its inception. The 10 item version used in this study was developed by Campbell-Sills et al. (
15). Normed on 764 individuals in a community sample, it has the advantage of reduced time for completion and a high correlation with the original 25 item CD-RISC. The original survey is a 25-item 5-point Likert-type assessment of “personal qualities that enable one to thrive in the face of adversity” (
8). Response categories are “not at all true,” “rarely true,” “sometimes true,” “often true,” and “true nearly all the time,” with responses of “not at all true” worth 0 and “true nearly all the time” worth 4. Participant scores are evaluated based on which quartile they fall into. For the CD-RISC 10 a score of 26 would fall in the lowest 25% of the population, a score of 36 would be the third quartile and 25% of the population would score higher (i.e. 37–40). Scores in the higher quartiles reflect greater levels of resilience. Both the CD-RISC 25 (
1) and the CD-RISC 10 (
16) have been used with infertility patients.
Participants were asked to “Please indicate how much you agree with the following statements as they apply to you over the last month. If a particular situation has not occurred recently, answer according to how you think you would have felt”. Items took the form: “Able to adapt to change”, “Can deal with whatever comes”, “See the humorous side of things”, etc.
Statistical analysis
R software (R version 3.2.3) (
17) was used to conduct the statistical analysis. Survey data including demographics, previous fertility diagnosis/treatment, COVID-19 experience, coping strategies, and STAI-6 and CDRISC-10 scores were summarized for the dataset. Means and standard deviations were calculated for quantitative data and counts and percentages were calculated for qualitative data. Correlations were then calculated between these survey data of demographic and fertility information, COVID-19 experience and coping strategies and our specific outcomes of interest which included CDRISC-10 scores, STAI-6 scores, stress of journey scores and hopefulness about having a child at the time of completion of the survey scores. Kendall rank correlations were calculated between continuous and ordinal variables, ordinal and ordinal variables, and between non-normally distributed continuous variables. Point biserial correlations were calculated between continuous and binary variables while rank biserial correlations were calculated between ordinal and binary variables. Correlations with a
p-value of < 0.05 with Bonferroni correction for multiple comparisons were considered significant.
Multivariate model selection using Least Absolute Shrinkage and Selection Operator (LASSO) with stability selection was then performed using the R ‘Stabs’ (
18) package to determine the most important variables in predicting the outcomes of interest. LASSO is a statistical method that uses regularization techniques for multivariate model selection. It was developed to reduce over-fitting and improve prediction accuracy over traditional stepwise regression statistical techniques. Stability selection further improves the variable selection process by reducing the number of falsely selected noise variables that can occur in high dimensional datasets. Stability selection with LASSO runs several multiple multivariate regression models on subsets of the full dataset and returns the proportion of times each variable was selected for by LASSO (
19). For the analysis, we normalized each of the variables and then sorted them by the proportion of times they were selected by LASSO with stability selection. We included the top five variables as predictors in our multivariate models to predict each of our outcomes of interest.
Discussion
This study surveys women from the Northeast US who were delayed in seeking infertility care in response to the ASRM guidelines surrounding the onset of the Covid-19 pandemic. Participants had been engaged in their workup or treatment at the time their care was paused. This study is unique in that the participants were surveyed regarding their psychological experience and coping strategies once they had resumed their care and not during their pause when the timetable for the resumption of care would have been uncertain and poorly defined. Furthermore, this study is novel in that it documents preferred strategies of coping by a group of women who were deferred in their fertility care due to the onset of a pandemic as well as highlights characteristics associated with and predictive of psychological outcomes of resilience, anxiety, stress and hopefulness.
The response rate of 29.2% was comparable to previous response rates reported on this topic ranging between 17 and 57% (
22‐
24). Other studies utilizing social media recruiting strategies have reported higher response rates (
5,
25). Our survey only contained de-identified data and for this reason it was not possible to follow up on those who did not respond. No financial incentive had been provided or social media employed to incentivize participation in this study. Higher response rates have been noted in those who use financial incentives, social media, or a combination of social media and clinic recruitment (
5‐
7). We acknowledge that a relatively low response rate of 29.2% introduces the potential of selection bias by which patients who chose to fill out the survey may have been different than those that did not and thus may limit the generalizability of the findings. However, this limitation exists for the vast majority of surveys that have been published on this challenging subject and thus must be taken into consideration when reviewing such studies until prospective ones are conducted.
The demographic profile of the surveyed group included respondents from the Northeast with a mean age in their mid-thirties, heterogeneous in race/ethnicity, well-educated, mostly coupled with a partner without any children who were fully employed and moderately affluent. These demographics are probably representative of most infertility practices in urban regions of the Northeast and therefore are a limited sample with respect to the entire US as well as having been disproportionately affected by COVID cases in the initial few months when the pause was in effect. These patients may have also been struggling with other stressors (including job impacts, illness in loved ones) pertinent to locations with higher COVID rates and therefore this may have contributed to a lower response rate. The participants reported a mean delay of 10 weeks after having been trying to conceive for a mean of 1.5 years. For those who had undergone previous treatment about a third were treated with IUI, a third with oral fertility medications and a third with assisted reproductive technology (ART) prior to their delay in treatment.
The mean anxiety score (STAI-6 score) was consistent with a state of high anxiety while the mean resilience score (CDRISC-10) indicated the lowest 25% of the general population for resilience at the time of resuming care. Esposito et al. (
5) found a mean STAI score of 49.8 which was consistent with our study’s findings. They had five top major concerns during the pause. These were in order of importance from most to least: mental health, physical health, personal safety, strain on their relationship with their partner and concern regarding their financial situation. These same concerns remained after the pause and upon resumption of care, but physical health became the first concern, while mental health was the second concern. It is speculated that during the delay the stress of not knowing when infertility care would resume accompanied by the additional stresses of daily living during the early phases of Covid − 19 resulted in the primary concern for participants’ mental health. Once fertility care resumed with likely increase in limited activity outside the home, concern over physical health took priority for participants. Those that could relate the stress of the pause that they were feeling after resumption of their care to a different life event compared it to changing jobs (> 13%), illness of a close family member (> 13%), moving their residence (< 10%) or having suffered a pregnancy loss (< 10%). The intensity of their responses seemed to have been less compared to those reported from an infertility practice at Columbia in New York City during the worse part of the pandemic (
23). Most likely this difference in perceived intensity was due to the difference in timing that each study made their inquiries ie. early beginning of pandemic in New York City (
23) versus our current study after the resumption of care months later during the pandemic.
The five most preferred coping strategies that may have helped in mitigating stress and anxiety included establishing a daily routine, going outside regularly, exercising, maintaining a social connection via phone, social media or Zoom or working from home. Each of these coping strategies offered psychological benefits which have been elaborated elsewhere. Hou et al. (
26) have discussed the value of primary routines such as work, maintaining hygiene and sleep as well as secondary routines such as exercise and social interaction, on mental health during periods of acute stress.
High anxiety scores and previous history of receiving oral medications correlated with having less resilience at the time of resuming fertility care. Expectedly, anxiety and resilience showed a negative correlation with one another. Participants were sheltered in place for a mean of 9.8 weeks and a delay in their resumption of care for a mean of 10 weeks. Our findings were consistent with those of other investigators. While quarantine (shelter in place) can be a necessary preventative measure during an infectious disease outbreak, it is often associated with a negative psychological impact (
27). According to data published by Ben-Kimhy et al. (
24), Covid-19 has introduced new stressors and levels of anxiety for infertility patients. Closures of clinics, which resulted in deferred fertility treatments, led to a sharp increase in anxiety and depression among patients undergoing IVF (
24). Many women in their mid-thirties are acutely aware that their fertility and the opportunity for treatment is time sensitive. As a result, the indefinite suspension of fertility treatment can have a large emotional, psychological, and financial impact on these patients (
23).
Women were more likely to be less stressed at the time of completing the survey if they tended to be optimistic and resilient about their reproductive future. Decreased anxiety was associated with increased hopefulness about having a child and higher resilience scores while increased anxiety was associated with higher reported stress scores. Variables associated with a more stressful journey included not feeling part of the decision-making process, having a higher anxiety score, having persistent feelings of frustration and anger about the pause, comparing the pause to a pregnancy loss and having an increased delay in treatment. Increased anxiety and having to change treatment plans due to financial considerations were associated with less hopefulness about having a child at the time of completing the survey.
A racial designation of Non-Hispanic Black was predictive of more resilience. There is some research to suggest that Black Americans may be more resilient than white Americans (
28). As Assari notes “… lack of preparedness and experience with previous stressors may place whites at the highest risk of poor outcomes when life gets out of control. Minority groups, on the other hand, have consistently lived under economic and social adversities which has given them firsthand experience and ability to believe that they can handle the new stressors. For blacks a stressor is anything but new. They have mastered their coping skills.” COVID-19 has been likened to life getting out of control.
It has been shown that anxiety is the biggest psychological obstacle for infertile patients (
29). However, social support is an important factor in mitigating the experience of anxiety. Personal resources work as a protective factor in times of crisis and aid in reducing levels of distress (
24). It has been noted that stress from infertility decreases as resources and strategies related to social coping increase (
30). Women with infertility experience more anxiety when they perceive low levels of social support from their partners and other family members (
29). Also, individuals with higher levels of resilience are better equipped to actively apply social coping methods (
31). Closures of clinics, which resulted in deferred fertility treatments, can lead to an increase in anxiety and depression among patients undergoing IVF (
24). For many, fertility treatments are time sensitive therefore, the indefinite suspension of fertility treatment can have a large emotional, psychological, and financial impact on patients (
23).
Alvord and Grados (
32) have noted that resiliency is a set of competencies and skills that can be learned. Others have noted that the availability of community support systems outside the family can bolster resilience (
33). They note that resilience training can be preventative for both healthy and at-risk populations as well as therapeutic for those with clinical symptoms. Fertility clinics with mental health providers embedded in them can provide such training or refer out to providers with the requisite knowledge to work with the infertility population.
Based on the findings of this survey and others (
5‐
7) it is likely that additional waves of this or other pandemics will interrupt service delivery. Prior to and in anticipation of a pause in treatment the clinical staff should consider the following. Employ pretreatment screening for psychological distress and provide referral sources (
34). Utilize a patient centered approach to care (
22,
35,
36). Approach each patient in the most reassuring manner possible while acknowledging that anxiety and stress are normal reactions to this type of situation. Include a discussion about resuming care as soon as clinical staff is convinced it is safe for patients to resume to minimize the indefiniteness of the situation. When possible, clinical staff should allow patients to be part of the decision-making process. A mention of coping skills that might be beneficial and address their potential mental or physical health concerns during the upcoming pause in care may mitigate their stress as they await a resumption of their care. Suggested coping skills might include establishing a daily routine, going outside regularly, exercising, maintaining a social connection via phone, social media or Zoom and/or working from home or anything they are aware of that was useful to them during their previous experience with the pandemic. Suggest, if patient is in a significant relationship, that leaning on each other’s partner during this crisis may be beneficial.
Conclusions
We conducted a patient survey of two Northeast academic fertility practices in the US at the time of resumption of fertility care to assess the psychological experience and coping strategies of patients pausing their care due to Covid-19. We determined specific factors that were associated and predictive of resilience, anxiety, stress and hopefulness.
The top 5 ranked coping skills from a choice of 19 were establishing a daily routine, going outside regularly, exercising, maintaining social connection via phone, social media or Zoom and continuing to work. Having a history of anxiety and having received oral medication as prior infertility treatment were associated with lower resilience. Increased hopefulness about having a child at the time of completing the survey and higher resilience scores were associated with decreased anxiety. Higher reported stress scores were associated with increased anxiety. Multiple multivariate regression showed being non-Hispanic black to be predictive of more resilience while variables predictive of less resilience were being a full-time homemaker, having received oral medication as prior infertility treatment and having higher scores on the STAI-6.
Prior to and in anticipation of further pauses in treatment the clinical staff should employ pretreatment screening for psychological distress and provide referral sources. In addition, utilization of patient centered approach to care should be considered. Other recommendations to mitigate stress are described.
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