The relationship between stress and infertility: We need to stop arguing about whether or not stress causes infertility and focus on what really matters: patient-centered care

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Author:

Alice D. Domar, Ph.D

Domar Centers for Mind/Body Health, Boston IVF, Harvard Medical School 

Abstract:

Since biblical times, there has been an assumption in human society that stress/sadness leads to female infertility. For the past century or more, women unable to conceive have heard a litany of supposedly helpful suggestions: “just relax”, “don’t try so hard”, “just adopt”. All of which contain the same assumption; anxiety or depression prevents conception in women and if said woman would simply cheer up, a baby would appear.  

In the latter half of the 20th century, the pendulum swung almost completely in the opposite direction. As technology improved, most cases of infertility were attributed to diagnoses in the female, male or both partners. Any psychological basis of infertility was dismissed.

Early in this century, however, as the mental health aspects of reproductive medicine were being explored more thoroughly, initial research indicated that in fact, distress might lower pregnancy rates from infertility treatment.  And the great debate began….

Does stress cause infertility or does infertility cause stress?

 

Consider This: 

Recent research has supported the theory that infertility does indeed lead to significant emotional distress. It is clear that both women and men experiencing infertility express symptoms of depression and anxiety. In a recent study of 352 women and 274 men undergoing infertility treatment (1), 56% of women and 32% of men scored in the clinical range for depression and 76% of women and 61% of men scored in the clinical range for anxiety. In an earlier study which included a structured psychiatric interview of women prior to being seen in an infertility clinic for the first time, 40% were diagnosed as having anxiety, depression or both (2).  Since distress increases as duration and intensity of treatment increases, it is likely that well over half of these women would report symptoms within a year.  In a summary of the literature, the prevalence of psychiatric issues among individuals with infertility ranged from 25-60% (3). In addition, the prevalence of anxiety and depression is significantly higher than amongst fertile controls and in the general population, and women with infertility express more emotional distress than their male partners.

Thus, it feels safe to conclude that individuals and couples who are experiencing infertility are in fact distressed and that the cause of this distress is infertility. Infertility causes stress. It is doubtful that anyone disagrees with this statement.

But does stress cause infertility? Many researchers over the past 20 years have attempted to determine if distress levels prior to an ART cycle are associated with pregnancy rates. Some of the studies have concluded that yes, anxiety and/or depression are in fact significantly correlated with pregnancy rates while others have not. In 2018, two meta-analyses on the impact of emotional distress on ART outcome came to opposite conclusions. One, which included 11 studies on 2202 patients, showed that depression and anxiety during treatment were significantly associated with lower pregnancy rates (4). The other included 20 studies on 4308 patients and the conclusions were that symptoms of distress during treatment were not associated with pregnancy rates (5).

There are a number of reasons why assessing distress levels of patients via self-report psychological questionnaires prior to and during an ART cycle will not reveal accurate data.

1.    Patients know their prognosis. A 25-year-old with blocked tubes and an AMH of 8 will have been told by her physician that her odds of conceiving are excellent. She is thus likely to report minimal distress. Conversely, a 42-year-old with an AMH of <.1 will likely have been told by her physician that her odds of are poor. And she is likely to report significant distress. So if the 25-year-old conceives and the 42-year-old does not, is it due to their emotional distress or their physiology?

2.    Some medical conditions which can contribute to infertility are independently associated with distress (ie endometriosis, PCOS) and studies to date have not controlled for diagnosis.

3.    The research is highly variable. Some studies measure distress two months prior to cycling, while others measure it the day stimulating medication is started, and some studies assess mood during the actual cycle.

4.    Patients tend to “fake good” with self-report questionnaires. They don’t want their physician to know how distressed they are so they tend to withhold information about their true distress level.

5.    Many ART patients feel a renewed sense of optimism prior to a cycle. Thus, measuring mood just before cycle start does not reveal their overall level of distress.

So in answer to the question, does stress cause infertility via decreasing the efficacy of ART outcome, the answer is, we don’t know.  It is certainly possible that future research can provide us with a more definitive answer but at this point in time, it is just not known.

There is some recent research on assessing cortisol levels in hair; two studies have now shown that elevated hair cortisol levels, which measure cortisol levels over the previous 3-6 months, are associated with decreases in ART success rates (6).  But the research is costly, time-consuming, and requires a chunk of hair, so recruiting subjects is challenging.  

Why do we care so much about the question- does stress impact fertility treatment outcome?

I have spent my entire 32-year career in reproductive psychology researching the stress/infertility relationship. I have received two NIMH awards as well as numerous privately funded grants and I have personally participated in three debates on this topic at ASRM with two of my mental health colleagues. Another session on the topic is scheduled for ESHRE 2020 between two well-regarded psychologists; one is speaking about the research which indicates that stress causes infertility and the other is speaking about research which fails to show such a connection. I have conducted two large randomized controlled trials, both of which showed that women who participated in a highly structured mind/body group program reported significantly higher pregnancy rates and lower distress levels than the control participants (7-9).  However, a 2016 Cochrane review which included 39 studies (10) emphasized that the true impact of psychological interventions is unknown due to the overall inconsistency of study findings as a result of poor study design and execution.

I get asked about the stress/infertility relationship by the media on a regular basis, including recently by the New York Times. Virtually every patient I have ever seen has asked me if their stress level could in fact be causing their infertility. We do know that stress-induced negative lifestyle habits, such as smoking, alcohol, a low or high BMI, and perhaps even poor sleep are associated with lower pregnancy rates (11). So stress can indirectly negatively impact fertility. But that is not what most people are implying. They ask their doctor or wonder themselves if their own stress level is keeping them from the thing they want most. And the field of reproductive medicine needs to have a consistent, scientifically based answer. Which could be:

Does stress cause infertility? We don’t know. We do know that infertility can cause high levels of distress, so feelings of anxiety, sadness, irritability and loneliness are normal reactions to such a challenging experience. But science might never be able to truly determine if stress can make treatment less successful. What we do know is that these negative feelings can truly decrease one’s quality of life, weaken coping strategies, and can make it harder to stay in treatment.

If we could simply stop arguing whether or not stress causes infertility, and accept the fact that the emotional burden of infertility treatment is a significant problem for the majority of our patients, we could instead come up with clear cut recommendations with the goal of improving patient-centered care.

Many physicians do not know why patients drop out of treatment, or even know how many of their patients simply don’t return. For patients without insurance or financial resources, the top reason is financial. But for patients with insurance or resources, the top reason for treatment termination is the emotional burden (12). Infertility treatment is just too stressful.

What can one do to decrease stress in infertility patients? Many things.

Support patients to learn strategies to increase coping, decrease anxiety, and develop resilience. Psychological interventions are associated with significant decreases in negative emotional symptoms (13).  And recent research is supporting the use of technology to decrease distress with this patient population. In one study, patients about to start their first ART cycle were randomized to receive a stress reduction instructional packet in the mail, versus routine care (14). The patients who received the packet were 67% less likely to drop out of treatment and reported significant improvements in coping and quality of life. A pilot RCT on the impact of an online stress management program indicated that patients accept this modality of an intervention and the patients randomized to the online program experienced significant improvements in psychological status and pregnancy rates when compared to the control group (15).

Reduce the burden of treatment by including the partner, simplifying treatment protocols, screening and identifying at risk patients and referring them for counseling, sharing decision-making, supporting lifestyle changes, and actively counseling those who have had a negative cycle (16).

Focus on empathic communication because infertility patients report a strong need to be understood and accepted by their health care team and the most common complaint amongst infertility patients is that physicians lack empathy (17).  Research has shown that training infertility doctors to speak more empathetically with patients can significantly improve patient satisfaction with their care.

Support nurses and other staff members because a stressed nurse, technician or support staff member can increase the stress level of the patient. In addition, compassion fatigue leads to burnout and increases in turnover. According to a recent Nursing Professional Group ASRM study, more than 70% of REI nurses reported that their stress levels had increased over the previous year. Recognize the workload and efforts of nurses/staff, aim to help them achieve a better work/life balance, and reward them for their extra efforts.

Conclusions: The relationship between stress and infertility is complex; it is clear that infertility causes stress but the jury is still out as to whether or not stress causes infertility, specifically by decreasing the efficacy of treatment. Continuing to debate whether or not psychological factors lead to treatment failure benefits no one. Instead we need to focus our time, energy, and resources to determine how best to psychologically support our patients by providing them with the physical and emotional care they need.

 

References:

1.    Pasch LA, Holley SR, Bleil ME, Shehab D, Katz PP, Adler NE. Addressing the needs of fertility treatment patients and their partners: are they informed of and do they receive mental health services? Fertil Steril 2016: 106: 209-15.

2.    Chen TH, Chang SP, Tsai CF, Juang KD. Prevalence of depressive and anxiety disorders in an assisted reproductive technique clinic. Hum Reprod 2004; 19: 2313-8.

3.    De Berardis D, Mazza M, Marini S, Del Nibletto L, Serroni N, Pino MC, Valchera A, Ortolani C, Ciarrocchi F, Martinotti G, Di Giannantonio M. Psychopathology, emotional aspects and psychological counselling in infertility: a review. Clin Ter 2014,165: 163-9.

4.    Purewal S, Chapman SCE, van den Akker OBA. Depression and state anxiety scores during assisted reproductive treatment are associated with outcome: a meta-analysis. Reprod Biomed Online 2018: 36: 646-57.

5.    Nicoloro-SantaBarbara J, Busso C, Moyer A, Lobel M. Just relax and you’ll get pregnant? Meta-anlaysis examining women’s emotional distress and the outcome of assisted reproductive technology. Soc Sci Med 2018; 213: 54-62.

6.    Massey AJ, Campbell BK, Raine-Fenning N, Pincott-Allen C, Perry J, Vedhara K. Relationship between hair and salivary cortisol and pregnancy rates in women undergoing IVF. Psychoneuroendocrinology 2016; 74: 397-405.

7.    Domar AD, Clapp D, Slawsby EA, Dusek J, Kessel B, Freizinger, M. Impact of group psychological interventions on pregnancy rates in infertile women. Fertil Steril 2000; 73: 805-11.

8.    Domar AD, Clapp D, Slawsby E, Kessel B, Orav J, Freizinger M. The impact of group psychological interventions on distress in infertile women. Health Psychol 2000; 19: 568-75.

9.    Domar AD, Rooney KL, Wiegand B, Orav EJ, Alper MM, Berger BM, Nikolovski K. Impact of a group mind/body intervention on pregnancy rates in IVF patients. Fertil Steril 2011; 95: 2269-73

10.Verkuijlen J, Verhaak C, Nelen W, Wilkinson J, Farquhar C. Psychological and educational interventions for subfertile men and women. Cochrane Review, 2016.

11.Hornstein M. Lifestyle and IVF outcomes. Reprod Sci 2016; 23: 1626-9.

12.Lande Y, Seidman DS, Maman E, Baum M, Hourvitz A. Why do couples discontinue unlimited free IVF treatments?  Gynecol Endocrinol 2015; 31: 233-6.

13.Frederiksen Y, Farver-Vestergaard I, Skovgard NG, Ingerslev HJ, Zachariae R. Efficacy of psychosocial interventions for psychological and pregnancy outcomes in infertile women and men: A systematic review and meta-analysis. BMJ Open 2015; 1-18.

14. Domar AD, Gross J, Rooney K, Boivin J. Exploratory randomized trial on the effect of a brief psychological intervention on emotions, quality of life, discontinuation, and pregnancy rates in in vitro fertilization patients. Fertil Steril 2015; 104: 440-51.

15.Clifton J, Parent J, Seehuus M, Worrall G, Forehand R, Domar A. An internet-based mind/body intervention to mitigate distress in women experiencing infertility: A randomized pilot trial. PLOS One, 2020, in press.

16.Gameiro S, Boivin J, Domar AD. Optimal in vitro fertilization in 2020 should reduce treatment burden and enhance care delivery for patients and staff. Fertil Steril 2013; 100: 302-9.

17.Garcia D, Baustista O, Venereo L, Coll O, Vassena R, Vernaeve V. Training in empathic skills improves the patient-physician relationship during the first consultation in a fertility clinic. Fertil Steril 2013; 99: 1413-8.

 

 

 

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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