LAUSR

The earliest description of infertility dates back thousands of years [1]. Infertility has a prehistory: it was, they say, preceded by barrenness and sterility, “used to connote a divine curse of biblical proportions” and “an absolutely irreversible physical condition,” respectively. Hippocrates, back in the fifth century B.C., was one of the first to connect a woman’s psychological state to her reproductive potential, theorizing that a physical sign of psychological stress in women (which scholars later dubbed “hysteria”) could lead to sterility. In medieval times, a German abbess and mystic named Hildegard of Bingen proposed women suffering from melancholy—a condition that we today might call depression—were infertile as a result. To determine the impact of stress, consider what is more distressing in the mind of a patient—a diagnosis of cancer or infertility? Domar et al. demonstrated an infertile woman’s anxiety and depression scores are equivalent to one diagnosed with cancer [2]. Women who struggle to conceive are twice as likely to suffer from emotional distress than fertile women [3]. A definitive conclusion of the relationship between stress and infertility has been a matter of ongoing controversy. The literature is conflicting and confusing due to a lack of controlled prospective longitudinal studies [4]. Ultimately, the issue begs the question which occurred first—the infertility or the stress, i.e., the chicken or the egg. While evidence is clear that infertility causes stress, the reverse is an arduous and complicated hypothesis to prove with, potentially, resultant emotional consequences to the infertility patient. The infertility patient takes offense and is psychologically damaged by the age-old advice of “just relax” because it indirectly places blame and additional stress on the already desperate and devastated woman while implying the patient has the ability to willfully rid the disease of infertility. Furthermore, by continuing to stress, the patient assumes responsibility for her heartache and her partner’s, if applicable. Most women do not begin their journey toward conception with a heightened level of stress. Unsurprisingly, stress is directly proportional to the duration of conception attempts, particularly once the women/couple are engaged in fertility treatment. An additive and unnecessary factor is the financial burden of therapy due to a lack of consistent insurance coverage. The woman/ couple increase their stress due to the guilt of submitting to the increased expense. If we consider the prevailing influencers of stress—the economy, political uncertainty, racial discrimination, personal relationships/health, job satisfaction, the country’s present and future status, and COVID-19—we can add the lack of certainty over insurance coverage for infertility treatment. Nevertheless, discontinuation of treatment is usually due to stress rather than from financial constraints or prognosis. It has been shown that acute and chronic stress affects not only biological end-points, such as the number of oocytes retrieved and fertilized, but also influences pregnancy, live birth delivery, birthweight, and multiple gestations; in contrast, procedural stress (defined as the entire process of experiencing, perceiving, and responding to a stressor) only influences biological end-points [5]. Women are not exclusively impacted by infertility. Stress can impact libido, ovulation function, and semen which can become compromised the longer the infertility endures and during IVF [6]. Neurobiology may provide a link. Ghrelin is a gut-derived hormone and a key regulator of the endocrine response to stress and of reproduction and is believed to play a substantial role linking stress with infertility [3]. Which leads us to this month’s JARG contribution from Negris et al. who present their findings of a self-administered * Mark P. Trolice [email protected]