Endometrial cortisol level and its relationship with psychological stress, molecular tissue changes, and clinical outcomes in infertile women

Despite fertility treatments are a stressful journey, there remains a lack of studies assessing how stress is affecting endometrial function in infertility. This prospective cohort study, including 84 endometrial biopsies, aims to elucidate the effect of stress, measured by different approaches, in the endometrial function in In Vitro Fertilization treatments. This population was molecularly characterized by measuring endometrial cortisol levels and endometrial transcriptomic profiles, and psychological aspects measured by the State-Trait Anxiety Inventory test. A relationship between endometrial cortisol levels and psychological stress punctuation was found. Psychologically stressed patients had increased endometrial cortisol levels (5.4 ng/g vs. 3.45 ng/g; p = 0.05, in the limit of significance) and cortisol levels correlated with psychological test punctuations (cor = 0.97, p < 0.05). From the clinical point of view, patients with cortisol levels ≥ 13.9 ng/g had a 32% relative higher risk of not becoming pregnant (p = 0.003). Molecular evidences showed, increased cortisol levels were significantly associated with changes in 182 genes in endometrium (p < 0.001) and psychological stress scores were significantly associated with changes in 12 genes involved in key functions for embryo implantation and development (p < 0.001). Psychological evaluation could serve as a less-invasive screening tool to identify at-risk infertility patients and implement preventive psychological interventions in the clinical setting.