A bridge between infertility and anxiety: a novel role for genes.

Graphical Abstract: Abstract: Psychological imbalance is hypothesized to negatively affect reproductive function and vice versa; however, the underlying mechanisms of this relationship remain poorly understood. Therefore, this study aimed to investigate the association between infertility and anxiety and/or depression by examining underlying genetic factors. The study was conducted in several stages: i) psychological assessment of women undergoing assisted reproductive technology (ART) due to couple infertility using the Hospital Anxiety and Depression Scale (HADS), ii) collection of endometrial samples before ART procedures, iii) isolation and cultivation of human endometrial-derived mesenchymal stromal cells (EnSCs), iv) analysis of 26 EnSC genes using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and v) statistical analysis. A total of 32 women were included in the study. Twelve participants reported considerable symptoms of anxiety, and one showed symptoms of depression. Nineteen women conceived after ART. Gene expression analysis suggested altered expression of genes involved in cell cycle regulation, transcription and translation, immune response, signal transduction, cell differentiation, secretion, angiogenesis, and hemostasis according to anxiety status. These mechanisms may influence, or at least reflect, pregnancy outcomes following ART. The findings suggest a potential relationship between anxiety symptoms and gene activity in the endometrium of women undergoing ART. However, the relatively small sample size limits the strength of the conclusions; therefore, the results should be interpreted as preliminary. Further studies with larger cohorts are required to confirm these observations and to better understand the interaction between psychological well-being and molecular mechanisms involved in fertility. Lay summary: Infertility affects many couples worldwide and can be emotionally challenging. People undergoing fertility treatment often experience stress or anxiety, but it is still unclear how emotional well-being may influence reproductive health. In this study, we explored whether anxiety might be linked to biological processes involved in fertility. Women undergoing assisted reproductive treatment completed a questionnaire about anxiety and depression symptoms. We also analyzed small tissue samples from the lining of the uterus, which is important for embryo implantation and pregnancy. Our findings suggested that women who reported higher anxiety levels showed differences in some biological processes compared with women who reported lower anxiety levels. Some of these differences were also observed in women who did not become pregnant after treatment. Although the study involved a small number of participants, the results suggest that emotional well-being may be connected to reproduction and highlight the importance of psychological support during fertility treatment.