Objective:

To investigate the association between psychological distress and single-time endocrine stress markers in women with unexplained infertility and to compare psychometric assessment with synchronized hormonal measurements.

Approach:

• Study Design: Prospective case-control study involving 50 women with primary unexplained infertility and 52 age-matched fertile controls.
• Psychological Assessment: Psychological distress was assessed using the Hospital Anxiety and Depression Scale (HADS), with clinically relevant distress defined as HADS-Anxiety ≥8 and/or HADS-Depression ≥8.
• Hormonal Measurements: Serum cortisol and DHEAS concentrations were measured under standardized morning fasting conditions during the early follicular phase.
• Statistical Analysis: Multivariable logistic regression analysis was performed adjusting for age, body mass index, smoking status, residential environment, cortisol level, and HADS-defined psychological distress.

Key Findings:

• Women with unexplained infertility had significantly higher HADS-Anxiety and HADS-Depression scores compared to fertile controls (p < 0.05).
• HADS-defined psychological distress was more prevalent in the unexplained infertility group (76.0% vs. 42.3%, p = 0.001).
• Follicle-stimulating hormone and estradiol levels differed significantly between groups, but all measured values remained within physiological reference ranges.
• No significant differences were found in cortisol, DHEAS, or anti-Müllerian hormone levels between groups.
• Psychological distress remained independently associated with unexplained infertility (adjusted OR 3.907, p = 0.003).
• Isolated single-time cortisol and DHEAS measurements showed limited discriminatory performance for identifying psychological distress.

Interpretation:

Psychological distress is more prevalent among women with unexplained infertility, while single-time serum endocrine stress markers do not differ significantly between groups. These findings support the relevance of psychological assessment in women with unexplained infertility.

Limitations:

• Thecross-sectionalcase-controldesigndoesnotallowforcausalinferenceregardingthedirectionoftheassociation.

Conclusion:

Psychological assessment is relevant in women with unexplained infertility, but further research is needed to understand the relationship between psychological distress and endocrine markers.