¹CHA University Ilsan Medical Center, Department of Psychiatry, Goyang, Korea, Republic of, ²Keyo Hospital, Department of Psychiatry, Uiwang-si, Korea, Republic of, ³National Traffic Injury Rehabilitation Hospital, Department of Psychiatry, Yangpyeong, Korea, Republic of, ⁴Seoul National University Hospital, Department of Neuropsychiatry, Seoul, Korea, Republic of, ⁵Hanyang University Guri Hospital, Department of Psychiatry, Guri, Korea, Republic of

Background: Depression is highly prevalent among women undergoing infertility treatment and has been implicated in both psychological distress and adverse reproductive outcomes. Despite this, the clinical decision to initiate or continue antidepressant therapy during fertility care remains challenging, largely due to concerns about potential negative effects on conception and pregnancy. Previous studies have reported inconsistent findings and often failed to disentangle the effects of active depression from those of antidepressant treatment itself. Large-scale real-world evidence addressing this distinction is limited, particularly in healthcare systems with broad access to both fertility and psychiatric services.

Aims & Objectives: This study aimed to examine the association between depression, antidepressant treatment status, and pregnancy outcomes among women receiving infertility care. Specifically, we sought to (1) compare pregnancy incidence across women without depression, women with past-treated depression, and those receiving ongoing or newly initiated antidepressant treatment, and (2) assess whether the duration and consistency of antidepressant use were associated with reproductive outcomes.

Method: We conducted a nationwide retrospective cohort study using de-identified claims data from the Korean Health Insurance Review and Assessment Service. Women aged 20–45 years with a first diagnosis of infertility between 2018 and 2023 were identified. After exclusions, 13,098 women were included and categorized into a non-depressed control group and a depression cohort, which was further stratified into past-treated, ongoing-treated, and new-onset depression groups based on antidepressant exposure during fertility treatment. The primary outcome was cumulative incidence of clinical pregnancy, accounting for treatment discontinuation as a competing risk. Fine–Gray subdistribution hazard models and multivariable logistic regression were used, adjusting for age, prior pregnancy history, and infertility-related factors. Antidepressant adherence was measured using the proportion of days covered.

Results: Pregnancy incidence differed significantly across groups. Women with past-treated depression who were not using antidepressants during fertility treatment showed the highest probability of pregnancy, exceeding that of non-depressed controls. In contrast, women receiving ongoing or newly initiated antidepressant treatment had substantially lower pregnancy rates and longer time-to-pregnancy. Adjusted analyses confirmed a reduced hazard of pregnancy failure in the past-treated group, whereas ongoing and new-onset antidepressant use were associated with markedly increased hazards of failing to conceive. Among antidepressant users, longer and more consistent medication adherence was associated with improved pregnancy outcomes, although higher adherence also appeared to reflect greater underlying depression severity. Secondary analyses showed a modestly increased risk of spontaneous abortion in antidepressant-exposed pregnancies, while other obstetric outcomes demonstrated mixed patterns.

Discussion & Conclusions: Depression severity, rather than antidepressant use alone, appears to be a key determinant of reproductive outcomes in women undergoing infertility treatment. Women with remitted depression who discontinued medication before fertility care experienced favorable outcomes, whereas active or worsening depression requiring pharmacologic treatment was associated with reduced pregnancy success. Importantly, consistent antidepressant adherence among treated women was linked to better outcomes, underscoring the potential benefits of effective symptom control. These findings suggest that avoiding or discontinuing antidepressants out of concern for fertility may be counterproductive when depression is clinically significant. Integrating systematic mental health assessment and timely psychiatric intervention into infertility care may improve reproductive outcomes.