ObjectiveThis study aimed to evaluate the effectiveness of double ABCX-based psychotherapy for psychological distress during in vitro fertilization-embryo transfer (IVF-ET) among a female group (FG), couple group (CoG) and control group (CG).MethodsA total of 201 women undergoing their first IVF-ET cycle were randomized into three groups. The 6-session intervention was delivered at each visit to the IVF clinic. The primary outcomes were depression and anxiety, and the secondary outcomes included sleep quality, serum cortisol (nmol/L) levels and the clinical pregnancy rate, which were assessed before and after the intervention.ResultsThe group-by-time effects were significant for depression, anxiety, sleep quality and serum cortisol levels, with larger effect sizes in the FG than in the CoG. There was no significant difference in the pregnancy rate among the three groups.ConclusionPsychotherapy effectively mitigated psychological distress, suggesting greater effectiveness for couples undergoing IVF couples than for women only. It is structured and easy to use during the IVF treatment cycle.Trial registration numberhttps://register.clinicaltrials.gov (NCT03931187, retrospectively registered on April 23, 2019)