Ten years of DuoStim in time-sensitive poor-prognosis IVF patients: real world cumulative outcomes and treatment trajectories

Aims: To evaluate DuoStim strategy across a decade from its clinical implementation in IVF by comparing embryological and clinical outcomes between the first and second ovarian stimulations (1st-OS and 2nd-OS) conducted within 30 days, focusing on treatment efficiency and time-to-conclusion. Methods: Retrospective single-center study (2015-2024) including 1656 poor-prognosis patients undergoing 1896 DuoStim cycles planned for ICSI and PGT-A at the blastocyst stage. Poor prognosis was defined as very advanced maternal age (≥40 years) and/or reduced ovarian reserve (AMH ≤1.2 ng/mL, AFC ≤5, or ≤3 oocytes in previous retrievals). Endpoints included all embryological, clinical and neonatal outcomes comparing 2nd-OS versus 1st-OS and cumulatively. Among 1561 concluded first DuoStim cycles, we calculated time-to-treatment-conclusion (TTC), stratified as without a live-birth (TTC-noLB) and with a live-birth (TTC-LB), and treatment discontinuation at our center after a first failed DuoStim attempt. Results: The use of DuoStim increased over time, reaching 34% of all cycles in 2024. The 2nd-OS yielded more oocytes and embryos than 1st-OS, while their competence was comparable. Consequently, the 2nd retrieval provided a cumulative incremental yield of 66% for cycles achieving ≥1 euploid blastocyst and 125% for cycles achieving ≥1 live birth (LB) compared with the 1st-OS alone. Median TTC was 40 days (quartile-1: 36, quartile-3: 118.5), while TTC-noLB and TTC-LB were 38 days (quartile-1: 35, quartile-3: 41.5) and 145 days (quartile-1: 112.25, quartile-3: 221), respectively. Embryological and clinical outcomes were stable across the years. Treatment discontinuation among patients without a LB after a first completed DuoStim decreased from 61% in 2015 to 44% in 2021, as second DuoStim attempts increased from 16% to 21% and transition to egg donation from 9% to 21%. Conclusion: DuoStim is a multicycle stimulation strategy that represents an alternative approach for patients requiring multiple treatment opportunities within a short timeframe. It shifts IVF toward a flexible personalized journey for poor prognosis patients. By enabling two stimulations within a single ovarian cycle, it achieved a cumulative live birth rate of 28.5% per concluded cycle in our cohort, within a consistently short timeframe in terms of both TTC-noLB and TTC-LB. Overall, DuoStim represents a treatment strategy that supports rapid and effective clinical decision-making in time-sensitive patients.