L26/O-232 Reducing treatment discontinuation between first and second IVF attempts: the value of a multicycle approach

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Abstract Study question What factors are associated with treatment discontinuation between first and second IVF attempts? Summary answer The gradual introduction of DuoStim and oocyte donation programs decreased treatment discontinuation between first and second attempts from 57% in 2014 to 33% in 2020. What is known already Among the factors preventing couples from fully exploiting their reproductive potential, treatment discontinuation is likely one of the main reasons. A cycle-by-cycle approach postpones decisions about whether and how to continue treatment until after failure. Conversely, a multicycle approach acknowledges the possibility of failure and emphasizes the benefits of additional attempts upfront aiming to increase the cumulative live birth rate (cLBR) and encouraging couples to continue with a new cycle or eventually considering oocyte donation. In this scenario, minimizing time-in-treatment, including adopting unconventional stimulation protocols like DuoStim, plays a pivotal role in keeping patients committed to the IVF journey. Study design, size, duration Observational study including 3542 naïve couples (median maternal age 38years,Q1:35;Q3:41; median AMH:1.2ng/ml,Q1:0.8,Q3:2.4; 18% severe male factor [SMF]) undergoing a first IVF attempt between 2014 and 2020 with ≥3-years follow-up. 328 patients underwent DuoStim. cLBR per first attempts was 35%(N = 1241/3542). Treatment discontinuation rate was 47%(N = 1083/2301). 97 patients switched to oocyte donation after first failures. cLBR among second attempts was 25%(N = 275/1121). Conservative-cLBR after two attempts was 43%(N = 1516/3542). Additional 207 patients switched to oocyte donation after second failures/DuoStim. Participants/materials, setting, methods All patients underwent conventional stimulation or DuoStim, ICSI, blastocyst culture, and fresh/vitrified-warmed untested/euploid single blastocyst transfer. The endpoints were cLBR per first attempts, time-to-conclude first attempts, treatment discontinuation after first attempts (primary outcome), time between first and second attempts, time-to-conclude two attempts, and rate of patients switching to oocyte donation. Regression analyses were conducted to outline associations between putative confounders and these endpoints, encompassing anamnestic features, IVF-cycle characteristics and outcomes of first attempts. Main results and the role of chance Maternal age (adjusted-OR:0.81), AMH (adjusted-OR:1.03) and SMF (adjusted-OR:0.75) were associated with cLBR per first attempts. First attempts’ length (median:50days,Q1:17,Q3:120) decreased with maternal age (-8days) and increased with AMH (+2days). Each blastocyst corresponded to 26 days longer attempts. Compared to attempts with LBs achieved (median:95days,Q1:67,Q3:160), no MII-oocyte obtained involved 126 days shorter attempts, no transferable blastocyst obtained involved 64 days shorter attempts, implantation failures involved 8 days longer attempts, increasing to 56 days if miscarriages also occurred. Treatment discontinuation was associated with maternal age (adjusted-OR:1.04), AMH (adjusted-OR:0.98), outcome of first attempts (no transferable blastocyst=46%; no MII=adjusted-OR:0.63; implantation failure(s)=adjusted-OR:1.5), and year of first attempts (adjusted-OR:0.86). Notably, treatment discontinuation decreased from 57% (2014) to 33% (2020), while DuoStim utilization increased from 0 to 17%. The time between consecutive attempts (median:147days,Q1:84,Q3:248) decreased with maternal age (-6days) and increased with AMH (+1.5days). Each blastocyst involved 13 days longer attempts. Compared to no transferable blastocyst obtained (median:107days,Q1:72,Q3:176), implantation failures and/or miscarriages involved 49 days extension. The time-to-conclude two attempts (median:193days,Q1:85,Q3:371) decreased with maternal age (-22days), and DuoStim utilization (-79days), and increased with AMH (+4days). The rate of patients switching to oocyte donation increased with maternal age (adjusted-OR:1.11), year of first attempt (adjusted-OR:1.5), and DuoStim utilization (adjusted-OR:2.2). Limitations, reasons for caution Retrospective single center study conducted at a private IVF clinic. Ideally, the analysis should extend to third attempts and treatments started beyond 2020. A detailed investigation of treatment discontinuation reasons, including psychological assessment and cost analysis, is warranted. Some patients might have continued their treatments at different IVF clinics. Wider implications of the findings The gradual implementation of DuoStim and oocyte donation programs has reduced treatment discontinuation rates and time to conclude each attempt, supporting multicycle counseling strategies that personalize reproductive journeys and help couples being prepared to cope with IVF failures. Trial registration number No

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