P-609 Negative outcomes of a first IVF attempt do not predict worse outcomes in second attempts. The earlier the better

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Abstract Study question Do the outcomes of first IVF attempts predict success in second attempts? Summary answer In second IVF attempts, the chances of obtaining more cumulus-oocyte-complexes (COCs), blastocysts, and ≥1 live-birth (LB) are independent of first attempts’ outcomes What is known already Treatment discontinuation after an unsuccessful first IVF cycle is a well-documented phenomenon, with high dropout rates limiting the overall effectiveness of fertility care. Delays between IVF attempts have been associated with reduced success rates, highlighting the need for timely intervention and a proactive, well-informed clinical strategy to optimize reproductive outcomes. Ensuring that early setbacks do not become major obstacles to future attempts is crucial. However, the predictive role of patients’ reproductive history - including previous failed IVF cycles, embryo transfers, live births, miscarriages, and the absence of euploid blastocysts within embryo cohorts - remains an area of ongoing research. Study design, size, duration Retrospective study including 1,286 second attempts planned for blastocyst-culture (years:2015-2021; median-age:39, median-AMH:1.2ng/ml). We analyzed the association between first attempts’ features (maternal-age, cause of infertility, basal-FSH, basal-AMH, embryological outcomes, reason of cycle conclusion, time retrieval-to-cycle-conclusion, time between first and second attempt, differences in total amount of gonadotrophins, length of stimulation, starting FSH dose and rec-LH/HMG use) with the outcomes of second attempts (chance of obtaining more cumulus-oocyte-complexes, more blastocysts, oocyte developmental competence, cumulative-live-birth-rate [cLBR]). Participants/materials, setting, methods Second attempts were conducted due to DuoStim (N = 332), no blastocyst obtained (N = 531), after ≥1 implantation-failure (N = 261), ≥1 miscarriage (N = 63), or ≥ 1 LB (N = 99). Only cycles with ovarian stimulation were included. Only ICSI on all MII-oocytes and blastocyst culture were conducted, and fresh/vitrified-warmed untested/euploid transfers. T-tests/ANOVA or Mann-Whitney-U/Kruskal-Wallis tests were performed after controlling the Gaussian distribution of continuous data, and Fisher’s-exact/Chi-squared tests for categorical data. Univariate/multivariate linear/logistic regressions were performed to confirm associations. Main results and the role of chance One-hundred-forty-nine patients collected the same number (11.6%) while 622 more COCs (48.4%) in their second attempts; the months between consecutive attempts (OR:0.965,95%CI:0.952-0.978, p < 0.001) and administration of higher total amount of gonadotrophins (OR:1.46,95%CI:1.163-1.832, p = 0.001) were associated with this chance. Oocyte developmental competence (i.e., “blastocyst rate per COCs”) was identical in 356 (27.7%) and higher in 521 (40.5%) patients in their second attempts (overall Δ:+3%,95%CI:+1.6% to + 4.5%,p<0.001); maternal-age (OR:0.959,95%CI:0.929-0.989,p=0.009) and the months between consecutive attempts (OR:0.977,95%CI:0.965-0.990,p<0.001) were associated with this chance. Overall, 156 patients had no blastocyst twice (12.1%) corresponding to 39.1% of patients having this outcome in their first attempt (N = 156/399). Three-hundred-twenty-six patients obtained the same number (25.6%) and 560 more blastocysts (43.5%) in their second attempts; maternal-age (OR:0.931,95%CI:0.902-0.961,p<0.001), AMH (OR:1.137,95%CI:1.052-1.229,p=0.001), and months between consecutive attempts (OR:0.969,95%CI:0.957-0.982,p<0.001) were associated with this chance. Maternal-age, AMH, cause of infertility, and reason for conclusion of the first attempt were all associated with the months between consecutive attempts (DuoStim:0.6months, no blastocysts:4.7, implantation failures:9.4, miscarriages:13.1;p<0.001). The cLBR of second attempts among 1222 patients concluding both cycles was 24% (N = 292/1222). This rate was independent of a LB achieved (N = 120)/not-achieved (N = 1102) in the first attempts, also after adjusting for age and AMH (OR:0.895,95%CI:0.516-1.553,p=0.694). Limitations, reasons for caution This is a retrospective study. Second cycles are conducted mostly by patients who failed their first IVF attempt rather than after a LB. Moreover, many patients discontinue their treatment already after the first failure. Wider implications of the findings Whenever a second IVF attempt is clinically feasible, couples should be reassured that a previous negative outcome does not determine future results. Furthermore, earlier attempts enhance the likelihood of success. Therefore, adopting a multicycle counseling approach from the very first consultation is crucial. Trial registration number No

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