Abstract Study question Do cumulative live birth rates(CLBRs) in the second cycle differ between blastocyst-stage and cleavage-stage transfer in women with low blastocyst progression during initial IVF ? Summary answer The CLBRs following subsequent oocyte retrievals were comparable for extended culture with blastocyst-stage embryo versus cleavage-stage transfers. What is known already Fresh blastocyst-stage embryo transfer increases live birth rates when compared to cleavage- stage embryo transfer in women with good prognosis. However, it remains unclear whether a blastocyst-culture approach can still be considered for women with a history of failed or reduced blastocyst formation. Study design, size, duration A retrospective cohort study evaluating outcomes of the second IVF/ICSI in women who had a history of poor blastocyst development in their first-time retrievals at a single fertility center from September 2019 to December 2021. Women fulfilled embryo quality criteria of having at least two good-quality cleavage-stage embryos (graded 1-2) on day 3 were included for analysis. Participants/materials, setting, methods A total of 396 patients were analyzed and categorized into two groups. Group D5/6: Extending culture of all embryos to blastocyst-stage in vitro followed by blastocyst transfer; Group D3: transfer or cryopreservation of one or two of the highest quality cleavage-stage embryo(s) on Day3.The main outcome measure was the CLBR per oocyte retrieval.Multivariable logistic regression analyses were used to assess the association between two culture approaches and live birth outcomes after adjusting for possible confounders. Main results and the role of chance The CLBRs (57.01% versus 49.48%) were numerically higher in women in D5/6 group (N = 107) than those in D3 group (N = 289) although the difference was attenuated and did not reach statistical significance after controlling for confounders (aOR: 1.27, 95%CI 0.78, 2.07,P=0.345). All subgroup analyses showed similar conclusions as the main model, even restricting on women with a limited number of quality embryos 3 days post-fertilization. Among cycles with only 2 or 3 good-quality cleavage embryos, Day3 transfers were still associated with lower CLBR compared to all blastocyst culture and transfer (aOR 0.66, 95% CI 0.51-0.87). Limitations, reasons for caution The retrospective nature of the present study, alongside the selection bias towards blastocyst culture, may predispose to the risk of residual confounding. The cohort of women characterized by previous failed or reduced blastocyst formation was comparatively small. Larger prospective studies focusing on the unique group are still needed. Wider implications of the findings Even in poor prognosis IVF patients with a history of poor blastocyst formation and/ or blastulation failure, all blastocyst culture and transfer can still be considered when at least two good-quality embryos are available at day 3. These findings are clinically relevant and require additional investigation. Trial registration number Not Applicable