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Study question Does blastocyst cohort size impact aneuploidy rates, evaluated by next generation sequencing (NGS)? Summary answer Embryo aneuploidy rates were independent of blastocyst cohort size across all patient ages. What is known already The effects of ovarian response on oocyte and embryo quality remain controversial. Several studies have proposed that a high response to ovarian stimulation may negatively impact oocyte competence. Alternatively, irrespective of maternal age, a poor ovarian response may potentially compromise embryo quality. Using blastocyst cohort size as an indirect measure of ovarian response, previous studies applying array comparative genomic hybridisation (aCGH) have demonstrated that the number of embryos available for biopsy does not impact embryo aneuploidy rates. Nevertheless, these findings remain to be confirmed in a comprehensive cohort, using current approaches for preimplantation genetic testing for aneuploidies (PGT-A). Study design, size, duration Retrospective, international, cohort study of 3998 patients from 16 clinics undergoing PGT-A from 2016–2020. We evaluated 11665 blastocysts, tested using trophectoderm (TE) biopsy and next generation sequencing (NGS). To eliminate bias of multiple treatments, we considered only the first PGT-A cycle for all patients. Both autologous and donation cycles were included in the analysis. Cycles were excluded if they utilised preimplantation genetic testing for monogenic disorders (PGT-M) or preimplantation genetic testing for structural rearrangements (PGT-SR). Participants/materials, setting, methods We evaluated aneuploidy and mosaicism rates, as well as the proportion of patients who had at least one euploid embryo suitable for transfer. Findings were stratified according to SART-defined maternal age groups, 42 (212/401 patients/blastocysts) and blastoycst cohort size (1–2, 3–5, 6–9 and 10 or more biopsied blastocysts). Main results and the role of chance The mean maternal age was 37.0±3.7. The overall embryo aneuploidy rate was 50.6% (5904/11665), while mosaicism was established in 4.0% (469/11665) of blastocysts. As expected, the proportion of aneuploid embryos increased steadily with advancing maternal age (31.8%, 41.5%, 58.4%, 71.2%, 87.8%; p 10 embryos had at least one euploid embryo in 100% of cases, across all ages. Albeit, the numbers of patients within this category was low, and decreased significantly with advancing maternal age. Limitations, reasons for caution While blastocyst cohort size is considered to be an indirect measure of ovarian reserve, the number of oocytes retrieved was not evaluated. Our study only included the first PGT-A cycle for all patients. Subsequent, alterations in stimulation protocols may have resulted in an improved response in some patients. Wider implications of the findings: The comprehensive nature of the study, based on current PGT-A approaches and a large number of cycles across 16 centres increases clinical confidence in the notion that ovarian response is independent of embryo aneuploidy. Importantly, our findings may serve as a valuable clinical resource to guide patient counselling strategies. Trial registration number NA

Study question Is delayed blastocyst development, assessed by the day of trophectoderm (TE) biopsy, associated with higher rates of aneuploidy? Summary answer Our findings show an association between delayed blastocyst development and poorer prognosis, in terms of euploidy rates, in patients of advanced maternal age. What is known already Extended culture of embryos past day 5 of development has become routine practice in all freeze-all cycles, including those applying preimplantation genetic testing for aneuploidies (PGT-A). As healthy live births have been obtained from day 6 and day 7 blastocysts, increasing the pool of embryos available for PGT-A is beneficial, particularly for patients of advanced maternal age who face higher cancellation rates. Nevertheless, the association between delayed blastocyst development and aneuploidy rates remains unclear. As current studies have reported opposing findings, detailed analysis of the chromosomal constitution of slowly developing embryos remains paramount. Study design, size, duration Retrospective, international, multicentre cohort study of 4211 patients undergoing preimplantation genetic testing for aneuploidy (PGT-A) from January 2016 to July 2020. We evaluated the chromosomal status of 14757 blastocysts tested using TE biopsy and next generation sequencing (NGS). Both autologous and donation cycles were included in the analysis. Cycles were excluded if they utilised preimplantation genetic testing for monogenic disorders (PGT-M) or preimplantation genetic testing for structural rearrangements (PGT-SR). Participants/materials, setting, methods We evaluated euploidy, aneuploidy and mosaicism rates reported in day 5 (n = 9560), day 6 (n = 4753) and day 7 (n = 262) blastocysts, stratified by SART-defined maternal age categories (42). We further assessed the type and frequency of abnormalities reported in all blastocysts classified as clinically unsuitable, according to the day of biopsy. Finally, we examined the specific chromosomes affected in embryos diagnosed with a single uniform (n = 3882) or single mosaic (n = 518) abnormality. Main results and the role of chance The mean maternal age within our patient cohort was 39.9±3.7. Overall, slowly developing blastocysts were significantly more likely to be classified as clinically unsuitable (60.6%) compared to day 5 embryos (55.2%; p Limitations, reasons for caution Due to the retrospective nature of the study, full elucidation of all potential confounders may not be possible in all instances. The low number of day 7 blastocysts limited statistical power. As such, the results from day 6 and day 7 embryos were evaluated together. Wider implications of the findings: Our findings offer an important clinical resource for counselling patients of advanced maternal age. Maternal aging may be associated with a higher incidence of aneuploidy in slowly developing blastocysts. Nevertheless, extended culture increases the pool of biopsiable blastocysts, ultimately improving the chance of having a euploid embryo for transfer. Trial registration number NA