Aneuploidy and implantation potential of euploid blastocysts cannot be predicted by non-invasive morphokinetic analysis during in vitro culture

Study question: Is morphokinetic assessment related to aneuploidy and/or implantation potential of euploid blastocysts? Summary answer: Morphokinetic parameters commonly assessed by timelapse investigation up to blastocyst stage are not related to aneuploidy. Moreover, euploid implanted and not implanted embryos have similar timings of cell division and blastocyst formation. What is known already: Recent studies have suggested a correlation between aneuploidy and/or implantation and morphokinetic parameters. However, there is not a general consensus on which parameter is the predictive one. Timing of singamy, to reach 5-cell-stage, and cell-cycle synchrony and duration have been suggested from some groups, timing to reach 8-cell stage from other, finally only correlations at blastocyst stage have been reported. Moreover, these studies were often underpowered and the results not adjusted for female age. Study design, size, duration: A longitudinal cohort study was performed from September 2012 and December 2013. A total of 455 blastocysts, derived from 136 patients, cultured in timelapse incubator and subjected to trophectoderm biopsy and comprehensive chromosomes screening for aneuploidies, have been included. Participants/materials, setting, methods: ICSI/PGS cycles due to advanced maternal age were analysed. 13 morphokinetic features were registered. Transfers were performed with single-vitrified-warmed-euploid blastocysts, and implantation (>12 weeks of gestation) was recorded. Logistic mixed effects models analysis adjusted for female age, with a subject-specific intercept was performed. Main results and the role of chance: 186/455 (40.9%) blastocysts resulted euploid. Logistic regression analysis found no statistical correlation between the 13 morphokinetic characteristics analysed (syngamy, completion of cleavage to 2, 3, 4, 5 and 8-cells, length of first and second cell cycle and synchrony in the 2 divisions; initiation of compaction, initiation of blastulation, completion of blastulation) and aneuploidy (24.5 ± 3.3, 27.1 ± 3.3, 37.9 ± 4.9, 39.8 ± 4.9, 51.7 ± 7.3, 61.7 ± 10.7, 2.6 ± 0.9, 10.8 ± 3.3, 1.9 ± 3.0, 10.1 ± 8.8, 91.7, 104.8 ± 9.5, 119.7 ± 11.6 and 24.6 ± 3.3, 27.2 ± 3.3, 38.2 ± 4.7, 40.1 ± 5.1, 52.1 ± 8.3, 61.9 ± 11.6, 2.5 ± 0.9, 11.1 ± 2.9, 1.9 ± 3.1, 9.7 ± 8.2, 92.0 ± 9.5, 104.0 ± 9.7, 120.7 ± 11.9 for euploid and aneuploid blastocysts, respectively). As expected advancing female age was significantly predictive of aneuploidy (P < 0.001). Out of 74 transferred blastocysts 37 implanted (50%). Implanted and not implanted blastocysts also had similar timings of development. Limitations, reason for caution: The study was restricted to a selected group of patients with increased risk of aneuploidy due to advanced maternal. A larger study would be required to prove if the findings are applicable for the whole cohort or other selected groups of patients. Furthermore, this study design did not allowed to distinguish between meiotic and mitotic derived aneuploidies. Future studies can be performed to specifically investigate the role of pre-compaction morphokinetic parameters in predicting mosaic aneuploidies. Wider implications of the findings: In contrast to several recent publications, our results suggest that morphokinetic analysis cannot be considered as a predictive indicator of aneuploidy and/or implantation potential of euploid blastocysts. The lack of correlation found in this selected group of patients, prone to aneuploidy, indicates at this day no clinical value of morphokinetic investigation to improve embryo selection in PGS cycles. Study funding/competing interest(s): Funding by hospital/clinic(s), none. Trial registration number: None.