Alternative patterns of partial embryo compaction: prevalence, morphokinetic history and possible implications

Abstract Research question The morula stage is a poorly understood developmental stage. In the morula, cell compaction can involve all blastomeres or only part of them, with largely unknown implications. Here, we investigated prevalence, underlying morphokinetic mechanisms and possible consequences of partial compaction. Design The study data concerned PGT-A cycles of women whose embryos were observed by time lapse technology. PGT-A data, generated by array-CGH analysis and assessed in three age groups (≤34, 35-39 and ≥40 years), were obtained from trophectoderm biopsies after development to the blastocyst stage. Results Compaction occurred according to three modalities: i) full compaction (fully compacted morulae, FCM), if all blastomeres compacted; partial compaction (partially compacted morulae, PCM), if blastomeres failed to compact because either ii) excluded from the outset (excluded-PCM) or iii) extruded after the beginning of compaction (extruded-PCM). Partial compaction occurred more frequently than full compaction. Excluded-PCM displayed the slowest morphokinetics at all stages and were mostly associated with abnormal cleavage. After compaction, embryo degeneration was more frequently associated with cell extrusion. In the excluded-PCM, loss of 2 or more cells impacted blastocyst rate. In embryos of both younger and older age groups, no statistical differences were observed in the rate of aneuploidy in relation to the three compaction groups. Differences in implantation rates after transfer of euploid blastocysts were also not statistically different between the three groups. Conclusions Alternative modalities of incomplete compaction were detected for the first time. Such patterns are characterized by different morphokinetic behaviours overarching the entire preimplantation development and by different developmental abilities.