Single blastomere biopsy of slow cleaving embryos can support subsequent development and implantation

Abstract

OBJECTIVE: Blastomere biopsy causes a reduction in total cytoplasmic volume that may affect subsequent development. Biopsy of slowly cleaving embryos results in a proportionately greater loss of embryonic volume. We have investigated the developmental potential of embryos with as few as 4 blastomeres, according to cell number at the time of single cell biopsy. DESIGN: Retrospective analysis. MATERIALS AND METHODS: Implantation rates of 412 embryos from 310 patients undergoing preimplantation genetic selection (PGS) by aneuploidy assessment and 50 patients undergoing preimplantation genetic diagnosis (PGD) for translocation diagnosis were analyzed. Only single embryo transfers or two-embryo transfers in which both embryos were at the same cell stage on Day 3 were considered. Compacted embryos were excluded. Implantation rate was determined as the number of deliveries per embryo transferred. Biopsy occurred early on the morning of Day 3 by removal of a single blastomere, followed by overnight FISH analysis and embryo transfer on Day 4. RESULTS: Slowly cleaving embryos (4-5 cells on Day 3) implanted and developed to term, albeit at a lower rate than 7-10 cell embryos (p<0.001) (Table 1).Table 1Delivery rate according to cell number on Day3Day 3 Cell NumberEmbryos TransferredDelivered4638 (12.7%)5607(11.7)6492 (4.1)76925 (36.2)814741 (27.9)9-10247 (29.2) Open table in a new tab Embryos that continued to develop slowly to Day 4 (<9 cells, no compaction) also displayed the ability to implant after transfer on Day 4 (Table 2).Table 2Delivery rate according to cell number on Day 4Day 4 Cell NumberEmbryos TransferredDelivered41505295 (17.2%)6485 (10.4)7309 (30)8272 (17.4) Open table in a new tab CONCLUSIONS: Embryos containing 4-5 cells on Day 3 implant and develop to term at a rate at least equal to that of six-cell embryos. Embryos such as these should be included during PGD treatment. The removal of no more than 1 blastomere from 4-5 cell embryos would seem to be essential, in order to avoid removal of more than 20% of the embryonic mass. The size of the blastomere selected for biopsy, an indication of whether it is a product of the second or third cleavage division, may also impact subsequent development. The demonstrated ability of slowly cleaving, non-compacted Day 4 embryos to develop to term suggests that standard measures of embryonic fitness may need to be modified for embryos recovering from biopsy. Embryo transfer on Day 4 may be one factor that improves the implantation potential of slowly cleaving embryos post-biopsy.