1. Ploidy, morphokinetics and time lapse imaging: The story so far.
Alison Campbell1, Simon Fishel1 and Darren Griffin2
1 CARE Fertility, John Webster House, Lawrence Rd, Nottingham Business Park, Nottingham, NG^ 8RX
2 Genetics, School of Biosciences, University of Kent, Canterbury. Kent, CT2 7NZ
Introduction
Time-lapse imaging has the potential to be either complementary or even an alternative option to PGS; it is reported to improve the chances of viable or euploid embryo selection. Here, we review, categorise and summarize scientific material ( ) using citation databases and conference proceedings that consider the association between embryo ploidy and morphokinetic criteria, revealed by time lapse imaging. A brief overview of studies is provided and common or conflicting findings highlighted and discussed.
Aneuploidy in preimplantation embryos is a leading cause of IVF failure. Preimplantation genetic screening can be used to infer embryo ploidy following biopsy. However PGS has limitations of accessibility, acceptability, invasiveness and cost. Embryo morphology remains the most commonly used embryo selection criterion in IVF treatment. Non invasive markers of ploidy and viability are sought as only weak associations between morphology and ploidy have been reported to date.
Methods
21 relevant studies were identified.17 abstracts compared pre-compaction (early) parameters in euploid and aneuploid embryos. Seven abstracts additionally considered late morphokinetics ,according to embryo ploidy. Four original articles were identified.
Outcomes - Early morphokinetics (to 8 cells) (Fig.1)
Five abstracts from 17 (29%) reported significant differences in morphokinetics of euploid and aneuploit embryos. Aneuploid embryos had increased multinucleation (2 studies); more irregular cleavage (one study); prolonged transition 2 to 4 cells (one study) and 5 to 8 cells (one study), compared with euploid. The remaining 12 (71%) abstracts reported no differences in early morphokinetics.
Two original articles considered early morphokinetic parameters of aneuploidy. One reported faster times to 5, from 2 and 3 cells in aneuploid embryos. The other concluded that cell cycle (prolonged first, and time between first and second divisions) and blastomere fragmentation parameters were diagnostic of ploidy.
Outcomes - Late morphokinetics (Fig.2)
7 abstracts additionally considered late morphokinetics.
5 (71%) reported peri-compaction and/or blastulation initiation and completion delays in aneuploid embryos compared with euploid, 2 (29%) found no differences.
Significant peri-blastulation delays in aneuploid embryos were found in one original article but not in another.
Difference reported are highlighted in the figures below
Figure 1. Reported early markers of embryo ploidy.
Figure 2. Reported late markers of embryo ploidy
Discussion
Findings from the multiple small investigations into ploidy and morphokinetics, presented as abstracts, are mixed. When considering early cleavage stage associations with ploidy, most studies did not report differences whereas, most of the abstracted data looking at later developmental associations did find delays in aneuploid embryos compared with euploid. Numbers remain small however and consensus has not been reached. Original articles, in this area, also remain few and findings are conflicting.
Associations between morphokinetics and ploidy require careful interpretation due to lack of consensus for definitions, variable PGS methodologies, sample sizes and time lapse devices used. Larger studies are needed but time lapse imaging remains a promising tool to enhance clinical outcome.
Full reference list available upon request