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American Society for Reproductive Medicine 2017 Scientific Congress & Expo
October 28 to November 1, 2017 San Antonio, TX, USA
Title:
THE ASSOCIATION BETWEEN ANEUPLOIDY AND THE RATE OF BLASTOCYST
DEVELOPMENT IS AGE DEPENDENT
Authors:
L Sekhon, T Nazem, JA Lee, C Briton-Jones, AB Copperman
Affiliations:
1. Reproductive Medicine Associates of New York, 635 Madison Ave 10th Floor New
York, New York, United States, 10022
2. Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount
Sinai, Klingenstein Pavilion 1176 Fifth Avenue 9th Floor New York, New York, United
States, 10029
Objective:
Modern preimplantation genetic testing (PGT) requires extended culture of embryos to the
blastocyst stage to facilitate trophectoderm biopsy. While PGT to select euploid blastocysts for
transfer have increased implantation and pregnancy rates, failed or slow development to the
blastocyst stage may preclude biopsy of embryos at the appropriate stage. We hypothesize that
embryos with a normal chromosomal complement are more likely to cavitate quickly.
Alternatively, some have proposed that very rapid cleavage may indicate embryonic dysfunction.
This study sought to evaluate the relationship between blastocyst development and the incidence
of chromosomal abnormalities in patients undergoing PGT with targeted NGS.
Design:
Retrospective, observational study
Materials and Methods:
The study included women that underwent IVF with trophectoderm biopsy for PGT, on day 5
and/or 6 of blastocyst development, from February 2016 to April 2017. Aneuploidy screening by
targeted NGS was performed. Embryos were cultured to the expanded blastocyst stage and
evaluated for potential day 5 biopsy based on morphological grading and development
(morphological grading criteria: ≥4BC). Embryos deemed unsuitable for biopsy on day 5 were
kept in culture and reevaluated for potential biopsy on day 6. The rate of aneuploidy was
compared according to maternal age (stratified by <38 vs. ≥38 years) and the day of embryo
development (stratified by day 5 vs. day 6 of embryo development). Chi square and linear
regression were used for analysis.
Results:
The rates of aneuploidy detected by targeted NGS were compared among blastocysts that
underwent trophectoderm biopsy on day 5 (n=1131) and 6 (n=525). The aneuploidy rate
increased significantly with increasing maternal age ( =0.036 p<0.0001). Overall, embryos
biopsied on day 6 had a higher rate of aneuploidy than those biopsied on day 5 (53.5% vs.
48.8%, p=0.07). This difference was more pronounced and statistically significant in patients
aged ≥38 years (74.0% vs. 66.2%, p<0.05) (Table 1).
Conclusion:
The association between slower embryo development and aneuploidy is more pronounced with
advancing age. This finding is consistent with prior studies that used lower resolution techniques
to interrogate chromosome copy number, but this is the first and largest study to demonstrate this
association using targeted NGS. While differences in the incidence of aneuploidy at discrete
checkpoints of blastocyst development were observed, the use of time-lapse imaging in future
studies may advance clinical understanding of the exact point in time at which embryos become
amenable to trophectoderm biopsy and the developmental threshold beyond which embryos are
more likely to be aneuploid. Clinical studies should aim to determine whether the implantation
potential of euploid embryos is impacted by their rate of development.
Support:
None
Table 1:
The rate of aneuploidy stratified by day of embryo development at time of trophectoderm biopsy
and patient age.
Age
Day 5 Biopsy
Day 6 Biopsy
P Value
All patients
48.8%
(552/1131)
53.5%
(281/525)
0.07
<38
38.1% (267/701)
40.0%
(127/317)
NS
≥38
66.3% (285/430)
74.0%
(154/208)
<0.05
