Abstract: P-113

Lower Embryonal Mitochondrial DNA Content is Associated with Better Quality Embryos.

Presenter: Amber Klimczak


Abstract


OBJECTIVE: Currently, there is no consensus on whether mitochondrial DNA (mtDNA) content is associated with embryo quality. Our objective was to determine if mtDNA content is a predictor of embryo quality.
DESIGN: Retrospective chart review. view more

OBJECTIVE: Currently, there is no consensus on whether mitochondrial DNA (mtDNA) content is associated with embryo quality. Our objective was to determine if mtDNA content is a predictor of embryo quality.
DESIGN: Retrospective chart review.
MATERIALS AND METHODS: We performed a retrospective chart review of subjects whose embryos underwent preimplantation genetic screening (PGS) in our center between 2013 and June 2016. A total of 259 subjects with 1510 blastocyst biopsies were included. Embryo grade was defined based on the Gardner blastocyst grading system as follows: 1—High (3-6 AA and 4-6 AB), 2—Mid (any BB, 1-3 AB, and 1-2 AA), and 3—Poor (any AC, CA, BC, CB, or CC). ‘Embryonal mtDNA content’ was defined as a ratio of mitochondrial DNA to nuclear DNA. Our primary outcome was to compare embryonal mtDNA content to embryo grade. For our secondary outcomes we compared mtDNA to age and repeated the analysis after excluding embryos with aneuploidy. Statistical analysis was performed using a multinomial logistic regression model of prediction and linear regression. P<0.05 was considered significant.
RESULTS: From a total of 1510 blastocyst biopsies, the majority of embryos consisted of Grade 1 (N=951; 62%), followed by Grade 2 (N=331; 21%) and Grade 3 embryos (N=228; 15%). Embryos with high mtDNA content were found to be of poorer quality (Grade 3) relative to grades 1 and 2. (RR 1.03 [95% CI 1.01-1.05]; P=0.003). Using a logistic model, mtDNA best predicted lowest and highest grades, but not mid-grade (Grade 2) embryos (data not shown). There was no correlation between mtDNA content and the subjects’ age (R-square = 0.0018). After excluding embryos with aneuploidy, a total of 717 euploid embryos were identified. In this subpopulation, a non-statistically significant trend was observed where poor quality embryos had higher mtDNA content (OR 1.16, [95% CI 0.27- 5.01]; P= 0.834).

TABLE
Subjects 259
Age (Median, range) 35 [31-38]
BMI (Median, range) 25 [22-28]
Ethnicity (N, %)
White 157 (60)
Black 22 (8)
Hispanic 34 (13)
Asian 46 (17)
Mitochondria DNA Content (Median, range)
All Embryos (N, %) 1510 (100) 0.000741 [0.0004375-0.00144]
High-1 951 (62) 0.000624 [0.000363-0.00097]
Mid-2 331 (21) 0.000623 [0.00037-0.00112]
Poor-3 228 (15) 0.000656 [0.0003915-0.0009345]
Euploid Embryos (N, %) 717 (100)
High-1 521 (72)
Mid-2 140 (20)
Poor-3 56 (8)

CONCLUSIONS: Our study is the largest to evaluate the association between mtDNA content and embryo quality. A higher quantity of embryonal mtDNA content suggests a poorer quality embryo, possibly due to greater oxidative stress. Conversely, lower mtDNA content suggests a higher quality embryo. In euploid embryos, mtDNA content may not be predictive of embryo quality. Further clinical trials are needed to further elucidate this relationship.

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