Levels of trophectoderm mitochondrial DNA do not predict the reproductive potential of sibling embryos.
What is the predictive value of trophectoderm mitochondrial DNA (mtDNA) quantity for blastocyst reproductive potential?



This study demonstrates that, within a given cohort, mtDNA quantitation does not distinguish between embryos that implant and embryos that do not implant after double embryo transfer (DET).



An association between implantation failure and increased quantities of mtDNA has been observed in two studies but not in a third.



A total of 187 patients (nine who received donor oocytes) with DET of one male and one female euploid blastocyst were included in this retrospective study, with 69 singleton deliveries providing the primary dataset to evaluate the predictive value of mtDNA for reproductive potential between January 2010 and July 2016.



MtDNA was quantified in cell lines to validate the quantitative PCR assay on limited quantities of starting material and then applied to 374 blastocyst biopsies. Pregnancies resulting in a singleton outcome were analyzed and newborn gender was utilized as a means to identify the implanted embryo. MtDNA quantity was then compared between implanted and non-implanted embryos in order to define the predictive value of mtDNA content for reproductive potential in this subset of patients.



An initial comparison of mtDNA levels between all successful and unsuccessful embryos revealed no significant differences. In order to control for patient-specific variables, gender was subsequently used to identify the implanted embryo in DETs resulting in a singleton (n = 69). No systematic difference in relative mtDNA quantity was detected between implanted and non-implanted embryos.



This study was conducted at a single center and did not evaluate the entire cohort of embryos from each patient to evaluate cohort specific variation in mtDNA quantity. Although the largest of its kind so far, the sample size of DETs leading to a singleton was relatively small.



These data highlight the importance of control over patient-specific variables when evaluating candidate biomarkers of reproductive potential. All current available data suggest that mtDNA quantification needs further study before its clinical use to augment embryo selection.



The authors have no potential conflict of interest to declare. No external funding was obtained for this study.



Not applicable.
Reproductive Medicine Associates of New Jersey, Basking Ridge, NJ, USA.|Rutgers-Robert Wood Johnson Medical School, NJ , USA.
Nathan R
NR
Treff
The Foundation for Embryonic Competence,NJ , USA..
Yiping
Y
Zhan
The Foundation for Embryonic Competence,NJ , USA..
Xin
X
Tao
Rutgers-Robert Wood Johnson Medical School, NJ , USA.
Meir
M
Olcha
The Foundation for Embryonic Competence,NJ , USA..
Michael
M
Han
The Foundation for Embryonic Competence,NJ , USA..
Jessica
J
Rajchel
The Foundation for Embryonic Competence,NJ , USA..
Liza
L
Morrison
Reproductive Medicine Associates of New Jersey, Basking Ridge, NJ, USA.|Sidney Kimmel Medical College, Thomas Jefferson University,Philadelphia, PA,  USA.
Scott J
SJ
Morin
Reproductive Medicine Associates of New Jersey, Basking Ridge, NJ, USA.|Sidney Kimmel Medical College, Thomas Jefferson University,Philadelphia, PA,  USA.
Richard T
RT
Scott
D001755:Blastocyst / Q000502:physiology*; D004272:DNA, Mitochondrial / Q000378:metabolism*; D010064:Embryo Implantation; D004624:Embryo Transfer; D047108:Embryonic Development; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D011247:Pregnancy; D012189:Retrospective Studies
D004272:DNA, Mitochondrial
IVF; blastocyst; comprehensive chromosome screening; embryo selection; mitochondrial DNA