Trophectoderm Mitochondrial DNA Content Associated with Embryo Quality and Day-5 Euploid Blastocyst Transfer Outcomes

Abstract

Mitochondria play a critical role in cell function and embryo development. Recently, increasing studies have investigated whether mitochondrial DNA (mtDNA) can be used as a predictive biomarker of embryo implantation. However, the results of its effect on implantation are still controversial. To further understand the clinical application value of mtDNA content for reproductive potential, we analyzed the influence of relative mtDNA quantity on embryo quality and transfer outcomes based on the results of second-generation sequencing of preimplantation genetic testing patients in our center. Biopsied trophectoderm (TE) from aneuploid blastocysts contained much larger amounts of mtDNA than those from euploid blastocysts ( p < 0.000). In an analysis of only euploid blastocysts (n = 769), female age had no effect on mtDNA content ( p = 0.216). TE cells biopsied on day 5 (n = 355) contained significantly higher amounts of mtDNA compared to those biopsied on day 6 (n = 388) or day 7 (n = 26) ( p < 0.000). Higher quality trophoblast was associated with lower mtDNA content ( p = 0.026), but quality of inner cell mass was not correlated with quantity of mtDNA ( p = 0.112). For transferred embryos, the biopsied date and mtDNA content were significantly associated with embryo implantation and live birth outcomes. Day-5 euploid blastocysts with lower quantities of mtDNA exhibited higher implantation rate and live birth rate. However, our data indicated that mtDNA content may not be considered an independent predictive marker, it may be a useful reference for the selection of day-5 transferred euploid blastocysts.

Mitochondrial DNA Content May Not Be a Reliable Screening Biomarker for Live Birth After Single Euploid Blastocyst Transfer

“…obtained the opposite results that mtDNA content decreased with advancing age ( 31 ). Other studies found no relation with maternal age ( 28 , 34 , 57 ), which is consistent with our finding. Although the hypothesis that reproductive ageing in older women is associated with the content of mtDNA in blastocyst-stage embryos is attractive ( 27 ), our results do not support this argument.…”

“…Although the hypothesis that reproductive ageing in older women is associated with the content of mtDNA in blastocyst-stage embryos is attractive ( 27 ), our results do not support this argument. We also found that blastocysts biopsied on Day 5 showed higher levels of mtDNA content compared with those biopsied on Day 6, which was consistent with previous studies ( 33 , 55 , 57 , 66 ). The replication of mtDNA will not be reactivated in the embryo until the blastocyst stage ( 67 ), blastocysts biopsied on Day 6 may undergo more cell divisions compared with blastocysts biopsied on Day 5, which may result in a reduction of mtDNA content in Day 6 blastocysts.…”

“…However, Wang et al. determined the mtDNA content using an NGS-based methodology with mathematical correction but reached the opposite conclusion ( 57 ). Wang et al.…”

Mitochondrial DNA Copy Number in Cleavage Stage Human Embryos—Impact on Infertility Outcome

“…As most of published studies concerning mtDNA copy number in human embryos were conducted using blastocysts from frozen IVF cycles [7][8][9][10][11][12][13]36], we decided to evaluate the end point parameters by assessing blastomeres biopsied at the cleavage stage that were transferred on day 5 of the same cycle. We aimed to evaluate the significance of the energy production process at such an early stage of embryo development.…”

“…In recent years, several studies have been performed to evaluate mtDNA as a potential biomarker of embryo vitality. However, there is a lot of controversy as studies performed have reached contradicting conclusions [4,[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24].…”