Does Trophectoderm Mitochondrial DNA Content Affect Embryo Developmental and Implantation Potential?

Abstract

A retrospective case control study was undertaken at the molecular biology department of a private center for reproductive medicine in order to determine whether any correlation exists between the mitochondrial DNA (mtDNA) content of trophectoderm and embryo developmental potential. A total of 275 couples underwent IVF treatment, producing a total of 716 embryos. The trophectoderm was biopsied from each embryo at the blastocyst stage (day 5 or day 6 post-fertilization) subjected to low-pass next-generation sequencing (NGS), for the purpose of detecting aneuploidy. For each sample, the number of mtDNA reads obtained after analysis using NGS was divided by the number of reads attributable to the nuclear genome. The mtDNA copy number was found to be higher in aneuploid embryos than in those that were euploid (mean mtDNA ratio ± SD: 1.13 ± 1.37 versus 1.45 ± 1.78, p = 0.02) and in day 5 biopsies compared to day 6 biopsies (1.41 ± 1.66 vs. 1.19 ± 1.27, p = 0.001), whereas no statistically significant differences in mtDNA content were seen in relation to embryo morphology (1.58 ± 2.44 vs. 2.19 ± 2.89, p = 0.12), genetic sex (1.27 ± 1.29 vs. 1.27 ± 1.18, p = 0.99), maternal age (1.31 ± 1.41 vs. 1.33 ± 1.29, p = 0.43), or its ability to implant (1.14 ± 0.88 vs. 1.21 ± 1.16, p = 0.39). mtDNA has small potential to serve as an additional, independent biomarker for embryo selection.

When the Embryo Meets the Endometrium: Identifying the Features Required for Successful Embryo Implantation

“…Victor and coworkers [70] were unable to find a relationship between mtDNA content and clinical outcomes in euploid embryos. Likewise, other studies did not identify any implantation benefits in embryos with reduced mtDNA content [71][72][73]. Moreover, the analysis of TE samples from 615 euploid human blastocysts showed that mtDNA content was not predictive of euploid human embryo reproductive competence [74].…”

Mechanisms of mitochondrial dysfunction in ovarian aging and potential interventions

“…Practically, the assessment of mtDNA quantity accompanying the preimplantation genetic testing for aneuploidy (PGT-A) of the trophectoderm biopsy has been used to predict embryo implantation potential. Studies in multiple clinics found that high mtDNA levels in blastocysts were related to aneuploidy embryos and implantation failure ( 216 – 218 ). The latest retrospective investigation analyzed the transfer cycle of frozen single euploid embryos, and the results showed that no correlation was observed between mtDNA content and blastocyst morphology grades or pregnancy outcomes ( 219 , 220 ).…”

“…Still, lower mtDNA content was associated with delayed blastocyst development ( 219 ). It should be noted that there is currently no consensus on the threshold for the mtDNA copy number of blastocysts, and the accuracy of using mtDNA copy number as a single predictive biomarker for embryo selection and developmental potential remains low ( 216 – 220 ).…”

Multichannel Recovery Potential with Activated Autologous Intraovarian Platelet-Rich Plasma and Its Derivatives

“…In human blastocysts with mtDNA copy number exceeding an established threshold, this ominous sign forecasts poor reproductive outcome [ 51 , 52 ]. For example, mtDNA copy number is much higher for aneuploid embryos [ 53 ], illustrating a ‘less is more’ relation for human embryos and mtDNA copy number [ 54 , 55 ]. Further IVF experience with human embryo culture has indeed shown how mtDNA levels are usually far lower for cases with successful live birth [ 56 ].…”