Mitochondrial DNA Copy Number in Cleavage Stage Human Embryos—Impact on Infertility Outcome
Amira Podolak | Joanna Liss | Jolanta Kiewisz | Sebastian Pukszta | Celina Cybulska | Michal Rychlowski | Aron Lukaszuk | Grzegorz Jakiel | Krzysztof Lukaszuk
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 mitochondrial DNA (mtDNA) content of cleavage-stage preimplantation embryos and their developmental potential. A total of 69 couples underwent IVF treatment (averaged women age: 36.5, SD 4.9) and produced a total of 314 embryos. A single blastomere was biopsied from each embryo at the cleavage stage (day-3 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 amount was found to be higher in aneuploid embryos than in those that were euploid (mean mtDNA ratio ± SD: 6.3 ± 7.5 versus 7.1 ± 5.8, <i>p</i> < 0.004; U Mann–Whitney test), whereas no statistically significant differences in mtDNA content were seen in relation to embryo morphology (6.6 ± 4.8 vs. 8.5 ± 13.6, <i>p</i> 0.09), sex (6.6 ± 4.1 vs. 6.2 ± 6.8, <i>p</i> 0.16), maternal age (6.9 ± 7.8 vs. 6.7 ± 4.5, <i>p</i> 0.14) or its ability to implant (7.4 ± 6.6 vs. 5.1 ± 4.6, <i>p</i> 0.18). The mtDNA content cannot serve as a useful biomarker at this point in development. However, further studies investigating both quantitative and qualitative aspects of mtDNA are still required to fully evaluate the relationship between mitochondrial DNA and human reproduction.
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