Analysis of mitochondrial DNA quantification in human blastocysts and assisted reproduction outcomes

Research question

Does the content of mitochondrial DNA (mtDNA) in human trophectoderm cells in blastocysts that received trophectoderm biopsy correlate with embryonic variables and the outcomes of assisted reproductive technology (ART)?

Design

To investigate whether the content of mtDNA in trophectoderm biopsies correlates with IVF outcome, 462 biopsies of blastocysts from 136 preimplantation genetic testing (PGT) cycles conducted between June 2022 and August 2024 were analysed. Euploid human blastocysts (n = 75) used in single frozen embryo transfer were studied. The mtDNA levels in trophectoderm cells were analysed by whole genome amplification and next-generation sequencing.

Results

Generalized linear regression analysis showed that only embryo euploidy was significantly associated with mitochondrial DNA copy number (MCN) (P < 0.0001). Progesterone and LH concentration on HCG trigger day were not associated with MCN. Meanwhile, aneuploids had more mtDNA quantities than the euploids after correcting for blastocyst morphology. No statistically significant differences were found in the MCN and pregnancy outcomes (P = 0.619), and there were also no statistically significant differences were found when divided into high and low groups based on the median value or four groups at the quartiles.

Conclusions

Regardless of blastocyst morphology, euploid embryos had significantly fewer mtDNA copy numbers than aneuploid embryos. Nevertheless, pregnancy outcomes showed no statistically significant variations, suggesting that mtDNA copy number may not be a good predictor of optimal clinical success and high competence potential in IVF.