P-139 Mitochondrial DNA copy number in trophectodermal cells (MITOSCORE) is related to embryo quality, but not to implantation potential
Authors: Gomez - Sanchez E , Pérez-Cárceles M  D , Diaz R , losá V  L , Montero-Venegas L , Almunia N , Valcárcel M , Jiménez R 
Published: July 2024

Abstract

Study question
Is mtDNA copy number in trophectodermal cells (MITOSCORE) related to the quality of euploid embryos in our PGT-A program? Is it related to implantation potential?

Summary answer
mtDNA copy number in trophectodermal cells (MITOSCORE) is related to embryo quality and morphokinetic, but no to implantation potential in our PGT-A program.

What is known already
Fertilization and embryonic development require energy, sourced from mitochondria. Research on human embryos indicates associations between aneuploidy and maternal age and increased mtDNA content. Consequently, exploring embryonic mtDNA levels as a quality marker gained momentum. Embryos with high mtDNA levels often correlate with poor implantation potential, leading to its adoption as a biomarker for selection. However, conflicting studies challenge this notion, failing to establish correlations between mtDNA levels and blastocyst grade, implantation, or ongoing pregnancy rates in patients with euploid embryos. Consequently, the predictive value of mtDNA levels for embryo implantation potential and pregnancy outcomes remains uncertain.

Study design, size, duration
A retrospective study was conducted to establish a relationship between MITOSCORE and the euploid embryo morphokinetics. It involved 59 embryos from 25 PGT-A cycles performed from January 2022 to December 2023. In addition, we retrospectively analysed 143 thawed single embryo transfers from three centres (October 2020 to December 2023) to assess the correlation between MITOSCORE and pregnancy outcomes. Embryos for transfer were selected based on morphology; mtDNA was considered only if two had similar morphology.

Participants/materials, setting, methods
Morphokinetic was determined using the AI tool CHLOE (Fairtility, Israel), which automatically provides morphokinetic parameters and also offers an additional score of embryo quality, EQ. mtDNA levels were estimated by NSG and the MITOSCORE score was provided by an algorithm (Igenomix, Spain). Pearson’s correlation analysis was employed to investigate the potential relationship between MITOSCORE results and embryonic morphokinetics. Mann-Whitney test was used to analyse the relationship of MITOSCORE levels with pregnancy.

Main results and the role of chance
A statistically significant correlation (p &lt; 0.05), albeit weak, was observed between MITOSCORE and embryonic quality evaluated through CHLOE EQ (r: -0.3858). It is noted that a higher EQ was associated with a lower value in MITOSCORE. Additionally, upon analysing morphokinetic parameters, it was found that the time to reach the stages of morula (r: 0.6876), early blastocyst (r: 0.6303), cavitated (r: 0.6823), and expanded (r: 0.5776) were significantly correlated (p &lt; 0.05) with MITOSCORE values. The slower the embryo development, the higher the MITOSCORE. Regarding implantation capacity and mtDNA levels, implanted euploid embryos had a MITOSCORE value of 20.35, which was not significantly different from that of non-implanted embryos, which was 21.65. The highest MITOSCORE value at which a full-term pregnancy was achieved was 32.34. However, no pregnancy was obtained with the three embryos with the highest scores (35.02, 45.02, and 48.17).

Limitations, reasons for caution
Morphokinetics correlation with MITOSCORE was analysed with a limited number of embryos (59). The highest MITOSCORE level was 48.17. The transfers were not fully blinded. A randomized clinical trial would be necessary to determine the true clinical benefits of mtDNA levels in the trophectoderm of euploid embryos in our clinics.

Wider implications of the findings
Trophectodermal mtDNA level is associated with morphokinetic parameters and blastocyst quality but not embryo implantation potential. In our PGT-A programme, and with our results, trophectodermal mtDNA copy numbers work as a biomarker of blastocyst quality but have not been correlated with clinical outcomes after the transfer of euploid embryos.

Trial registration number
NOT APPLICABLE