Levels of trophectoderm mitochondrial DNA do not predict the reproductive potential of sibling embryos

Abstract

STUDY QUESTIONWhat is the predictive value of trophectoderm mitochondrial DNA (mtDNA) quantity for blastocyst reproductive potential?SUMMARY ANSWERThis study demonstrates that, within a given cohort, mtDNA quantitation does not distinguish between embryos that implant and embryos that do not implant after double embryo transfer (DET).WHAT IS ALREADY KNOWNAn association between implantation failure and increased quantities of mtDNA has been observed in two studies but not in a third.STUDY DESIGN, SIZE AND DURATIONA total of 187 patients (nine who received donor oocytes) with DET of one male and one female euploid blastocyst were included in this retrospective study, with 69 singleton deliveries providing the primary dataset to evaluate the predictive value of mtDNA for reproductive potential between January 2010 and July 2016.PARTICIPANTS/MATERIALS, SETTING AND METHODMtDNA was quantified in cell lines to validate the quantitative PCR assay on limited quantities of starting material and then applied to 374 blastocyst biopsies. Pregnancies resulting in a singleton outcome were analyzed and newborn gender was utilized as a means to identify the implanted embryo. MtDNA quantity was then compared between implanted and non-implanted embryos in order to define the predictive value of mtDNA content for reproductive potential in this subset of patients.MAIN RESULTS AND THE ROLE OF CHANCEAn initial comparison of mtDNA levels between all successful and unsuccessful embryos revealed no significant differences. In order to control for patient-specific variables, gender was subsequently used to identify the implanted embryo in DETs resulting in a singleton (n = 69). No systematic difference in relative mtDNA quantity was detected between implanted and non-implanted embryos.LIMITATIONS, REASONS FOR CAUTIONThis study was conducted at a single center and did not evaluate the entire cohort of embryos from each patient to evaluate cohort specific variation in mtDNA quantity. Although the largest of its kind so far, the sample size of DETs leading to a singleton was relatively small.WIDER IMPLICATIONS OF THE FINDINGSThese data highlight the importance of control over patient-specific variables when evaluating candidate biomarkers of reproductive potential. All current available data suggest that mtDNA quantification needs further study before its clinical use to augment embryo selection.STUDY FUNDING/COMPETING INTERESTSThe authors have no potential conflict of interest to declare. No external funding was obtained for this study.TRIAL REGISTRATION NUMBERNot applicable.

No association of mitochondrial DNA levels in trophectodermal cells with the developmental competence of the blastocyst and pregnancy outcomes

“…However, three additional studies have failed to show any such correlation. Treff and group reported no association between mtDNA levels in implanted and non-implanted embryos (Treff et. al., 2017).…”

The mitochondrial DNA content can not predict the embryo viability

“…Recently, the mtDNA content was further indicated to be negatively related to embryo viability and proposed to be used as a biomarker in the prediction of implanation outcome (4, 12, 14, 15). But these results were still under debate (16–18). Victor et al reported a modified method that demonstrated mtDNA lacked of predictive value (17).…”

“…Three independent studies presented that mtDNA content failed to establish predictive power of implantation at the conference of Preimplantation Genetic Diagnosis International Society (PGDIS) (19–21). Moreover, Treff et al demonstrated that levels of mtNDA didn’t predict the reproductive potential in the similar gold standard : double embryo transfer (DET)(18). What is the cause of this inconsistency?…”

“…not scientific for analyzing the mtDNA content in embryo which came from many IVF clinics together. Thirdly, the previous studies just used next generation sequencing (NGS) or array Comparative Genomic Hybridization (aCGH) to determine each embryo chromosome status(12, 13, 18), it is worthy to note that the consistency of the results based on NGS and aCGH platform is not perfectly 100% (22–24). That also could cause some deviations when do classification based on embryo chromosome status.…”

Renaissance, reinvention, or rhetoric: mitochondria in reproductive medicine 2017

“…Burdening patients with the expense associated with tests requiring further scrutiny seems an unfair course of action, at least until a consensus can be reached on platforms for discovery that satisfy standards of genetic testing accepted by the broader medical communities around the world [10].…”