Abstract


OBJECTIVE: Limited evidence is available regarding the influence of mitochondrial DNA (mtDNA) on embryo implantation, and its relationship to outcomes remains controversial. The goal of our study is to further elucidate the association between the amount of embryonal mtDNA and implantation.
DESIGN: Retrospective cohort analysis. view more

OBJECTIVE: Limited evidence is available regarding the influence of mitochondrial DNA (mtDNA) on embryo implantation, and its relationship to outcomes remains controversial. The goal of our study is to further elucidate the association between the amount of embryonal mtDNA and implantation.
DESIGN: Retrospective cohort analysis.
MATERIALS AND METHODS: We performed a retrospective chart review of subjects whose embryos underwent preimplantation genetic screening (PGS) prior to single embryo transfer in our center between 2013 and 2016. A total of 153 embryo transfers from 144 subjects were included. We compared mtDNA content—ratio of mtDNA to nuclear DNA—between No Implantation and Implantation groups. Secondary outcomes of interest were clinical and ongoing pregnancy. Multinomial logistic regression was used for data analysis between dependent categorical outcomes and continuous independent variables. In an attempt to identify an amount of embryonal mtDNA predictive of implantation, the mtDNA was divided into percentiles. Fisher’s exact, Pearson’s chi-squared, or Wilcoxon rank-sum were used as appropriate with P<0.05 considered significant.
RESULTS: The Implantation and No Implantation groups were similar with respect to age, BMI, and gravida and para (Table). Although there was no statistically significant difference in mtDNA content between the Implantation and No Implantation groups (P=0.29), upper quartile percentiles of mtDNA content were inversely proportional to implantation rates (Upper 75%ile: 25% vs 13%; P=0.05; Upper 90%ile: 20% vs 10%, P= 0.07; and Upper 95%ile, 5% vs 0%, P=0.05) (Table). No associations were observed between mtDNA content and clinical or ongoing pregnancy (data from logistic regression analyses not shown).

Characteristics No Implantation (N=59) Implantation (N=94) P value*
Age (y) 35 (32-39) 34 (32-37) 0.32
BMI (Kg/m2) 25 (22-29) 26 (22-31) 0.26
BMI >30 (Kg/m2) 24(40%) 30 (30%) 0.184
Ethnicity 0.04
White 27 (52%) 65 (73%)
Black 5 (9%) 3 (3%)
Hispanic 11 (21%) 8 (9%)
Asian 9 (17%) 13 (14%)
Gravida 1 (0-2) 1 (0-2) 0.26
Para 0 (0-1) 0 (0-1) 0.6
Mitochondrial DNA 0.000618 (0.000385-0.00129) 0.000644(0.000363-0.000995) 0.29
mtDNA25(25%ile or less) 13 (23%) 25 (25%) 0.83
mtDNA10 (10%ile or less) 2 (3%) 10 (10%) 0.123
mtDNA5 (5%ile or less) 0 5 (5%) 0.159
mtDNA75 (75%ile or more) 15 (25%) 13 (13%) 0.05
mtDNA90 (90%ile or more) 12 (20%) 10 (10%) 0.07
mtDNA95 (95%ile or more) 3 (5%) 0 (0%) 0.05
mtDNA99 (99%ile or more) 1(1%) 0 (0%) 0.37

CONCLUSIONS: This is the largest study to evaluate the relationship between embryonal mtDNA content and embryo transfer outcomes. In contrast to some prior published studies, our data did not show an association between mtDNA content and implantation. We did find that embryos with mtDNA content in the upper quartile percentiles were less likely to implant. However, cut-offs for mtDNA content predictive of implantation or failure could not be established. These data are limited to high-quality embryos selected for transfer, and prospective clinical studies are needed.

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