Suboptimal trophectoderm mitochondrial DNA level is associated with delayed blastocyst development

Wu, Frank; Weng, Shaoping; Shen, Meng-Shun; Ma, Pei-Chun; Wu, Po-Kuan; Lee, Ni‐Chung

doi:10.1007/s10815-020-02045-5

Cited by 14 publications

(31 citation statements)

References 46 publications

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“…Although the hypothesis that reproductive ageing in older women is associated with the content of mtDNA in blastocyst-stage embryos is attractive ( 27 ), our results do not support this argument. We also found that blastocysts biopsied on Day 5 showed higher levels of mtDNA content compared with those biopsied on Day 6, which was consistent with previous studies ( 33 , 55 , 57 , 66 ). The replication of mtDNA will not be reactivated in the embryo until the blastocyst stage ( 67 ), blastocysts biopsied on Day 6 may undergo more cell divisions compared with blastocysts biopsied on Day 5, which may result in a reduction of mtDNA content in Day 6 blastocysts.…”

Section: Discussionsupporting

confidence: 92%

“…The replication of mtDNA will not be reactivated in the embryo until the blastocyst stage (67), blastocysts biopsied on Day 6 may undergo more cell divisions compared with blastocysts biopsied on Day 5, which may result in a reduction of mtDNA content in Day 6 blastocysts. However, one study by Wu et al suggest another explanation (66), they proposed a hypothesis claiming that Day 6 blastocysts are developed from those oocytes which contain lower levels of mtDNA content. This means more time and efforts would be required for these embryos to develop into the blastocyst stage.…”

Section: Discussionmentioning

confidence: 99%

“…However, one study by Wu et al. suggest another explanation ( 66 ), they proposed a hypothesis claiming that Day 6 blastocysts are developed from those oocytes which contain lower levels of mtDNA content. This means more time and efforts would be required for these embryos to develop into the blastocyst stage.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Mitochondrial DNA Content May Not Be a Reliable Screening Biomarker for Live Birth After Single Euploid Blastocyst Transfer

et al. 2021

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An increasing number of studies have related the mitochondrial DNA (mtDNA) content to embryo viability and transfer outcomes. However, previous studies have focused more on the relationship between mtDNA and embryo implantation, few studies have studied the effect of the mtDNA content on live birth. In the study, we investigated whether mtDNA content is a reliable screening biomarker for live birth after single blastocyst transfer. A total of 233 couples with 316 blastocyst stage embryos undergoing in vitro fertilization treatment and pre-implantation genetic testing analysis were included in the study. All embryos were chromosomally normal and had undergone single-embryo transfers. There was no significant difference observed in the blastocyst mtDNA content among the live birth, miscarriage and non-implanted groups (p=0.999), and the mtDNA content in blastocysts from the miscarriage and live birth groups was similar [median (interquartile range), 1.00*108(7.59*107- 1.39*108) vs 1.01*108 (7.37*107- 1.32*108)]. Similarly, no significant association was observed between mtDNA content and embryo implantation potential (p=0.965). After adjusting for multiple confounders in a logistic regression analysis with generalized estimating equations, no associations between mtDNA content and live birth were observed in all blastocysts, Day-5 and Day-6 blastocysts (p=0.567, p=0.673, p=0.165, respectively). The live birth rate was not significantly different between blastocysts with an elevated mtDNA content and blastocysts with a normal mtDNA content (26.7% vs 33.6% p=0.780). Additionally, there was no linear correlation between the mtDNA content and maternal age (p=0.570). In conclusion, the mtDNA content does not seem to be a potential biomarker for embryo transfer outcomes (i.e., implantation and live birth) based on the existing testing tools. Embryos with an elevated mtDNA content also have development potential for successful live birth.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Mitochondrial DNA Content May Not Be a Reliable Screening Biomarker for Live Birth After Single Euploid Blastocyst Transfer

et al. 2021

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“…In recent years, several studies have been performed to evaluate mtDNA as a potential biomarker of embryo vitality. However, there is a lot of controversy as studies performed have reached contradicting conclusions [4,[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA Copy Number in Cleavage Stage Human Embryos—Impact on Infertility Outcome

Podolak¹,

Liss

Kiewisz

et al. 2022

CIMB

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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, p < 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, p 0.09), sex (6.6 ± 4.1 vs. 6.2 ± 6.8, p 0.16), maternal age (6.9 ± 7.8 vs. 6.7 ± 4.5, p 0.14) or its ability to implant (7.4 ± 6.6 vs. 5.1 ± 4.6, p 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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“…Biochemical, metabolic and epigenetic processes that affect the rate of blastulation, independent of chromosome numeration and maternal age, are potential contributors to the observed halving of the implantation rate for D7 euploid blastocysts. Further investigation into molecular differences between D5 and D7 embryos, such as mitochondrial function (Wu et al 2021) and sperm characteristics, is needed to determine the mechanisms involved in our clinical observations. Limited data suggest that transfer of D7 embryos may also be related to increased incidence of very-large-for-gestational-age births (Huang et al 2020), warranting further investigation into obstetric and perinatal differences related to delayed blastulation.…”

Section: Discussionmentioning

confidence: 99%

Euploid day 7 blastocysts of infertility patients with only slow embryo development have reduced implantation potential

Lane¹,

Reed²,

Schoolcraft³

et al. 2022

Reproductive BioMedicine Online

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show abstract

Suboptimal trophectoderm mitochondrial DNA level is associated with delayed blastocyst development

Cited by 14 publications

References 46 publications

Mitochondrial DNA Content May Not Be a Reliable Screening Biomarker for Live Birth After Single Euploid Blastocyst Transfer

Mitochondrial DNA Content May Not Be a Reliable Screening Biomarker for Live Birth After Single Euploid Blastocyst Transfer

Mitochondrial DNA Copy Number in Cleavage Stage Human Embryos—Impact on Infertility Outcome

Euploid day 7 blastocysts of infertility patients with only slow embryo development have reduced implantation potential

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