Variables associated with mitochondrial copy number in human blastocysts: what can we learn from trophectoderm biopsies?

Santos, María José de los; Juan, A. Diez; Mifsud, Amparo; Mercader, Amparo; Meseguer, Marcos; Rubio, Carmen; Pellicer, António

doi:10.1016/j.fertnstert.2017.09.022

Cited by 61 publications

(42 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, mtDNA content in trophectoderm biopsies at the blastocyst stage has been proposed as a putative biomarker of implantation potential. However, the clinical studies conducted to date reported controversial results ( 48 , 51 – 54 ). Indeed, lately, Humaidan and colleagues warned that it is still difficult to discriminate between “fact and fiction” in the current scenario and mtDNA cannot be considered a new biomarker of embryonic implantation potential ( 55 ): extensive validation, as well as more pre-clinical and possibly non-selection data, are yet required.…”

Section: Putative Mechanisms Impaired By Aging and Leading To A Reducmentioning

confidence: 99%

Impact of Maternal Age on Oocyte and Embryo Competence

et al. 2018

View full text Add to dashboard Cite

The overall success of human reproduction, either spontaneously or after IVF, is highly dependent upon maternal age. The main reasons for age-related infertility include reduced ovarian reserve and decreased oocyte/embryo competence due to aging insults, especially concerning an increased incidence of aneuploidies and possibly decreased mitochondrial activity. Age-related chromosomal abnormalities mainly arise because of meiotic impairments during oogenesis, following flawed chromosome segregation patterns such as non-disjunction, premature separation of sister chromatids, or the recent reverse segregation. In this review, we briefly discuss the main mechanisms putatively impaired by aging in the oocytes and the deriving embryos. We also report the main strategies proposed to improve the management of advanced maternal age women in IVF: fertility preservation through oocyte cryopreservation to prevent aging; optimization of the ovarian stimulation and enhancement of embryo selection to limit its effects; and oocyte donation to circumvent its consequences.

show abstract

Section: Putative Mechanisms Impaired By Aging and Leading To A Reducmentioning

confidence: 99%

Impact of Maternal Age on Oocyte and Embryo Competence

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The underlying biological explanation remains to be confirmed, but is very likely tied to embryo staging and morphology. Several studies have reported an inverse correlation between mtDNA levels and embryo cellularity/developmental progression/expansion [179,180,184]. This is reasonable given that no mtDNA replication occurs between zygote and blastocyst stage, and the initial pool of mtDNA molecules becomes diluted between dividing cells [185][186][187].…”

Section: Mitochondrial Dna Quantitation During Pgt-a: Where Are We Nowmentioning

confidence: 79%

Preimplantation Genetic Testing for Chromosomal Abnormalities: Aneuploidy, Mosaicism, and Structural Rearrangements

Viotti

2020

Genes

108

View full text Add to dashboard Cite

There is a high incidence of chromosomal abnormalities in early human embryos, whether they are generated by natural conception or by assisted reproductive technologies (ART). Cells with chromosomal copy number deviations or chromosome structural rearrangements can compromise the viability of embryos; much of the naturally low human fecundity as well as low success rates of ART can be ascribed to these cytogenetic defects. Chromosomal anomalies are also responsible for a large proportion of miscarriages and congenital disorders. There is therefore tremendous value in methods that identify embryos containing chromosomal abnormalities before intrauterine transfer to a patient being treated for infertility—the goal being the exclusion of affected embryos in order to improve clinical outcomes. This is the rationale behind preimplantation genetic testing for aneuploidy (PGT-A) and structural rearrangements (-SR). Contemporary methods are capable of much more than detecting whole chromosome abnormalities (e.g., monosomy/trisomy). Technical enhancements and increased resolution and sensitivity permit the identification of chromosomal mosaicism (embryos containing a mix of normal and abnormal cells), as well as the detection of sub-chromosomal abnormalities such as segmental deletions and duplications. Earlier approaches to screening for chromosomal abnormalities yielded a binary result of normal versus abnormal, but the new refinements in the system call for new categories, each with specific clinical outcomes and nuances for clinical management. This review intends to give an overview of PGT-A and -SR, emphasizing recent advances and areas of active development.

show abstract

“…Thus, failure to replicate mtDNA prevents embryonic stem cells from completing differentiation [ 18 ]. But the embryos can establish compensation mechanism for the respiratory chain defect resulting from high mutation levels, and it was reported that elevated mtDNA copy number was related to aneuploidy and lower implantation potential in women undergoing IVF treatment [ 19 – 23 ]. However, our data did not confirm low or high mtDNA copy numbers in the SA group compared to the IA group, and we observed no statistical difference between the aneuploid and euploid groups.…”

Section: Discussionmentioning

confidence: 99%

Deep sequencing shows that accumulation of potentially pathogenic mtDNA mutations rather than mtDNA copy numbers may be associated with early embryonic loss

Liao

Yang

et al. 2020

J Assist Reprod Genet

View full text Add to dashboard Cite

Purpose To explore the relationship between mitochondrial DNA quantity and heteroplasmy and early embryonic loss. Methods A total of 150 villous samples from patients with spontaneous abortion (SA, n = 75) or induced abortion (IA, n = 75) were collected. qPCR and next-generation sequencing (NGS) were used to test mitochondrial DNA quantity and heteroplasmy. Missense mutations with a CADD score > 15 and heteroplasmy ≥ 70% were defined as potentially pathogenic mutations. Results With respect to mitochondrial DNA copy numbers, there was no significant difference between the SA and IA groups (median (IQR), 566 (397–791) vs. 614 (457–739); P = 0.768) or between the euploid and aneuploid groups (median (IQR), 516 (345–730) vs. 599 (423–839); P = 0.107). mtDNA copy numbers were not associated with spontaneous abortion using logistic regression analysis (P = 0.196, 95% CI 1.000–1.001). In addition, more patients harbored possibly pathogenic mtDNA mutations in their chorionic villi in the SA group (70.7%, 53/75) compared with the IA group (54.7%, 41/75; P < 0.05). However, there was no statistical difference between the euploid (80%, 24/30) and aneuploid groups (64.4%, 29/45; p = 0.147). Conclusion Early embryonic loss and the formation of aneuploidy were not related to mtDNA copy number. Patients with spontaneous abortion were more likely to have possibly pathogenic mutations in their mtDNA, and this may assist in purifying pathogenic mtDNA. However, whether the accumulation of these potentially morbific mtDNA mutations caused early embryonic loss requires further investigation.

show abstract

Variables associated with mitochondrial copy number in human blastocysts: what can we learn from trophectoderm biopsies?

Cited by 61 publications

References 47 publications

Impact of Maternal Age on Oocyte and Embryo Competence

Impact of Maternal Age on Oocyte and Embryo Competence

Preimplantation Genetic Testing for Chromosomal Abnormalities: Aneuploidy, Mosaicism, and Structural Rearrangements

Deep sequencing shows that accumulation of potentially pathogenic mtDNA mutations rather than mtDNA copy numbers may be associated with early embryonic loss

Contact Info

Product

Resources

About