Digital PCR Detection of mtDNA/gDNA Ratio in Embryo Culture Medium for Prediction of Embryo Development Potential

Zhang, Qing; Ji, Hong; Shi, Jing; Wang, Longmei; Ding, Lu; Jiang, Yonglei; Huang, Xiang; Qiu, Pingping; Li, Ping

doi:10.2147/pgpm.s304747

Cited by 4 publications

(3 citation statements)

References 36 publications

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“…Studies have shown that the quality of transferred embryos is one of the key factors affecting the pregnancy outcome of patients. [16] The morphological rating of an embryo reflects a very short timepoint in its development and cannot represent its entire development, but it reflects its developmental potential to some extent. [17] Clinical pregnancy and IRs improve with the embryo grade, therefore, the higher the embryo quality, the better the clinical pregnancy results.…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes after elective double-embryo transfer in frozen cycles for women of advanced maternal age

et al. 2022

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We aimed to determine the clinical outcome of double cleavage-stage embryo transfers in frozen-thawed embryo transfer cycles for older women.This study analyzed a total of 8189 cleavage-stage frozen-thawed embryo transfer cycles between January 2013 and December 2017 at Sir Run Run Shaw Hospital. All cycles were sorted into 3 groups based on patient age: 35 years (Group A), 36 to 37 years (Group B), and ≥38 years (Group C). The clinical pregnancy rate (CPR), implantation rate (IR), live birth rate (LBR), miscarriage rate, multiple pregnancy rate (MPR), preterm birth rate, and low-birth-weight rate were compared between the 3 groups.Significant differences in CPR, IR, LBR, MPR, and premature birth rate were found among the 3 groups. The CPR, IR, LBR, and MPR in Group A were higher than those in Group C. Transfers of 2 high-quality embryos resulted in significant differences in CPR, IR, LBR, MPR, and neonatal weight among the 3 groups, but no differences in premature birth and abortion rates were observed. Transfers with 1 high-quality and 1 fair-quality embryo resulted in significant differences in CPR, IR, and LBR among the 3 groups. Comparison of transfers of 2 high-quality embryos with 1 high-quality and 1 fair-quality embryo showed that the CPR and LBR were significantly lower for the latter in Groups A and C, but Group B had no salient changes.Higher IR and LBR and lower MPR may be achieved by selection of optimal embryo types for patients of different ages. Two highquality embryos need to be transferred in women older than 38 years. For women aged 36 to 37 years, 1 high-quality embryo or 1 high-quality plus 1 fair-quality embryo should be singled out for transfer. For women younger than 35 years, a single high-quality embryo should be selected for transfer. Abbreviations: BMI = body mass index, CPR = clinical pregnancy rate, FET = frozen-thawed embryo transfers, HCG = human chorionic gonadotropin, HMG = human menopausal gonadotropin, ICSI = intracytoplasmic sperm injection, IR = implantation rate, IVF = in vitro fertilization, LBR = live birth rate, MPR = multiple pregnancy rate.

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Section: Discussionmentioning

confidence: 99%

Clinical outcomes after elective double-embryo transfer in frozen cycles for women of advanced maternal age

et al. 2022

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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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“…Furthermore, advanced and sensitive molecular genetic approaches have been successfully applied to spent embryo culture media (SECM), which can be easily obtained during in vitro embryo culture. It is possible to analyze small amounts of cell-free DNA (cfDNA), mitochondrial DNA, microRNA, and long non-coding RNA secreted from embryos using real-time polymerase chain reaction (PCR) or digital PCR, as well as next-generation sequencing (NGS) [5][6][7]. In addition, studies have evaluated the developmental ability of embryos by analyzing substrates and metabolites produced during in vitro culture, which will be discussed further below [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Non-invasive evaluation of embryo quality for the selection of transferable embryos in human in vitro fertilization-embryo transfer

Kim

Lee

Jun

2022

Clin Exp Reprod Med

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The ultimate goal of human assisted reproductive technology is to achieve a healthy pregnancy and birth, ideally from the selection and transfer of a single competent embryo. Recently, techniques for efficiently evaluating the state and quality of preimplantation embryos using time-lapse imaging systems have been applied. Artificial intelligence programs based on deep learning technology and big data analysis of time-lapse monitoring system during in vitro culture of preimplantation embryos have also been rapidly developed. In addition, several molecular markers of the secretome have been successfully analyzed in spent embryo culture media, which could easily be obtained during in vitro embryo culture. It is also possible to analyze small amounts of cell-free nucleic acids, mitochondrial nucleic acids, miRNA, and long non-coding RNA derived from embryos using real-time polymerase chain reaction (PCR) or digital PCR, as well as next-generation sequencing. Various efforts are being made to use non-invasive evaluation of embryo quality (NiEEQ) to select the embryo with the best developmental competence. However, each NiEEQ method has some limitations that should be evaluated case by case. Therefore, an integrated analysis strategy fusing several NiEEQ methods should be urgently developed and confirmed by proper clinical trials.

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Digital PCR Detection of mtDNA/gDNA Ratio in Embryo Culture Medium for Prediction of Embryo Development Potential

Cited by 4 publications

References 36 publications

Clinical outcomes after elective double-embryo transfer in frozen cycles for women of advanced maternal age

Clinical outcomes after elective double-embryo transfer in frozen cycles for women of advanced maternal age

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

Non-invasive evaluation of embryo quality for the selection of transferable embryos in human in vitro fertilization-embryo transfer

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