Yi-Xuan Lee1,2, Chi-Huang Chen2,3, Shyr-Yeu Lin2,3, Yi-Hui Lin4,5, Chii-Ruey Tzeng6,7,8. 1. Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan. 2. Division of Infertility, Department of Obstetrics and Gynecology, Taipei Medical University Hospital, No.250, Wusing St., Sinyi District, Taipei City, 110, Taiwan. 3. Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 4. Department of Obstetrics and Gynecology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. 5. Genetics Generation Advancement Corporation (GGA Corp.), Taipei, Taiwan. 6. Division of Infertility, Department of Obstetrics and Gynecology, Taipei Medical University Hospital, No.250, Wusing St., Sinyi District, Taipei City, 110, Taiwan. tzengcr@tmu.edu.tw. 7. Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. tzengcr@tmu.edu.tw. 8. Center for Reproductive Medicine, Taipei Medical University Hospital, No.250, Wusing St., Sinyi District, Taipei City, 110, Taiwan. tzengcr@tmu.edu.tw.
Abstract
OBJECTIVE: To evaluate the feasibility of adjusted mitochondrial DNA quantification in human embryos as a biomarker for implantation potential. DESIGN: Double-blind, observational, prospective analysis of an Asian population in a single university-affiliated in vitro fertilization center. A total of 1617 embryos derived from 380 infertile couples were collected. The DNA from blastomere biopsy (n = 99) or trophectoderm biopsy (n = 1518) were analyzed with next-generation sequencing. RESULTS: The adjusted mtDNA quantification followed a non-normal distribution in both types of the embryos. When stratified by ploidy status, the adjusted mtDNA quantification was significantly higher in aneuploid trophectoderm than in euploid cells, but not in blastomeres. The adjusted mtDNA quantification of embryos showed significant but very weak positive correlation in total trophectoderm cells with maternal age (Spearman's correlation, r = 0.095, p = 0.0028) but neither in blastomeres nor stratified by ploidy status. The median adjusted mtDNA quantification was also significantly higher in aneuploid blastocysts than in euploid ones while corrected with embryo morphology. Viable embryos did not contain significantly different quantities of adjusted mtDNA compared with nonviable embryos (implanted n = 103, non-implanted n = 164; median 0.00097 vs. 0.00088, p = 0.21) in 267 transferred blastocysts. CONCLUSION: Quantification of adjusted mitochondria DNA in human embryos was significantly lower in euploid blastocysts than in aneuploid blastocysts. However, no statistically significant differences regarding implantation outcome were evident. To our best knowledge, this study provides the largest scale and the first correlation data between mitochondria copy number and human embryo implantation potential in Asians.
OBJECTIVE: To evaluate the feasibility of adjusted mitochondrial DNA quantification in human embryos as a biomarker for implantation potential. DESIGN: Double-blind, observational, prospective analysis of an Asian population in a single university-affiliated in vitro fertilization center. A total of 1617 embryos derived from 380 infertile couples were collected. The DNA from blastomere biopsy (n = 99) or trophectoderm biopsy (n = 1518) were analyzed with next-generation sequencing. RESULTS: The adjusted mtDNA quantification followed a non-normal distribution in both types of the embryos. When stratified by ploidy status, the adjusted mtDNA quantification was significantly higher in aneuploid trophectoderm than in euploid cells, but not in blastomeres. The adjusted mtDNA quantification of embryos showed significant but very weak positive correlation in total trophectoderm cells with maternal age (Spearman's correlation, r = 0.095, p = 0.0028) but neither in blastomeres nor stratified by ploidy status. The median adjusted mtDNA quantification was also significantly higher in aneuploid blastocysts than in euploid ones while corrected with embryo morphology. Viable embryos did not contain significantly different quantities of adjusted mtDNA compared with nonviable embryos (implanted n = 103, non-implanted n = 164; median 0.00097 vs. 0.00088, p = 0.21) in 267 transferred blastocysts. CONCLUSION: Quantification of adjusted mitochondria DNA in human embryos was significantly lower in euploid blastocysts than in aneuploid blastocysts. However, no statistically significant differences regarding implantation outcome were evident. To our best knowledge, this study provides the largest scale and the first correlation data between mitochondria copy number and human embryo implantation potential in Asians.
Entities:
Keywords:
Biomarker; Correction factors; IVF; Mitochondrial DNA copy number; PGT-A