Reduced mitochondrial DNA content correlate with poor clinical outcomes in cryotransfers with day 6 single euploid embryos
ObjectiveTo investigate whether the mitochondrial DNA (mtDNA) content of a single biopsy at trophoblast correlates with the developmental potential and reproductive outcomes of blastocyst.MethodsA retrospective analysis applied the dataset of 1,675 embryos with preimplantation genetic testing for an...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.1066530/full |
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| author | Tzu-Hsuan Chuang Tzu-Hsuan Chuang Chih-Yen Chen Chin-Sheng Kuan Hsing-Hua Lai Chia-Lin Hsieh Meng-Ju Lee Yi-Ting Liang Yu-Jen Chang Chien-Yu Chen Shee-Uan Chen |
| author_facet | Tzu-Hsuan Chuang Tzu-Hsuan Chuang Chih-Yen Chen Chin-Sheng Kuan Hsing-Hua Lai Chia-Lin Hsieh Meng-Ju Lee Yi-Ting Liang Yu-Jen Chang Chien-Yu Chen Shee-Uan Chen |
| author_sort | Tzu-Hsuan Chuang |
| collection | DOAJ |
| description | ObjectiveTo investigate whether the mitochondrial DNA (mtDNA) content of a single biopsy at trophoblast correlates with the developmental potential and reproductive outcomes of blastocyst.MethodsA retrospective analysis applied the dataset of 1,675 embryos with preimplantation genetic testing for aneuploidy (PGT-A) from 1,305 individuals, and 1,383 embryos involved cryotransfers of single euploid embryo between January 2015 and December 2019. The studied cohort was divided for algorithm establishment on the NGS platform (n=40), correlation of biological features (n=1,635), and correlation of reproductive outcomes (n=1,340). Of the algorithm derived from the NGS platform, the reliability and repeatability were validated via qPCR assay and inter-run controls, respectively. Of the correlation across biological features, stratification analyses were applied to evaluate the effect from a single contributor. Eventually, the correlation between the mtDNA ratios and reproductive outcomes was adjusted according to the significant effector(s).ResultsThe mtDNA ratios showed statistically different between embryos with different days of blastocyst formation ([Day 5]: 1.06 vs. [Day 6]: 0.66, p=0.021), and between embryos with different expansion stages ([Expansion 5]: 1.05 vs. [Expansion 6]: 0.49, p=0.012). None or weakly correlated with the maternal age, morphology, ploidy, and gender. Analyzed by the different days of blastocyst formation with fixed expansion score as 5 in the euploid single embryo transfers (eSET), the day 6 eSET showed significantly lower reduced mtDNA ratio (n=139) in failure groups of fetal heartbeat (p=0.004), ongoing pregnancy (p=0.007), and live birth (p=0.01); however, no correlation between mtDNA ratios and pregnancy outcomes was observed in the day 5 eSET (n=1,201).ConclusionsThe study first demonstrated that mtDNA ratio was dependent on the days of blastocyst formation while expansion stage was fixed. Lower mtDNA ratios were observed in the day 6 eSET with adverse outcomes. The present stratification analyses reveal that the timeline of embryo is an important covariate to the mtDNA content. |
| first_indexed | 2024-04-11T01:02:28Z |
| format | Article |
| id | doaj.art-d82521db7baf47f2812e9466b10a0999 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-11T01:02:28Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-d82521db7baf47f2812e9466b10a09992023-01-04T15:10:59ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-01-011310.3389/fendo.2022.10665301066530Reduced mitochondrial DNA content correlate with poor clinical outcomes in cryotransfers with day 6 single euploid embryosTzu-Hsuan Chuang0Tzu-Hsuan Chuang1Chih-Yen Chen2Chin-Sheng Kuan3Hsing-Hua Lai4Chia-Lin Hsieh5Meng-Ju Lee6Yi-Ting Liang7Yu-Jen Chang8Chien-Yu Chen9Shee-Uan Chen10Stork Fertility Center, Stork Ladies Clinic, Hsinchu, TaiwanGraduate Institute of Clinical Medicine, National Taiwan University and College of Medicine, Taipei, TaiwanStork Fertility Center, Stork Ladies Clinic, Hsinchu, TaiwanStork Fertility Center, Stork Ladies Clinic, Hsinchu, TaiwanStork Fertility Center, Stork Ladies Clinic, Hsinchu, TaiwanStork Fertility Center, Stork Ladies Clinic, Hsinchu, TaiwanStork Fertility Center, Stork Ladies Clinic, Hsinchu, TaiwanStork Fertility Center, Stork Ladies Clinic, Hsinchu, TaiwanBioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, TaiwanDepartment of Biomechatronics Engineering, National Taiwan University, Taipei, TaiwanDepartment of Obstetrics and Gynecology, National Taiwan University Hospital and College of Medicine, Taipei, TaiwanObjectiveTo investigate whether the mitochondrial DNA (mtDNA) content of a single biopsy at trophoblast correlates with the developmental potential and reproductive outcomes of blastocyst.MethodsA retrospective analysis applied the dataset of 1,675 embryos with preimplantation genetic testing for aneuploidy (PGT-A) from 1,305 individuals, and 1,383 embryos involved cryotransfers of single euploid embryo between January 2015 and December 2019. The studied cohort was divided for algorithm establishment on the NGS platform (n=40), correlation of biological features (n=1,635), and correlation of reproductive outcomes (n=1,340). Of the algorithm derived from the NGS platform, the reliability and repeatability were validated via qPCR assay and inter-run controls, respectively. Of the correlation across biological features, stratification analyses were applied to evaluate the effect from a single contributor. Eventually, the correlation between the mtDNA ratios and reproductive outcomes was adjusted according to the significant effector(s).ResultsThe mtDNA ratios showed statistically different between embryos with different days of blastocyst formation ([Day 5]: 1.06 vs. [Day 6]: 0.66, p=0.021), and between embryos with different expansion stages ([Expansion 5]: 1.05 vs. [Expansion 6]: 0.49, p=0.012). None or weakly correlated with the maternal age, morphology, ploidy, and gender. Analyzed by the different days of blastocyst formation with fixed expansion score as 5 in the euploid single embryo transfers (eSET), the day 6 eSET showed significantly lower reduced mtDNA ratio (n=139) in failure groups of fetal heartbeat (p=0.004), ongoing pregnancy (p=0.007), and live birth (p=0.01); however, no correlation between mtDNA ratios and pregnancy outcomes was observed in the day 5 eSET (n=1,201).ConclusionsThe study first demonstrated that mtDNA ratio was dependent on the days of blastocyst formation while expansion stage was fixed. Lower mtDNA ratios were observed in the day 6 eSET with adverse outcomes. The present stratification analyses reveal that the timeline of embryo is an important covariate to the mtDNA content.https://www.frontiersin.org/articles/10.3389/fendo.2022.1066530/fullmitochondriablastocyst formation daypreimplantation genetic testing for aneuploidy(PGT-A)next-generation sequencingsingle embryo transfer (SET) |
| spellingShingle | Tzu-Hsuan Chuang Tzu-Hsuan Chuang Chih-Yen Chen Chin-Sheng Kuan Hsing-Hua Lai Chia-Lin Hsieh Meng-Ju Lee Yi-Ting Liang Yu-Jen Chang Chien-Yu Chen Shee-Uan Chen Reduced mitochondrial DNA content correlate with poor clinical outcomes in cryotransfers with day 6 single euploid embryos Frontiers in Endocrinology mitochondria blastocyst formation day preimplantation genetic testing for aneuploidy(PGT-A) next-generation sequencing single embryo transfer (SET) |
| title | Reduced mitochondrial DNA content correlate with poor clinical outcomes in cryotransfers with day 6 single euploid embryos |
| title_full | Reduced mitochondrial DNA content correlate with poor clinical outcomes in cryotransfers with day 6 single euploid embryos |
| title_fullStr | Reduced mitochondrial DNA content correlate with poor clinical outcomes in cryotransfers with day 6 single euploid embryos |
| title_full_unstemmed | Reduced mitochondrial DNA content correlate with poor clinical outcomes in cryotransfers with day 6 single euploid embryos |
| title_short | Reduced mitochondrial DNA content correlate with poor clinical outcomes in cryotransfers with day 6 single euploid embryos |
| title_sort | reduced mitochondrial dna content correlate with poor clinical outcomes in cryotransfers with day 6 single euploid embryos |
| topic | mitochondria blastocyst formation day preimplantation genetic testing for aneuploidy(PGT-A) next-generation sequencing single embryo transfer (SET) |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.1066530/full |
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