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Preimplantation genetic testing using comprehensive genomic copy number analysis is beneficial for balanced translocation carriers

Journal of Human Genetics volume 69, pages 41–45 (2024)Cite this article

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Abstract

Balanced chromosomal translocation is one of chromosomal variations. Carriers of balanced chromosomal translocations have an increased risk of spontaneous miscarriage. To avoid the risk, preimplantation genetic testing (PGT) using comprehensive genomic copy number analysis has been developed. This study aimed to verify whether and how embryos from couples in which one partner is a balanced translocation carrier have a higher ratio of chromosomal abnormalities. A total of 894 biopsied trophectoderms (TEs) were obtained from 130 couples in which one partner was a balanced translocation carrier (Robertsonian translocation, reciprocal translocation, or intrachromosomal inversion) and grouped as PGT-SR. Conversely, 3269 TEs from 697 couples who experienced recurrent implantation failure or recurrent pregnancy loss were included in the PGT-A group. The transferable blastocyst ratio was significantly lower in the PGT-SR group, even when bias related to the sample number and patient age was corrected. Subgroup analysis of the PGT-SR group revealed that the transferable blastocyst ratio was higher in the Robertsonian translocation group. Because the PGT-SR group had a higher proportion of untransferable embryos than the PGT-A group, PGT using comprehensive genomic copy number analysis was more beneficial for balanced translocation carriers than for infertility patients without chromosomal translocations. The frequencies of de novo aneuploidies were further analyzed, and the frequency in the PGT-SR group was lower than that in the PGT-A group. Therefore, we could not confirm the existence of interchromosomal effects in this study.

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References

  1. Jacobs PA, Browne C, Gregson N, Joyce C, White H. Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding. J Med Genet. 1992;29:103–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sugiura-Ogasawara M, Ozaki Y, Sato T, Suzumori N, Suzumori K. Poor prognosis of recurrent aborters with either maternal or paternal reciprocal translocations. Fertil Steril. 2004;81:367–73.

    Article  PubMed  Google Scholar 

  3. Madan K, Nieuwint AW, van Bever Y. Recombination in a balanced complex translocation of a mother leading to a balanced reciprocal translocation in the child. Review of 60 cases of balanced complex translocations. Hum Genet. 1997;99:806–15.

    Article  CAS  PubMed  Google Scholar 

  4. Ogilvie CM, Braude P, Scriven PN. Successful pregnancy outcomes after preimplantation genetic diagnosis (PGD) for carriers of chromosome translocations. Hum Fertil (Camb). 2001;4:168–71.

    Article  CAS  PubMed  Google Scholar 

  5. Kato K, Aoyama N, Kawasaki N, Hayashi H, Xiaohui T, Abe T, et al. Reproductive outcomes following preimplantation genetic diagnosis using fluorescence in situ hybridization for 52 translocation carrier couples with a history of recurrent pregnancy loss. J Hum Genet. 2016;61:687–92.

    Article  CAS  PubMed  Google Scholar 

  6. Kurahashi H, Kato T, Miyazaki J, Nishizawa H, Nishio E, Furukawa H, et al. Preimplantation genetic diagnosis/screening by comprehensive molecular testing. Reprod Med Biol. 2016;15:13–19.

    Article  CAS  PubMed  Google Scholar 

  7. Tulay P, Gultomruk M, Findikli N, Yagmur E, Bahceci M. Is the interchromosomal effect present in embryos derived from Robertsonian and reciprocal translocation carriers particularly focusing on chromosome 10 rearrangements? Zygote 2015;23:908–15.

    Article  CAS  PubMed  Google Scholar 

  8. Bartels CB, Makhijani R, Godiwala P, Bartolucci A, Nulsen JC, Grow DR, et al. In vitro fertilization outcomes after preimplantation genetic testing for chromosomal structural rearrangements comparing fluorescence in-situ hybridization, microarray comparative genomic hybridization, and next-generation sequencing. F S Rep. 2020;1:249–56.

    PubMed  PubMed Central  Google Scholar 

  9. Nakano T, Ammae M, Satoh M, Mizuno S, Nakaoka Y, Morimoto Y. Analysis of clinical outcomes and meiotic segregation modes following preimplantation genetic testing for structural rearrangements using aCGH/NGS in couples with balanced chromosome rearrangement. Reprod Med Biol. 2022;21:e12476.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Viotti M. Preimplantation genetic testing for chromosomal abnormalities: aneuploidy, mosaicism, and structural rearrangements. Genes. 2020;11:602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bono S, Biricik A, Spizzichino L, Nuccitelli A, Minasi MG, Greco E, et al. Validation of a semiconductor next-generation sequencing-based protocol for preimplantation genetic diagnosis of reciprocal translocations. Prenat Diagn. 2015;35:938–44.

    Article  CAS  PubMed  Google Scholar 

  12. Iwasa T, Kuwahara A, Takeshita T, Taniguchi Y, Mikami M, Irahara M. Preimplantation genetic testing for aneuploidy and chromosomal structural rearrangement: a summary of a nationwide study by the Japan Society of Obstetrics and Gynecology. Reprod Med Biol. 2023;22:e12518.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kato K, Kuroda T, Yamadera-Egawa R, Ezoe K, Aoyama N, Usami A, et al. Preimplantation genetic testing for aneuploidy for recurrent pregnancy loss and recurrent implantation failure in minimal ovarian stimulation cycle for women aged 35-42 years: live birth rate, developmental follow-up of children, and embryo ranking. Reprod Sci. 2023;30:974–83.

    Article  CAS  PubMed  Google Scholar 

  14. Takeuchi K. Pre-implantation genetic testing: past, present, future. Reprod Med Biol. 2021;20:27–40.

    Article  PubMed  Google Scholar 

  15. Sato T, Sugiura-Ogasawara M, Ozawa F, Yamamoto T, Kato T, Kurahashi H, et al. Preimplantation genetic testing for aneuploidy: a comparison of live birth rates in patients with recurrent pregnancy loss due to embryonic aneuploidy or recurrent implantation failure. Hum Reprod. 2019;34:2340–8.

    Article  PubMed  Google Scholar 

  16. Ma X, Xu X, Mao B, Liu H, Li H, Liu K, et al. Chromosomal analysis for embryos from balanced chromosomal rearrangement carriers using next generation sequencing. Mol Reprod Dev. 2021;88:362–70.

    Article  CAS  PubMed  Google Scholar 

  17. Shetty S, Nair J, Johnson J, Shetty N, Kumar AJ, Thondehalmath N, et al. Preimplantation genetic testing for couples with balanced chromosomal rearrangements. J Reprod Infertil. 2022;23:213–23.

    PubMed  PubMed Central  Google Scholar 

  18. Park SJ, Min JY, Kang JS, Yang BG, Hwang SY, Han SH. Chromosomal abnormalities of 19,000 couples with recurrent spontaneous abortions: a multicenter study. Fertil Steril. 2022;117:1015–25.

    Article  CAS  PubMed  Google Scholar 

  19. Ogur C, Kahraman S, Griffin DK, Cinar Yapan C, Tufekci MA, Cetinkaya M, et al. PGT for structural chromosomal rearrangements in 300 couples reveals specific risk factors but an interchromosomal effect is unlikely. Reprod Biomed Online. 2023;46:713–27.

    Article  CAS  PubMed  Google Scholar 

  20. Xie Y, Xu Y, Wang J, Miao B, Zeng Y, Ding C, et al. Preliminary analysis of numerical chromosome abnormalities in reciprocal and Robertsonian translocation preimplantation genetic diagnosis cases with 24-chromosomal analysis with an aCGH/SNP microarray. J Assist Reprod Genet. 2018;35:177–86.

    Article  PubMed  Google Scholar 

  21. Grande M, Borrell A, Garcia-Posada R, Borobio V, Muñoz M, Creus M, et al. The effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage. Hum Reprod. 2012;27:3109–17.

    Article  PubMed  Google Scholar 

  22. Yuan P, Zheng L, Ou S, Zhao H, Li R, Luo H, et al. Evaluation of chromosomal abnormalities from preimplantation genetic testing to the reproductive outcomes: a comparison between three different structural rearrangements based on next-generation sequencing. J Assist Reprod Genet. 2021;38:709–18.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Estop AM, Cieply K, Munne S, Surti U, Wakim A, Feingold E. Is there an interchromosomal effect in reciprocal translocation carriers? Sperm FISH studies. Hum Genet. 2000;106:517–24.

    Article  CAS  PubMed  Google Scholar 

  24. Miller DE. The interchromosomal effect: different meanings for different organisms. Genetics. 2020;216:621–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Boynukalin FK, Gultomruk M, Turgut NE, Rubio C, Rodrigo L, Yarkiner Z, et al. The impact of patient, embryo, and translocation characteristics on the ploidy status of young couples undergoing preimplantation genetic testing for structural rearrangements (PGT-SR) by next generation sequencing (NGS). J Assist Reprod Genet. 2021;38:387–96.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Fan J, Zhang X, Chen Y, Zhang J, Zhang L, Bi X, et al. Exploration of the interchromosomal effects in preimplantation genetic testing for structural rearrangements based on next-generation sequencing. Mol Genet Genom Med. 2022;10:e2017.

    Article  CAS  Google Scholar 

  27. Mayeur A, Ahdad N, Hesters L, Grynberg M, Romana S, Sonigo C, et al. Does the prognosis after PGT for structural rearrangement differ between female and male translocation carriers? Reprod Biomed Online. 2020;40:684–92.

    Article  CAS  PubMed  Google Scholar 

  28. Wang J, Li D, Xu Z, Diao Z, Zhou J, Lin F, et al. Analysis of meiotic segregation modes in biopsied blastocysts from preimplantation genetic testing cycles of reciprocal translocations. Mol Cytogenet. 2019;12:11.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank all the subjects for participating in this study. We also thank Yumiko Ondo and Rino Abiru for technical assistance.

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Authors and Affiliations

  1. Division of Gene Medicine, Graduate School of Medical Science, Tokyo Women’s Medical University, Tokyo, 162-8666, Japan

    Aya Yamazaki & Toshiyuki Yamamoto

  2. Institute of Medical Genetics, Tokyo Women’s Medical University, Tokyo, 162-8666, Japan

    Aya Yamazaki, Keiko Shimojima Yamamoto & Toshiyuki Yamamoto

  3. Kato Ladies Clinic, Tokyo, 160-0023, Japan

    Tomoko Kuroda, Nami Kawasaki & Keiichi Kato

  4. Department of Transfusion Medicine and Cell Processing, Tokyo Women’s Medical University, Tokyo, 162-8666, Japan

    Keiko Shimojima Yamamoto

  5. Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, 770-0042, Japan

    Takeshi Iwasa, Akira Kuwahara, Yuka Taniguchi & Minoru Irahara

  6. Clinic Cosmos, Kochi, 780-0072, Japan

    Akira Kuwahara

  7. Department of Obstetrics and Gynecology, Nippon Medical University, Tokyo, 113-8602, Japan

    Toshiyuki Takeshita

  8. Takeshita Ladies Clinic, Tokyo, 160-0017, Japan

    Toshiyuki Takeshita

  9. Department of Psychology, Faculty of Letters, Keio University, Tokyo, 108-8345, Japan

    Yosuke Kita

  10. Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, 259-1143, Japan

    Mikio Mikami

Authors
  1. Aya Yamazaki
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  2. Tomoko Kuroda
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  3. Nami Kawasaki
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  4. Keiichi Kato
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  6. Takeshi Iwasa
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  8. Yuka Taniguchi
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  9. Toshiyuki Takeshita
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  10. Yosuke Kita
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  12. Minoru Irahara
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  13. Toshiyuki Yamamoto
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Contributions

TY designed the study. AY organized the study and drafted the manuscript. TK, NK, KK contributed to acquisition of data. KSY and YK analyzed the data. TI, AK, TT, YT, MM, MI reviewed the manuscript critically. All authors contributed to the data interpretation. All authors agree to be accountable for all aspects of the work and ensure that questions related to the accuracy or integrity of any part of the study are appropriately investigated and resolved.

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Correspondence to Toshiyuki Yamamoto.

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Yamazaki, A., Kuroda, T., Kawasaki, N. et al. Preimplantation genetic testing using comprehensive genomic copy number analysis is beneficial for balanced translocation carriers. J Hum Genet 69, 41–45 (2024). https://doi.org/10.1038/s10038-023-01202-9

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  • DOI: https://doi.org/10.1038/s10038-023-01202-9

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