Preimplantation Genetic Testing for Couples with Balanced Chromosomal Rearrangements

Shetty, Sachin; Nair, Jiny; Johnson, Jnapti; Shetty, Navya; Kumar J, Ajay; Thondehalmath, Nirmala; Ganesh, Deepanjali; Bhat, Vidyalakshmi R; M, Sajana; R, Anjana; Nayak, Rajsekhar; Gunasheela, Devika; Kadandale, Jayarama; Shetty, Swathi

doi:10.18502/jri.v23i3.10013

Preimplantation Genetic Testing for Couples with Balanced Chromosomal Rearrangements

Authors

Sachin Shetty ¹

Jiny Nair ¹

Jnapti Johnson ¹

Navya Shetty ¹

Ajay Kumar J ¹

Nirmala Thondehalmath ²

Deepanjali Ganesh ²

Vidyalakshmi R Bhat ²

Sajana M ²

Anjana R ²

Rajsekhar Nayak ³

Devika Gunasheela ³

Jayarama Kadandale ⁴

Swathi Shetty ⁴

¹ Tattvagene Pvt. Ltd, Bangalore, India

² Gunasheela Surgical and Maternity Hospital, Bangalore, India

³ Tattvagene Pvt. Ltd, Bangalore, India; Gunasheela Surgical and Maternity Hospital, Bangalore, India

⁴ Gunasheela Surgical and Maternity Hospital, Bangalore, India; Centre for Human Genetics Biotech Park, Bengaluru, India

10.18502/jri.v23i3.10013

Abstract

Background: Chromosomal rearrangements play an important role in infertility. Carriers of chromosomal rearrangements have a lower chance of producing normal or balanced gametes due to abnormal segregation of chromosomes at meiosis, which leads to recurrent spontaneous abortions and infertility. Preimplantation genetic testing for structural chromosome rearrangements (PGT-SR) is offered to couples who have balanced chromosomal rearrangements in order to select embryos with a balanced karyotype prior to implantation, thereby increasing the chances of pregnancy. The purpose of the current study was to assess the outcomes of PGT-SR in patients carrying various balanced chromosomal rearrangements and to assess their clinical pregnancy outcome after in vitro fertilization (IVF). Methods: In this study, infertile couples with balanced chromosomal abnormalities undergoing PGT-SR were retrospectively analyzed at a single fertility center from January 2016 to December 2019. Results: PGT-SR was performed on 87 embryos from 22 couples in whom one partner carried a balanced translocation or an inversion. Fifty-seven (65.5%) of these embryos had unbalanced or sporadic aneuploidies, 30 (34.5%) embryos were normal or chromosomally balanced, which were then transferred in 18 couples. A higher rate of unbalanced translocations in comparison to sporadic aneuploidies was observed in couples with reciprocal translocation. The live birth rate per embryo transfer was found to be 66.6% (12/18). Conclusion: PGT-SR is a useful tool in selecting normal or balanced embryos for transfer in IVF, which could lead to a pregnancy by reducing the chance of miscarriages due to chromosome aneuploidy in couples with balanced chromosomal rearrangements.

Keywords

Aneuploidy

Balanced chromosomal rearrangements

In vitro fertilization

Inversion

Preimplantation genetic testing

Reciprocal translocation

Recurrent miscarriages

Robertsonian translocation

Zorrilla M, Yatsenko AN. The genetics of infertility: current status of the field. Curr Genet Med Rep. 2013;1(4):1-22.

Pylyp LY, Spinenko LO, Verhoglyad NV, Kashevarova OO, Zukin VD. [Chromosomal abnormalities in patients with infertility]. Tsitol Genet. 2015;49(3):33-9. Russian.

Liu Y, Kong XD, Wu QH, Li G, Song L, Sun YP. Karyotype analysis in large-sample infertile couples living in Central China: a study of 14965 couples. J Assist Reprod Genet. 2013;30(4):547-53.

Kayed HF, Mansour RT, Aboulghar MA, Serour GI, Amer AE, Abdrazik A. Screening for chromosomal abnormalities in 2650 infertile couples undergoing ICSI. Reprod Biomed Online. 2006;12(3):359-70.

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(6):806-15.

Foresta C, Ferlin A, Gianaroli L, Dallapiccola B. Guidelines for the appropriate use of genetic tests in infertile couples. Eur J Hum Genet. 2002;10(5):303-12.

Zhang YP, Xu JZ, Yin M, Chen MF, Ren DL. [Pregnancy outcomes of 194 couples with balanced translocations]. Zhonghua Fu Chan Ke Za Zhi. 2006;41(9):592-6. Chinese.

Priya PK, Mishra VV, Roy P, Patel H. A study on balanced chromosomal translocations in couples with recurrent pregnancy loss. J Hum Reprod Sci. 2018;11(4):337-42.

ESHRE PGT-SR/PGT-A Working Group, Coonen E, Rubio C, Christopikou D, Dimitriadou E, Gontar J, et al. ESHRE PGT Consortium good practice recommendations for the detection of structural and numerical chromosomal aberrations. Hum Reprod Open. 2020;2020(3):hoaa017.

Martín J, Cervero A, Mir P, Martinez-Conejero JA, Pellicer A, Simón C. The impact of next-generation sequencing technology on preimplantation genetic diagnosis and screening. Fertil Steril. 2013;99(4):1054-61.

Yang Z, Lin J, Zhang J, Fong WI, Li P, Zhao R, et al. Randomized comparison of next-generation sequencing and array comparative genomic hybridization for preimplantation genetic screening: a pilot study. BMC Med Genom. 2015;8:30.

Rooney DE, Czepulkowski. Human Cytogenetics. a practical approach. 1st ed. Oxford: IRL Press;1992. 260 p.

Shaffer LG, McGowan J, Schmid M. ISCN 2013 An international system for human cytogenetic nomenclature. Published in collaboration with cytogenetic and genome research. Switzerland: Karger; 2013. 141 p.

Merrion K, Maisenbacher M. Pericentric inversion (Inv) 9 variant-reproductive risk factor or benign finding? J Assist Reprod Genet. 2019;36(12):2557-61.

Jungheim ES, Meyer MF, Broughton DE. Best practices for controlled ovarian stimulation in in vitro fertilization. Semin Reprod Med. 2015;33(2):77-82.

Stephenson MD, Sierra S. Reproductive outcomes in recurrent pregnancy loss associated with a parental carrier of a structural chromosome rearrangement. Hum Reprod. 2006;21(4):1076-82.

Munné S. Analysis of chromosome segregation during preimplantation genetic diagnosis in both male and female translocation heterozygotes. Cytogenet Genome Res. 2005;111(3-4):305-9.

Vozdova M, Kasikova K, Oracova E, Prinosilova P, Rybar R, Horinova V, et al. The effect of the swim-up and hyaluronan-binding methods on the frequency of abnormal spermatozoa detected by FISH and SCSA in carriers of balanced chromosomal translocations. Hum Reprod. 2012;27(3):930-7.

Ishikawa T, Shiotani M, Izumi Y, Hashimoto H, Kokeguchi S, Goto S, et al. Fertilization and pregnancy using cryopreserved testicular sperm for intracytoplasmic sperm injection with azoospermia. Fertil Steril. 2009;92(1):174‑9.

Lledo B, Ortiz JA, Morales R, Ten J, de la Fuente PE, Garcia-Ochoa C, et al. The paternal effect of chromosome translocation carriers observed from meiotic segregation in embryos. Hum Reprod. 2010;25(7):1843-8.

Morin SJ, Eccles J, Iturriaga A, Zimmerman RS. Translocations, inversions and other chromosome rearrangements. Fertil Steril. 2017;107(1):19-26.

Alfarawati S, Fragouli E, Colls P, Wells D. Embryos of robertsonian rranslocation carriers exhibit a mitotic interchromosomal effect that enhances genetic instability during early development. PLoS Genet. 2012;8(10):e1003025.

Simon A, Laufer N. Assessment and treatment of repeated implantation failure (RIF). J Assist Reprod Genet. 2012;29(11):1227-39.

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(2):367-73.

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(10):938-44.