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Published in: Journal of Assisted Reproduction and Genetics 7/2014

01-07-2014 | Genetics

Two different microarray technologies for preimplantation genetic diagnosis and screening, due to reciprocal translocation imbalances, demonstrate equivalent euploidy and clinical pregnancy rates

Authors: Kyle J. Tobler, Paul R. Brezina, Andrew T. Benner, Luke Du, Xin Xu, William G. Kearns

Published in: Journal of Assisted Reproduction and Genetics | Issue 7/2014

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Abstract

Purpose

To compare single nucleotide polymorphism (SNP) and comparative genomic hybridization (aCGH) microarray platforms to evaluate embryos for parental translocation imbalances and aneuploidy.

Methods

A retrospective review of preimplantation genetic diagnosis and screening (PGD/PGS) results of 498 embryos from 63 couples undergoing 75 in vitro fertilization cycles due to parental carriers of a reciprocal translocation.

Results

There was no significant difference between SNP and aCGH microarrays when comparing the prevalence of embryos that were euploid with no translocation imbalance, euploidy with a parental translocation imbalance or aneuploid with or without the parental chromosome imbalance. The clinical pregnancy rates were also equivalent for SNP (60 %) versus aCGH (65 %) microarrays. Of 498 diagnosed embryos, 45 % (226/498) were chromosomally normal without translocation errors or aneuploidy, 22 % (112/498) were euploid but had a parentally derived unbalanced chromosomal segregant, 8 % (42/498) harbored both a translocation imbalance and aneuploidy and 24 % (118/498) of embryos were genetically balanced for the parental reciprocal translocation but were aneuploid for other chromosomes. The overall clinical pregnancy rate per IVF cycle following SNP or aCGH microarray analysis was 61 % and was higher if the biopsy was done on blastocysts (65 %) versus cleavage stage embryos (59 %), although not statistically significant.

Conclusions

SNP or aCGH microarray technologies demonstrate equivalent clinical findings that maximize the pregnancy potential in patients with known parental reciprocal chromosomal translocations.
Literature
1.
go back to reference Gardner RJM, Sutherland GR. Chromosome abnormalities and genetic counseling. 3rd ed. Oxford University Press; 2004. Gardner RJM, Sutherland GR. Chromosome abnormalities and genetic counseling. 3rd ed. Oxford University Press; 2004.
3.
go back to reference Fryns JP, Van Buggenhout G. Structural chromosome rearrangements in couples with recurrent fetal wastage. Eur J Obstet Gynecol Reprod Biol. 1998;81(2):171–6.PubMedCrossRef Fryns JP, Van Buggenhout G. Structural chromosome rearrangements in couples with recurrent fetal wastage. Eur J Obstet Gynecol Reprod Biol. 1998;81(2):171–6.PubMedCrossRef
4.
go back to reference Robert L. Nussbaum MD, McInnes RR, Huntington F. Willard PD. Thompson & Thomspon Genetics in Medicine. 7th ed. Elsevier Science Health Science Division; 2007. Robert L. Nussbaum MD, McInnes RR, Huntington F. Willard PD. Thompson & Thomspon Genetics in Medicine. 7th ed. Elsevier Science Health Science Division; 2007.
5.
go back to reference Chen CP, Wu PC, Lin CJ, Chern SR, Tsai FJ, Lee CC, et al. Unbalanced reciprocal translocations at amniocentesis. Taiwan J Obstet Gynecol. 2011;50(1):48–57.PubMedCrossRef Chen CP, Wu PC, Lin CJ, Chern SR, Tsai FJ, Lee CC, et al. Unbalanced reciprocal translocations at amniocentesis. Taiwan J Obstet Gynecol. 2011;50(1):48–57.PubMedCrossRef
6.
go back to reference Escudero T, Estop A, Fischer J, Munne S. Preimplantation genetic diagnosis for complex chromosome rearrangements. Am J Med Genet A. 2008;146A(13):1662–9.PubMedCrossRef Escudero T, Estop A, Fischer J, Munne S. Preimplantation genetic diagnosis for complex chromosome rearrangements. Am J Med Genet A. 2008;146A(13):1662–9.PubMedCrossRef
7.
go back to reference Grati FR, Barlocco A, Grimi B, Milani S, Frascoli G, Di Meco AM, et al. Chromosome abnormalities investigated by non-invasive prenatal testing account for approximately 50 % of fetal unbalances associated with relevant clinical phenotypes. Am J Med Genet A. 2010;152A(6):1434–42.PubMed Grati FR, Barlocco A, Grimi B, Milani S, Frascoli G, Di Meco AM, et al. Chromosome abnormalities investigated by non-invasive prenatal testing account for approximately 50 % of fetal unbalances associated with relevant clinical phenotypes. Am J Med Genet A. 2010;152A(6):1434–42.PubMed
8.
go back to reference Treff NR, Northrop LE, Kasabwala K, Su J, Levy B, Scott Jr RT. Single nucleotide polymorphism microarray-based concurrent screening of 24-chromosome aneuploidy and unbalanced translocations in preimplantation human embryos. Fertil Steril. 2011;95(5):1606–12.PubMedCrossRef Treff NR, Northrop LE, Kasabwala K, Su J, Levy B, Scott Jr RT. Single nucleotide polymorphism microarray-based concurrent screening of 24-chromosome aneuploidy and unbalanced translocations in preimplantation human embryos. Fertil Steril. 2011;95(5):1606–12.PubMedCrossRef
9.
go back to reference Lim CK, Cho JW, Song IO, Kang IS, Yoon YD, Jun JH. Estimation of chromosomal imbalances in preimplantation embryos from preimplantation genetic diagnosis cycles of reciprocal translocations with or without acrocentric chromosomes. Fertil Steril. 2008;90(6):2144–51.PubMedCrossRef Lim CK, Cho JW, Song IO, Kang IS, Yoon YD, Jun JH. Estimation of chromosomal imbalances in preimplantation embryos from preimplantation genetic diagnosis cycles of reciprocal translocations with or without acrocentric chromosomes. Fertil Steril. 2008;90(6):2144–51.PubMedCrossRef
10.
go back to reference Beyazyurek C, Ekmekci CG, Saglam Y, Cinar C, Kahraman S. Preimplantation genetic diagnosis (PGD) for extremes–successful birth after PGD for a consanguineous couple carrying an identical balanced reciprocal translocation. Fertil Steril. 2010;93(7):1–5. Beyazyurek C, Ekmekci CG, Saglam Y, Cinar C, Kahraman S. Preimplantation genetic diagnosis (PGD) for extremes–successful birth after PGD for a consanguineous couple carrying an identical balanced reciprocal translocation. Fertil Steril. 2010;93(7):1–5.
11.
go back to reference Huang J, Lian Y, Qiao J, Chen Y, Ren X, Liu P. Characteristics of embryo development in Robertsonian translocations' preimplantation genetic diagnosis cycles. Prenat Diagn. 2009;29(12):1167–70.PubMedCrossRef Huang J, Lian Y, Qiao J, Chen Y, Ren X, Liu P. Characteristics of embryo development in Robertsonian translocations' preimplantation genetic diagnosis cycles. Prenat Diagn. 2009;29(12):1167–70.PubMedCrossRef
12.
go back to reference Ko DS, Cho JW, Park SY, Kim JY, Koong MK, Song IO, et al. Clinical outcomes of preimplantation genetic diagnosis (PGD) and analysis of meiotic segregation modes in reciprocal translocation carriers. Am J Med Genet A. 2010;152A(6):1428–33.PubMed Ko DS, Cho JW, Park SY, Kim JY, Koong MK, Song IO, et al. Clinical outcomes of preimplantation genetic diagnosis (PGD) and analysis of meiotic segregation modes in reciprocal translocation carriers. Am J Med Genet A. 2010;152A(6):1428–33.PubMed
13.
go back to reference Kuliev A, Verlinsky Y. Current features of preimplantation genetic diagnosis. Reprod BioMed Online. 2002;5(3):294–9.PubMedCrossRef Kuliev A, Verlinsky Y. Current features of preimplantation genetic diagnosis. Reprod BioMed Online. 2002;5(3):294–9.PubMedCrossRef
14.
go back to reference Munne 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.PubMed Munne 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.PubMed
15.
go back to reference Munne S, Morrison L, Fung J, Marquez C, Weier U, Bahce M, et al. Spontaneous abortions are reduced after preconception diagnosis of translocations. J Assist Reprod Genet. 1998;15(5):290–6.PubMedCentralPubMedCrossRef Munne S, Morrison L, Fung J, Marquez C, Weier U, Bahce M, et al. Spontaneous abortions are reduced after preconception diagnosis of translocations. J Assist Reprod Genet. 1998;15(5):290–6.PubMedCentralPubMedCrossRef
16.
go back to reference Munne S, Sandalinas M, Escudero T, Fung J, Gianaroli L, Cohen J. Outcome of preimplantation genetic diagnosis of translocations. Fertil Steril. 2000;73(6):1209–18.PubMedCrossRef Munne S, Sandalinas M, Escudero T, Fung J, Gianaroli L, Cohen J. Outcome of preimplantation genetic diagnosis of translocations. Fertil Steril. 2000;73(6):1209–18.PubMedCrossRef
17.
go back to reference Otani T, Roche M, Mizuike M, Colls P, Escudero T, Munne S. Preimplantation genetic diagnosis significantly improves the pregnancy outcome of translocation carriers with a history of recurrent miscarriage and unsuccessful pregnancies. Reprod BioMed Online. 2006;13(6):869–74.PubMedCrossRef Otani T, Roche M, Mizuike M, Colls P, Escudero T, Munne S. Preimplantation genetic diagnosis significantly improves the pregnancy outcome of translocation carriers with a history of recurrent miscarriage and unsuccessful pregnancies. Reprod BioMed Online. 2006;13(6):869–74.PubMedCrossRef
18.
go back to reference Harper JC, Wilton L, Traeger-Synodinos J, Goossens V, Moutou C, SenGupta SB, et al. The ESHRE PGD Consortium: 10 years of data collection. Hum Reprod Update. 2012;18(3):234–47.PubMedCrossRef Harper JC, Wilton L, Traeger-Synodinos J, Goossens V, Moutou C, SenGupta SB, et al. The ESHRE PGD Consortium: 10 years of data collection. Hum Reprod Update. 2012;18(3):234–47.PubMedCrossRef
19.
go back to reference Fragouli E, Wells D. Aneuploidy screening for embryo selection. Semin Reprod Med. 2012;30(4):289–301.PubMedCrossRef Fragouli E, Wells D. Aneuploidy screening for embryo selection. Semin Reprod Med. 2012;30(4):289–301.PubMedCrossRef
20.
go back to reference Dierssen M, Herault Y, Estivill X. Aneuploidy: from a physiological mechanism of variance to down syndrome. Physiol Rev. 2009;89(3):887–920.PubMedCrossRef Dierssen M, Herault Y, Estivill X. Aneuploidy: from a physiological mechanism of variance to down syndrome. Physiol Rev. 2009;89(3):887–920.PubMedCrossRef
22.
go back to reference Alfarawati S, Fragouli E, Colls P, Wells D. First births after preimplantation genetic diagnosis of structural chromosome abnormalities using comparative genomic hybridization and microarray analysis. Hum Reprod. 2011;26(6):1560–74.PubMedCrossRef Alfarawati S, Fragouli E, Colls P, Wells D. First births after preimplantation genetic diagnosis of structural chromosome abnormalities using comparative genomic hybridization and microarray analysis. Hum Reprod. 2011;26(6):1560–74.PubMedCrossRef
23.
go back to reference Fiorentino F, Spizzichino L, Bono S, Biricik A, Kokkali G, Rienzi L, et al. PGD for reciprocal and Robertsonian translocations using array comparative genomic hybridization. Hum Reprod. 2011;26(7):1925–35.PubMedCrossRef Fiorentino F, Spizzichino L, Bono S, Biricik A, Kokkali G, Rienzi L, et al. PGD for reciprocal and Robertsonian translocations using array comparative genomic hybridization. Hum Reprod. 2011;26(7):1925–35.PubMedCrossRef
24.
go back to reference Colls P, Escudero T, Fischer J, Cekleniak NA, Ben-Ozer S, Meyer B, et al. Validation of array comparative genome hybridization for diagnosis of translocations in preimplantation human embryos. Reprod BioMed Online. 2012;24(6):621–9.PubMedCrossRef Colls P, Escudero T, Fischer J, Cekleniak NA, Ben-Ozer S, Meyer B, et al. Validation of array comparative genome hybridization for diagnosis of translocations in preimplantation human embryos. Reprod BioMed Online. 2012;24(6):621–9.PubMedCrossRef
25.
go back to reference Tan YQ, Tan K, Zhang SP, Gong F, Cheng DH, Xiong B, et al. Single-nucleotide polymorphism microarray-based preimplantation genetic diagnosis is likely to improve the clinical outcome for translocation carriers. Hum Reprod. 2013;28(9):2581–92.PubMedCrossRef Tan YQ, Tan K, Zhang SP, Gong F, Cheng DH, Xiong B, et al. Single-nucleotide polymorphism microarray-based preimplantation genetic diagnosis is likely to improve the clinical outcome for translocation carriers. Hum Reprod. 2013;28(9):2581–92.PubMedCrossRef
26.
go back to reference Huang CC, Chang LJ, Tsai YY, Hung CC, Fang MY, Su YN, et al. A feasible strategy of preimplantation genetic diagnosis for carriers with chromosomal translocation: Using blastocyst biopsy and array comparative genomic hybridization. J Formos Med Assoc. 2013;112(9):537–44.PubMedCrossRef Huang CC, Chang LJ, Tsai YY, Hung CC, Fang MY, Su YN, et al. A feasible strategy of preimplantation genetic diagnosis for carriers with chromosomal translocation: Using blastocyst biopsy and array comparative genomic hybridization. J Formos Med Assoc. 2013;112(9):537–44.PubMedCrossRef
27.
go back to reference Ata B, Kaplan B, Danzer H, Glassner M, Opsahl M, Tan SL, et al. Array CGH analysis shows that aneuploidy is not related to the number of embryos generated. Reprod BioMed Online. 2012;24(6):614–20.PubMedCrossRef Ata B, Kaplan B, Danzer H, Glassner M, Opsahl M, Tan SL, et al. Array CGH analysis shows that aneuploidy is not related to the number of embryos generated. Reprod BioMed Online. 2012;24(6):614–20.PubMedCrossRef
28.
go back to reference Rubio C, Rodrigo L, Mercader A, Mateu E, Buendia P, Pehlivan T, et al. Impact of chromosomal abnormalities on preimplantation embryo development. Prenat Diagn. 2007;27(8):748–56.PubMedCrossRef Rubio C, Rodrigo L, Mercader A, Mateu E, Buendia P, Pehlivan T, et al. Impact of chromosomal abnormalities on preimplantation embryo development. Prenat Diagn. 2007;27(8):748–56.PubMedCrossRef
29.
go back to reference Magli MC, Jones GM, Gras L, Gianaroli L, Korman I, Trounson AO. Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro. Hum Reprod. 2000;15(8):1781–6.PubMedCrossRef Magli MC, Jones GM, Gras L, Gianaroli L, Korman I, Trounson AO. Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro. Hum Reprod. 2000;15(8):1781–6.PubMedCrossRef
30.
go back to reference Gutierrez-Mateo C, Colls P, Sanchez-Garcia J, Escudero T, Prates R, Ketterson K, et al. Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Fertil Steril. 2011;95(3):953–8.PubMedCrossRef Gutierrez-Mateo C, Colls P, Sanchez-Garcia J, Escudero T, Prates R, Ketterson K, et al. Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Fertil Steril. 2011;95(3):953–8.PubMedCrossRef
31.
go back to reference Hodes-Wertz B, Grifo J, Ghadir S, Kaplan B, Laskin CA, Glassner M, et al. Idiopathic recurrent miscarriage is caused mostly by aneuploid embryos. Fertil Steril. 2012;98(3):675–80.PubMedCrossRef Hodes-Wertz B, Grifo J, Ghadir S, Kaplan B, Laskin CA, Glassner M, et al. Idiopathic recurrent miscarriage is caused mostly by aneuploid embryos. Fertil Steril. 2012;98(3):675–80.PubMedCrossRef
32.
go back to reference Kearns WG. I10 PGS/PGD evaluation of 7059 embryos from 872 in vitro fertilization (IVF) cycles using 23-chromosome single nucleotide polymorphism (SNP) or 23-chromosome comparative genomic hybridization (aCGH) microarrays. Reprod BioMed Online. 2013;26:S4.CrossRef Kearns WG. I10 PGS/PGD evaluation of 7059 embryos from 872 in vitro fertilization (IVF) cycles using 23-chromosome single nucleotide polymorphism (SNP) or 23-chromosome comparative genomic hybridization (aCGH) microarrays. Reprod BioMed Online. 2013;26:S4.CrossRef
33.
go back to reference Northrop LE, Treff NR, Levy B, Scott Jr RT. SNP microarray-based 24 chromosome aneuploidy screening demonstrates that cleavage-stage FISH poorly predicts aneuploidy in embryos that develop to morphologically normal blastocysts. Mol Hum Reprod. 2010;16(8):590–600.PubMedCentralPubMedCrossRef Northrop LE, Treff NR, Levy B, Scott Jr RT. SNP microarray-based 24 chromosome aneuploidy screening demonstrates that cleavage-stage FISH poorly predicts aneuploidy in embryos that develop to morphologically normal blastocysts. Mol Hum Reprod. 2010;16(8):590–600.PubMedCentralPubMedCrossRef
34.
go back to reference Treff NR, Levy B, Su J, Northrop LE, Tao X, Scott Jr RT. SNP microarray-based 24 chromosome aneuploidy screening is significantly more consistent than FISH. Mol Hum Reprod. 2010;16(8):583–9.PubMedCentralPubMedCrossRef Treff NR, Levy B, Su J, Northrop LE, Tao X, Scott Jr RT. SNP microarray-based 24 chromosome aneuploidy screening is significantly more consistent than FISH. Mol Hum Reprod. 2010;16(8):583–9.PubMedCentralPubMedCrossRef
35.
go back to reference Voullaire L, Wilton L, McBain J, Callaghan T, Williamson R. Chromosome abnormalities identified by comparative genomic hybridization in embryos from women with repeated implantation failure. Mol Hum Reprod. 2002;8(11):1035–41.PubMedCrossRef Voullaire L, Wilton L, McBain J, Callaghan T, Williamson R. Chromosome abnormalities identified by comparative genomic hybridization in embryos from women with repeated implantation failure. Mol Hum Reprod. 2002;8(11):1035–41.PubMedCrossRef
36.
go back to reference Scott Jr RT, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, et al. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril. 2013;100(3):697–703.PubMedCrossRef Scott Jr RT, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, et al. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril. 2013;100(3):697–703.PubMedCrossRef
37.
go back to reference Kearns WG, Benner A, Nguyen KHD, Chipko C, Widra E, Leach R. Validation of single nucleotide polymorphism (SNP) microarray PGD on single cell (s) from embryos. Fertil Steril. 2010;94(4):S124.CrossRef Kearns WG, Benner A, Nguyen KHD, Chipko C, Widra E, Leach R. Validation of single nucleotide polymorphism (SNP) microarray PGD on single cell (s) from embryos. Fertil Steril. 2010;94(4):S124.CrossRef
Metadata
Title
Two different microarray technologies for preimplantation genetic diagnosis and screening, due to reciprocal translocation imbalances, demonstrate equivalent euploidy and clinical pregnancy rates
Authors
Kyle J. Tobler
Paul R. Brezina
Andrew T. Benner
Luke Du
Xin Xu
William G. Kearns
Publication date
01-07-2014
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 7/2014
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-014-0230-3

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