Infertility patients with chromosome inversions are not susceptible to an inter-chromosomal effect

  • D. Young
  • D. Klepacka
  • M. McGarvey
  • W. B. Schoolcraft
  • M. G. Katz-Jaffe



The aim of this study was to evaluate the incidence of an inter-chromosomal effect (ICE) in blastocyst-stage embryos from carriers of balanced chromosome inversions.


Infertility patients (n = 52) with balanced inversions (n = 66 cycles), and maternal age-matched controls that concurrently cycled (n = 66), consented to an IVF cycle with preimplantation genetic testing for aneuploidy (PGT-A). Blastocyst-stage embryos underwent trophectoderm biopsy for PGT-A with only euploid blastocysts transferred in a subsequent frozen embryo transfer. Subtypes of inversions were included in aggregate: paracentric/pericentric, polymorphic/non-polymorphic, male/female carriers, and varying inversion sizes.


The incidence of aneuploidy was not significantly higher for the inversion patients compared to the controls (inversion = 48.8% vs. control = 47.2% ns). Following euploid blastocyst transfer, there were excellent live birth outcomes.


Carriers of balanced chromosome inversions did not exhibit higher aneuploidy rates for chromosomes that were not involved in the inversion compared to maternal age-matched controls, signifying the absence of an inter-chromosomal effect for this data set. These results provide the largest investigation of blastocyst embryos regarding the debated existence of an ICE resulting from the presence of an inversion during meiosis. However, further studies are warranted to investigate an ICE among inversions subtypes that were outside the scope of this study.


Inter-chromosomal effect Balanced inversion carriers Preimplantation genetic testing-aneuploidy Structural chromosome rearrangement 



  1. 1.
    Campana M, Serra A, Neri G. Role of chromosome aberrations in recurrent abortion: a study of 269 balanced translocations. Am J Med Genet. 1986;24:341–56.CrossRefGoogle Scholar
  2. 2.
    Fryns JP, Van Buggenhout G. Structural chromosome rearrangements in couples with recurrent fetal wastage. Eur J Obstet Gynecol Reprod Biol. 1998;81:171–6.CrossRefGoogle Scholar
  3. 3.
    Collinson MN, Fisher AM, Walker J, Currie J, Williams L, Roberts P. Inv(10)(p11.2q21.2), a variant chromosome. Hum Genet. 1997;101:175–80.CrossRefGoogle Scholar
  4. 4.
    Feuk L. Inversion variants in the human genome: role in disease and genome architecture. Genome Med. 2010;2(2):11.CrossRefGoogle Scholar
  5. 5.
    Tam E, Young EJ, Morris CA, Marshall CR, Loo W, Scherer SW, et al. The common inversion of the Williams-Beuren syndrome region at 7q11.23 does not cause clinical symptoms. Am J Med Genet A. 2008;146A:1797–806.CrossRefGoogle Scholar
  6. 6.
    Joyce EF, McKim KS. Chromosome axis defects induce a checkpoint-mediated delay and interchromosomal effect on crossing over during Drosophila meiosis. PLoS Genet. 2010;6(8):e1001059.CrossRefGoogle Scholar
  7. 7.
    Anton E, Blanco J, Egozcue J, Vidal F. Sperm studies in heterozygote inversion carriers: a review. Cytogenet Genome Res. 2005;111:297–304.CrossRefGoogle Scholar
  8. 8.
    Anton E, Vidal F, Blanco J. Interchromosomal effect analyses by sperm FISH: incidence and distribution among reorganization carriers. Syst Biol Reprod Med. 2011;57:268–78.CrossRefGoogle Scholar
  9. 9.
    Gardner R, Sutherland G. Chromosome abnormalities and genetic counseling. Oxford: Oxford University Press; 1996.Google Scholar
  10. 10.
    Lejeune J. Autosomal disorders. Pediatrics. 1963;32:326–37.PubMedGoogle Scholar
  11. 11.
    Anton E, Vidal F, Egozcue J, Blanco J. Genetic reproductive risk in inversion carriers. Fertil Steril. 2006;85:661–6.CrossRefGoogle Scholar
  12. 12.
    Caer E, Perrin A, Douet-Guilbert N, Amice V, De Braekeleer M, Morel F. Differing mechanisms of meiotic segregation in spermatozoa from three carriers of a pericentric inversion of chromosome 8. Fertil Steril. 2008;89:1637–40.CrossRefGoogle Scholar
  13. 13.
    Morel F, Laudier B, Guérif F, Couet ML, Royère D, Roux C, et al. Meiotic segregation analysis in spermatozoa of pericentric inversion carriers using fluorescence in-situ hybridization. Hum Reprod Oxf Engl. 2007;22:136–41.CrossRefGoogle Scholar
  14. 14.
    Amiel A, Sardos-Albertini F, Fejgin MD, Sharony R, Diukman R, Bartoov B. Interchromosomal effect leading to an increase in aneuploidy in sperm nuclei in a man heterozygous for pericentric inversion (inv 9) and C-heterochromatin. J Hum Genet. 2001;46:245–50.CrossRefGoogle Scholar
  15. 15.
    Mikhaail-Philips MM, Ko E, Chernos J, Greene C, Rademaker A, Martin RH. Analysis of chromosome segregation in sperm from a chromosome 2 inversion heterozygote and assessment of an interchromosomal effect. Am J Med Genet A. 2004;127A:139–43.CrossRefGoogle Scholar
  16. 16.
    Mikhaail-Philips MM, McGillivray BC, Hamilton SJ, Ko E, Chernos J, Rademaker A, et al. Unusual segregation products in sperm from a pericentric inversion 17 heterozygote. Hum Genet. 2005;117:357–65.CrossRefGoogle Scholar
  17. 17.
    Vialard F, Delanete A, Clement P, Simon-Bouy B, Aubriot FX, Selva J. Sperm chromosome analysis in two cases of paracentric inversion. Fertil Steril. 2007;87:418.e1–5.Google Scholar
  18. 18.
    Blanco J, Egozcue J, Vidal F. Interchromosomal effects for chromosome 21 in carriers of structural chromosome reorganizations determined by fluorescence in situ hybridization on sperm nuclei. Hum Genet. 2000;106:500–5.CrossRefGoogle Scholar
  19. 19.
    Ferfouri F, Clement P, Gomes DM, Minz M, Amar E, Selva J, et al. Is classic pericentric inversion of chromosome 2 inv(2)(p11q13) associated with an increased risk of unbalanced chromosomes? Fertil Steril. 2009;92:1497.e1–4.CrossRefGoogle Scholar
  20. 20.
    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 Oxf Engl. 2011;26:1560–74.CrossRefGoogle Scholar
  21. 21.
    Schoolcraft WB, Treff NR, Stevens JM, Ferry K, Katz-Jaffe M, Scott RT. Live birth outcome with trophectoderm biopsy, blastocyst vitrification, and single-nucleotide polymorphism microarray-based comprehensive chromosome screening in infertile patients. Fertil Steril. 2011;96:638–40.CrossRefGoogle Scholar
  22. 22.
    Treff NR, Su J, Tao X, Levy B, Scott RT. Accurate single cell 24 chromosome aneuploidy screening using whole genome amplification and single nucleotide polymorphism microarrays. Fertil Steril. 2010;94:2017–21.CrossRefGoogle Scholar
  23. 23.
    Franasiak JM, Forman EJ, Hong KH, Werner MD, Upham KM, Treff NR, et al. Aneuploidy across individual chromosomes at the embryonic level in trophectoderm biopsies: changes with patient age and chromosome structure. J Assist Reprod Genet. 2014;31:1501–9.CrossRefGoogle Scholar
  24. 24.
    Schoolcraft WB, Katz-Jaffe MG. Comprehensive chromosome screening of trophectoderm with vitrification facilitates elective single-embryo transfer for infertile women with advanced maternal age. Fertil Steril. 2013;100:615–9.CrossRefGoogle Scholar
  25. 25.
    Schoolcraft WB, Katz-Jaffe MG, Stevens J, Rawlins M, Munne S. Preimplantation aneuploidy testing for infertile patients of advanced maternal age: a randomized prospective trial. Fertil Steril. 2009;92:157–62.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • D. Young
    • 1
  • D. Klepacka
    • 1
  • M. McGarvey
    • 2
  • W. B. Schoolcraft
    • 3
  • M. G. Katz-Jaffe
    • 4
  1. 1.Department of GeneticsColorado Center for Reproductive MedicineLone TreeUSA
  2. 2.Department of GeneticsColorado Center for Reproductive MedicineLone TreeUSA
  3. 3.Colorado Center for Reproductive MedicineLone TreeUSA
  4. 4.Colorado Center for Reproductive MedicineLone TreeUSA

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