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Journal of Assisted Reproduction and Genetics

, Volume 30, Issue 10, pp 1333–1339 | Cite as

Preimplantation Genetic Screening (PGS) with Comparative Genomic Hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages

  • Martin D. KeltzEmail author
  • Mario Vega
  • Ido Sirota
  • Matthew Lederman
  • Erin L. Moshier
  • Eric Gonzales
  • Daniel Stein
Assisted Reproduction Technologies

Abstract

Purpose

To determine benefits of cleavage-stage preimplantation genetic screening (PGS) by array comparative genomic hybridization (CGH).

Methods

A retrospective case–control study was performed at a tertiary care university-affiliated medical center. Implantation rate was looked at as a primary outcome. Secondary outcomes included clinical and ongoing pregnancy rates, as well as multiple pregnancy and miscarriage rates. Thirty five patients underwent 39 fresh cycles with PGS by aCGH and 311 similar patients underwent 394 invitro fertilization cycles.

Result(s)

The implantation rate in the CGH group doubled when compared to the control group (52.63 % vs. 19.15 %, p = <0.001), clinical pregnancy rate was higher (69.23 % vs. 43.91 %, p = 0.0002), ongoing pregnancy rate almost doubled (61.54 % vs. 32.49 %, p = <0.0001), multiple pregnancy rate decreased (8.33 % vs. 34.38 %, p = 0.0082) and miscarriage rate trended lower (11.11 % vs. 26.01 %, p = 0.13).

Conclusion

Cleavage stage PGS with CGH is a feasible and safe option for aneuploidy screening that shows excellent outcomes when used in fresh cycles. This is the first report of cleavage stage PGS by CGH showing improved ongoing pregnancy rates.

Keywords

Preimplantation genetic screening Aneuploidy Comparative genomic hybridization Blastomere biopsy 

Notes

Acknowledgments

The authors thank the office and embryology staff of the Continuum Reproductive Center, and wish to acknowledge the assistance of Carolyn Waldron, MS, MA.

Disclosure

The authors have nothing to disclose.

References

  1. 1.
    Assou S, Haouzi D, De Vos J, Hamamah S. Human cumulus cells as biomarkers for embryo and pregnancy outcomes. Mol Hum Reprod. 2010;16(8):531–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Brison DR, Houghton FD, Falconer D, Roberts SA, Hawkhead J, Humpherson PG, et al. Identification of viable embryos in IVF by non-invasive measurement of amino acid turnover. Hum Reprod. 2004;19(10):2319–24.PubMedCrossRefGoogle Scholar
  3. 3.
    Capalbo A, Bono S, Spizzichino L, Biricik A, Baldi M, Colamaria S, et al. Sequential comprehensive chromosome analysis on polar bodies, blastomeres and trophoblast: insights into female meiotic errors and chromosomal segregation in the preimplantation window of embryo development. Hum Reprod. 2013;28(2):509–18.PubMedCrossRefGoogle Scholar
  4. 4.
    Cruz M, Gadea B, Garrido N, Pedersen KS, Martínez M, Pérez-Cano I, et al. Embryo quality, blastocyst and ongoing pregnancy rates in oocyte donation patients whose embryos were monitored by time-lapse imaging. J Assist Reprod Genet. 2011;28(7):569–73.PubMedCrossRefGoogle Scholar
  5. 5.
    Delhanty JD, Griffin DK, Handyside AH, Harper J, Atkinson GH, Pieters MH, et al. Detection of aneuploidy and chromosomal mosaicism in human embryos during preimplantation sex determination by fluorescent in situ hybridisation, (FISH). Hum Mol Genet. 1993;2(8):1183–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Drugan A, Koppitch 3rd FC, Williams 3rd JC, Johnson MP, Moghissi KS, Evans MI. Prenatal genetic diagnosis following recurrent early pregnancy loss. Obstet Gynecol. 1990;75(3 Pt 1):381–4.PubMedGoogle Scholar
  7. 7.
    Fauser BC. Screening of embryos for numerical chromosome abnormalities during in-vitro fertilisation is not useful for application in daily practice. Ned Tijdschr Geneeskd. 2008;152(13):734–6.PubMedGoogle Scholar
  8. 8.
    Fishel S, Gordon A, Lynch C, Dowell K, Ndukwe G, Kelada E, et al. Live birth after polar body array comparative genomic hybridization prediction of embryo ploidy-the future of IVF? Fertil Steril. 2010;93(3):1006.e1007–10.CrossRefGoogle Scholar
  9. 9.
    Fragouli E, Wells D. Aneuploidy screening for embryo selection. Semin Reprod Med. 2012;30(4):289–301.PubMedCrossRefGoogle Scholar
  10. 10.
    Fritz MA. Perspectives on the efficacy and indications for preimplantation genetic screening: where are we now? Hum Reprod. 2008;23(12):2617–21.PubMedCrossRefGoogle Scholar
  11. 11.
    Hardarson T, Hanson C, Lundin K, Hillensjo T, Nilsson L, Stevic J, et al. Preimplantation genetic screening in women of advanced maternal age caused a decrease in clinical pregnancy rate: a randomized controlled trial. Hum Reprod. 2008;23(12):2806–12.PubMedCrossRefGoogle Scholar
  12. 12.
    Harper J, Coonen E, De Rycke M, Fiorentino F, Geraedts J, Goossens V, et al. What next for preimplantation genetic screening (PGS)? A position statement from the ESHRE PGD Consortium Steering Committee. Hum Reprod. 2010;25(4):821–3.PubMedCrossRefGoogle Scholar
  13. 13.
    Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. 2001;2(4):280–91.PubMedCrossRefGoogle Scholar
  14. 14.
    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.PubMedCrossRefGoogle Scholar
  15. 15.
    Huang JY, Rosenwaks Z. In vitro fertilisation treatment and factors affecting success. Best Pract Res Clin Obstet Gynaecol. 2012;26(6):777–88.PubMedCrossRefGoogle Scholar
  16. 16.
    Kamiguchi Y, Rosenbusch B, Sterzik K, Mikamo K. Chromosomal analysis of unfertilized human oocytes prepared by a gradual fixation-air drying method. Hum Genet. 1993;90(5):533–41.PubMedCrossRefGoogle Scholar
  17. 17.
    Katz-Jaffe MG, McReynolds S, Gardner DK, Schoolcraft WB. The role of proteomics in defining the human embryonic secretome. Mol Hum Reprod. 2009;15(5):271–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Katz-Jaffe MG, Schoolcraft WB, Gardner DK. Analysis of protein expression (secretome) by human and mouse preimplantation embryos. Fertil Steril. 2006;86(3):678–85.PubMedCrossRefGoogle Scholar
  19. 19.
    Lemmen JG, Agerholm I, Ziebe S. Kinetic markers of human embryo quality using time-lapse recordings of IVF/ICSI-fertilized oocytes. Reprod Biomed Online. 2008;17(3):385–91.PubMedCrossRefGoogle Scholar
  20. 20.
    Mastenbroek S, Twisk M, van Echten-Arends J, Sikkema-Raddatz B, Korevaar JC, Verhoeve HR, et al. In vitro fertilization with preimplantation genetic screening. N Engl J Med. 2007;357(1):9–17.PubMedCrossRefGoogle Scholar
  21. 21.
    Meseguer M, Rubio I, Cruz M, Basile N, Marcos J, Requena A. Embryo incubation and selection in a time-lapse monitoring system improves pregnancy outcome compared with a standard incubator: a retrospective cohort study. Fertil Steril. 2012;98(6):1481–1489.e1410.PubMedCrossRefGoogle Scholar
  22. 22.
    Munne S, S ES, Grifo J, Marut E, Opsahl M and Taylor TH “Preimplantation genetic diagnosis using a-CGH significantly increases ongoing pregnancy rates per transfer.” Fertil Steril 2010; 94(S81).Google Scholar
  23. 23.
    Munne S, Lee A, Rosenwaks Z, Grifo J, Cohen J. Diagnosis of major chromosome aneuploidies in human preimplantation embryos. Hum Reprod. 1993;8(12):2185–91.PubMedGoogle Scholar
  24. 24.
    Palermo GD, Munne S, Colombero LT, Cohen J, Rosenwaks Z. Genetics of abnormal human fertilization. Hum Reprod. 1995;10 Suppl 1:120–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Pribenszky C, Losonczi E, Molnár M, Lang Z, Mátyás S, Rajczy K, et al. Prediction of in-vitro developmental competence of early cleavage-stage mouse embryos with compact time-lapse equipment. Reprod Biomed Online. 2010;20(3):371–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Pribenszky C, Mátyás S, Kovács P, Losonczi E, Zádori J, Vajta G. Pregnancy achieved by transfer of a single blastocyst selected by time-lapse monitoring. Reprod Biomed Online. 2010;21(4):533–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Rabinowitz A, Beltsos A, D Potter, Bush M, Givens C and D Smotrich. “Effects of advanced maternal age are abrogated in 122 patients undergoing transfer of embryos with euploid microarray screening results at cleavage stage.” Fertil Steril 2010;94(S80).Google Scholar
  28. 28.
    Rubio C, Simón C, Vidal F, Rodrigo L, Pehlivan T, Remohí J, et al. Chromosomal abnormalities and embryo development in recurrent miscarriage couples. Hum Reprod. 2003;18(1):182–8.PubMedCrossRefGoogle Scholar
  29. 29.
    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(1):157–62.PubMedCrossRefGoogle Scholar
  30. 30.
    Scott R, Seli E, Miller K, Sakkas D, Scott K, Burns DH. Noninvasive metabolomic profiling of human embryo culture media using Raman spectroscopy predicts embryonic reproductive potential: a prospective blinded pilot study. Fertil Steril. 2008;90(1):77–83.PubMedCrossRefGoogle Scholar
  31. 31.
    Seli E, Sakkas D, Scott R, Kwok SC, Rosendahl SM, Burns DH. Noninvasive metabolomic profiling of embryo culture media using Raman and near-infrared spectroscopy correlates with reproductive potential of embryos in women undergoing in vitro fertilization. Fertil Steril. 2007;88(5):1350–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Seli E, Vergouw CG, Morita H, Botros L, Roos P, Lambalk CB, et al. Noninvasive metabolomic profiling as an adjunct to morphology for noninvasive embryo assessment in women undergoing single embryo transfer. Fertil Steril. 2010;94(2):535–42.PubMedCrossRefGoogle Scholar
  33. 33.
    Staessen C, Platteau P, Van Assche E, Michiels A, Tournaye H, Camus M, et al. Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomized controlled trial. Hum Reprod. 2004;19(12):2849–58.PubMedCrossRefGoogle Scholar
  34. 34.
    Staessen C, Verpoest W, Donoso P, Haentjens P, Van der Elst J, Liebaers I, et al. Preimplantation genetic screening does not improve delivery rate in women under the age of 36 following single-embryo transfer. Hum Reprod. 2008;23(12):2818–25.PubMedCrossRefGoogle Scholar
  35. 35.
    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.PubMedCrossRefGoogle Scholar
  36. 36.
    Twisk M, Mastenbroek S, Hoek A, Heineman MJ, van der Veen F, Bossuyt PM, et al. No beneficial effect of preimplantation genetic screening in women of advanced maternal age with a high risk for embryonic aneuploidy. Hum Reprod. 2008;23(12):2813–7.PubMedCrossRefGoogle Scholar
  37. 37.
    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.PubMedCrossRefGoogle Scholar
  38. 38.
    Wells D, Delhanty JD. Comprehensive chromosomal analysis of human preimplantation embryos using whole genome amplification and single cell comparative genomic hybridization. Mol Hum Reprod. 2000;6(11):1055–62.PubMedCrossRefGoogle Scholar
  39. 39.
    Wilton L, Voullaire L, Sargeant P, Williamson R, McBain J. Preimplantation aneuploidy screening using comparative genomic hybridization or fluorescence in situ hybridization of embryos from patients with recurrent implantation failure. Fertil Steril. 2003;80(4):860–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Martin D. Keltz
    • 1
    • 3
    Email author
  • Mario Vega
    • 1
  • Ido Sirota
    • 1
  • Matthew Lederman
    • 1
  • Erin L. Moshier
    • 2
  • Eric Gonzales
    • 1
  • Daniel Stein
    • 1
  1. 1.Continuum Reproductive Center, Department of Obstetrics and Gynecology, St. Luke’s-Roosevelt Hospital CenterColumbia University, College of Physicians and SurgeonsNew YorkUSA
  2. 2.Department of Community and Preventive MedicineIcahn School of Medicine at Mount SinaiNew YorkUSA
  3. 3.Director Division of Reproductive Endocrinology, The Continuum Reproductive CenterSt. Luke’s-Roosevelt Hospital CenterNew YorkUSA

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