Download PDF
Semin Reprod Med 2014; 32(02): 100-106
DOI: 10.1055/s-0033-1363551
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Embryo Biopsy for Aneuploidy Detection in the General Infertility Population

Daniel J. Kaser
1   Division of Reproductive Medicine, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Elizabeth S. Ginsburg
1   Division of Reproductive Medicine, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
› Author Affiliations
Further Information

Publication History

Publication Date:
10 February 2014 (online)

    Permissions and Reprints

Abstract

Since report of the first live birth following preimplantation genetic screening (PGS) in 1995, the procedure and available technologies for aneuploidy detection have rapidly evolved. Through these efforts, the biology of meiotic and mitotic segregation errors has been partially elucidated. A process that began with polar body biopsy and four-color fluorescence in situ hybridization to detect copy number in a limited number of chromosomes is now hardly recognizable: current molecular methods permit high-density screening of the entire human genome for copy number variants, structural rearrangements, microdeletions, and polyploids to a resolution of 35 kilobases in less than 48 hours. Indeed, with the advent of real-time quantitative analyses of ploidy status that allow same-day trophectoderm biopsy with fresh transfer of a euploid blastocyst, the future is bright for PGS. Questions remain about how best to safely offer this technology to patients, and which patients, if any, will benefit from routine biopsy. Herein, we will review the limited available evidence for application of PGS in the general infertility population as an adjunct method to optimize live birth rates.

Keywords

aneuploidy - comprehensive chromosome screening - fluorescence in situ hybridization - preimplantation genetic screening - trophectoderm biopsy
 

  • References

  • 1 Verlinsky Y, Cieslak J, Freidine M , et al. Pregnancies following pre-conception diagnosis of common aneuploidies by fluorescent in-situ hybridization. Hum Reprod 1995; 10 (7) 1923-1927
    PubMedGoogle Scholar
  • 2 Brezina PR, Elias RT, Schattman G, Kearns WG. Preimplantation genetic testing: aAvailable and emerging technologies. In: Racowsky C, Ginsburg ES, , eds. In Vitro Fertilization. New York: Springer; 2012: 115-143
    CrossrefGoogle Scholar
  • 3 Mastenbroek S, Twisk M, van Echten-Arends J , et al. In vitro fertilization with preimplantation genetic screening. N Engl J Med 2007; 357 (1) 9-17
    CrossrefPubMedGoogle Scholar
  • 4 Staessen C, Platteau P, Van Assche E , 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) 2849-2858
    CrossrefPubMedGoogle Scholar
  • 5 Rubio C, Bellver J, Rodrigo L , et al. Preimplantation genetic screening using fluorescence in situ hybridization in patients with repetitive implantation failure and advanced maternal age: two randomized trials. Fertil Steril 2013; 99 (5) 1400-1407
    CrossrefPubMedGoogle Scholar
  • 6 Platteau P, Staessen C, Michiels A, Van Steirteghem A, Liebaers I, Devroey P. Preimplantation genetic diagnosis for aneuploidy screening in patients with unexplained recurrent miscarriages. Fertil Steril 2005; 83 (2) 393-397 , quiz 525–526
    CrossrefPubMedGoogle Scholar
  • 7 Munné S, Sandalinas M, Escudero T , et al. Improved implantation after preimplantation genetic diagnosis of aneuploidy. Reprod Biomed Online 2003; 7 (1) 91-97
    CrossrefPubMedGoogle Scholar
  • 8 Fragouli E, Katz-Jaffe M, Alfarawati S , et al. Comprehensive chromosome screening of polar bodies and blastocysts from couples experiencing repeated implantation failure. Fertil Steril 2010; 94 (3) 875-887
    CrossrefPubMedGoogle Scholar
  • 9 Gianaroli L, Magli MC, Ferraretti AP, Munné S. Preimplantation diagnosis for aneuploidies in patients undergoing in vitro fertilization with a poor prognosis: identification of the categories for which it should be proposed. Fertil Steril 1999; 72 (5) 837-844
    CrossrefPubMedGoogle Scholar
  • 10 Forman EJ, Tao X, Ferry KM, Taylor D, Treff NR, Scott Jr RT. Single embryo transfer with comprehensive chromosome screening results in improved ongoing pregnancy rates and decreased miscarriage rates. Hum Reprod 2012; 27 (4) 1217-1222
    CrossrefPubMedGoogle Scholar
  • 11 Forman EJ, Hong KH, Ferry KM , et al. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril 2013; 100 (1) 100 , e1
    CrossrefPubMedGoogle Scholar
  • 12 Staessen C, Verpoest W, Donoso P , 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) 2818-2825
    CrossrefPubMedGoogle Scholar
  • 13 Meyer LR, Klipstein S, Hazlett WD, Nasta T, Mangan P, Karande VC. A prospective randomized controlled trial of preimplantation genetic screening in the “good prognosis” patient. Fertil Steril 2009; 91 (5) 1731-1738
    CrossrefPubMedGoogle Scholar
  • 14 Jansen RPS, Bowman MC, de Boer KA, Leigh DA, Lieberman DB, McArthur SJ. What next for preimplantation genetic screening (PGS)? Experience with blastocyst biopsy and testing for aneuploidy. Hum Reprod 2008; 23 (7) 1476-1478
    CrossrefPubMedGoogle Scholar
  • 15 Mastenbroek S, Twisk M, van der Veen F, Repping S. Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Hum Reprod Update 2011; 17 (4) 454-466
    CrossrefPubMedGoogle Scholar
  • 16 ACOG Committee Opinion No. 430: preimplantation genetic screening for aneuploidy. Obstet Gynecol 2009; 113 (3) 766-767
    CrossrefPubMedGoogle Scholar
  • 17 Practice Committee of Society for Assisted Reproductive Technology; Practice Committee of American Society for Reproductive Medicine. Preimplantation genetic testing: a Practice Committee opinion. Fertil Steril 2008; 90 (5, Suppl): S136-S143
    PubMedGoogle Scholar
  • 18 Harper J, Coonen E, De Rycke M , et al. What next for preimplantation genetic screening (PGS)? A position statement from the ESHRE PGD Consortium Steering Committee. Hum Reprod 2010; 25 (4) 821-823
    CrossrefPubMedGoogle Scholar
  • 19 Treff NR, Su J, Tao X, Levy B, Scott Jr RT. Accurate single cell 24 chromosome aneuploidy screening using whole genome amplification and single nucleotide polymorphism microarrays. Fertil Steril 2010; 94 (6) 2017-2021
    CrossrefPubMedGoogle Scholar
  • 20 Scott Jr RT, Ferry K, Su J, Tao X, Scott K, Treff NR. Comprehensive chromosome screening is highly predictive of the reproductive potential of human embryos: a prospective, blinded, nonselection study. Fertil Steril 2012; 97 (4) 870-875
    CrossrefPubMedGoogle Scholar
  • 21 Treff NR, Tao X, Ferry KM, Su J, Taylor D, Scott Jr RT. Development and validation of an accurate quantitative real-time polymerase chain reaction-based assay for human blastocyst comprehensive chromosomal aneuploidy screening. Fertil Steril 2012; 97 (4) 819-824
    CrossrefPubMedGoogle Scholar
  • 22 Treff NR, Scott Jr RT. Four-hour quantitative real-time polymerase chain reaction-based comprehensive chromosome screening and accumulating evidence of accuracy, safety, predictive value, and clinical efficacy. Fertil Steril 2013; 99 (4) 1049-1053
    CrossrefPubMedGoogle Scholar
  • 23 Forman EJ, Hong KH, Treff NR, Scott RT. Comprehensive chromosome screening and embryo selection: moving toward single euploid blastocyst transfer. Semin Reprod Med 2012; 30 (3) 236-242
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Tsuchiya KD. Fluorescence in situ hybridization. Clin Lab Med 2011; 31 (4) 525-542 , vii–viii
    CrossrefPubMedGoogle Scholar
  • 25 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) 583-589
    CrossrefPubMedGoogle Scholar
  • 26 Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 2008; 3 (6) 1101-1108
    CrossrefPubMedGoogle Scholar
  • 27 Capalbo A, Bono S, Spizzichino L , 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) 509-518
    CrossrefPubMedGoogle Scholar
  • 28 Baart EB, Martini E, van den Berg I , et al. Preimplantation genetic screening reveals a high incidence of aneuploidy and mosaicism in embryos from young women undergoing IVF. Hum Reprod 2006; 21 (1) 223-233
    PubMedGoogle Scholar
  • 29 Fragouli E, Alfarawati S, Daphnis DD , et al. Cytogenetic analysis of human blastocysts with the use of FISH, CGH and aCGH: scientific data and technical evaluation. Hum Reprod 2011; 26 (2) 480-490
    CrossrefPubMedGoogle Scholar
  • 30 Munné S, Velilla E, Colls P , et al. Self-correction of chromosomally abnormal embryos in culture and implications for stem cell production. Fertil Steril 2005; 84 (5) 1328-1334
    CrossrefPubMedGoogle Scholar
  • 31 Fragouli E, Lenzi M, Ross R, Katz-Jaffe M, Schoolcraft WB, Wells D. Comprehensive molecular cytogenetic analysis of the human blastocyst stage. Hum Reprod 2008; 23 (11) 2596-2608
    CrossrefPubMedGoogle Scholar
  • 32 Scott Jr RT, Upham KM, Forman EJ, Zhao T, Treff NR. Cleavage-stage biopsy significantly impairs human embryonic implantation potential while blastocyst biopsy does not: a randomized and paired clinical trial. Fertil Steril 2013; 100 (3) 624-630
    CrossrefPubMedGoogle Scholar
  • 33 Forman EJ, Kerry KM, Gueye NA , et al. Trophectoderm biopsy for single-gene disorder preimplantation genetic diagnosis is significantly more reliable than day 3 blastomere biopsy. Fertil Steril 2011; 96 (3) S222
    PubMedGoogle Scholar