Journal of Assisted Reproduction and Genetics

, Volume 24, Issue 1, pp 37–41 | Cite as

Discordance among blastomeres renders preimplantation genetic diagnosis for aneuploidy ineffective

  • C. B. Coulam
  • R. S. Jeyendran
  • M. Fiddler
  • E. Pergament
Original paper

Abstract

Purpose: To investigate the contribution of discordance among blastomeres from the same embryo in the interpretation of blastomeres biopsied from day 3 embryos.

Methods: 228 IVF embryos had two blastomeres removed and fluorescent in situ hybridization (FISH) was used to detect aneuploidy of chromosomes 13, 15, 16, 18, 21, 22, X and Y. Of the 228 embryos, 102 had complete FISH results for both blastomeres.

Results: When the 2 blastomeres of 102 embryos with successful FISH results were compared, 26 (25.5%) were concordant for all 8 chromosomes and 76 (74.5%) were discordant for one or more chromosomes. Among the 102 embryos, 12 (12%) were disomy in both blastomeres and 37 (36%) were disomic in all 8 chromosomes in one of the two blastomeres.

Conclusion: Discordance among blastomeres from the same embryo appears to present a significant problem in interpreting results of embryos biopsied on day 3 and analyzed by FISH especially when most PGD’s are done on single blastomeres.

Keywords

Preimplantation genetic diagnosis Aneuploidy screening Discordance among blastomeres Chromosomal discordance 

References

  1. 1.
    Handyside AH, Pattinson JK, Penketh RJA, Delhauty JDA, Wintson RML, Tuddenham EGD. Biopsy of human preimplantation embryos and sexing by DNA amplification. Lancet 1989;1:347–9PubMedCrossRefGoogle Scholar
  2. 2.
    Smith KE, Buylos RP. The profound impact of patient age on pregnancy outcome after early detection of fetal cardiac activity. Fertil Steril 1996;65:35–40PubMedGoogle Scholar
  3. 3.
    Rubio C, Rodrigo L, Perez-Cano, Mercader A, Mateu E, Buendia, Remohi J, Simon C, Pellicer A. FISH screening of aneuploidies in preimplantation embryos to improve IVF outcome. Reprod Biomed Online 2005;11:497–506PubMedGoogle Scholar
  4. 4.
    Munne S, Alikani M, Tomkin G, Grifo J, Cohen J. Embryo morphology, development rates, and maternal age are correlated with chromosome abnormalities. Fertil Steril 1995;64:382–91PubMedGoogle Scholar
  5. 5.
    Marquez C, Sandalinas M, Bahce M, Alikani M, Munne S .Chromosome abnormalities in 1255 cleavage-stage human embryos. Reprod Biomed Online 2000;1:17–26PubMedGoogle Scholar
  6. 6.
    Taranissi M, El-Toukhy T, Gorgy A, Verlinsky Y. Influence of maternal age on the outcome of PGD for aneuploidy in patients with recurrent implantation failure. Reprod Biomed Online 2005;4:521–4Google Scholar
  7. 7.
    Warburton D, Kline J, Stein Z, Strobino B. Cytogenetic abnormalities in spontaneous abortions of recognized conceptions. In: Porter IH, Wiley A, editors. Perinatal genetics: diagnosis and treatment. New York Academic Press; 1986, p. 133–48Google Scholar
  8. 8.
    Gianaroli L, Magli MC, Munne S, Florentino A, Montanaro N, Ferraretti A. Will preimplantation genetic diagnosis assist patients with a poor prognosis to achieve pregnancy? Hum Reprod 1997;12:1762–7PubMedCrossRefGoogle Scholar
  9. 9.
    Munne S, Magli C, Cohen J, Morton P, Sadowy S, Gianaroli L, Tucker M, Márquez C; Sable D, Ferraretti AP, Massey JB, Scott R. Positive outcome after preimplantation diagnosis of aneuploidy in human embryos. Hum Reprod 1999;14:2191–9PubMedCrossRefGoogle Scholar
  10. 10.
    Kahraman S, Bahce M, Samli H, Imirzahoglu N, Yakisn K, Cengiz G, Dönmez E. Healthy births and ongoing pregnancies obtained by preimplantation genetic diagnosis in patients with advanced maternal age and recurrent implantation failure. Hum Reprod 2000;15:2003–7PubMedCrossRefGoogle Scholar
  11. 11.
    Pehlivan T, Rubio C, Rodrigo L, Romero J, Remohl J, Simon C, Pellicer A. Impact of preimplantation genetic diagnosis on IVF outcome in implantation failure patients. Reprod Biomed Online 2003;6:232–7PubMedGoogle Scholar
  12. 12.
    Gianaroli L, Magli MC, Ferraretti AP, Tabanelli C, Farfalli V, Cavallini G, Me R. The beneficial effects of preimplantation genetic diagnosis for aneuploidy support extensive clinical application. Reprod Biomed Online 2005;10:633–40PubMedGoogle Scholar
  13. 13.
    Staessen C, Platteau P, Van Assche E, Michiels A, Tournaye H, Camus M, Devroey P, Liebaers I, Van Steirteghem A. Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomized controlled study. Hum Reprod 2004;19:2849–58PubMedCrossRefGoogle Scholar
  14. 14.
    Verlinsky Y. Over a decade of experience with preimplantation genetic diagnosis. Fertil Steril 2004;82:302–3PubMedCrossRefGoogle Scholar
  15. 15.
    Platteau P, Staessen C, Michiels A, Van Steirteghem A, Liebaers I, Devroey P. Preimplantation genetic diagnosis for aneuploidy screening in patients with unexplained miscarriages. Fertil Steril 2005;83:393–7PubMedCrossRefGoogle Scholar
  16. 16.
    Sugiura-Ogasawara M, Suzumori K. Can preimplantation genetic diagnosis improve success rates in recurrent aborters with translocations? Hum Reprod 2005;20:3267–70PubMedCrossRefGoogle Scholar
  17. 17.
    Veiga A, Gil Y, Boada M, Carrera M, Vidal F, Boiso L, Ménézo Y, Barri PN. Confirmation of diagnosis in preimplantation genetic diagnosis (PGD) through blastocyst culture: Preliminary experience. Prenat Diagnosis 1999;19:1242–7CrossRefGoogle Scholar
  18. 18.
    Ruangvutilert P, Delhanty JDA, Serhal P, Simopoulou M, Rodeck CH, Harper JC. FISH analysis on day 5 post inseminations of human arrested and blastocyst stage embryos. Prenatal Diagnosis 2000;20:552–60PubMedCrossRefGoogle Scholar
  19. 19.
    Ziebe S, Lundin K, Loft A, Bergh C, Nyboe-Andersen A, Skelleskog U, Nielsen D, Grondahl C, Kim H, Acre JC. FISH analysis for chromosomes 13, 16, 18, 21, 22, X and Y in all blastomeres of IVF pre-embryos from 144 randomly selected donated human oocytes and impact on pre-embryo morphology. Hum Reprod 2003;18:2575–81PubMedCrossRefGoogle Scholar
  20. 20.
    Li M, De Ugarte CM, Surrey M, Danzer H, De Cherney A, Hill DL. Fluorescence in situ hybridization reanalysis of day 6 human blastocysts diagnosed with aneuploidy on day 3. Fertil Steril 2005;84:1395–1400PubMedCrossRefGoogle Scholar
  21. 21.
    Baart EB, Martini E, Van Den Berg I, Macklon NS, Galjaard RJH, Fauser BCJM, Van Opstal D. Preimplantation genetic screening reveals a high incidence of aneuploidy and mosiacism in embryos from young women undergoing IVF. Hum Reprod 2006;21:223–33PubMedCrossRefGoogle Scholar
  22. 22.
    Dozortsev DI, McGinnis KT. An improved fixation technique for fluorencence in situ hybridization for preimplantation genetic diagnosis. Fertil Steril 2001;76:186–8PubMedCrossRefGoogle Scholar
  23. 23.
    Munne S, Marquez, Magli C, Morton P, Morrison L. Scoring criteria for preimplantation genetic diagnosis of numerical abnormalities for chromosomes X, Y, 13, 16, 18 and 21. Hum Mol Genet 1998;4:863–70Google Scholar
  24. 24.
    Munne S, Lee A, Rosenwak Z, Grifo J, Cohen J. Diagnosis of major chromosome aneuploidies in human preimplantation embryos. Hum Reprod 1993;8:2185–91PubMedGoogle Scholar
  25. 25.
    Velilla E, Escudero T, Munne S. Blastomere fixation techniques and risk of misdiagnosis for preimplantation genetic diagnosis of aneuploidy. Reprod Biomed Online 2002;4:210–7PubMedCrossRefGoogle Scholar
  26. 26.
    Wells WAE. The spindle assembly checkpoint: Aiming for a perfect mitosis every time. Trends in Cell Biol 1996;6:228–34CrossRefGoogle Scholar
  27. 27.
    Magli MC, Jones GM, Gras L, Gianaroli L, Korman I, Trouson AO. Chromosome mosaics in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro. Hum Reprod 2000;15:1781–6PubMedCrossRefGoogle Scholar
  28. 28.
    Munne S, Velilla E, Colls P, Bermudez MG, Vemuri MC, Steuerwald N, Garrisi J, Cohen J. Self-correction of chromosomally abnormal embryos in culture and implications for stem cell production. Fertil Steril 2005;84:1328–34PubMedCrossRefGoogle Scholar
  29. 29.
    Kalousek DK, Howard-Peebles PN, Magenis RE, Barret IJ, Dorfmann A, Black SH, Schulman JD, Wilson RD. Confirmation of CVS mosaicism in term placentae and high frequency of intrauterine growth retardation associated with confined placental mosaicism. Prenatal Diagnosis 1991;11:743–50PubMedGoogle Scholar
  30. 30.
    Tarin JJ, Conaghan J, Winston RML, Handyside AH. Human embryo biopsy on the second day after insemination for preimplantation diagnosis: Removal of a quarter of embryo retards cleavage. Fertil Steril 1992;58:970–6PubMedGoogle Scholar
  31. 31.
    Verjalav LO, Mikkelsom M. European collaborative study on mosiacism in chorionic villus sampling: Data from 1986–1987. Prenatal Diagnosis 1989;9:575–88Google Scholar
  32. 32.
    Ledbetter DH, Zachary JM, Simpson JL, Globus MS, Pergament E, Jackson L, Mahoney MJ, Desnick RJ, Schulman J, Copeland KL. Cytogenetics results from the US collaborative study on CVS. Prenatal Diagnosis 1992;12:317–154PubMedGoogle Scholar
  33. 33.
    Kalousek DK, Langlois S, Barrett IJ, Yam I, Wilson DR, Howard-Peebles PN, Johnson MP, Giorgiutti E. Uniparental disomy for chromosome 16 in humans. Am J Hum Genet 1993;52:8–16PubMedGoogle Scholar
  34. 34.
    Wilton L. Preimplantation genetic diagnosis for aneuploidy screening in early human embryos: A review. Prenatal Diagnosis 2002;22:512–8PubMedCrossRefGoogle Scholar
  35. 35.
    Shanine LK, Cedars MI. Preimplantation genetic diagnosis does not increase pregnancy rates in patients at risk for aneuploidy. Fertil Steril 2006;85:51–6CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • C. B. Coulam
    • 1
  • R. S. Jeyendran
    • 2
  • M. Fiddler
    • 3
  • E. Pergament
    • 4
  1. 1.Pregnancy Success Center of the Rinehart Center for Reproductive MedicineChicagoUSA
  2. 2.Andrology Laboratory ServicesChicagoUSA
  3. 3.DePaul UniversityChicagoUSA
  4. 4.Northwestern Reproductive GeneticsChicagoUSA

Personalised recommendations