Journal of Assisted Reproduction and Genetics

, Volume 36, Issue 1, pp 145–151 | Cite as

The number of biopsied trophectoderm cells may affect pregnancy outcomes

  • Luis GuzmanEmail author
  • D. Nuñez
  • R. López
  • N. Inoue
  • J. Portella
  • F. Vizcarra
  • L. Noriega-Portella
  • L. Noriega-Hoces
  • S. Munné
Assisted Reproduction Technologies



To study if the number of trophectoderm (TE) biopsied cells has an impact on implantation rates.


A retrospective cohort study in a single-center study.


In vitro fertilization center.


Patients who underwent PGT-A from January 2013 to March 2016. In total, 482 vitrified/warmed single embryo transfers were included.



Main outcome measures

Clinical pregnancies rate, implantation rate.


Overall, clinical pregnancies per embryo transfer were higher when a regular TE were biopsied compared to larger size biopsy cells (66% (175/267) vs 53% (115/215) (p < 0.005) respectively). Pregnancy rates were also analyzed according to embryo morphology at the moment of embryo biopsy, when a good-quality embryo was transferred the clinical outcome was 75% (81/108) in group 1 and 61% (60/99) in group 2 (p < 0.05). Data was also stratified by age in patients ≤ 35 years and > 35 years. The clinical pregnancy was 67% (51/76) in women ≤ 35 years and 65% (124/191) in women > 35 years when a regular size biopsy was performed. These results significantly reduced when a larger size biopsy was performed 54% (49/91) and 53% (66/124), respectively (p < 0.05). Further investigation indicated that miscarriage rate was similar between these groups (4% (7/182) in group 1 and 5% (6/121) in group 2).


These findings underscore that when a large amount of TE cells are biopsied, it may negatively affect implantation rates, but once implanted, the embryos have the same chance to miscarry or reach term.


TE cells biopsy PGT-A aCGH SNP-arrays Pregnancy outcomes 


  1. 1.
    Munne S, Alikani M, Tomkin G, Grifo J, Cohen J. Embryo morphology, developmental rates, and maternal age are correlated with chromosome abnormalities. Fertil Steril. 1995;64:382–91.CrossRefGoogle Scholar
  2. 2.
    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;24:614–20.CrossRefGoogle Scholar
  3. 3.
    Dahdouh EM, Balayla J, Garcia-Velasco JA. Impact of blastocyst biopsy and comprehensive chromosome screening technology on preimplantation genetic screening: a systematic review of randomized controlled trials. Reprod BioMed Online. 2015;30:281–9.CrossRefGoogle Scholar
  4. 4.
    Harper JC, Sengupta SB. Preimplantation genetic diagnosis: state of the art 2011. Hum Genet. 2012;131:175–86.CrossRefGoogle Scholar
  5. 5.
    Munne S, Lee A, Rosenwaks Z, Grifo J, Cohen J. Diagnosis of major chromosome aneuploidies in human preimplantation embryos. Hum Reprod. 1993;8:2185–91.CrossRefGoogle Scholar
  6. 6.
    Munne S, Magli C, Cohen J, Morton P, Sadowy S, Gianaroli L, et al. Positive outcome after preimplantation diagnosis of aneuploidy in human embryos. Hum Reprod. 1999;14:2191–9.CrossRefGoogle Scholar
  7. 7.
    Munne S, Sandalinas M, Escudero T, Velilla E, Walmsley R, Sadowy S, et al. Improved implantation after preimplantation genetic diagnosis of aneuploidy. Reprod BioMed Online. 2003;7:91–7.CrossRefGoogle Scholar
  8. 8.
    Colls P, Escudero T, Cekleniak N, Sadowy S, Cohen J, Munne S. Increased efficiency of preimplantation genetic diagnosis for infertility using “no result rescue”. Fertil Steril. 2007;88:53–61.CrossRefGoogle Scholar
  9. 9.
    Verlinsky Y, Tur-Kaspa I, Cieslak J, Bernal A, Morris R, Taranissi M, et al. Preimplantation testing for chromosomal disorders improves reproductive outcome of poor-prognosis patients. Reprod BioMed Online. 2005;11:219–25.CrossRefGoogle Scholar
  10. 10.
    Rubio C, Buendia P, Rodrigo L, Mercader A, Mateu E, Peinado V, et al. Prognostic factors for preimplantation genetic screening in repeated pregnancy loss. Reprod BioMed Online. 2009;18:687–93.CrossRefGoogle Scholar
  11. 11.
    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;98:675–80.CrossRefGoogle Scholar
  12. 12.
    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;95:953–8.CrossRefGoogle Scholar
  13. 13.
    Schoolcraft WB, Treff NR, Stevens JM, Ferry K, Katz-Jaffe M, Scott RT Jr. 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
  14. 14.
    Forman EJ, Tao X, Ferry KM, Taylor D, Treff NR, Scott RT Jr. Single embryo transfer with comprehensive chromosome screening results in improved ongoing pregnancy rates and decreased miscarriage rates. Hum Reprod. 2012;27:1217–22.CrossRefGoogle Scholar
  15. 15.
    Wells D. Next-generation sequencing: the dawn of a new era for preimplantation genetic diagnostics. Fertil Steril. 2014;101:1250–1.CrossRefGoogle Scholar
  16. 16.
    Cobo A, Vajta G, Remohi J. Vitrification of human mature oocytes in clinical practice. Reprod BioMed Online. 2009;19(Suppl 4):4385.Google Scholar
  17. 17.
    Van Landuyt L, Verpoest W, Verheyen G, De Vos A, Van de Velde H, Liebaers I, et al. Closed blastocyst vitrification of biopsied embryos: evaluation of 100 consecutive warming cycles. Hum Reprod. 2011;26:316–22.CrossRefGoogle Scholar
  18. 18.
    Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. High ongoing pregnancy rates after deferred transfer through bipronuclear oocyte cryopreservation and post-thaw extended culture. Fertil Steril. 2009;92:1594–9.CrossRefGoogle Scholar
  19. 19.
    Yang Z, Liu J, Collins GS, Salem SA, Liu X, Lyle SS, et al. Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet. 2012;5:24.CrossRefGoogle Scholar
  20. 20.
    Scott RT Jr, 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;100:697–703.CrossRefGoogle Scholar
  21. 21.
    Forman EJ, Upham KM, Cheng M, Zhao T, Hong KH, Treff NR, et al. Comprehensive chromosome screening alters traditional morphology-based embryo selection: a prospective study of 100 consecutive cycles of planned fresh euploid blastocyst transfer. Fertil Steril. 2013;100:718–24.CrossRefGoogle Scholar
  22. 22.
    Capalbo A, Ubaldi FM, Cimadomo D, Maggiulli R, Patassini C, Dusi L, et al. Consistent and reproducible outcomes of blastocyst biopsy and aneuploidy screening across different biopsy practitioners: a multicentre study involving 2586 embryo biopsies. Hum Reprod. 2016;31:199–208.CrossRefGoogle Scholar
  23. 23.
    Ahlstrom A, Westin C, Reismer E, Wikland M, Hardarson T. Trophectoderm morphology: an important parameter for predicting live birth after single blastocyst transfer. Hum Reprod. 2011;26:3289–96.CrossRefGoogle Scholar
  24. 24.
    Zhang S, Luo K, Cheng D, Tan Y, Lu C, He H, et al. Number of biopsied trophectoderm cells is likely to affect the implantation potential of blastocysts with poor trophectoderm quality. Fertil Steril. 2016;105:1222–7 e4.CrossRefGoogle Scholar
  25. 25.
    Sepulveda S, Garcia J, Arriaga E, Diaz J, Noriega-Portella L, Noriega-Hoces L. In vitro development and pregnancy outcomes for human embryos cultured in either a single medium or in a sequential media system. Fertil Steril. 2009;91:1765–70.CrossRefGoogle Scholar
  26. 26.
    Racowsky C, Vernon M, Mayer J, Ball GD, Behr B, Pomeroy KO, et al. Standardization of grading embryo morphology. Fertil Steril. 2010;94:1152–3.CrossRefGoogle Scholar
  27. 27.
    Rabinowitz M, Ryan A, Gemelos G, Hill M, Baner J, Cinnioglu C, et al. Origins and rates of aneuploidy in human blastomeres. Fertil Steril. 2012;97:395–401.CrossRefGoogle Scholar
  28. 28.
    Johnson DS, Gemelos G, Baner J, Ryan A, Cinnioglu C, Banjevic M, et al. Preclinical validation of a microarray method for full molecular karyotyping of blastomeres in a 24-h protocol. Hum Reprod. 2010;25:1066–75.CrossRefGoogle Scholar
  29. 29.
    Munne S, Alikani M, Barritt J, Hesla J, Kaplan B, Alper M, et al. Egg donor aneuploidy rates significantly differ between fertility centers. Fertil Steril. 2014;102:0–354.Google Scholar
  30. 30.
    Treff NR, Su J, Kasabwala N, Tao X, Miller KA, Scott RT Jr. Robust embryo identification using first polar body single nucleotide polymorphism microarray-based DNA fingerprinting. Fertil Steril. 2010;93:2453–5.CrossRefGoogle Scholar
  31. 31.
    Bisignano A, Wells D, Harton G, Munne S. PGD and aneuploidy screening for 24 chromosomes: advantages and disadvantages of competing platforms. Reprod BioMed Online. 2011;23:677–85.CrossRefGoogle Scholar
  32. 32.
    Cohen J, Wells D, Munne S. Removal of 2 cells from cleavage stage embryos is likely to reduce the efficacy of chromosomal tests that are used to enhance implantation rates. Fertil Steril. 2007;87:496–503.CrossRefGoogle Scholar
  33. 33.
    De Vos A, Staessen C, De Rycke M, Verpoest W, Haentjens P, Devroey P, et al. Impact of cleavage-stage embryo biopsy in view of PGD on human blastocyst implantation: a prospective cohort of single embryo transfers. Hum Reprod. 2009;24:2988–96.CrossRefGoogle Scholar
  34. 34.
    Scott KL, Hong KH, Scott RT Jr. Selecting the optimal time to perform biopsy for preimplantation genetic testing. Fertil Steril. 2013;100:608–14.CrossRefGoogle Scholar
  35. 35.
    Thompson SM, Onwubalili N, Brown K, Jindal SK, McGovern PG. Blastocyst expansion score and trophectoderm morphology strongly predict successful clinical pregnancy and live birth following elective single embryo blastocyst transfer (eSET): a national study. J Assist Reprod Genet. 2013;30:1577–81.CrossRefGoogle Scholar
  36. 36.
    Van den Abbeel E, Balaban B, Ziebe S, Lundin K, Cuesta MJ, Klein BM, et al. Association between blastocyst morphology and outcome of single-blastocyst transfer. Reprod BioMed Online. 2013;27:353–61.CrossRefGoogle Scholar
  37. 37.
    Ahlstrom A, Westin C, Wikland M, Hardarson T. Prediction of live birth in frozen-thawed single blastocyst transfer cycles by pre-freeze and post-thaw morphology. Hum Reprod. 2013;28:1199–209.CrossRefGoogle Scholar
  38. 38.
    Hill MJ, Richter KS, Heitmann RJ, Graham JR, Tucker MJ, DeCherney AH, et al. Trophectoderm grade predicts outcomes of single-blastocyst transfers. Fertil Steril. 2013;99:1283–9 e1.CrossRefGoogle Scholar
  39. 39.
    Honnma H, Baba T, Sasaki M, Hashiba Y, Ohno H, Fukunaga T, et al. Trophectoderm morphology significantly affects the rates of ongoing pregnancy and miscarriage in frozen-thawed single-blastocyst transfer cycle in vitro fertilization. Fertil Steril. 2012;98:361–7.CrossRefGoogle Scholar
  40. 40.
    Norwitz ER, Schust DJ, Fisher SJ. Implantation and the survival of early pregnancy. N Engl J Med. 2001;345:1400–8.CrossRefGoogle Scholar
  41. 41.
    Licht P, Russu V, Lehmeyer S, Wildt L. Molecular aspects of direct LH/hCG effects on human endometrium--lessons from intrauterine microdialysis in the human female in vivo. Reprod Biol. 2001;1:10–9.Google Scholar
  42. 42.
    Tsampalas M, Gridelet V, Berndt S, Foidart JM, Geenen V, Perrier d’Hauterive S. Human chorionic gonadotropin: a hormone with immunological and angiogenic properties. J Reprod Immunol. 2010;85:93–8.CrossRefGoogle Scholar
  43. 43.
    Parks JC, McCallie BR, Janesch AM, Schoolcraft WB, Katz-Jaffe MG. Blastocyst gene expression correlates with implantation potential. Fertil Steril. 2011;95:1367–72.CrossRefGoogle Scholar
  44. 44.
    Jones GM, Cram DS, Song B, Kokkali G, Pantos K, Trounson AO. Novel strategy with potential to identify developmentally competent IVF blastocysts. Hum Reprod. 2008;23:1748–59.CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.PRANOR LaboratorioGrupo de Reproducción AsistidaLimaPeru
  2. 2.ADN DiagnosticoLimaPeru
  3. 3.Clínica MonterricoLimaPeru
  4. 4.CooperGenomicsLivingstonUSA

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