Skip to main content
SpringerLink
Log in

Novel embryo selection techniques to increase embryo implantation in IVF attempts

  • Review
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

The final success of an IVF attempt depends on several steps and decisions taken during the ovarian stimulation, the oocyte retrieval, the embryo culture and the embryo transfer. The final selection of the embryos most likely to implant is the final step in this process and the responsibility of the lab. Apart from strict morphologic criteria that historically have been used in embryo selection, additional information on genetic, metabolomic and morphokinetic characteristics of the embryo is recently combined to morphology to select the embryo most likely to produce a pregnancy. In this manuscript, we review the most recent information on the current methods used for embryo selection presenting the predictive capability of each one.

Methods

A literature search was performed on Pubmed, Medline and Cochrane Database of Systematic Reviews for published studies using appropriate key words and phrases with no limits placed on time.

Results

It seems that the combination of morphologic criteria in conjunction to embryo kinetics as documented by time-lapse technology provides the most reliable information on embryo quality. Blastocyst biopsy with subsequent comprehensive chromosome analysis allows the selection of the euploid embryos with the higher implantation potential.

Conclusion

Embryo time-lapse imaging and blastocyst biopsy combined to comprehensive chromosome analysis are the most promising technologies to increase pregnancy rates and reduce the possibility of multiple pregnancies. However, further studies will demonstrate the capability of routinely using these technologies to significantly improve IVF outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Schoolcraft WB, Surrey ES, Gardner DK (2001) Embryo transfer: techniques and variables affecting success. Fertil Steril 76(5):863–870

    Article  CAS  PubMed  Google Scholar 

  2. Revel A (2012) Defective endometrial receptivity. Fertil Steril 97(5):1028–1032

    Article  PubMed  Google Scholar 

  3. Montag M, Toth B, Strowitzki T (2013) New approaches to embryo selection. Reprod Biomed Online 27(5):539–546

    Article  PubMed  Google Scholar 

  4. Dal Canto M et al (2012) Cleavage kinetics analysis of human embryos predicts development to blastocyst and implantation. Reprod Biomed Online 25(5):474–480

    Article  PubMed  Google Scholar 

  5. Seli E et al (2007) 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 88(5):1350–1357

    Article  PubMed  Google Scholar 

  6. Scott RT Jr et al (2013) 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 100(3):697–703

    Article  PubMed  Google Scholar 

  7. Alpha Scientists in Reproductive, M, E.S.I.G.o. Embryology (2011) The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod 26(6):1270–1283

    Article  Google Scholar 

  8. Hamatani T et al (2006) Global gene expression profiling of preimplantation embryos. Hum Cell 19(3):98–117

    Article  PubMed  Google Scholar 

  9. Blake DA et al (2007) Cleavage stage versus blastocyst stage embryo transfer in assisted conception. Cochrane Database Syst Rev 17(4):CD002118

    Google Scholar 

  10. Glujovsky D et al (2012) Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev 7:CD002118

    Google Scholar 

  11. Glujovsky D et al (2016) Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev 6:CD002118

    Google Scholar 

  12. Shapiro BS et al (2011) Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfer in normal responders. Fertil Steril 96(2):344–348

    Article  PubMed  Google Scholar 

  13. Kallen B et al (2010) Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome? Fertil Steril 94(5):1680–1683

    Article  PubMed  Google Scholar 

  14. Maheshwari A et al (2013) Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of blastocyst-stage versus cleavage-stage embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril 100(6):1615–1621 (e1–10)

    Article  PubMed  Google Scholar 

  15. Batcheller A et al (2011) Are there subtle genome-wide epigenetic alterations in normal offspring conceived by assisted reproductive technologies? Fertil Steril 96(6):1306–1311

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lane M, Gardner DK (2003) Ammonium induces aberrant blastocyst differentiation, metabolism, pH regulation, gene expression and subsequently alters fetal development in the mouse. Biol Reprod 69(4):1109–1117

    Article  CAS  PubMed  Google Scholar 

  17. Young LE et al (2001) Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat Genet 27(2):153–154

    Article  CAS  PubMed  Google Scholar 

  18. Gizewska M et al (2014) The significance of molecular studies in the long-term follow-up of children with beckwith-wiedemann syndrome. Turk J Pediatr 56(2):177–182

    PubMed  Google Scholar 

  19. DeBaun MR, Niemitz EL, Feinberg AP (2003) Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am J Hum Genet 72(1):156–160

    Article  CAS  PubMed  Google Scholar 

  20. Lim D et al (2009) Clinical and molecular genetic features of Beckwith-Wiedemann syndrome associated with assisted reproductive technologies. Hum Reprod 24(3):741–747

    Article  PubMed  Google Scholar 

  21. Chang AS et al (2005) Association between Beckwith-Wiedemann syndrome and assisted reproductive technology: a case series of 19 patients. Fertil Steril 83(2):349–354

    Article  PubMed  PubMed Central  Google Scholar 

  22. Racowsky C et al (2000) The number of eight-cell embryos is a key determinant for selecting day 3 or day 5 transfer. Fertil Steril 73(3):558–564

    Article  CAS  PubMed  Google Scholar 

  23. Thomas MR et al (2010) Clinical predictors of human blastocyst formation and pregnancy after extended embryo culture and transfer. Fertil Steril 94(2):543–548

    Article  PubMed  Google Scholar 

  24. Meseguer M et al (2011) The use of morphokinetics as a predictor of embryo implantation. Hum Reprod 26(10):2658–2671

    Article  PubMed  Google Scholar 

  25. Wong CC et al (2010) Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage. Nat Biotechnol 28(10):1115–1121

    Article  CAS  PubMed  Google Scholar 

  26. Hashimoto S et al (2012) Selection of high-potential embryos by culture in poly(dimethylsiloxane) microwells and time-lapse imaging. Fertil Steril 97(2):332–337

    Article  PubMed  Google Scholar 

  27. Chavez SL et al (2012) Dynamic blastomere behaviour reflects human embryo ploidy by the four-cell stage. Nat Commun 3:1251

    Article  PubMed  PubMed Central  Google Scholar 

  28. Campbell A et al (2013) Retrospective analysis of outcomes after IVF using an aneuploidy risk model derived from time-lapse imaging without PGS. Reprod Biomed Online 27(2):140–146

    Article  PubMed  Google Scholar 

  29. Basile N et al (2014) Increasing the probability of selecting chromosomally normal embryos by time-lapse morphokinetics analysis. Fertil Steril 101(3):699–704

    Article  PubMed  Google Scholar 

  30. Ottolini C, Rienzi L, Capalbo A (2014) A cautionary note against embryo aneuploidy risk assessment using time-lapse imaging. Reprod Biomed Online 28(3):273–275

    Article  PubMed  Google Scholar 

  31. Armstrong S et al (2015) Time-lapse systems for embryo incubation and assessment in assisted reproduction. Cochrane Database Syst Rev 2:CD011320

    Google Scholar 

  32. Polanski LT et al (2014) Time-lapse embryo imaging for improving reproductive outcomes: systematic review and meta-analysis. Ultrasound Obstet Gynecol 44(4):394–401

    Article  CAS  PubMed  Google Scholar 

  33. Kaser DJ, Racowsky C (2014) Clinical outcomes following selection of human preimplantation embryos with time-lapse monitoring: a systematic review. Hum Reprod Update 20(5):617–631

    Article  PubMed  Google Scholar 

  34. Goodman LR et al (2016) Does the addition of time-lapse morphokinetics in the selection of embryos for transfer improve pregnancy rates? A randomized controlled trial. Fertil Steril 105(2):275–285 (e10)

    Article  PubMed  Google Scholar 

  35. Ciray HN et al (2012) Time-lapse evaluation of human embryo development in single versus sequential culture media–a sibling oocyte study. J Assist Reprod Genet 29(9):891–900

    Article  PubMed  PubMed Central  Google Scholar 

  36. Gardner DK et al (2011) Glucose consumption of single post-compaction human embryos is predictive of embryo sex and live birth outcome. Hum Reprod 26(8):1981–1986

    Article  CAS  PubMed  Google Scholar 

  37. Hardy K et al (1989) Non-invasive measurement of glucose and pyruvate uptake by individual human oocytes and preimplantation embryos. Hum Reprod 4(2):188–191

    CAS  PubMed  Google Scholar 

  38. Brison DR et al (2004) Identification of viable embryos in IVF by non-invasive measurement of amino acid turnover. Hum Reprod 19(10):2319–2324

    Article  CAS  PubMed  Google Scholar 

  39. Bellver J et al (2015) Day-3 embryo metabolomics in the spent culture media is altered in obese women undergoing in vitro fertilization. Fertil Steril 103(6):1407–1415 (e1)

    Article  CAS  PubMed  Google Scholar 

  40. Tejera A et al (2012) Time-dependent O2 consumption patterns determined optimal time ranges for selecting viable human embryos. Fertil Steril 98(4):849–857 (e1–3)

    Article  PubMed  Google Scholar 

  41. Tejera A et al (2016) Combination of metabolism measurement and a time-lapse system provides an embryo selection method based on oxygen uptake and chronology of cytokinesis timing. Fertil Steril 106(1):119–126 (e2)

    Article  PubMed  Google Scholar 

  42. Vergouw CG et al (2014) No evidence that embryo selection by near-infrared spectroscopy in addition to morphology is able to improve live birth rates: results from an individual patient data meta-analysis. Hum Reprod 29(3):455–461

    Article  CAS  PubMed  Google Scholar 

  43. Uyar A, Torrealday S, Seli E (2013) Cumulus and granulosa cell markers of oocyte and embryo quality. Fertil Steril 99(4):979–997

    Article  CAS  PubMed  Google Scholar 

  44. Feuerstein P et al (2007) Gene expression in human cumulus cells: one approach to oocyte competence. Hum Reprod 22(12):3069–3077

    Article  CAS  PubMed  Google Scholar 

  45. Gebhardt KM et al (2011) Human cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer. Fertil Steril 96(1):47–52 (e2)

    Article  CAS  PubMed  Google Scholar 

  46. Ekart J et al (2013) Ranking and selection of MII oocytes in human ICSI cycles using gene expression levels from associated cumulus cells. Hum Reprod 28(11):2930–2942

    Article  CAS  PubMed  Google Scholar 

  47. Iager AE et al (2013) Identification of a novel gene set in human cumulus cells predictive of an oocyte’s pregnancy potential. Fertil Steril 99(3):745–752 (e6)

    Article  CAS  PubMed  Google Scholar 

  48. Assou S et al (2008) A non-invasive test for assessing embryo potential by gene expression profiles of human cumulus cells: a proof of concept study. Mol Hum Reprod 14(12):711–719

    Article  CAS  PubMed  Google Scholar 

  49. Haouzi D et al (2012) Altered gene expression profile in cumulus cells of mature MII oocytes from patients with polycystic ovary syndrome. Hum Reprod 27(12):3523–3530

    Article  CAS  PubMed  Google Scholar 

  50. McReynolds S et al (2012) Impact of maternal aging on the molecular signature of human cumulus cells. Fertil Steril 98(6):1574–1580 (e5)

    Article  CAS  PubMed  Google Scholar 

  51. Borgbo T et al (2013) Comparison of gene expression profiles in granulosa and cumulus cells after ovulation induction with either human chorionic gonadotropin or a gonadotropin-releasing hormone agonist trigger. Fertil Steril 100(4):994–1001

    Article  CAS  PubMed  Google Scholar 

  52. Capalbo A et al (2014) Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts. Hum Reprod 29(6):1173–1181

    Article  PubMed  Google Scholar 

  53. Fragouli E et al (2014) Morphological and cytogenetic assessment of cleavage and blastocyst stage embryos. Mol Hum Reprod 20(2):117–126

    Article  CAS  PubMed  Google Scholar 

  54. Scott KL, Hong KH, Scott RT Jr (2013) Selecting the optimal time to perform biopsy for preimplantation genetic testing. Fertil Steril 100(3):608–614

    Article  PubMed  Google Scholar 

  55. Salvaggio CN et al (2014) Polar body based aneuploidy screening is poorly predictive of embryo ploidy and reproductive potential. J Assist Reprod Genet 31(9):1221–1226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Keltz MD et al (2013) 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. J Assist Reprod Genet 30(10):1333–1339

    Article  PubMed  PubMed Central  Google Scholar 

  57. Kirkegaard K, Hindkjaer JJ, Ingerslev HJ (2012) Human embryonic development after blastomere removal: a time-lapse analysis. Hum Reprod 27(1):97–105

    Article  PubMed  Google Scholar 

  58. Scott RT Jr et al (2013) Cleavage-stage biopsy significantly impairs human embryonic implantation potential while blastocyst biopsy does not: a randomized and paired clinical trial. Fertil Steril 100(3):624–630

    Article  PubMed  Google Scholar 

  59. Schoolcraft WB et al (2010) Clinical application of comprehensive chromosomal screening at the blastocyst stage. Fertil Steril 94(5):1700–1706

    Article  PubMed  Google Scholar 

  60. Scott RT Jr et al (2012) Comprehensive chromosome screening is highly predictive of the reproductive potential of human embryos: a prospective, blinded, nonselection study. Fertil Steril 97(4):870–875

    Article  PubMed  Google Scholar 

  61. Forman EJ et al (2013) In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril 100(1):100–107 (e1)

    Article  PubMed  Google Scholar 

  62. Twisk M et al (2008) No beneficial effect of preimplantation genetic screening in women of advanced maternal age with a high risk for embryonic aneuploidy. Hum Reprod 23(12):2813–2817

    Article  PubMed  Google Scholar 

  63. Mastenbroek S et al (2011) Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Hum Reprod Update 17(4):454–466

    Article  CAS  PubMed  Google Scholar 

  64. Staessen C et al (2008) Preimplantation genetic screening does not improve delivery rate in women under the age of 36 following single-embryo transfer. Hum Reprod 23(12):2818–2825

    Article  CAS  PubMed  Google Scholar 

  65. Lathi RB, Westphal LM, Milki AA (2008) Aneuploidy in the miscarriages of infertile women and the potential benefit of preimplanation genetic diagnosis. Fertil Steril 89(2):353–357

    Article  PubMed  Google Scholar 

  66. Jobanputra V et al (2002) Multiplex interphase FISH as a screen for common aneuploidies in spontaneous abortions. Hum Reprod 17(5):1166–1170

    Article  CAS  PubMed  Google Scholar 

  67. Mastenbroek S et al (2007) In vitro fertilization with preimplantation genetic screening. N Engl J Med 357(1):9–17

    Article  CAS  PubMed  Google Scholar 

  68. Handyside AH (2013) 24-chromosome copy number analysis: a comparison of available technologies. Fertil Steril 100(3):595–602

    Article  PubMed  Google Scholar 

  69. Fragouli E et al (2011) Cytogenetic analysis of human blastocysts with the use of FISH, CGH and aCGH: scientific data and technical evaluation. Hum Reprod 26(2):480–490

    Article  CAS  PubMed  Google Scholar 

  70. Harper JC, Harton G (2010) The use of arrays in preimplantation genetic diagnosis and screening. Fertil Steril 94(4):1173–1177

    Article  CAS  PubMed  Google Scholar 

  71. Tobler KJ et al (2014) Two different microarray technologies for preimplantation genetic diagnosis and screening, due to reciprocal translocation imbalances, demonstrate equivalent euploidy and clinical pregnancy rates. J Assist Reprod Genet 31(7):843–850

    Article  PubMed  PubMed Central  Google Scholar 

  72. Fiorentino F et al (2014) Development and validation of a next-generation sequencing-based protocol for 24-chromosome aneuploidy screening of embryos. Fertil Steril 101(5):1375–1382

    Article  CAS  PubMed  Google Scholar 

  73. Fiorentino F et al (2014) Application of next-generation sequencing technology for comprehensive aneuploidy screening of blastocysts in clinical preimplantation genetic screening cycles. Hum Reprod 29(12):2802–2813

    Article  PubMed  Google Scholar 

  74. Barbash-Hazan S et al (2009) Preimplantation aneuploid embryos undergo self-correction in correlation with their developmental potential. Fertil Steril 92(3):890–896

    Article  PubMed  Google Scholar 

  75. Gueye NA et al (2014) Uniparental disomy in the human blastocyst is exceedingly rare. Fertil Steril 101(1):232–236

    Article  PubMed  Google Scholar 

  76. Northrop LE et al (2010) SNP microarray-based 24 chromosome aneuploidy screening demonstrates that cleavage-stage FISH poorly predicts aneuploidy in embryos that develop to morphologically normal blastocysts. Mol Hum Reprod 16(8):590–600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Gleicher N, Kushnir VA, Barad DH (2014) Preimplantation genetic screening (PGS) still in search of a clinical application: a systematic review. Reprod Biol Endocrinol 12:22

    Article  PubMed  PubMed Central  Google Scholar 

  78. Mastenbroek S (2013) One swallow does not make a summer. Fertil Steril 99(5):1205–1206

    Article  PubMed  Google Scholar 

  79. Lee E et al (2015) The clinical effectiveness of preimplantation genetic diagnosis for aneuploidy in all 24 chromosomes (PGD-A): systematic review. Hum Reprod 30(2):473–483

    Article  PubMed  Google Scholar 

  80. Chen M et al (2015) Can comprehensive chromosome screening technology improve IVF/ICSI outcomes? A meta-analysis. PLoS One 10(10):e0140779

    Article  PubMed  PubMed Central  Google Scholar 

  81. Dahdouh EM, Balayla J, Garcia-Velasco JA (2015) Impact of blastocyst biopsy and comprehensive chromosome screening technology on preimplantation genetic screening: a systematic review of randomized controlled trials. Reprod Biomed Online 30(3):281–289

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. 2nd Department of Obstetrics and Gynecology, Aretaieion Hospital, University of Athens, Vas. Sofias Str. 76, 11528, Athens, Greece

    George Α. Sigalos & Nikos F. Vlahos

  2. Reproductive Medicine Unit, “Lito” Maternity Hospital, Mouson Str. 7-13, 11524, Athens, Greece

    George Α. Sigalos & Olga Triantafyllidou

Authors
  1. George Α. Sigalos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olga Triantafyllidou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nikos F. Vlahos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George Α. Sigalos.

Ethics declarations

Conflict of interest

All authors declare they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sigalos, G.Α., Triantafyllidou, O. & Vlahos, N.F. Novel embryo selection techniques to increase embryo implantation in IVF attempts. Arch Gynecol Obstet 294, 1117–1124 (2016). https://doi.org/10.1007/s00404-016-4196-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-016-4196-5

Keywords

Search

Navigation