Archives of Gynecology and Obstetrics

, Volume 286, Issue 3, pp 755–761 | Cite as

Comprehensive genetic assessment of the human embryo: can empiric application of microarray comparative genomic hybridization reduce multiple gestation rate by single fresh blastocyst transfer?

  • Eric Scott Sills
  • Zhihong Yang
  • David J. Walsh
  • Shala A. Salem
Reproductive Medicine

Abstract

Purpose

The unacceptable multiple gestation rate currently associated with in vitro fertilization (IVF) would be substantially alleviated if the routine practice of transferring more than one embryo were reconsidered. While transferring a single embryo is an effective method to reduce the clinical problem of multiple gestation, rigid adherence to this approach has been criticized for negatively impacting clinical pregnancy success in IVF. In general, single embryo transfer is viewed cautiously by IVF patients although greater acceptance would result from a more effective embryo selection method.

Methods

Selection of one embryo for fresh transfer on the basis of chromosomal normalcy should achieve the dual objective of maintaining satisfactory clinical pregnancy rates and minimizing the multiple gestation problem, because embryo aneuploidy is a major contributing factor in implantation failure and miscarriage in IVF. The initial techniques for preimplantation genetic screening unfortunately lacked sufficient sensitivity and did not yield the expected results in IVF. However, newer molecular genetic methods could be incorporated with standard IVF to bring the goal of single embryo transfer within reach.

Results

Aiming to make multiple embryo transfers obsolete and unnecessary, and recognizing that array comparative genomic hybridization (aCGH) will typically require an additional 12 h of laboratory time to complete, we propose adopting aCGH for mainstream use in clinical IVF practice.

Conclusion

As aCGH technology continues to develop and becomes increasingly available at lower cost, it may soon be considered unusual for IVF laboratories to select a single embryo for fresh transfer without regard to its chromosomal competency. In this report, we provide a rationale supporting aCGH as the preferred methodology to provide a comprehensive genetic assessment of the single embryo before fresh transfer in IVF. The logistics and cost of integrating aCGH with IVF to enable fresh embryo transfer are also discussed.

Keywords

Assisted fertility IVF Single embryo transfer Comprehensive chromosomal Screening Array CGH 

References

  1. 1.
    Le Lannou D, Griveau JF, Laurent MC, Gueho A, Veron E, Morcel K (2006) Contribution of embryo cryopreservation to elective single embryo transfer in IVF-ICSI. Reprod Biomed Online 13:368–375PubMedCrossRefGoogle Scholar
  2. 2.
    Lukassen HG, Braat DD, Wetzels AM et al (2005) Two cycles with single embryo transfer versus one cycle with double embryo transfer: a randomized controlled trial. Hum Reprod 20:702–708PubMedCrossRefGoogle Scholar
  3. 3.
    Leese B, Denton J (2010) Attitudes towards single embryo transfer, twin and higher order pregnancies in patients undergoing infertility treatment: a review. Hum Fertil (Camb) 13:28–34CrossRefGoogle Scholar
  4. 4.
    Alfarawati S, Fragouli E, Colls P, Stevens J, Gutiérrez-Mateo C, Schoolcraft WB, Katz-Jaffe MG, Wells D (2011) The relationship between blastocyst morphology, chromosomal abnormality, and embryo gender. Fertil Steril 95:520–524PubMedCrossRefGoogle Scholar
  5. 5.
    Kern SI (2009) ‘Octomom’ case shines light on standards of care. Med Econ 86:38PubMedGoogle Scholar
  6. 6.
    Walker MC, Murphy KE, Pan S, Yang Q, Wen SW (2004) Adverse maternal outcomes in multifetal pregnancies. BJOG 111:1294–1296PubMedCrossRefGoogle Scholar
  7. 7.
    Bergh T, Ericson A, Hillensjo T, Nygren KG, Wennerholm UB (1999) Deliveries and children born after in vitro fertilisation in Sweden 1982–1995: a retrospective cohort study. Lancet 354:1579–1585PubMedCrossRefGoogle Scholar
  8. 8.
    Stromberg B, Dahlquist G, Ericson A, Finnstrom O, Koster M, Stjernqvist K (2002) Neurological sequelae in children born after in vitro fertilisation: a population-based study. Lancet 359:461–465PubMedCrossRefGoogle Scholar
  9. 9.
    Pinborg A, Loft A, Schmidt L, Andersen AN (2003) Morbidity in a Danish national cohort of 472 IVF/ICSI twins, 1132 non-IVF/ICSI twins and 634 IVF/ICSI singletons: health-related and social implications for the children and their families. Hum Reprod 18:1234–1243PubMedCrossRefGoogle Scholar
  10. 10.
    Fauser BC (2008) Screening of embryos for numerical chromosome abnormalities during in vitro fertilisation is not useful for application in daily practice. Ned Tijdschr Geneeskd 152:734–736PubMedGoogle Scholar
  11. 11.
    Twisk M, Mastenbroek S, Hoek A 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 23:2813–2817PubMedCrossRefGoogle Scholar
  12. 12.
    Gerris J (2007) The near elimination of triplets in IVF. Reprod Biomed Online 15(Suppl 3):40–44PubMedCrossRefGoogle Scholar
  13. 13.
    Cummins JM, Breen TM, Harrison KL, Shaw JM, Wilson LM, Hennessey JF (1986) A formula for scoring human embryo growth rates in in vitro fertilization: its value in predicting pregnancy and in comparison with visual estimates of embryo quality. J In Vitro Fert Embryo Transf 3:284–295PubMedCrossRefGoogle Scholar
  14. 14.
    Puissant F, Van Rysselberge M, Barlow P, Deweze J, Leroy F (1987) Embryo scoring as a prognostic tool in IVF treatment. Hum Reprod 2:705–708PubMedGoogle Scholar
  15. 15.
    Van Royen E, Mangelschots K, De Neubourg D et al (1999) Characterization of a top quality embryo, a step towards single-embryo transfer. Hum Reprod 14:2345–2349PubMedCrossRefGoogle Scholar
  16. 16.
    Centers for Disease Control and Prevention (2006) Assisted reproductive technology success rates: preliminary data national summary and fertility clinic reports (2008)Google Scholar
  17. 17.
    Sunde A (2007) Significant reduction of twins with single embryo transfer in IVF. Reprod Biomed Online 15(Suppl 3):28–34PubMedCrossRefGoogle Scholar
  18. 18.
    Maheshwari A, Griffiths S, Bhattacharya S (2011) Global variations in the uptake of single embryo transfer. Hum Reprod Update 17:107–120PubMedCrossRefGoogle Scholar
  19. 19.
    Shurpyak SA, Walsh AP, Walsh DJ, Sills ES (2009) A need for definition: a matter of life and death for human embryos. Ir Med J 102:235PubMedGoogle Scholar
  20. 20.
    Delhanty JD, Griffin DK, Handyside AH et al (1993) Detection of aneuploidy and chromosomal mosaicism in human embryos during preimplantation sex determination by fluorescent in situ hybridisation, (FISH). Hum Mol Genet 2:1183–1185PubMedCrossRefGoogle Scholar
  21. 21.
    Kamiguchi Y, Rosenbusch B, Sterzik K, Mikamo K (1993) Chromosomal analysis of unfertilized human oocytes prepared by a gradual fixation-air drying method. Hum Genet 90:533–541PubMedCrossRefGoogle Scholar
  22. 22.
    Munné S, Lee A, Rosenwaks Z, Grifo J, Cohen J (1993) Diagnosis of major chromosome aneuploidies in human preimplantation embryos. Hum Reprod 8:2185–2191PubMedGoogle Scholar
  23. 23.
    Hassold TJ, Jacobs PA (1994) Annu Rev Genet 18:69–97CrossRefGoogle Scholar
  24. 24.
    Menasha J, Levy B, Hirschhorn K, Kardon NB (2005) Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from a 12-year study. Genet Med 7:251–263PubMedCrossRefGoogle Scholar
  25. 25.
    Gutiérrez-Mateo C, Benet J, Wells D et al (2004) Aneuploidy study of human oocytes first polar body comparative genomic hybridization and metaphase II fluorescence in situ hybridization analysis. Hum Reprod 19:2859–2868PubMedCrossRefGoogle Scholar
  26. 26.
    Fragouli E, Wells D, Thornhill A et al (2006) Comparative genomic hybridization analysis of human oocytes and polar bodies. Hum Reprod 21:2319–2328PubMedCrossRefGoogle Scholar
  27. 27.
    Hassold T, Hall H, Hunt P (2007) The origin of human aneuploidy: where we have been, where we are going. Hum Mol Genet 16:R203–R208PubMedCrossRefGoogle Scholar
  28. 28.
    Sher G, Keskintepe L, Keskintepe M et al (2007) Oocyte karyotyping by comparative genomic hybridization provides a highly reliable method for selecting ‘competent’ embryos, markedly improving in vitro fertilization outcome: a multiphase study. Fertil Steril 2007(87):1033–1040CrossRefGoogle Scholar
  29. 29.
    Højgaard A, Ottosen LD, Kesmodel U, Ingerslev HJ (2007) Patient attitudes towards twin pregnancies and single embryo transfer—a questionnaire study. Hum Reprod 22:2673–2678PubMedCrossRefGoogle Scholar
  30. 30.
    Yang Z, Liu J, Collins GS et al (2012) 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 Cytogen 5:24CrossRefGoogle Scholar
  31. 31.
    Kirkegaard K, Hindkjaer JJ, Ingerslev HJ (2012) Human embryonic development after blastomere removal: a time-lapse analysis. Hum Reprod 27:97–105PubMedCrossRefGoogle Scholar
  32. 32.
    Brodie D, Beyer CE, Osborne E, Kralevski V, Rasi S, Osianlis T (2012) Preimplantation genetic diagnosis for chromosome rearrangements—one blastomere biopsy versus two blastomere biopsy. J Assist Reprod Genet 12 PMID:22581430Google Scholar
  33. 33.
    de Die-Smulders CE, Land JA, Dreesen JC, Coonen E, Evers JL, Geraedts JP (2004) Results from 10 years of preimplantation-genetic diagnostics in The Netherlands. Ned Tijdschr Geneeskd 148:2491–2496PubMedGoogle Scholar
  34. 34.
    Gianaroli L, Magli MC, Ferraretti AP, Fiorentino A, Garrisi J, Munné S (1997) Preimplantation genetic diagnosis increases the implantation rate in human in vitro fertilization by avoiding the transfer of chromosomally abnormal embryos. Fertil Steril 68:1128–1131PubMedCrossRefGoogle Scholar
  35. 35.
    Griffin DK, Wilton LJ, Handyside AH, Winston RM, Delhanty JD (1992) Dual fluorescent in situ hybridisation for simultaneous detection of X and Y chromosome-specific probes for the sexing of human preimplantation embryonic nuclei. Hum Genet 89:18–22PubMedCrossRefGoogle Scholar
  36. 36.
    Gianaroli L, Magli MC, Ferraretti AP, Munné S (1999) 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 72:837–844PubMedCrossRefGoogle Scholar
  37. 37.
    Munné S, Chen S, Fischer J et al (2005) Preimplantation genetic diagnosis reduces pregnancy loss in women aged 35 years and older with a history of recurrent miscarriages. Fertil Steril 84:331–335PubMedCrossRefGoogle Scholar
  38. 38.
    McArthur SJ, Leigh D, Marshall JT, de Boer KA, Jansen RP (2005) Pregnancies and live births after trophectoderm biopsy and preimplantation genetic testing of human blastocysts. Fertil Steril 84:1628–1636PubMedCrossRefGoogle Scholar
  39. 39.
    Yang Z, Salem S, Salem-Lyle S, Bayrak A, Salem RD (2011) Trophectoderm cells derived from blastocyst biopsy are suitable for array CGH analysis of 24 chromosomes. Fertil Steril 95(Suppl 1):S23Google Scholar
  40. 40.
    Katz-Jaffe MG, McReynolds S, Gardner DK, Schoolcraft WB (2009) The role of proteomics in defining the human embryonic secretome. Mol Hum Reprod 15:271–277PubMedCrossRefGoogle Scholar
  41. 41.
    Nel-Themaat L, Nagy ZP (2011) A review of the promises and pitfalls of oocyte and embryo metabolomics. Placenta 32(Suppl 3):S257–S263PubMedCrossRefGoogle Scholar
  42. 42.
    Assou S, Haouzi D, De Vos J, Hamamah S (2010) Human cumulus cells as biomarkers for embryo and pregnancy outcomes. Mol Hum Reprod 16:531–538PubMedCrossRefGoogle Scholar
  43. 43.
    Assou S, Haouzi D, Mahmoud K, Aouacheria A, Guillemin Y, Pantesco V, Rème T, Dechaud H, De Vos J, Hamamah S (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 14:711–719PubMedCrossRefGoogle Scholar
  44. 44.
    Wang SX (2011) The past, present, and future of embryo selection in in vitro fertilization: frontiers in reproduction conference. Yale J Biol Med 84:487–490PubMedGoogle Scholar
  45. 45.
    Hu DG, Webb G, Hussey N (2004) Aneuploidy detection in single cells using DNA array-based comparative genomic hybridization. Mol Hum Reprod 10:283–289PubMedCrossRefGoogle Scholar
  46. 46.
    Wells D, Bermudez MG, Steuerwald N et al (2004) Microarrays for analysis and diagnosis of human embryos. In: Papp Z, Rodeck C (eds) Recent advances in prenatal genetic diagnosis. Medimond Press, Englewood, pp 9–17Google Scholar
  47. 47.
    Le Caignec C, Spits C, Sermon K et al (2006) Single-cell chromosomal imbalances detection by array CGH. Nucleic Acids Res 34:e68PubMedCrossRefGoogle Scholar
  48. 48.
    Treff NR, Scott RT Jr (2012) Methods for comprehensive chromosomal screening of oocytes and embryos: capabilities, limitations, and evidence of validity. J Assist Reprod Genet [Epub ahead of print]Google Scholar
  49. 49.
    Wells D, Alfarawati S, Fragouli E (2008) Use of comprehensive chromosomal screening for embryo assessment: microarrays and CGH. Mol Hum Reprod 14:703–710PubMedCrossRefGoogle Scholar
  50. 50.
    Ly KD, Agarwal A, Nagy ZP (2011) Preimplantation genetic screening: does it help or hinder IVF treatment and what is the role of the embryo? J Assist Reprod Genet 28:833–849PubMedCrossRefGoogle Scholar
  51. 51.
    Scriven PN, Ogilvie CM, Khalaf Y (2012) Embryo selection in IVF: is polar body array comparative genomic hybridization accurate enough? Hum Reprod 27:951–953PubMedCrossRefGoogle Scholar
  52. 52.
    Fishel S, Gordon A, Lynch C et al (2010) Live birth after polar body array comparative genomic hybridization prediction of embryo ploidy—the future of IVF? Fertil Steril 93:1006e7–1006e10CrossRefGoogle Scholar
  53. 53.
    Geraedts J, Montag M, Magli MC et al (2011) Polar body array CGH for prediction of the status of the corresponding oocyte. Part I: clinical results. Hum Reprod 26:3173–3180PubMedCrossRefGoogle Scholar
  54. 54.
    Bisignano A, Wells D, Harton G, Munné S (2011) PGD and aneuploidy screening for 24 chromosomes: advantages and disadvantages of competing platforms. Reprod Biomed Online 23:677–685PubMedCrossRefGoogle Scholar
  55. 55.
    Treff NR, Tao X, Schillings WJ, Bergh PA, Scott RT Jr, Levy B (2011) Use of single nucleotide polymorphism microarrays to distinguish between balanced and normal chromosomes in embryos from a translocation carrier. Fertil Steril 96:e58–e65PubMedCrossRefGoogle Scholar
  56. 56.
    Barbash-Hazan S, Frumkin T, Malcov M et al (2009) Preimplantation aneuploid embryos undergo self-correction in correlation with their developmental potential. Fertil Steril 92:890–896PubMedCrossRefGoogle Scholar
  57. 57.
    Treff NR, Su J, Tao X, Miller KA, Levy B, Scott RT Jr (2009) A novel single-cell DNA fingerprinting method successfully distinguishes sibling human embryos. Fertil Steril 94:477–484PubMedCrossRefGoogle Scholar
  58. 58.
    Schoolcraft WB, Katz-Jaffe MG, Stevens J, Rawlins M, Munne S (2009) Preimplantation aneuploidy testing for infertile patients of advanced maternal age: a randomized prospective trial. Fertil Steril 92:157–162PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Eric Scott Sills
    • 1
  • Zhihong Yang
    • 1
  • David J. Walsh
    • 2
  • Shala A. Salem
    • 1
  1. 1.Reproductive Research DivisionPacific Reproductive CenterIrvineUSA
  2. 2.Division of Reproductive Endocrinology, Department of Obstetrics and Gynaecology, The Sims Institute/Sims IVF, School of MedicineRoyal College of Surgeons in IrelandDublinIreland

Personalised recommendations