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The clinical need for a method of identification of embryos destined to become a blastocyst in assisted reproductive technology cycles

  • ASSISTED REPRODUCTION TECHNOLOGIES
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To provide a rationale for continuation of efforts to improve the outcome of Assisted Reproductive Technology outcomes, thereby increasing the likelihood of the live birth of healthy neonates.

Methods

Description of rationale and a framework leading to improvement in Assisted Reproductive Technology outcomes.

Results

The opportunity for improvement in the success rate for Assisted Reproductive Technology outcome is predicated on selection of the highest quality embryo(s) for transfer. However, such approaches must be balanced by a limit to the number of embryos transferred so as to reduce the risk for multiple births and particularly higher order multiple gestations. Blastocyst transfer offers one such successful approach, but is confounded by suggestions of an increased risk of both pregnancy complications and epigenetic disorders.

Conclusion

There is a need for development of approaches which, individually or in combination, may assist in the early detection of embryos destined to develop into blastocysts.

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References

  1. Bergh T, Ericson A, Hillensjo T, Nygren KG, Wennerholm UB. Deliveries and children born after in-vitro fertilization in Sweden 1982–95: a retrospective cohort study. Lancet. 1999;354(9190):1579–85. doi:10.1016/S0140-6738(99)04345-7.

    Article  PubMed  CAS  Google Scholar 

  2. Blake DA, Farquhar CM, Johnson N, Proctor M. Clevage stage versus blastocyst embryo stage embryo transfer in assisted conception. Cochrane Database System Reviews 2007;CD002118, doi:10.1002/14651858.CD002118.pub3

  3. Blennborn M, Nilsson S, Hillervik C, Hellberg D. The couple’s decision-making in IVF: one or two embryos at a transfer? Hum Reprod. 2005;20:292–7. doi:10.1093/humrep/deh785.

    Article  Google Scholar 

  4. Botting BJ, Davies IM, Macfarlane AJ. Recent trends in the incidence of multiple births and associated mortality. Arch Dis Child. 1987;62:941–50. PMICD: PMC1778571.

    Article  PubMed  CAS  Google Scholar 

  5. Callahan TL, Hall JE, Ettner SL, Christiansen CL, Greene MF, Crowley Jr WF. The economic impact of multiple-gestation pregnancies and the contribution of assisted-reproduction techniques to the incidence. N Engl J Med. 1994;331(4):244–9.

    Article  PubMed  CAS  Google Scholar 

  6. Ceelen M, van Weissenbruch MM, Vermeiden JP, van Leeuwen FE, Delemarre-van de Waal HA. Cardiometabolic differences in children born after in vitro fertilization: follow-up study. J Clin Endocrinol Metab. 2008;93(5):1682–8. doi:10.1210/jc.2007-2432.

    Article  PubMed  CAS  Google Scholar 

  7. Center for Disease Control 2008 Assisted Reproductive Technology Report, “http://www.cdc.gov/art/ART2008/”

  8. Collins MS, Bleyl JA. Seventy-one quadruplet pregnancies: management and outcome. Am J Obstet Gynecol. 1990;162(6):1384–9.

    PubMed  CAS  Google Scholar 

  9. Crump C, Sundquist K, Sundquist J. Gestational age at birth and mortality in young adulthood. JAMA. 2011;306(11):1233–40. doi:10.1001/jama.2011.1331.

    Article  PubMed  CAS  Google Scholar 

  10. DeMuylder X, Moutquin JM, Desfranges MF, Leduc B, Lazaro-Lopez F. Obstetrical profile of twin pregnancies: a retrospective review of 11 years (1969–1979) at Hospital Notre-Dame, Montreal, Canada. Acta Genetics Medicine Gemellol (Roma). 1982;31(3–4):149–55.

    CAS  Google Scholar 

  11. Dessolle L, Freour T, Barrier P, Darai E, Ravel C, Jean M, et al. A cycle-based model to predict blastocyst transfer cancellation. Hum Reprod. 2010;25(3):598–604. doi:10.1093/humrep/dep439.

    Article  PubMed  Google Scholar 

  12. Devine PC, Malone FD, Athanassiou A, Harvey-Wilkes K, D’Alton ME. Maternal and neonatal outcome of 100 consecutive triplet pregnancies. Am J Perinatol. 2001;18(4):225–35. doi:10.1055/s-2001-15505.

    Article  PubMed  CAS  Google Scholar 

  13. Downey J, Yingling S, McKinney M, Husami N, Jewelewicz R, Maidman J. Mood disorders, psychiatric symptoms, and distress in women presenting for infertility evaluation. Fertil Steril. 1989;52(3):425–32.

    PubMed  CAS  Google Scholar 

  14. Elster AD, Bleyl JL, Craven TE. Birth weight standards for triplets under modern obstetric care in the United States, 1984–1989. Obstet Gynecol. 1991;77(3):387–93.

    PubMed  CAS  Google Scholar 

  15. Gardner DK, Vella P, Lane M, Wagley L, Schlenker T, Schoolcraft WB. Culture and transfer of human blastocysts increases implantation rates and reduces the need for multiple embryo transfers. Fertil Steril. 1998;69:84–8. doi:10.1016/S0015-0282(97)00438-X.

    Article  PubMed  CAS  Google Scholar 

  16. Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000;73:1155–8. doi:10.1016/S0015-0282(00)00518-5.

    Article  PubMed  CAS  Google Scholar 

  17. Guerif F, Ale G, Giraudeau B, Poindron J, Bidault R, Gasnier O, et al. Limited value of morphological assessment at days 1 and 2 to predict blastocyst development potential: a prospective study based on 4042 embryos. Hum Reprod. 2007;22(7):1973–81. doi:10.1093/humrep/dem100.

    Article  PubMed  CAS  Google Scholar 

  18. Guerif F, Lemseffer M, Bidault R, Gasnier O, Saussereau MH, Cadoret V, et al. Single Day 2 versus blastocyst-stage transfer: a prospective study integrating fresh and frozen embryo transfers. Hum Reprod. 2009;24:1051–8. doi:10.1093/humrep/dep018.

    Article  PubMed  CAS  Google Scholar 

  19. Jain T, Missmer SA, Hornstein MD. Trends in embryo-transfer practice and in outcomes of the use of assisted reproductive technologies in the United States. N Engl J Med. 2004;350(16):1639–45.

    Article  PubMed  CAS  Google Scholar 

  20. Jones GM, Trounson AO, Gardner DK, Kausche A, Lolatgis N, Wood C. Evolution of a culture protocol for successful blastocyst development and pregnancy. Hum Reprod. 1998;13:169–77. doi:10.1093/humrep/13.1.169.

    Article  PubMed  CAS  Google Scholar 

  21. Kallen B, Finnstrom O, Lindam A, Nilsson E, Nygren KG, Olausson PO. Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome? Fertil Steril. 2010;94(5):1680–3. doi:10.1016/j.fertnstert.2009.12.027.

    Article  PubMed  Google Scholar 

  22. Kalra SK, Ratcliffe SJ, Barnhart KT, Coutifaris C. Day 3 vs. blastocyst embryo transfer: extended embryo culture is associated with an increased risk of preterm delivery. Fertil Steril. 2010;94(4):S242. doi:10.1016/j.fertnstert.2010.07.938.

    Article  Google Scholar 

  23. Katari S, Turan N, Bibikova M, Erinie O, Chalian R, Foster M, et al. DNA methylation and gene expression differences in children conceived in vitro or in vivo. Hum Mol Genet. 2009;18:3769–78. doi:10.1093/hmg/ddp319.

    Article  PubMed  CAS  Google Scholar 

  24. Kaufman GE, Malone FD, Harvey-Wilkes KB, Chelmow D, Penzias AS, D’Alton ME. Neonatal morbidity and mortality associated with triplet pregnancies. Obstet Gynecol. 1998;91(3):342–8.

    Article  PubMed  CAS  Google Scholar 

  25. Khosla S, Dean W, Reik W, Feil R. Culture of preimplantation embryos and its long-term effects on gene expression and phenotype. Hum Reprod Updat. 2001;7(4):419–27. doi:10.1093/humupd/7.4.419.

    Article  CAS  Google Scholar 

  26. Kiely JL, Kleinman JC, Kiely M. Triplets and higher-order multiple births. Time trends and infant mortality. Am J Dis Child. 1992;146(7):862–8.

    PubMed  CAS  Google Scholar 

  27. Leach L, Mann GE. Consequences of fetal programming for cardiovascular disease in adulthood. Microcirculation. 2011;18(4):253–5. doi:10.1111/j.1549-8719.2011.00097.x.

    Article  PubMed  Google Scholar 

  28. Leese B, Denton J. Attitudes towards single embryo transfer, twin and higher order pregnancies in patients undergoing infertility treatment: a review. Hum Fertil. 2010;13:28–34. doi:10.3109/14647270903586364.

    Article  Google Scholar 

  29. Levene MI, Wild J, Steer P. Higher multiple births and the modern management of infertility in Britain. The British association of perinatal medicine. Br J Obstet Gynaecol. 1992;99(7):607–13.

    Article  PubMed  CAS  Google Scholar 

  30. Lim D, Bowdin SC, Tee L, Kirby GA, Blair E, Fryer A, et al. Clinical and molecular genetic features of Beckwith-Wiedemann syndrome associated with assisted reproductive technologies. Hum Reprod. 2009;24(3):741–7. doi:10.1093/humrep/den406.

    Article  PubMed  Google Scholar 

  31. Lipitz S, Reichman B, Paret G, Modan M, Shalev J, Serr DM, et al. The improving outcome of triplet pregnancies. Am J Obstet Gynecol. 1989;161(5):1279–84. PMID: 2589451.

    PubMed  CAS  Google Scholar 

  32. Lipitz S, Frenkel Y, Watts C, Ben-Fafael Z, Barkai G, Reichman B. High-order multifetal gestation—management and outcome. Obstet Gynecol. 1990;76(2):215–8.

    PubMed  CAS  Google Scholar 

  33. Lucifero D, Chaillet JR, Trasler JM. Potential significance of genomic imprinting defects for reproduction and assisted reproductive technology. Hum Reprod Updat. 2004;10:3–18. doi:10.1093/humupd/dmh002.

    Article  CAS  Google Scholar 

  34. Marek D, Langley M, Gardner DK, Confer N, Doody KM, Doody KJ. Introduction of blastocyst culture and transfer for all patients in an in vitro fertilization program. Fertil Steril. 1999;72:1035–40.

    Article  PubMed  CAS  Google Scholar 

  35. Newman RB, Hamer C, Miller MC. Outpatient triplet management: a contemporary review. Am J Obstet Gynecol. 1989;161(3):547–53.

    PubMed  CAS  Google Scholar 

  36. Papanikolaou EG, D’haeseleer E, Verheyen G, Van de Velde H, Camus M, Van Steirteghem A, et al. Live birth rate is significantly higher after blastocyst transfer than after cleavage-stage embryo transfer when at least four embryos are available on day 3 of embryo culture. A randomized prospective study. Hum Reprod. 2005;20(11):3198–203. doi:10.1093/humrep/dei217.

    Article  PubMed  Google Scholar 

  37. Papanikoleau EG, Camus M, Kolibianakis EM, VanLanduyt L, Van Steirteghem A, Devroey P. In vitro fertilization with single Blastocyst-stage versus single Clevage-stage embryos. N Engl J Med. 2006;354:1139–46.

    Article  Google Scholar 

  38. Pilgaard K, Færch K, Carstensen B, Poulsen P, Pisinger C, Pedersen O, et al. Low birthweight and premature birth are both associated with type 2 diabetes in a random sample of middle-aged Danes. Diabetologia. 2010;53:2526–30. doi:10.1007/s00125-010-1917-3.

    Article  PubMed  CAS  Google Scholar 

  39. Pudawer R. Unnatural Selection. The New York Times Magazine. 2011.

  40. Racowsky C, Jackson KV, Cekleniak NA, Fox JH, Hornstein MD, Ginsburg ES. The number of eight-cell embryos is a key determinant for selecting day 3 or day 5 transfer. Fertil Steril. 2000;73(3):558–64.

    Article  PubMed  CAS  Google Scholar 

  41. Rijnders PM, Jansen CAM. The predictive value of day 3 embryo morphology regarding blastocyst formation, pregnancy and implantation rate after day 5 transfer following in-vitro fertilization or intracytopasmic sperm injection. Hum Reprod. 1998;13(10):2869–73. doi:10.1093/humrep/13.10.2869.

    Article  PubMed  CAS  Google Scholar 

  42. Scholtes MCW, Zeilmaker GH. A prospective, randomized study of embryo transfer results after 3 or 5 days of embryo culture in in vitro fertilization. Fertil Steril. 1996;65:1245–8.

    PubMed  CAS  Google Scholar 

  43. Schroeder P. Infertility and the world outside. Fertil Steril. 1988;49(5):765–7.

    PubMed  CAS  Google Scholar 

  44. Smith C, Wright N, Wales J, Mackenzie C, Primhak R, Eastell R, et al. Very low birth weight survivors have reduced peak bone mass and reduced insulin sensitivity. Clin Endocrinol. 2011;75(4):443–9. doi:10.1111/j.1365-2265.2011.04118.x.

    Article  CAS  Google Scholar 

  45. Skiadas CC, Missmer SA, Benson CB, Gee RE, Racowsky C. Risk factors associated with pregnancies containing a monochorionic air following assisted reproductive technologies. Hum Reprod. 2008;23(6):1366–71. doi:10.1093/humrep/den045.

    Article  PubMed  Google Scholar 

  46. Stephen EH, Chandra A. Updated projections of infertility in the United States. Fertil Steril. 1998;70:30–4.

    Article  PubMed  CAS  Google Scholar 

  47. Tsirigotis M. Blastocyst stage transfer: pitfalls and benefits. Too soon to abandon current practice? Hum Reprod. 1998;13:3285–9. doi:10.1093/humrep/13.12.3285.

    Article  PubMed  CAS  Google Scholar 

  48. Watkins AJ, Fleming TP. Blastocyst environment and its influence on offspring cardiovascular health: the heart of the matter. J Anat. 2009;215:52–9. doi:10.1111/j.1469-7580.2008.01033.x.

    Article  PubMed  Google Scholar 

  49. Wehkalampi K, Hovi P, Dunkel L, Strang-Karlsson S, Järvenpää AL, Eriksson JG, et al. Advanced pubertal growth spurt in subjects born preterm: the Helsinki study of very low birth weight adults. J Clin Endocrinol Metab. 2011;96:525–33. doi:10.1210/jc.2010-1523.

    Article  PubMed  CAS  Google Scholar 

  50. Whiteford LM, Gonzalez L. Stigma: the hidden burden of infertility. Soc Sci Med. 1995;40(1):27–36. doi:10.1016/0277-9536(94)00124-C.

    Article  PubMed  CAS  Google Scholar 

  51. Wong CC, Loewke KE, Bossert NL, Behr B, De Jonge CJ, Baer TM, et al. Non-Invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage. Nat Biotechnol. 2010;28(10):1115–21. doi:10.1038/nbt.1686.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

MPD and PC have served as a consultants to Auxogyn Inc. MC receives funding from ROI-HD-054956-A2.

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Authors and Affiliations

  1. Wayne State University, 60 West Hancock, Detroit, MI, USA

    Michael P. Diamond

  2. Reproductive Science Center, San Ramon, CA, USA

    Susan Willman

  3. Pacific Fertility Center, San Francisco, CA, USA

    Philip Chenette

  4. University of California at San Francisco, San Francisco, CA, USA

    Marcelle I. Cedars

Authors
  1. Michael P. Diamond
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  2. Susan Willman
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  3. Philip Chenette
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  4. Marcelle I. Cedars
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Correspondence to Michael P. Diamond.

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Capsule

A clinical need exist for establishment of approaches which can be utilized to assist in identification of embryos destined to develop into blastocysts.

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Diamond, M.P., Willman, S., Chenette, P. et al. The clinical need for a method of identification of embryos destined to become a blastocyst in assisted reproductive technology cycles. J Assist Reprod Genet 29, 391–396 (2012). https://doi.org/10.1007/s10815-012-9732-z

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  • DOI: https://doi.org/10.1007/s10815-012-9732-z

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