Amino Acid Turnover as a Biomarker of Embryo Viability

  • Christine Leary
  • Danielle G. Smith
  • Henry J. Leese
  • Roger G. Sturmey
Chapter
First Online:

Abstract

Selection of the most viable embryo to transfer and at which stage of development remains one of the most challenging aspects of in vitro fertilization. There is little consensus regarding the observations to make and how frequently to record them. Many schemes use a combination of criteria, including the addition of pronuclear morphological scores, early cleavage, and more controversially aneuploidy screening, as adjuncts to those used routinely. Attempts to draw conclusions on the effectiveness of current observational embryo grading and selection tools have been hampered by a lack of generic terminology and methodology. There is a clear need for a standard embryo scoring/selection system and the introduction of external quality assessment schemes, currently being piloted in the UK. It is hoped that with the introduction of consistent terminology and reduced operator scoring variability, this will permit large-center studies and allow more definitive correlations to be drawn leading us closer to defining what indicates a viable embryo. There is increasing evidence to support the proposition that amino acid profiling reflects the developmental capacity of early embryos. By measuring a group of 18 compounds, amino acid profiling provides a snapshot of embryo phenotype by virtue of the many roles played by amino acids during embryo development. Amino acid profiling differs from conventional metabolic assays, where typically, only one or two metabolites are measured.

Keywords

Biomarkers of embryo viability Early embryo metabolism High performance liquid chromatography Tools for single embryo transfer 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Cummins JM, Breen TM, Harison KL, et al. 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. 1986;3:284–95.PubMedCrossRefGoogle Scholar
  2. 2.
    Giorgetti C, Terriou P, Auquier P, et al. Embryo score to predict implantation after in-vitro fertilization: based on 957 single embryo transfers. Hum Reprod. 1995;10:2427–31.PubMedGoogle Scholar
  3. 3.
    Hardarson T, Hanson C, Sjogren A, Lundin K. Human embryos with uneven sized blastomeres have lower pregnancy and implantation rates: indications for aneuploidy and multinucleation. Hum Reprod. 2001;16:313–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Munne S, Cohen J. Unsuitability of multinucleated human blastomeres for preimplantation genetic diagnosis. Hum Reprod. 1998;8:1120–5.Google Scholar
  5. 5.
    Alikani M, Cohen J, Tomkin G, et al. Human embryo fragmentation in vitro and its implications for pregnancy and implantation. Fertil Steril. 1999;71:836–42.PubMedCrossRefGoogle Scholar
  6. 6.
    Magli M, Jones G, Gras L, et al. Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro. Hum Reprod. 2000;15(8):1781–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Lane M, Gardner D. Selection of viable mouse blastocysts prior to transfer using metabolic criterion. Hum Reprod. 1996;11:1975–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Lamb V, Leary C, Herbert M, Murdoch A. Embryo selection in assisted conception. Curr Obstet Gynaecol. 2004;14:291–3.CrossRefGoogle Scholar
  9. 9.
    Partridge RJ, Leese HJ. Consumption of amino acids by bovine preimplantation embryos. J Reprod Fertil. 1996;102(2):299–306.Google Scholar
  10. 10.
    Orsi NM, Leese HJ. Amino acid metabolism of preimplantation bovine embryos cultured with bovine serum albumin or polyvinyl alcohol. Theriogenology. 2004;61:561–72.PubMedCrossRefGoogle Scholar
  11. 11.
    Gopichandran N, Leese HJ. Metabolic characterization of the bovine blastocyst, inner cell mass, trophectoderm and blastocoel fluid. Reproduction. 2003;126:299–308.PubMedCrossRefGoogle Scholar
  12. 12.
    Sturmey RG, Bermejo-Alvarez P, Gutierrez-Adan A, Rizos D, Leese HJ, Lonergan P. Amino acid metabolism of bovine blastocysts: a biomarker of sex and viability. Mol Reprod Dev. 2010;77:285–96.PubMedCrossRefGoogle Scholar
  13. 13.
    Humpherson PG, Leese HJ, Sturmey RG. Amino acid metabolism of the porcine blastocyst. Theriogenology. 2005;64:1852–66.PubMedCrossRefGoogle Scholar
  14. 14.
    Houghton FD, Hawkhead JA, Humpherson PG, Hogg JE, Balen AH, Rutherford AJ, Leese HJ. Non-invasive amino acid turnover predicts human embryo developmental capacity. Hum Reprod. 2002;17:999–1005 [Erratum in: Hum Reprod. 2003;18: 1756–7].PubMedCrossRefGoogle Scholar
  15. 15.
    Sturmey RG, Hawkhead JA, Barker EA, Leese HJ. DNA damage and metabolic activity in the preimplantation embryo. Hum Reprod. 2009;24:81–91.PubMedCrossRefGoogle Scholar
  16. 16.
    Brison DR, Houghton FD, Falconer D, Roberts SA, Hawkhead JA, Humpherson PG, Lieberman BA, Leese HJ. Identification of viable embryos in IVF by non-invasive measurement of amino acid turnover. Hum Reprod. 2004;19:2319–24.PubMedCrossRefGoogle Scholar
  17. 17.
    Epstein CJ, Smith SA. Amino acid uptake and protein synthesis in preimplantation mouse embryos. Dev Biol. 1973;33:171–84.PubMedCrossRefGoogle Scholar
  18. 18.
    Leese, H.J. (1991). Metabolism of the preimplantation mammalian embryo. In SR Milligan ed. Oxford reviews of reproductive biology, Vol. 13, pp 35-72 Oxford University Press.Google Scholar
  19. 19.
    Leese HJ. Energy metabolism in preimplantation development. In: Bavister BD, editor. Preimplantation embryo development. New York: Springer; 1993. p. 73–82.CrossRefGoogle Scholar
  20. 20.
    Booth PJ, Humpherson PG, Watson TJ, Leese HJ. Amino acid depletion and appearance during porcine preimplantation embryo development in vitro. Reproduction. 2005;130:655–68.PubMedCrossRefGoogle Scholar
  21. 21.
    Buttgereit F, Brand MD. A hierarchy of ATP-consuming processes in mammalian cells. Biochem J. 1995;312:163–7.PubMedGoogle Scholar
  22. 22.
    Rolfe DF, Brown GC. Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev. 1997;77:731–58.PubMedGoogle Scholar
  23. 23.
    Wieser W, Krumschnabel G. Hierarchies of ATP-consuming processes: direct compared with indirect measurements and comparative aspects. Biochem J. 2001;355:389–95.PubMedCrossRefGoogle Scholar
  24. 24.
    Leese HJ, Donnay I, Macmillan D, Houghton F. Metabolism of the early embryo: energy production and utilisation. In: Gardner DK, Lane M, editors. ART and the human blastocyst. New York: Springer; 2001. p. 61–6.CrossRefGoogle Scholar
  25. 25.
    Alexiou M, Leese HJ. Purine utilization, de novo synthesis and degradation in mouse preimplantation embryos. Development. 1992;114:183–92.Google Scholar
  26. 26.
    Anas MK, Hammer MA, Lever M, Stanton JA, Baltz JM. The organic osmolytes betaine and proline are transported by a shared system in early preimplantation mouse embryos. J Cell Physiol. 2007;210:266.PubMedCrossRefGoogle Scholar
  27. 27.
    Manser RC, Leese HJ, Houghton FD. Effect of inhibiting nitric oxide production on mouse preimplantation embryo development and metabolism. Biol Reprod. 2004;71:528–33.PubMedCrossRefGoogle Scholar
  28. 28.
    Manser RC, Houghton FD. Ca2+-linked upregulation and mitochondrial production of nitric oxide in the mouse preimplantation embryo. J Cell Sci. 2006;119:2048–55.PubMedCrossRefGoogle Scholar
  29. 29.
    Lipari CW, Garcia JE, Zhao Y, Thrift K, Vaidya D, Rodriguez A. Nitric oxide metabolite production in the human preimplantation embryo and successful blastocyst formation. Fertil Steril. 2009;91:1316–8.PubMedCrossRefGoogle Scholar

Further Reading

  1. Fallon A, Booth RF, Bell LD. Applications of HPLC in biochemistry. In: Burdon RH, van Knippenberg PH, editors. Laboratory techniques in biochemistry and molecular biology. Amsterdam: Elsevier Science; 1987. p. 89.Google Scholar
  2. Blake D, Farquhar C, Johnson N, Proctor M. Cleavage stage versus blastocyst stage embryo transfer in assisted conception. Cochrane Database Syst Rev. 2007;(4):CD002118.Google Scholar
  3. Bolton V, Hawes S, Taylor C, et al. Development of spare human preimplantation embryos in vitro: an analysis of the correlations among gross morphology, cleavage rates and development to the blastocyst. J In Vitro Fert Embryo Transfer. 1989;6:30–5.CrossRefGoogle Scholar
  4. Khalaf Y, El-Toukhy T, Coomarasamy A, et al. Selective single blastocyst transfer reduces the multiple pregnancy rate and increases pregnancy rates: a pre and post intervention study. BJOG. 2008;115:385–90.PubMedCrossRefGoogle Scholar
  5. Papanikoloau E, D’haeseleer E, Verheyen G, et al. Live birth rate is significantly higher after blastocyst transfer than after cleavage stage embryo transfer when at least 4 embryos are available on day 3 of embryo culture. A randomized prospective study. Hum Reprod. 2005;20:3198–203.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Christine Leary
    • 1
  • Danielle G. Smith
    • 2
  • Henry J. Leese
    • 3
  • Roger G. Sturmey
    • 4
  1. 1.Hull IVF Unit, East Riding Fertility ServicesThe Women and Children’s Hospital, Hull Royal InfirmaryHullUK
  2. 2.Leeds Institute of Molecular MedicineUniversity of Leeds, St James’s University HospitalLeedsUK
  3. 3.Hull York Medical SchoolUniversity of HullHullUK
  4. 4.Centre for Cardiovascular and Metabolic Research, Hull York Medical SchoolUniversity of HullHullUK

Personalised recommendations