Human Reproduction, Vol. 17, No. 4, 999-1005,
April 2002
© 2002 European Society of Human Reproduction and Embryology
Non-invasive amino acid turnover predicts human embryo developmental capacity
1 Department of Biology, University of York, PO Box 373, York YO10 5YW and 2 Assisted Conception Unit, Clarendon Wing, Leeds General Infirmary, Leeds LS1 9NS, UK
BACKGROUND: IVF is limited by low success rates and a confounding high multiple birth rate contributing to prematurity, increased neonatal mortality and child handicap. These problems could be overcome if single embryos of known developmental competence could be selected for transfer on day 2/3 of development, but current methods, which rely on morphological appearance, are poor predictors of viability. METHODS: We have measured non-invasively the depletion/appearance (i.e. turnover) of a physiological mixture of 18 amino acids by single human embryos during in-vitro culture using high performance liquid chromatography. RESULTS: From the time of transfer (day 2/3), embryos with future competence to develop to the blastocyst stage (day 5/6) exhibit amino acid flux patterns distinct from those of embryos with similar morphological appearance which arrest. Significantly, the profiles of Ala, Arg, Gln, Met and Asn flux predict blastocyst potentiality at >95%. The amino acid most consistently depleted throughout development by those embryos which form blastocysts was leucine. Of the amino acids which were produced, the most striking was alanine, which appeared in increasing amounts throughout development. CONCLUSIONS: Non-invasive amino acid profiling has the potential to select developmentally competent single embryos for transfer, thereby increasing the success rate and eliminating multiple births in IVF.
Key words: amino acids/developmental potential/human preimplantation embryo culture/IVF
3 To whom correspondence should be addressed. E-mail: fdh1{at}york.ac.uk
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
R. G. Sturmey, J. A. Hawkhead, E. A. Barker, and H. J. Leese DNA damage and metabolic activity in the preimplantation embryo Hum. Reprod., January 1, 2009; 24(1): 81 - 91. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Botros, D. Sakkas, and E. Seli Metabolomics and its application for non-invasive embryo assessment in IVF Mol. Hum. Reprod., December 1, 2008; 14(12): 679 - 690. [Abstract] [Full Text] [PDF] |
||||
![]() |
C.G. Vergouw, L.L. Botros, P. Roos, J.W. Lens, R. Schats, P.G.A. Hompes, D.H. Burns, and C.B Lambalk Metabolomic profiling by near-infrared spectroscopy as a tool to assess embryo viability: a novel, non-invasive method for embryo selection Hum. Reprod., July 1, 2008; 23(7): 1499 - 1504. [Abstract] [Full Text] [PDF] |
||||
![]() |
S J Kimber, S F Sneddon, D J Bloor, A M El-Bareg, J A Hawkhead, A D Metcalfe, F D Houghton, H J Leese, A Rutherford, B A Lieberman, et al. Expression of genes involved in early cell fate decisions in human embryos and their regulation by growth factors Reproduction, May 1, 2008; 135(5): 635 - 647. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. J Booth, T. J Watson, and H. J Leese Prediction of Porcine Blastocyst Formation Using Morphological, Kinetic, and Amino Acid Depletion and Appearance Criteria Determined During the Early Cleavage of In Vitro-Produced Embryos Biol Reprod, November 1, 2007; 77(5): 765 - 779. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. J. Eckert, F. D. Houghton, J. A. Hawkhead, A. H. Balen, H. J. Leese, H. M. Picton, I. T. Cameron, and T. P. Fleming Human embryos developing in vitro are susceptible to impaired epithelial junction biogenesis correlating with abnormal metabolic activity Hum. Reprod., August 1, 2007; 22(8): 2214 - 2224. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. J. Stokes, J. A. Hawkhead, R. K. Fawthrop, H. M. Picton, V. Sharma, H. J. Leese, and F. D. Houghton Metabolism of human embryos following cryopreservation: Implications for the safety and selection of embryos for transfer in clinical IVF Hum. Reprod., March 1, 2007; 22(3): 829 - 835. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. C. Manser and F. D. Houghton Ca2+-linked upregulation and mitochondrial production of nitric oxide in the mouse preimplantation embryo J. Cell Sci., May 15, 2006; 119(10): 2048 - 2055. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Haggarty, M. Wood, E. Ferguson, G. Hoad, A. Srikantharajah, E. Milne, M. Hamilton, and S. Bhattacharya Fatty acid metabolism in human preimplantation embryos Hum. Reprod., March 1, 2006; 21(3): 766 - 773. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. J Booth, P. G Humpherson, T. J Watson, and H. J Leese Amino acid depletion and appearance during porcine preimplantation embryo development in vitro Reproduction, November 1, 2005; 130(5): 655 - 668. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M.R. Gerris Single embryo transfer and IVF/ICSI outcome: a balanced appraisal Hum. Reprod. Update, March 1, 2005; 11(2): 105 - 121. [Abstract] [Full Text] [PDF] |
||||
![]() |
D.R. Brison, F.D. Houghton, D. Falconer, S.A. Roberts, J. Hawkhead, P.G. Humpherson, B.A. Lieberman, and H.J. Leese Identification of viable embryos in IVF by non-invasive measurement of amino acid turnover Hum. Reprod., October 1, 2004; 19(10): 2319 - 2324. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. P. Fleming, W. Y. Kwong, R. Porter, E. Ursell, I. Fesenko, A. Wilkins, D. J. Miller, A. J. Watkins, and J. J. Eckert The Embryo and Its Future Biol Reprod, October 1, 2004; 71(4): 1046 - 1054. [Abstract] [Full Text] [PDF] |
||||
![]() |
R.C. Manser, H.J. Leese, and F.D. Houghton Effect of Inhibiting Nitric Oxide Production on Mouse Preimplantation Embryo Development and Metabolism Biol Reprod, August 1, 2004; 71(2): 528 - 533. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. M. Martin, A. E. Sutherland, and L. J. Van Winkle Amino Acid Transport Regulates Blastocyst Implantation Biol Reprod, October 1, 2003; 69(4): 1101 - 1108. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. R. Ghassemifar, J. J. Eckert, F. D. Houghton, H. M. Picton, H. J. Leese, and T. P. Fleming Gene expression regulating epithelial intercellular junction biogenesis during human blastocyst development in vitro Mol. Hum. Reprod., May 1, 2003; 9(5): 245 - 252. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. M. Schultz and C. J. Williams The Science of ART Science, June 21, 2002; 296(5576): 2188 - 2190. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. R. Ghassemifar, B. Sheth, T. Papenbrock, H. J. Leese, F. D. Houghton, and T. P. Fleming Occludin TM4-: an isoform of the tight junction protein present in primates lacking the fourth transmembrane domain J. Cell Sci., January 8, 2002; 115(15): 3171 - 3180. [Abstract] [Full Text] [PDF] |
||||






