Amino Acid Turnover as a Biomarker of Embryo Viability
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 s
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Amino Acid Turnover as a Biomarker of Embryo Viability Christine Leary, Danielle G. Smith, Henry J. Leese, and Roger G. Sturmey 44.1
Why the Need for Objective Markers of Viability? – 550
44.2
Amino Acid Profiling – 551
44.3
The Biology of Amino Acids – 551
44.3.1 44.3.2 44.3.3 44.3.4 44.3.5 44.3.6
rotein Synthesis – 551 P Energy Sources – 551 Nucleotide Synthesis – 551 Osmolytes – 551 Provision of 1-Carbon Units – 551 Signaling Molecule Precursors – 551
44.4
How to Measure Amino Acids – 552
44.4.1
rinciple of Chromatography/High-Performance Liquid P Chromatography – 552 Chemical Properties of Amino Acids – 552 Chemical Principles of Amino Acid Derivatization – 552 Equipment and Consumables Required – 553
44.4.2 44.4.3 44.4.4
44.5
ow to Prepare Samples and Perform High-Performance H Liquid Chromatography – 554
44.5.1 44.5.2 44.5.3
ata Interpretation – 555 D Statistics and Power – 555 Relating to Outcome – 555
Review Questions – 555 References – 555
© Springer Nature Switzerland AG 2019 Z. P. Nagy et al. (eds.), In Vitro Fertilization, https://doi.org/10.1007/978-3-319-43011-9_44
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Learning Objectives 55 To define the benefits of embryo selection and/or ranking during IVF treatment 55 To review how traditional embryo assessment may not be sufficient for efficient embryo selection and what alternative options exist 55 To describe how amino acid turnover is related to embryo development and viability 55 To review the technological aspects of performing amino acid measurement from spent culture medium 55 To present how amino acid profiling may be used as an additional tool for embryo selection
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Most of the rise in multiple births observed since the 1980s has been attributed to the increased use of IVF and the practice of replacing more than one embryo into the uterus in order to improve the chances of success. In response to the unacceptably high risks associated with multiple births, several countries have introduced single embryo transfer policies. However, to maintain acceptable pregnancy rates, the pressure to identify the most viable embryo for transfer has intensified. The most widely used method of embryo selection has been to assign scores on day 2 or day 3 post insemination on the basis of the embryo’s cleavage rate and morphological appearance. Studies have shown that correlations exist between these observational cues of embryo quality and their capacity for continued development and subsequent implantation. However, appropriate temporal developmental patterns are critical to predicting embryo viability. For example, Cummins et al. [1] assigned scores based on the ratio between the time at which an embryo was observed at a given stage of development and the expected time taken to reach that particular stage and showed that pregnancy rates were lower for those with above or below average scores. In a powerful study based on observations from single embryo transfer, Giorgetti et al. [2] demonstrated the additional benefit of incl
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