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Mathematically optimized cryoprotectant equilibration procedures for cryopreservation of human oocytes

Show simple item record Davidson, Allyson Fry en_US Benson, James D. en_US Higgins, Adam Z. en_US 2018-01-09T20:41:13Z 2018-01-09T20:41:13Z 2014-03-20
dc.identifier.citation Davidson, A.F., Benson, J.D. & Higgins, A.Z. Theor Biol Med Model (2014) 11: 13. en_US
dc.description.abstract Background Simple and effective cryopreservation of human oocytes would have an enormous impact on the financial and ethical constraints of human assisted reproduction. Recently, studies have demonstrated the potential for cryopreservation in an ice-free glassy state by equilibrating oocytes with high concentrations of cryoprotectants (CPAs) and rapidly cooling to liquid nitrogen temperatures. A major difficulty with this approach is that the high concentrations required for the avoidance of crystal formation (vitrification) also increase the risk of osmotic and toxic damage. We recently described a mathematical optimization approach for designing CPA equilibration procedures that avoid osmotic damage and minimize toxicity, and we presented optimized procedures for human oocytes involving continuous changes in solution composition. Methods Here we adapt and refine our previous algorithm to predict piecewise-constant changes in extracellular solution concentrations in order to make the predicted procedures easier to implement. Importantly, we investigate the effects of using alternate equilibration endpoints on predicted protocol toxicity. Finally, we compare the resulting procedures to previously described experimental methods, as well as mathematically optimized procedures involving continuous changes in solution composition. Results For equilibration with CPA, our algorithm predicts an optimal first step consisting of exposure to a solution containing only water and CPA. This is predicted to cause the cells to initially shrink and then swell to the maximum cell volume limit. To reach the target intracellular CPA concentration, the cells are then induced to shrink to the minimum cell volume limit by exposure to a high CPA concentration. For post-thaw equilibration to remove CPA, the optimal procedures involve exposure to CPA-free solutions that are predicted to cause swelling to the maximum volume limit. The toxicity associated with these procedures is predicted to be much less than that of conventional procedures and comparable to that of the corresponding procedures with continuous changes in solution composition. Conclusions The piecewise-constant procedures described in this study are experimentally facile and are predicted to be less toxic than conventional procedures for human oocyte cryopreservation. Moreover, the mathematical optimization approach described here will facilitate the design of cryopreservation procedures for other cell types. en_US
dc.description.sponsorship This work was supported by a National Science Foundation grant (#1150861) to Adam Higgins. This article is made openly accessible in part by an award from the Northern Illinois University Libraries’ Open Access Publishing Fund. en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.rights © Davidson et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. en_US
dc.subject Optimization en_US
dc.subject Toxicity en_US
dc.subject Vitrification en_US
dc.subject Cell membrane transport en_US
dc.subject Permeability en_US
dc.title Mathematically optimized cryoprotectant equilibration procedures for cryopreservation of human oocytes en_US
dc.type.genre Article en_US
dc.type Text en_US
dc.contributor.department Department of Mathematical Sciences en_US
dc.rights.statement In Copyright en_US

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