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Mathematically optimized cryoprotectant equilibration procedures for cryopreservation of human oocytes

ScholarsArchive at Oregon State University

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Title Mathematically optimized cryoprotectant equilibration procedures for cryopreservation of human oocytes
Names Davidson, Allyson Fry (creator)
Benson, James D. (creator)
Higgins, Adam Z. (creator)
Date Issued 2014-03-20 (iso8601)
Note This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by BioMed Central Ltd. The published article can be found at: http://www.tbiomed.com/.
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.
Genre Article
Access Condition http://creativecommons.org/licenses/by/3.0/us/
Topic Optimization
Identifier Davidson, A. F., Benson, J. D., & Higgins, A. Z. (2014). Mathematically optimized cryoprotectant equilibration procedures for cryopreservation of human oocytes. Theoretical Biology and Medical Modelling, 11, 13. doi:10.1186/1742-4682-11-13

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