Mathematically optimized cryoprotectant equilibration procedures for cryopreservation of human oocytes

Davidson, Allyson Fry; Benson, James D.; Higgins, Adam Z.
May 2014
Theoretical Biology & Medical Modelling;2014, Vol. 11 Issue 1, p1
Academic Journal
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.


Related Articles

  • Long-term cryostorage does not adversely affect the outcome of oocyte thawing cycles. Parmegiani, L.; Garello, C.; Granella, F.; Guidetti, D.; Bernardi, S.; Cognigni, G. E.; Revelli, A.; Filicori, M. // Reproductive BioMedicine Online (Reproductive Healthcare Limited;Sep2009, Vol. 19 Issue 3, p374 

    This multi-centre study evaluated systematically the influence of the duration of cryostorage on the outcome of thawing cycles when using slow-frozen oocytes. The thawing cycles were retrospectively divided into three main groups based on cryostorage duration: group A, 1-3 months; group B, 4-6...

  • Beyond experimental - delaying fertility with frozen eggs.  // Mayo Clinic Health Letter;Mar2014, Vol. 32 Issue 3, p4 

    The article reports on the expectation of specialists at the medical center Mayo Clinic for an increased women's interest on oocyte cryopreservation as they become more proactive in fertility preservation.

  • Comparison of Two Slow Cooling Protocols for Cryopreserved Human Oocytes.  // Fertility Weekly;6/14/2010, p6 

    The article presents a comparison between one-step or two-step propanediol (PrOH), two slow cooling protocols for cryopreserved human oocytes in a study in Italy. According to the research, a human oocyte may be sustaining damage from cryopreservation whether the process utilizes the two steps...

  • Children born after cryopreservation of embryos or oocytes: a systematic review of outcome data. Wennerholm, U. -B.; Anttila, V. Söderström; Bergh, C.; Aittomäki, K.; Hazekamp, J.; Nygren, K. -G.; Selbing, A.; Loft, A. // Human Reproduction;Sep2009, Vol. 24 Issue 9, p2158 

    BACKGROUND: An estimated 3.5 million children have been born to date using assisted reproduction technologies. We reviewed the data in order to evaluate current knowledge of medical outcome for IVF/ICSI children born after cryopreservation, slow freezing and vitrification of early cleavage stage...

  • Effects of sucrose concentration on the developmental potential of human frozen–thawed oocytes at different stages of maturity. Z.J. Chen; M. Li; Y. Li; L.X. Zhao; R. Tang; Y. Sheng; X. Gao; C.H. Chang; H.L. Feng // Human Reproduction;Oct2004, Vol. 19 Issue 10, p2345 

    BACKGROUD: Success of human oocyte cryopreservation depends on multiple cryobiological factors that could influence the developmental potential of the oocytes. The objective of this study was to examine the effects of different sucrose concentrations on the developmental potential of human...

  • Objective evaluation of the viability of cryopreserved oocytes. De Santis, L.; Cino, I.; Coticchio, G.; Fusi, F. M.; Papaleo, E.; Rabellotti, E.; Brigante, C.; Borini, A.; Ferrari, A. // Reproductive BioMedicine Online (Reproductive Healthcare Limited;Sep2007, Vol. 15 Issue 3, p338 

    Recent studies of fundamental cryobiology, empirical observations and more systematic clinical experiences have generated a renewed interest in oocyte cryopreservation. Poor survival rate has long been the limiting factor which has prevented widespread adoption of oocyte storage. Slow-cooling...

  • History of oocyte cryopreservation. Gook, Debra A. // Reproductive BioMedicine Online (Reproductive Healthcare Limited;Sep2011, Vol. 23 Issue 3, p281 

    The potential advantages of being able to cryopreserve oocytes have been apparent for many decades. Technical difficulties associated with the unique properties of the mammalian oocyte initially retarded rapid development in this area but recent advances have overcome many of the problems. A...

  • Theoretical considerations for oocyte cryopreservation by freezing. Fahy, Gregory M. // Reproductive BioMedicine Online (Reproductive Healthcare Limited;Jun2007, Vol. 14 Issue 6, p709 

    Attempts to cryopreserve oocytes by freezing have, to date, been based mostly on empirical approaches rather than on basic principles, and perhaps in part for this reason have not been very successful. Theoretical considerations suggest some fairly 'heretical' conclusions, The concentrations of...

  • Oocyte cryopreservation: the birth of the first Hungarian babies from frozen oocytes. Konc, Janos; Kanyo, Katalin; Varga, Erika; Kriston, Rita; Cseh, Sandor // Journal of Assisted Reproduction & Genetics;Jul2008, Vol. 25 Issue 7, p349 

    Purpose To present data obtained with clinical application of oocyte cryopreservation. Methods Slow freezing/rapid thawing in PBS based medium containing 1.5 M propanediol+0.3 M sucrose. Results A total of 127 embryos were transferred into 54 patients (1.9 embryo/cycle, 64 transfer cycles)....


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics