In the United States, the total number of In-vitro Fertilization (IVF) clinics has stayed relatively stagnant throughthe past decade, and the IVF-cycles per million women remains significantly lower than in other developedcountries. The greatest challenge for widespread use of IVF includes its high cost, driven by the need for complexand expensively equipped IVF laboratories and highly-trained embryologists. The high cost and accessibilityof IVF clinics is the leading reason why couples are unable to undergo or delay IVF treatment and/or eggbanking. Our company's goal is to automate various functions within an embryology lab to decrease the costand improve the overall accessibility of IVF treatments and fertility preservation. We are aiming to achieve thisby reducing the equipment and personnel requirements so as to pave the way towards de-centralization of IVF.Towards this goal, our proposed new technology "OvaSafe" will facilitate vitrification of oocytes prior to thembeing transferred to central embryology labs for fertilization or long-term storage facilities for preservation.OvaSafe will complement the ongoing project, OvaReady, which automatically prepares oocytes for vitrification.OvaSafe will utilize microfluidic devices to load cryoprotectant agents (CPA) rapidly and gradually tooocytes, and automatically transfer the oocytes into silica capillary carriers prior to them being plungedinto liquid nitrogen to complete the vitrification process. In addition to improving the accessibility by enablingprocessing of gametes at satellite clinics, performing gradual CPA loading using microfluidic devices will reducethe CPA exposure, toxicity, and osmotic stress to oocytes. Automated CPA loading and utilization of a closedvitrification carrier will eliminate variations between operators and clinics. Although the scope of this proposal islimited to oocyte vitrification, the technology can also be applicable to embryo vitrification in the future.In our preliminary studies, we demonstrated that gradual CPA loading using microfluidics and silica capillaryvitrification are both practical methods which can improve vitrification outcomes. We showed that gradual CPAloading decreases the total CPA exposure to oocytes, and reduces the osmotic stress driven by cell shrinkagewhich is a response to standard step-wise CPA loading protocols. We also demonstrated that silica capillariescan achieve ultra-rapid cooling and warming rates that are comparable to standard open carrier methods, andthe vitrification outcomes with silica capillaries are comparable or superior to standard methods. In the proposedwork, we will build on these innovations and integrate both methods in a simple, reliable, and closed system toautomate the oocyte vitrification process. Through this Fast-Track application, we propose and plan to completethe following aims in this order: develop a microfluidic CPA loading device; modify CPA loading device forautomated oocyte loading to silica capillaries; have plastic microfluidic devices and customized silica capillariesmanufactured to improve usability; design and build an automated control system; demonstrate success of theautomated workflow with vitrification of mouse and donated human oocytes.
Public Health Relevance Statement: Project Narrative
While the demand for fertility treatments is on the rise because of the increasing age that women seek to become
pregnant, the high cost and accessibility of IVF is the leading reason why couples choose not to undergo and/or
delay the treatment. The ability to automate various functions of an embryology lab will enable decentralization
of IVF and pave the way to reduced treatment costs and improved accessibility. We will develop and
commercialize a novel microfluidic system, OvaSafe, for standardized and automated vitrification of oocytes, in
order to support an approach of providing IVF services in remote and small clinics.
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