Improvement in Oocyte In Vitro Maturation (IVM) Using Microfluidic Culture

DESCRIPTION (provided by applicant): In vitro maturation (IVM) is an emerging technology in assisted reproduction. In the process of IVM, immature oocytes are collected from a woman's ovary and cultured in vitro to complete their maturation instead of in a woman's body. This process avoids expensive daily gonadotropin stimulations, medication side effects, and health risks to patients compared with traditional in vitro fertilization (IVF). At the current time, however, IVM is considered an experimental procedure due to its inability to deliver consistent pregnancy results. The developmental potential of an oocyte is associated with its culture condition. Conventional Petri dish culture does not effectively mimic the natural in vivo microenvironment, thus making it difficult to design the optimal conditions for maturation. New technologies that recreate a physiologically relevant environment outside the body may allow immature oocytes to grow more effectively. This Phase I SBIR proposal is to develop an automated microfluidic IVM culture system to improve oocyte maturation, fertilization, and embryo development rates. Technological innovations include an oocyte culture cartridge and an electromechanical microfluidic pump. The long-term goal is to improve oocyte quality and reproductive competence for IVF treatment. A prototype microfluidic embryo culture system has been developed by Incept BioSystems, Inc. and produced successful results in fluidic manipulation, embryo handling, and embryo development. Additional advancements are needed to adopt this technology for immature oocyte culture, and to demonstrate enhanced oocyte recovery with strong subsequent embryo and fetal development. The hypothesis is that an IVM culture system with media flow will effectively support in vitro oocyte maturation, resulting in maturation, fertilization and blastocyst development percentages greater than those obtained by traditional static culture. The specific aims are: 1) Design and fabricate an in vitro maturation cartridge for bovine cumulus-oocyte-complexes (COCs). 2) Perform IVM of bovine COCs in cartridges under dynamic flow conditions. 3) Perform IVM of bovine COCs followed by IVF, and in vitro embryo culture. Phase II objectives of this project will be to optimize the culture system for human use and conduct a clinical trial. A microfluidic IVM system based on dynamic regulation of the culture environment could advance the production of high quality mature oocytes. A substantial increase in mature oocyte production and their development competence has the potential to transform Assisted Reproductive Technologies, where IVM combined with natural-cycle IVF could become the first option of treatment for many patients. It will also expand the available oocytes for domestic animal production and stem cell technologies. The development of a new microfluidic IVM technology has promising commercial potential and could provide significant benefits to the millions of people facing infertility in the U.S. PUBLIC HEALTH RELEVANCE: Infertility impacts about 7.3 million reproductive age women and their partners in the United States. This project aims to enhance the efficiency of infertility treatment using an innovative microfluidic in vitro maturation system, which would replace current Petri-dish based oocyte culture techniques. This system will make in vitro maturation a more effective, affordable and safer option for patients seeking assisted reproduction.