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

使用微流体培养改善卵母细胞体外成熟 (IVM)

基本信息

批准号：
7999501
负责人：
Arthur Gershowitz
金额：
$ 12.76万
依托单位：
INCEPT BIOSYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-15 至 2011-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7999501
关键词：
Adopted Adoption Adverse effects Affect Age Assisted Reproductive Technology Cattle Centers for Disease Control and Prevention (U.S.)Child Clinic Clinical Clinical Trials Competence Complex Country Culture Media Culture Techniques Development Devices Domestic Animals Drug Formulations Electrolytes Embryo Embryonic Development Embryonic and Fetal Development Emerging Technologies Environment Evaluation Fertility Fertility Agents Fertilization Fertilization in Vitro Goals Gonadotropins Government Growth Growth Factor Health Hormones Hour Human In Vitro Industry Infertility Joints Knowledge Liquid substance Live Birth Marketing Metaphase Microfluidics Modeling Nutrient Oocytes Ovarian Hyperstimulation Syndrome Ovary Patients Penetration Perfusion Persons Pharmaceutical Preparations Phase Pre-implantation Embryo Development Pregnancy Procedures Process Production Pump Recovery Regulation Reporting Reproductive Technology Risk Safety Sales Small Business Innovation Research Grant Specialist Staging Superovulation System Technology Time Transportation United States Vesicle Waste Products Woman World Health Organization assisted reproduction base blastocyst cost design embryo culture experience improved in vivo innovation miniaturize nano new technology novel oocyte maturation prototype public health relevance reproductive shear stress stem cell technology technological innovation telophase zygote

项目摘要

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.

描述（由申请人提供）：体外成熟（IVM）是辅助生殖领域的一项新兴技术。在IVM过程中，从女性卵巢中收集未成熟的卵母细胞，并在体外培养以完成成熟，而不是在女性体内进行。与传统的体外受精（IVF）相比，这一过程避免了昂贵的日常促性腺激素刺激、药物副作用和对患者的健康风险。然而，目前 IVM 被认为是一种实验程序，因为它无法提供一致的妊娠结果。卵母细胞的发育潜力与其培养条件有关。传统的培养皿培养不能有效模拟体内自然微环境，因此难以设计最佳的成熟条件。在体外重建生理相关环境的新技术可能会让未成熟的卵母细胞更有效地生长。该第一期 SBIR 提案旨在开发一种自动化微流体 IVM 培养系统，以提高卵母细胞成熟、受精和胚胎发育率。技术创新包括卵母细胞培养盒和机电微流体泵。长期目标是提高 IVF 治疗的卵母细胞质量和生殖能力。 Incept BioSystems, Inc. 开发了原型微流体胚胎培养系统，并在流体操作、胚胎处理和胚胎发育方面取得了成功的结果。需要进一步的进步才能采用这项技术进行未成熟卵母细胞培养，并证明卵母细胞恢复能力增强以及后续胚胎和胎儿发育的强劲。假设具有培养基流的 IVM 培养系统将有效支持体外卵母细胞成熟，从而导致成熟、受精和囊胚发育百分比高于传统静态培养所获得的百分比。具体目标是：1）设计和制造牛卵丘卵母细胞复合体（COC）的体外成熟盒。 2) 在动态流动条件下对盒中的牛 COC 进行 IVM。 3) 对牛 COC 进行 IVM，然后进行 IVF 和体外胚胎培养。该项目第二阶段的目标是优化人类使用的培养系统并进行临床试验。基于培养环境动态调节的微流控 IVM 系统可以促进高质量成熟卵母细胞的产生。成熟卵母细胞产量及其发育能力的大幅增加有可能改变辅助生殖技术，其中 IVM 与自然周期 IVF 相结合可能成为许多患者的首选治疗选择。它还将扩大用于家畜生产和干细胞技术的可用卵母细胞。一种新的微流体 IVM 技术的开发具有广阔的商业潜力，可以为美国数百万面临不孕不育的人们带来巨大的好处！公共卫生相关性：不孕不育影响着美国约 730 万育龄妇女及其伴侣。该项目旨在使用创新的微流体体外成熟系统来提高不孕症治疗的效率，该系统将取代目前基于培养皿的卵母细胞培养技术。该系统将使体外成熟成为寻求辅助生殖的患者更有效、更实惠、更安全的选择。