Cooperative Multicenter Reproductive Medicine Network (U10)

多中心生殖医学合作网络（U10）

• 批准号: 8588627
• 负责人: MARCELLE Ivonne CEDARS
• 金额: $ 24.97万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-24 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8588627
• 关键词: Affect; Age; Aging; Ancillary Study; Aneuploidy; Antioxidants; Apoptosis; Basic Science; Biological; Birth Rate; Blast Cell; California; Cell physiology; Cells; Characteristics; Childbirth; Chromosome Segregation; Clinic; Clinical Research; Clinical Trials; Coenzyme Q10; Coenzymes; Communities; Competence; Complex; Congenital Abnormality; Couples; DNA copy number; Development; Embryo; Embryonic Development; Enrollment; Ensure; Enzyme Gene; Enzymes; Evaluation; Fertility; Fertilization; Fertilization in Vitro; First Births; Follicular Fluid; Gene Expression; General Hospitals; Genetic Screening; Infertility; Intracytoplasmic Sperm Injections; Isoprostanes; Laboratories; Leadership; Live Birth; Mediating; Meiosis; Mitochondria; Mitochondrial DNA; Oocyte Donation; Oocytes; Outcome; Ovarian; Ovarian Follicle; Ovarian Stimulations; Oxidative Stress; Pathway interactions; Patient Care; Patients; Positioning Attribute; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Primordial Follicle; Principal Investigator; Production; Reactive Oxygen Species; Reproductive Health; Reproductive Medicine; Research; Respiration; Risk; Role; San Francisco; Series; Spontaneous abortion; Stress; Supplementation; TdT-Mediated dUTP Nick End Labeling Assay; Testing; Time; Translating; Treatment Protocols; Universities; Woman; caspase-3; experience; failure Implantation; gene synthesis; improved; innovation; intrauterine insemination; novel; older women; preimplantation; programs; public health relevance; racial and ethnic; randomized placebo controlled trial; sperm cell; success; ubiquinone 6; young woman

DESCRIPTION (provided by applicant): The Center for Reproductive Health (CRN) at the University of California, San Francisco (UCSF) is uniquely positioned to participate in the Cooperative Multicenter Reproductive Medicine Network (RMN). The CRN takes a multi-disciplinary approach to patient care and will benefit from community involvement of Kaiser-Permanente San Francisco and San Francisco General Hospital (SFGH). This partnership allows a robust practice volume that will facilitate subject enrollment, and the diverse racial, ethnic, and socio-demographic characteristics of our patients will increase the generalizability of treatment protocols. Equally important, we have the leadership and experience in clinical trials to ensure success. Clinical research is a key step in translating basic science to the bedside, and the application of this research directly affects patient care. Over the last four decades, women in the developed world have delayed childbirth. Fertility decreases with age, and live birth rates are lower in women over 35 than in younger women. The decline in live birth rate reflects an increase in oocyte aneuploidy, leading to failure of implantation and increased risk for miscarriages and birth defects. Older infertility patients appear to have abnormal mitochondrial activity in oocytes and reduced production of ATP, which limits normal oocyte chromosomal disjunction and embryo development. Without sufficient ATP, the meiotic spindle, which is crucial for normal chromosome segregation, may not form properly, and altered spindles result in aneuploid embryos. In older women, the cumulus oocyte complex (COC) in primordial follicles is exposed to low levels of reactive oxygen species (ROS) produced by mitochondrial respiration over decades. The resultant cumulative damage to mtDNA and enzymes involved in coQ10 synthesis would reduce the substrate for ATP production by the mitochondria. We hypothesize that altered mitochondrial function in oocytes reflects diminished availability of coQ10 with age. If our hypothesis is correct, we may be able to partially reverse oocyte aging by giving coQ10 to increase ATP production and increase anti-oxidant activity, thereby reducing damage to the COC. To test this hypothesis, we propose a multicenter, placebo-controlled, randomized trial with the following aims: 1) Determine if coQ10 supplementation reduces time to delivery after ovarian stimulation and intrauterine insemination followed by in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI); 2) Determine if coQ10 supplementation affects oocyte developmental competence, intrafollicular oxidative stress, and mitochondrial function; and 3) Determine if oxidative stress in the follicle is relatedto ovarian/chronological aging and to the developmental competence of oocytes. Our study is innovative in its approach - which combines a large multicenter randomized placebo-controlled trial of coQ10, with laboratory evaluation of ovarian follicles, to characterize the role of oxidatve stress (OS) and coQ10 in ovarian aging. Additionally, a positive result would offer women the first treatment to overcome the impact of aging on the oocyte and the resultant lowered pregnancy potential.

描述（由申请人提供）：加州大学旧金山分校（UCSF）生殖健康中心（CRN）是参与合作多中心生殖医学网络（RMN）的独特定位。CRN采用多学科方法对患者进行护理，并将受益于旧金山凯泽永久医疗机构和旧金山总医院（SFGH）的社区参与。这种伙伴关系允许一个强大的实践量，将促进受试者登记，和多样化的种族，民族，和我们的患者的社会人口特征将增加推广