Prospective Paired Study on the Effectiveness of MitoGrade
试验速览
- 阶段
- 不适用
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Implantation rates between MitoGrade normal and MitoGrade elevated embryos
研究概览
简要总结
Chromosomal abnormalities are a major cause of pregnancy loss. Preimplantation Genetic Screening (PGS) using Next Generation Sequencing (NGS) allows the effective detection of these abnormalities and improves clinical outcomes. However even the transfer of a chromosomally normal embryo does not guarantee successful implantation. Recent research by Fragouli, et. al. 2015 has demonstrated a strong association between mitochondrial DNA quantities (also known as MitoGradeTM) and implantation outcomes in embryos that are already classified by PGS as chromosomally normal. Investigators have also demonstrated in a clinical study that MitoGradeTM normal and PGS normal embryos have higher chances of implantation than MitoGrade elevated PGS normal embryos. Transferring MitoGrade elevated PGS normal embryos results in less than 10% implantation rates while MitoGrade normal PGS normal embryos resulted in more than 65% implantation rates. The risk of miscarriage after replacing either type is very low (about 8%).
In order to understand the complete effectiveness of the test, investigators are conducting a paired prospective study. This means that investigators will be transferring a MitoGrade normal and a MitoGrade elevated embryo at the same time to see if one implants better than the other. It is expected that patients joining this study will benefit from knowing that at least one embryo is MitoGrade normal PGS normal.
详细描述
Mitochondria are considered the powerhouses of cells. These membrane-bound organelles play a vital role in embryonic development and are essential for various cellular functions. And unlike other cellular organelles, they contain their own DNA (also known as mitochondrial DNA or mtDNA). Embryonic development is a complex energy-driven process and is thought to be highly dependent on mitochondrial function and mtDNA gene expression. It is believed that amounts of mtDNA remain constant in first three days of preimplantation development. Significant alterations in mtDNA are not initiated until after day 5 when the embryo has undergone the first cellular differentiation into trophectoderm (TE) and inner cell mass. It is possible that mtDNA variation may account chromosomal abnormalities by affecting the accuracy of chromosome segregation.
In addition to describing the relationship between mtDNA expression and clinical outcomes, Reprogenetics and Fragouli et al. (2015) were able to establish a threshold over which no clinical pregnancy was established. These results were further validated in a prospective blinded study and independently validated using Next Generation Sequencing (NGS) analysis. The quantification of mtDNA therefore provides important information in selecting the best embryos for transfer. MitoGradeTM is a real-time polymerase chain reaction (PCR) based method developed to quantify the amount of mitochondrial DNA (mtDNA) present in human preimplantation embryos. It is believed that a chromosomally normal embryo with a MitoGradeTM score lower than the established threshold will have a higher chance of successful implantation in comparison to a similar embryo with a higher MitoGradeTM score.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —(Adult, Older Adult)
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Center criteria:
- •Offered only to those clinics with >20% MitoGrade elevated embryos
- •Patient criteria:
- •Persons undergoing IVF and Preimplantation genetic screening (PGS) through Next Generation Sequencing (NGS) will be eligible to be a part of the study.
- •The study will be limited to those patients who have 4 or more PGS-classified normal embryos
- •Patients not undergoing PGS will not be included as part of the study.
- •Patients undergoing PGD (for genetic disorders) plus PGS will be excluded.
排除标准
- •No other specific group of individuals (age, ethnicity, egg donation, etc) will be excluded.
结局指标
主要结局
Implantation rates between MitoGrade normal and MitoGrade elevated embryos
时间窗: Post natal analysis (9-10 months after replacement)
Using DNA fingerprinting (via cheek swab) to determine which embryo implanted
次要结局
未报告次要终点
