Implantation success as determined by blastocoel fluid components
Inventors
Roudebush, William • Chosed, Renee
Assignees
Publication Number
US-12305227-B2
Publication Date
2025-05-20
Expiration Date
2039-10-07
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Abstract
The current disclosure explains that cfDNA levels, specific gene expression profiles (assessed via altered mRNA levels of specific gene transcripts), specific protein levels, and potentially noncoding RNAs in blastocoel fluid are all factors that can be used to forecast/determine the implantation potential in IVF patients.
Core Innovation
The invention provides methods and systems for determining the implantation potential of in vitro fertilization (IVF) embryos by analyzing components within blastocoel fluid, specifically cell-free DNA (cfDNA), gene expression profiles (such as altered mRNA levels of specific gene transcripts), specific protein levels, and potentially noncoding RNAs. The approach involves minimally or noninvasive extraction of blastocoel fluid through blastocentesis, measurement of cfDNA or RNA content, and evaluation of apoptotic gene expression to assess embryo viability and forecast implantation outcomes.
The problem being addressed is the limited ability of current embryo selection techniques, such as morphological assessment and preimplantation genetic testing for aneuploidies (PGT-A), to reliably predict which euploid embryos will successfully implant and achieve live birth. Existing protocols do not fully detect biological issues at the cellular or molecular level that may impact embryo competence, especially in cases where euploid embryos fail to implant. There is a need for more informative biomarkers to enhance embryo selection and improve IVF outcomes.
The disclosed invention addresses this gap by measuring and correlating blastocoel fluid cfDNA content, apoptotic gene expression (via real-time PCR), and molecular markers to embryo morphology, ploidy status, and subsequent implantation success. It introduces a weighted embryo morphology algorithm and proposes that elevated cfDNA and specific apoptotic gene expression signatures can indicate higher implantation potential, thus offering a new tool for embryo grading and transfer decision-making.
Claims Coverage
There are two independent claims covering two main inventive features.
Method for determining embryonic viability using blastocoel fluid cfDNA and apoptotic gene expression
This inventive feature involves: - Obtaining blastocoel fluid via blastocentesis from at least one embryo. - Employing an algorithm (Weighted Embryo Morphology Score = (Expansion grade*3) + (ICM grade*2) + (TE grade*1)) via software on a processor to assess embryo viability. - Analyzing cell-free DNA levels in the blastocoel fluid for apoptotic gene expression via real-time PCR for at least one human apoptosis gene. - Determining the extent of apoptotic cell elimination based on the presence of apoptotic remnants in cfDNA. - Quantifying average apoptotic remnant of cell-free DNA amount via fluorospectrometer. - Recognizing that euploid embryos have a higher average amount of apoptotic remnant cfDNA in blastocoel fluid compared to aneuploid embryos. - Combining the weighted significance and cfDNA data to calculate implantation success, and confirming the presence of at least one molecular marker that enhances IVF embryo transfer rate before implanting the embryo.
Minimally invasive embryo evaluation method utilizing blastocoel fluid analysis
This inventive feature includes: - Employing blastocentesis to obtain blastocoel fluid from at least one embryo. - Using an algorithm via software on a processor to calculate a weighted significance for embryo viability with the formula (Expansion grade*3) + (ICM grade*2) + (TE grade*1), where ICM is inner cell mass and TE is trophectoderm grade. - Analyzing cell-free DNA levels in the blastocoel fluid for apoptotic gene expression levels via real-time PCR for at least one human apoptosis gene. - Deriving a level of apoptotic cell elimination from the measured cfDNA apoptotic remnant. - Quantifying average apoptotic remnant of cell-free DNA by fluorospectrometry. - Recognizing that average apoptotic remnant of cfDNA is higher in euploid embryos as compared to aneuploid embryos. - Combining the weighted significance and average cfDNA remnant to calculate embryo implantation success, and confirming presence of at least one molecular marker to enhance embryo transfer success prior to implantation.
The independent claims cover methods for determining embryonic viability and implantation potential through analysis of cfDNA and apoptotic gene expression in blastocoel fluid, quantified with a weighted embryo morphology algorithm and molecular marker detection to enhance IVF transfer success rates.
Stated Advantages
The methods allow for improved prediction of embryo implantation potential by integrating molecular markers found in blastocoel fluid.
The approach is minimally or noninvasive because blastocoel fluid is collected during standard IVF procedures, mitigating risk to embryo viability.
The system provides embryologists an additional tool for better selection of embryos for transfer, potentially increasing IVF embryo transfer success rates.
Documented Applications
Grading and selecting in vitro fertilization (IVF) embryos for transfer to improve uterine implantation rates.
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