Blastocoel Fluid cfDNA Analysis for Embryo Implantation Prediction

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Solution Overview

Problem

Current methods for selecting embryos for implantation, such as preimplantation genetic testing for aneuploidies (PGT-A), have limited success in predicting implantation potential, as they do not account for biological markers unique to implanted euploid embryos.

Innovation Solution

The method involves analyzing cell-free DNA (cfDNA) and RNA levels in blastocoel fluid to determine apoptotic cell elimination and embryo viability, using techniques such as RT-PCR and fluorospectrometry to assess cfDNA content and caspase-3 activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If preimplantation genetic testing for aneuploidies (PGT-A) is used to identify euploid embryos, then chromosomal abnormalities can be detected, but implantation success rate remains less than 60% because biological markers of implantation potential are not assessed

Engineering Contradiction:
Improveploidy status detection accuracyVSAvoidimplantation prediction reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The evaluation of embryo quality is segmented into multiple independent assessments: chromosomal ploidy status (via PGT-A), apoptotic cell elimination (via cfDNA levels), and implantation potential (via gene expression profiles). This segmentation allows each parameter to be measured and optimized independently, revealing that euploid embryos with high apoptotic activity and specific gene expression patterns have superior implantation outcomes

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The blastocoel fluid serves as an intermediary medium that contains and transports multiple biological markers (cfDNA, mRNAs, proteins) from the embryo to the external environment. By analyzing this fluid, the patent enables non-invasive assessment of embryo quality parameters without directly interfering with embryo development, thereby improving implantation prediction while maintaining measurement precision

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If apoptosis is enhanced to eliminate aneuploid cells during preimplantation development, then embryo self-correction capability improves, but measurement of apoptotic activity and its correlation with implantation potential becomes more complex

Engineering Contradiction:
Improveembryo self-correction capabilityVSAvoidapoptotic activity measurement complexity
Core Design Contradiction:
ReliabilityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent establishes a feedback mechanism where apoptotic activity in the embryo is measured indirectly through cfDNA levels in the blastocoel fluid. This feedback loop allows clinicians to assess the embryo's self-correction capability and implantation potential without direct intervention, using quantifiable markers that correlate with developmental competence

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

Direct observation and measurement of apoptotic processes within the embryo are replaced by analyzing molecular markers (cfDNA fragmentation patterns, caspase-3 activity, apoptotic gene expression) in the blastocoel fluid. This substitution transforms an inherently complex cellular process into measurable biochemical parameters that can be assessed using standard laboratory techniques

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Higher levels of cfDNA in blastocoel fluid are correlated with euploid embryos and may indicate successful apoptotic cell elimination, potentially improving the prediction of implantation potential and selecting the best embryo for transfer.

Implementation Method 1

cell free DNA/RNA may be assessed using fluorospectronomy

Methodology Applied
Scientific EffectFluorospectrometry: Fluorescence

Implementation Method 2

analyzing cell free DNA/RNA levels in the blastocel fluid

Methodology Applied
Scientific EffectRT-PCR:

Data Source

PatentUS12305227B2Implantation success as determined by blastocoel fluid components
Publication Date: 2025.05.20 UNIVERSITY OF SOUTH CAROLINA
  • US12305227B2 patent drawing
  • US12305227B2 patent drawing
  • US12305227B2 patent drawing

AI summary

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.