Non-invasive Embryo Genetic Screening via Laser Zona Breaching
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Solution Overview
Problem
Current preimplantation genetic testing (PGT) methods for aneuploidy, particularly trophectoderm biopsy, are invasive, labor-intensive, and prone to sampling bias, with risks of maternal contamination and variable accuracy in embryo screening.
Innovation Solution
A non-invasive method involving the collection of spent blastocyst culture media and blastocoel fluid to increase the quantity and quality of cell-free embryonic DNA, using laser zona breaching and whole genome amplification (WGA) for genetic screening, which reduces maternal contamination and improves accuracy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If trophectoderm biopsy is performed for preimplantation genetic testing, then genetic screening for aneuploidy can be achieved, but the procedure becomes invasive and carries risks to the embryo
Solution Approach 1:
The patent extracts cell-free DNA from the culture medium surrounding the embryo instead of taking tissue samples from the embryo itself. This extraction approach allows genetic analysis to be performed on DNA that has naturally shed into the medium, avoiding any invasive procedures on the embryo while still obtaining sufficient genetic material for aneuploidy screening
Solution Approach 2:
The culture medium serves as an intermediary between the embryo and the analysis system. By collecting and analyzing DNA present in the medium, the patent creates an indirect method of genetic screening that eliminates the need for direct embryo manipulation, thus reducing procedural risks while maintaining screening accuracy
2Ease of operation
If only spent culture media is used for DNA collection, then the procedure remains non-invasive, but the quantity and quality of cell-free embryonic DNA is insufficient
Solution Approach 1:
The patent merges two previously separate sampling approaches into a single integrated method: collecting both the spent culture medium and the blastocoel fluid together. This combination leverages the non-invasive nature of culture medium collection while supplementing it with blastocoel fluid that contains additional cell-free embryonic DNA, thereby increasing the total quantity and quality of DNA available for analysis without requiring invasive embryo manipulation
3Ease of manufacture
If residual cumulus/corona cells are not removed, then the procedure is simpler, but maternal contamination increases reducing screening accuracy
Solution Approach 1:
The patent performs preliminary removal of residual cumulus and corona cells from the culture medium before DNA extraction and analysis. This preliminary cleaning step eliminates a major source of maternal DNA contamination that would otherwise interfere with accurate embryonic genetic screening, ensuring that the DNA analyzed truly represents the embryo's genetic material
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
This method provides reliable and accurate non-invasive preimplantation genetic screening for aneuploidy, increasing the chances of successful reproductive outcomes by minimizing invasive procedures and improving embryo selection accuracy.
Implementation Method 1
exposing said expanded blastocyst to a laser pulse to extrude blastocoel fluid containing embryonic cell free DNA (cfDNA) in the fresh drop of culture medium
Data Source
AI summary
A non-invasive method for genetic screening prior to embryo implantation is described. Fertilized oocytes are cultured on day 1 followed by removal of residual cumulus/corona cells, reducing maternal contamination; isolating oocytes and culturing individually from days 1-4 with serum protein supplement; conducting laser zona breaching on day 4 allowing embryonic cell free DNA (cfDNA) into the culture medium; washing oocytes with fresh medium to produce a medium containing day 4 cfDNA; transferring into fresh medium under oil, and culturing until day 5, 6, or 7 to form an expanded blastocyst which is transferred on day 5/6/7 into a drop of medium; exposing the expanded blastocyst to laser pulse to extrude blastocoel fluid containing embryonic cfDNA, obtaining day 5/6/7 cfDNA; and conducting genetic screening of cfDNA using whole genome amplification (WGA). The method may be used for genetic screening of embryos for aneuploidy by testing WGA for whole chromosome copy number.