FLIM Embryo Selection via NADH Autofluorescence
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Solution Overview
Problem
Current methods for assessing embryo quality in assisted reproductive technologies are invasive, unreliable, and result in low success rates, leading to high costs and increased risks of multiple gestations and complications.
Innovation Solution
An automated system using fluorescence lifetime imaging microscopy (FLIM) to non-invasively assess the metabolic state of oocytes and embryos by analyzing NADH and FAD autofluorescence, allowing for objective selection of viable embryos for in vitro fertilization or implantation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If standard transmitted light microscopy is used to examine embryo morphology, then embryo quality assessment is performed, but the selection criteria remain subjective and success rates are limited to 35%
Solution Approach 1:
The patent replaces subjective visual morphological assessment with objective metabolic state measurement using fluorescence lifetime imaging microscopy (FLIM). This substitutes the mechanical/optical observation system with a biochemical detection system that measures NADH and FAD fluorescence lifetimes, providing quantitative metabolic parameters that objectively indicate embryo viability and implantation potential.
Solution Approach 2:
The patent changes the assessment parameters from morphological features (shape, size, cell structure) to metabolic parameters (NADH fluorescence lifetime, FAD fluorescence lifetime, metabolic ratio). This parameter transformation enables objective quantification of embryo quality based on cellular metabolic activity, which correlates with developmental potential and implantation success.
2Measurement precision
If genomic, transcriptomic or proteomic based assays are used to assess embryo quality, then more reliable selection may be achieved, but embryo biopsy is required which is invasive and significantly reduces rates of embryo survival
Solution Approach 1:
The patent employs autofluorescence imaging of endogenous metabolic cofactors (NADH and FAD) that naturally exist in living embryos without requiring external dyes, labels, or biopsies. The embryos' own metabolic molecules serve as the fluorescent probes, enabling non-invasive assessment of metabolic state and quality while preserving embryo integrity and survival rates.
Solution Approach 2:
The patent replaces invasive physical biopsy with non-invasive optical detection. Instead of removing cells for genomic, transcriptomic, or proteomic analysis, the system uses fluorescence lifetime imaging to detect metabolic state through intact embryo autofluorescence, eliminating mechanical damage while providing comparable or superior quality assessment.
3Measurement precision
If metabolomic assessment by measuring changes in metabolites in embryo culture media is used, then metabolic state can be assessed, but a prospective randomized trial failed to show improvement over morphologic evaluation alone
Solution Approach 1:
The patent extracts and measures metabolic information directly from the embryo itself rather than inferring metabolism from culture media composition. By imaging NADH and FAD fluorescence lifetimes within the embryo, the system obtains direct metabolic readout from the embryonic cells, bypassing the indirect and unreliable route of analyzing culture media metabolite changes.
Solution Approach 2:
The patent replaces chemical analysis of culture media with optical detection of embryonic autofluorescence. This substitution provides direct visualization and quantification of metabolic state through fluorescence lifetime measurements, offering superior reliability compared to indirect metabolomic assessment of culture conditions.
4Reliability
If multiple embryos are transferred to increase pregnancy rates, then more opportunities for successful implantation are provided, but rates of multiple gestations increase greatly increasing mortality rates and suffering
Solution Approach 1:
The patent performs preliminary metabolic assessment of multiple embryos before transfer using FLIM imaging. By evaluating NADH and FAD fluorescence lifetimes and calculating metabolic ratios, the system identifies the single highest-quality embryo with greatest implantation potential, enabling selective single-embryo transfer that achieves high pregnancy rates while avoiding multiple gestations.
Solution Approach 2:
The patent inverts the traditional approach of transferring multiple embryos to ensure pregnancy. Instead, it uses precise metabolic characterization to identify and transfer the single best embryo, achieving high success rates through quality over quantity. This inversion eliminates multiple gestation risks while maintaining or improving pregnancy outcomes.
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 a minimally invasive, rapid, and reliable means to select healthy embryos, potentially increasing pregnancy rates, reducing multiple pregnancy risks, and lowering healthcare costs by improving the accuracy of embryo selection.
Implementation Method 1
fluorescence lifetime imaging microscopy (FLIM) of NADH and/or FAD
Implementation Method 2
analyzing NADH and FAD autofluorescence
Data Source
AI summary
The invention provides novel non-invasive in vitro methods for assessing the metabolic condition of oocytes and/or embryos with fluorescence lifetime imaging microscope, that can be used, for example, in assessment of oocytes and embryos in assisted reproductive technologies.