Non-linear Imaging for Egg Maturity Assessment

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Solution Overview

Problem

Current methods for assessing embryo quality in assisted reproductive technologies (ART) are inefficient, with low success rates and high costs due to subjective evaluation of embryo morphology and invasive procedures, and none have been clinically proven to be more effective than traditional light microscopy.

Innovation Solution

The use of non-linear imaging systems, such as two-photon microscopy, to visualize and analyze polar bodies within egg follicles, allowing for the determination of egg maturity and viability without invasive methods or altering metabolic states.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If transmitted light microscopy is used to examine embryo morphology, then the current standard practice for embryo selection is maintained, but the success rate remains low at 10%-35% and the evaluation is subjective

Engineering Contradiction:
Improveembryo quality assessment accuracyVSAvoidsuccess rate
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent replaces conventional transmitted light microscopy with non-linear optical imaging (two-photon microscopy) to visualize polar bodies. This substitution enables objective, quantitative assessment of egg maturity through polar body characteristics (size, shape, position) rather than subjective morphological evaluation, directly addressing the low success rate and subjectivity problems

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

Solution Approach 2:

The patent utilizes fluorescence imaging where polar bodies exhibit distinct fluorescent signals compared to surrounding cumulus cells. By detecting these optical signal differences, the system can automatically identify and characterize polar bodies, transforming the subjective visual assessment into an objective, measurable process that improves reliability

Inventive Principle:
Principle #32Color changes

2Measurement precision

If genomic, transcriptomic or proteomic assays are used to determine egg and embryo quality, then more comprehensive quality information is obtained, but the procedures are highly invasive and severely reduce embryo survival rates

Engineering Contradiction:
Improvequality assessment comprehensivenessVSAvoidembryo damage
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces invasive biochemical assays (genomic, transcriptomic, proteomic) with non-invasive optical imaging. Two-photon microscopy allows visualization of polar bodies and assessment of egg maturity without physical contact or chemical extraction, completely avoiding the embryo damage and reduced survival rates associated with biopsy-based methods

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

Solution Approach 2:

The patent creates optical copies (images) of the polar bodies and egg structures for analysis. By capturing and analyzing fluorescent images, the system obtains comprehensive quality information without physically altering or removing any embryonic material, thus eliminating the harmful effects of invasive procedures

Inventive Principle:
Principle #26Copying

3Measurement precision

If metabolic state assays are used to measure changes in metabolites, then indirect quality information is obtained, but the procedures are challenging and can adversely affect the embryo due to the need to change metabolite levels

Engineering Contradiction:
Improvemetabolic state informationVSAvoidembryo adverse effects
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces metabolic assays that require medium changes and metabolite manipulation with direct optical imaging. Two-photon microscopy visualizes polar bodies and their characteristics without altering the culture environment, eliminating the adverse effects caused by metabolite level changes while still providing quality assessment information

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

4Reliability

If multiple embryos are transferred to improve pregnancy odds, then the success rate increases, but multiple gestations occur which greatly increase mortality rates and suffering

Engineering Contradiction:
Improvepregnancy success rateVSAvoidmultiple gestation complications
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent replaces subjective morphological assessment with objective polar body imaging to accurately identify mature eggs and select the single best embryo for transfer. This improved selection accuracy increases the success rate of single-embryo transfer, eliminating the need for multiple embryo transfers and thereby preventing multiple gestation complications

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

This approach enables accurate identification of mature eggs, potentially increasing ART success rates and reducing costs by providing a non-invasive, reliable method for selecting healthy embryos for fertilization.

Implementation Method 1

non-linear imaging systems, such as two-photon microscopy

Methodology Applied
Scientific EffectTwo-photon absorption:

Implementation Method 2

The non-linear images can be fluorescence images of endogenous NADH (nicotinamide adenine dinucleotide with hydrogen) and/or FAD (flavin adenine dinucleotide)

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS9984278B2Non-linear imaging systems and methods for assisted reproductive technologies
Publication Date: 2018.05.29 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • US9984278B2 patent drawing
  • US9984278B2 patent drawing
  • US9984278B2 patent drawing

AI summary

The present invention generally relates to non-linear imaging systems and methods for use in various assisted reproductive technologies and other applications. In one aspect, the present invention is generally directed to two-photon and other non-linear microscope techniques that can be used to determine the status or maturity state of eggs or egg follicles, for example by determining the presence of polar bodies within the egg follicles. In some embodiments, endogenous metabolites, such as NADH or FAD, can be determined, and in some cases without externally altering those metabolite concentrations or without adding other compounds. Other embodiments of the invention are also directed to computer programs or systems that can be used to determine the status or maturity state of eggs or egg follicles, kits in such systems, or the like.