GM1 Biomarker Sperm Capacitation Assessment

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Solution Overview

Problem

Current methods for assessing male fertility, particularly sperm capacitation, are inadequate as they do not effectively determine fertilizing potential and are influenced by cryopreservation, which can alter sperm viability and function, and lack sensitive and simple biomarkers for capacitation.

Innovation Solution

The method involves using the Cap-Score ™< Test, which measures the percentage of specific GM1 localization patterns in sperm to determine capacitation status and fertility potential, allowing for the identification of optimal insemination timing and reproductive approaches based on capacitation time and fertility status.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If standard semen analysis is used to assess male fertility, then the assessment is simple and widely available, but it does not effectively determine fertilizing potential

Engineering Contradiction:
Improvefertilizing potential assessmentVSAvoidassessment method complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces traditional mechanical/physical semen analysis methods with a biochemical assay system that measures sperm capacitation biomarkers. This substitution enables accurate assessment of fertilizing potential by detecting molecular changes during capacitation, rather than relying on simple morphological and motility parameters.

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

Solution Approach 2:

The patent introduces specific biomarkers as intermediaries to bridge the gap between simple semen analysis and accurate fertilizing potential assessment. These biomarkers serve as measurable indicators that reflect the complex physiological state of sperm capacitation, enabling indirect but accurate measurement of fertilizing capability.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Duration of action of stationary object

If cryopreservation is used to preserve sperm for extended periods, then sperm can be stored for future use, but freezing and thawing negatively affect sperm viability and function

Engineering Contradiction:
Improvesperm storage durationVSAvoidsperm viability and function
Core Design Contradiction:
Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent performs capacitation assessment before cryopreservation to determine the optimal timing for insemination. By evaluating biomarker levels in pre-frozen samples, clinicians can plan post-thaw insemination timing to coincide with the sperm's natural capacitation window, thereby maintaining high fertilizing potential despite the freezing process.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses biomarker measurement as feedback to adjust insemination timing recommendations based on individual sperm samples. This feedback mechanism allows customization of insemination protocols to account for variations in capacitation rates, ensuring optimal fertilization timing even after cryopreservation.

Inventive Principle:
Principle #23Feedback

3Duration of action of stationary object

If cryopreservation is used to preserve sperm, then sperm can be stored, but the fertilization window is shifted or limited

Engineering Contradiction:
Improvesperm storage durationVSAvoidfertilization window
Core Design Contradiction:
Duration of action of stationary objectVSLoss of time

Solution Approach 1:

The patent performs capacitation assessment before cryopreservation to determine the optimal timing for insemination. By evaluating biomarker levels in pre-frozen samples, clinicians can plan post-thaw insemination timing to coincide with the sperm's natural capacitation window, thereby maintaining high fertilizing potential despite the freezing process.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent dynamically adjusts insemination timing recommendations based on measured biomarker levels. Rather than using fixed time windows, the system adapts the optimal insemination time to each individual sample's capacitation status, maximizing the utilization of the fertilization window after cryopreservation.

Inventive Principle:
Principle #15Dynamics

4Measurement precision

If phosphorylation of tyrosine residues is used as a capacitation biomarker, then capacitation can be assessed, but the evaluation takes multiple days and provides only semi-quantitative assessment

Engineering Contradiction:
Improvecapacitation assessment accuracyVSAvoidevaluation time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces complex multi-day phosphorylation assays with a simplified biochemical detection system using ELISA or similar rapid assays. This substitution maintains the ability to detect capacitation biomarkers while reducing the evaluation time from multiple days to a single day or less, and providing quantitative rather than semi-quantitative results.

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 provides a reliable and reproducible method to assess sperm capacitation and fertility, enabling tailored reproductive strategies that improve fertilization chances by identifying appropriate insemination timing and techniques, complementing traditional semen analysis.

Implementation Method 1

treating a first sample of t0-in vitro capacitated sperm cells with a fixative and a fluorescence label; treating a second sample of t1-in vitro capacitated sperm cells with a fixative and a fluorescence label

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP3936850B1A method to identify an approach for achieving mammalian fertilization and time period for insemination
Publication Date: 2023.08.09 ANDROVIA LIFE SCI LLC
  • EP3936850B1 patent drawingFigure 1A~1B
  • EP3936850B1 patent drawingFigure 2A~2B
  • EP3936850B1 patent drawingFigure 3A~3B

AI summary

The diagnosis of male infertility is based predominantly on the results of standard semen analysis for concentration, total motility, progressive motility, volume, pH, viscosity and/or morphology. When sperm enter the female reproductive tract, they must undergo a series of physiological changes, known as capacitation, in order to fertilize an egg. This process involves plasma membrane changes that occur in response to stimuli within the female tract. These changes include removal of sterols and redistribution of the ganglioside GM1. Semen analysis identifies only half the cases of male infertility due to standard semen analysis providing little information on sperm functional competence. Previous data demonstrated that localization of the ganglioside, GM1, identifies sub-populations of sperm capable of undergoing the functional maturation process known as capacitation and tracks strongly with fertility.