Oocyte Co-Culture With Ovarian Support Cells for In Vitro Maturation
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Solution Overview
Problem
Current methods for in vitro oocyte maturation (IVM) are inefficient, resulting in low oocyte quality and poor embryo viability, with traditional spike-in methods like follicle-stimulating hormone (FSH) achieving only 5-40% maturation and embryo viability rates under 17%, while immature oocytes are often discarded, limiting the available oocyte pool for IVF.
Innovation Solution
Co-culturing oocytes with a population of ovarian support cells, such as granulosa and stroma cells, optionally modified to express FOXL2, NR5A1, GATA4, RUNX1, and RUNX2, to promote oocyte maturation, potentially using follicular triggering agents like FSH, clomiphene citrate, and hCG to enhance the process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional spike-in methods like FSH are used for in vitro maturation, then the process is simple to implement, but the maturation rate is low (5-40%) and embryo viability is poor (under 17%)
Solution Approach 1:
The patent introduces ovarian support cells (granulosa cells and stroma cells) as intermediary elements that mediate between the culture medium and the oocytes. These cells provide paracrine support and create a more physiological microenvironment, leading to improved maturation rates and embryo viability compared to direct spike-in methods
Solution Approach 2:
The invention recreates the in vivo ovarian follicular environment by culturing oocytes with ovarian support cells in vitro. This copying of the natural microenvironment allows immature oocytes to mature properly, achieving maturation rates exceeding 70% and embryo viability rates over 50%
2Quantity of substance
If immature oocytes are discarded traditionally, then the available oocyte pool for IVF is limited, but maintaining all retrieved oocytes increases culture complexity and reduces oocyte quality
Solution Approach 1:
The ovarian support cell culture system serves multiple functions simultaneously: it supports maturation of immature oocytes, maintains the quality of matured oocytes, and can be applied to all retrieved oocytes regardless of initial maturity stage. This universal approach expands the usable oocyte pool while maintaining quality through the protective microenvironment
3Productivity
If the follicular triggering period is extended beyond 8 days, then oocyte maturation may be enhanced, but the treatment duration increases and patient burden increases
Solution Approach 1:
The patent performs in vitro maturation of oocytes after retrieval, which is a preliminary action that completes the maturation process outside the body. This eliminates the need for extended in vivo follicular triggering, reducing treatment duration to under 8 days while maintaining high maturation efficiency through the ovarian support cell culture system
Data Source
AI summary
Featured are methods, compositions, and apparatuses for the in vitro maturation of oocytes. In particular, the disclosure features methods of inducing oocyte maturation in vitro, by co-culturing a female subject's oocytes with an ex vivo composition containing a plurality of ovarian support cells (e.g., granulosa cells). Additional methods for administering follicular triggering agents and retrieving oocytes from the female subject are provided. Such methods, compositions, and apparatuses are particularly useful for assisted reproduction technology (ART) procedures.