Methods for measuring gene expression levels to identify viable oocytes
Inventors
Kordus, Richard • Lavoie, Holly
Assignees
Publication Number
US-11988674-B2
Publication Date
2024-05-21
Expiration Date
2039-03-07
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Abstract
The present invention is directed to non-invasive methods for performing selection of ova, otherwise referred to as oocytes, and/or embryos produced from fertilized oocytes. In an embodiment, performing the selection can include comparing the expression level of a gene in cumulus cell masses harvested from at least two oocytes or at least two embryos, the embryos formed by fertilizing the oocyte. In another embodiment, performing the selection can include comparing the expression level of a gene in a cumulus cell mass harvested from an oocyte or an embryo to a population value. By comparing the expression level of a gene (e.g., using either mRNA expression or protein expression) the embodiments and methods disclosed can provide advantages in selecting an egg for fertilization or an embryo for implantation, such as increasing the chances of successful fertilization and/or live birth. Aspects of this disclosure can provide methods for improving the outcome of in vitro fertilization (IVF) protocols through non-invasive genetic testing using a set of markers for determining or predicting the embryo ploidy status and live birth outcome.
Core Innovation
The invention provides non-invasive methods for selecting oocytes (eggs) and embryos by measuring and comparing the expression levels of specific genes in the cumulus cell mass that surrounds the oocyte. These methods include harvesting cumulus cell masses from at least two oocytes or embryos and analyzing gene expression using mRNA or protein levels, particularly for genes such as AREG, HSD3B1, LHCGR, and PAPPA. The selection may be performed by either comparing gene expression among multiple cumulus cell masses or by comparing the expression from a single mass to a population value derived from known outcomes.
The problem addressed by the invention is the inefficiency and invasiveness of current methods for selecting viable oocytes and embryos in IVF. Traditional selection relies on morphological assessment, which is subjective and not quantitatively comparable, or on invasive genetic testing procedures requiring cell extraction from the embryo, which cannot guarantee live birth and carry risks. There is a need for predictive, quantitative, and non-invasive selection techniques using reliable biomarkers.
The invention solves this problem by using gene expression profiles from cumulus cell masses, which are typically discarded during IVF, as predictive markers for outcomes such as embryo ploidy status and live birth. By using comparative or population-reference analyses of gene expression, the methods enable more informed and non-invasive choices about which oocytes to fertilize or embryos to implant, seeking to improve IVF success rates and reduce unnecessary treatments.
Claims Coverage
There are two independent claims in the patent, each outlining a distinct method for oocyte selection and fertilization using gene expression analysis.
Non-invasive selection of oocytes using comparative mRNA expression analysis of cumulus cells
The method involves obtaining at least two cumulus-oocyte complexes from a donor and harvesting a cumulus cell mass from each. It requires measuring mRNA expression levels of a specified set of genes (AREG, HSD3B1, LHCGR, and PAPPA) from each cumulus cell mass, comparing these between at least two cumulus cell masses, and selecting the oocyte based on relative expression profiles. The inventive step is the determination that a relative decrease in AREG and/or HSD3B1 or a relative increase in PAPPA and/or LHCGR mRNA expression in the cumulus cell mass is indicative of a live birth outcome. The selected oocyte is fertilized and the embryo is implanted in a patient.
Selection of an oocyte for fertilization by comparing gene mRNA expression to a population value
This method involves harvesting a cumulus cell mass from an oocyte, measuring the mRNA expression level of a set of genes (AREG, HSD3B1, LHCGR, and PAPPA), and comparing each gene’s expression value to a population value determined from outcomes of other cumulus cell masses. The inventive feature is selecting the oocyte for fertilization based on the comparison with the population value, with a relative decrease of AREG and/or HSD3B1 or a relative increase of PAPPA and/or LHCGR indicating increased likelihood of live birth. The selected oocyte is fertilized and the resulting embryo is implanted in a patient.
The claims are primarily directed to non-invasive, biomarker-based selection of oocytes or embryos by using quantitative gene expression levels in cumulus cells, either via direct comparison between samples or against population norms, to predict and improve IVF outcomes.
Stated Advantages
The method provides a non-invasive protocol for selecting oocytes and embryos, reducing the need for invasive genetic testing.
The approach uses cumulus cell masses that would otherwise be discarded, minimizing risk to the oocyte or embryo and improving safety.
By providing predictive, quantitative markers, the method enables more informed selection, increasing the chances of successful fertilization, implantation, and live birth.
The patent states potential for reducing the number of embryos implanted, number of IVF cycles, and genetic tests needed, thus saving patients time and costs.
Implementation of the methods can make IVF procedures more cost-effective for patients and clinics.
Documented Applications
Selecting oocytes or embryos for fertilization and implantation in in vitro fertilization (IVF) protocols using non-invasive genetic markers.
Improving the outcome of IVF procedures by aiding selection of eggs or embryos likely to result in euploid embryos and live birth.
Providing recommendations about fertilizing or implanting oocytes or embryos based on quantified gene expression in cumulus cells.
Reducing healthcare costs and the number of IVF cycles required for patients seeking fertility treatment.
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