Follicular fluid biomarkers that predict oocytes with high pregnancy rates

Selection of oocytes using follicular fluid miRNA markers that correlate with pregnancy outcome can provide fertility treatments with high pregnancy rates

Advantage and Core Benefit

  • Possible to predict the probability of having a live baby based on the expression of miRNAs in follicular fluid as an indicator
  • It can be used as an indicator for storage and freezing decisions for each oocyte and fertilized egg
  • Provides a qualitative assessment that is different from grading by visual findings

Background and Technology

It is estimated that 10-15% of couples who wish to have children are infertile, and the importance and necessity of ART (assisted reproductive technology = ICSI/IVF) in reproductive medicine is increasing.
The general flow of ART is as follows: (1) Multiple follicles in the ovary are matured by fertility drugs, and follicular fluid is obtained by follicle puncture.  (2) Eggs are retrieved from the follicular fluid and fertilized with sperm in culture medium or under a microscope to obtain fertilized eggs.  (3) When multiple fertilized eggs are obtained, one or two of the highest-grade fertilized eggs are selected and returned to the uterus according to visual grading criteria. (4) If there are any remaining high grade fertilized eggs, they may be cryopreserved.
Although some techniques have been developed to evaluate the grade of fertilized eggs by combining microscopic images and AI, these techniques are not sufficient in terms of qualitative evaluation. In addition, some studies have focused on oocyte quality and compared molecular markers, but few studies have resulted in pregnancy outcomes.
The inventors performed a comprehensive analysis focusing on small RNAs in the extracellular vesicles (EVs) of the follicular fluid obtained at the time of egg retrieval, and identified a group of miRNAs that are characteristically expressed in fertilized eggs that resulted in pregnancy and live births. By analyzing the EVs in follicular fluid at the time of egg retrieval, it is expected to contribute to important selection criteria such as the selection of frozen eggs and embryos for transfer by enabling objective evaluation of appropriate eggs.

Data

  • Expression of miR-16-2-3p, miR-378a-3p, and miR-483-5p in EVs in follicular fluid of oocytes that resulted in pregnancy (Pregnancy) and those that did not (Non-Pregnancy) (A) and correlation between the three marker expressions and pregnancy outcome (B)

Patent

Pending in Japan

Researcher

Dr. Akira Yokoi and Dr. Hiroaki Kajiyama (Department of obstetrics and gynecology, Nagoya University)

Expectations

We are seeking diagnostics companies to work on the practical application of the miRNA marker of this invention and look forward to collaborating with companies that are good at miRNA and EV analysis. We also welcome the participation of women’s clinics that are willing to cooperate in joint research to demonstrate the usefulness of this biomarker.

 

Project No. WL-04383

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