Improving human oocyte and embryo ploidy, using cFEE peptide: interest for women's fertility. – FERTILIVE

Women's fertility is linked to their oocytes quality. Indeed, before ovulation, oocytes have to resume their meiosis, then to activate the zygote upon fertilization and finally to support the embryonic development for the 5 days of tubal transit before implantation in the uterus. This represents a burst of energy, which is mostly supported by their mitochondria. But their mitochondrial activity permanently decreases with the women’s age leading to aneuploid oocytes and infertility.
Furthermore, nowadays young women are increasingly delaying their first pregnancy for social reasons. Indeed, today, the age of the first delivery is at 31, compared with 23, 30 years ago. It reduces dramatically the length of their genital life, since the oocytes quality drops dramatically around 37 years old.
It is a major social problem leading to procreative tourism towards countries with less care to ethical behavior and women's rights, since Assisted Reproductive Technology (ART) by itself does not improve the oocyte’s quality. Actually, before 35 years old an oocyte has 4.5% chance to give a child: at 40 years old, it takes 140 oocytes to have a baby, while the ovarian reserve falls.
Many attempts have been run to solve the problem, mostly based on mitochondrial transfer. They are either banned because of heteroplasmy or are difficult to implement requiring surgical procedures and ovarian biopsies prior to ART attempt.

The Fertiline molecule that we discovered (Patents No. FR0313545 and No. FR1558899) represents a real new solution. Just supplementing the medium with the molecule, it improves the gametes metabolism of energy. In mice, it increases the fertilization rates, the blastoformation by more than 20% and the percentage of healthy offsprings per embryo transferred by more than 30%.
In a prospective randomized clinical trial, authorized by the “Agence de la BioMedecine” (ABM) (Clinicaltrial.gov: NCT02161861), it improved the in vitro maturation rate of immature oocytes by more than 50% and reduced the miscarriages rate, suggesting an improvement of the oocyte and embryo ploidy.
A complete transcriptomic analysis of embryos will be conducted by RNA seq, CGH array and methylome analysis in three species, with particular attention being paid to imprinted genes expression.
- In mice which has the advantage of quick gestation,
- In bovine which, as human being, belongs to mono-ovulating species with heterogeneous follicular cohorts,
- In humans, using embryos donated for research.
Our project will be complemented by a prospective, randomized clinical trial at the Cochin Hospital for which the authorization is being asked to ANSM and ABM who already authorized the first clinical trial.

Our hypothesis is that in humans Fertiline should significantly improve the percentage of mature oocytes and baby born by ART, even for women over 37 years old, thus answering to the Societal Challenge 4 "Life, health and well-being”.
The study of the mechanism of action of the molecule will furthermore be a very significant scientific advance in the understanding of cellular mechanisms of energy regulation, and the production of transcriptomic data in three species an important step in the comparative analysis of species evolution. Our consortium combining fundamental research, exploration in several species and a clinical application will be able to ensure the success of the project.
There are 140,000 attempts of ART in France, more than one million in the world for which more than 40% of women are over 35 years old. It is therefore a major issue for women’s fertility and couple’s life.