Since 2021, the law of bioethics allows any woman aged between 29 and 37 to self-preserve her eggs without medical advice. This conservation is then a first step towards a potential PMA (Medically Assisted Reproduction) possible up to 45 years old. A way to offer additional storage to the ovarian reserve and thus, offer a serious medical response to average age of first birth which recedes from year to year (31,1 ans in 2023 – source INED) as well as additional ammunition for demographic rearmament (only 1.8 children per woman in 2022, the lowest figure since 1946 according to INED).
We are only at the beginning of fertility preservation!
Although the 2021 law theoretically allows any woman to preserve her oocytes before the age of 37, the question of slow access to fertility preservation still discourages candidates, particularly older ones: “As soon as the law was passed, there were a lot of requests for egg preservation without medical reasons. The average time for non-medical treatment is six months to a year to have an appointment then an additional year for the puncture. So in our hospital in Cochin it can take around a year and a half, but it varies from one center to another.”
If the deadlines are this long, they sometimes allow the project to mature. Dr. Aubin Garcia insists on this figure: only 10% to 15% frozen oocytes will actually be used for future assisted reproduction. “Many women are between 32 and 35 years old and have varying projects. We really study on a case-by-case basis, even if it means recommending against the course if it is not relevant, for example if a pregnancy project is already underway.” Because this health journey is not a long quiet river, it requires two grueling steps: a stimulation using hormone injections, then a puncture of oocytes under local or general anesthesia, more or less painful, with (minimal) risks of infection. The puncture allows the conservation of 10 to 15 oocytes of varying quality and it is sometimes necessary to repeat the maneuver with age to maximize the number of oocytes preserved.
Even in the case of an optimal puncture, return on investment is not guaranteed. The chances of having a child through this process involving IVF (In Vitro Fertilization) are estimated at around 70% for eggs frozen before the age of 35, and 30% for oocytes frozen between 36 and 40 years old. Those of having a complicated pregnancy (pre-eclampsia, gestational diabetes, etc.) also increase with the age of the body.
For all these reasons, oocyte preservation without medical advice cannot today be considered as a guaranteed life project. It simply remains a plan Ban additional option to natural fertilization. But tomorrow, perhaps medical will be seen as a more solid route?
Improving fertility preservation for women, the challenge of tomorrow
One thing is certain: research is progressing to facilitate parental plans and compensate for declining fertility. Thinking about less invasive methods in the stimulation process ovarian its currently in progress. In particular by using an oral pill rather than a skin injection. Dr. Aubin Garcia specifies: “In recent years, we have started to see protocols developed with pills combined with injections. It works quite well, we can imagine that it will develop over the years.“
Another major research topic: biomarker detection making it possible to specify the quality of a frozen oocyte: “The quality of the oocyte is current research, and this will help improve the chances of pregnancy for patients.” rejoices Dr. Aubin Garcia.
As for the quality of the implanted embryo, the research is more complex because it comes up against bioethics laws. In France, the biological information collected in the context of egg freezing followed by assisted reproduction is governed by legislation vigilant against eugenic abuses. In particular theprohibition of communicating a DPI-A (Pre-Implantatory Diagnosis of Aneuploidies), that is to say possible anomalies in the number of chromosomes, reveals the conflict between the interests of the future mother and eugenic excesses. Without this prior diagnosis, an embryo carrying a chromosomal abnormality can be implanted in the body of the future mother.
Caroline C., a 34-year-old Parisian, decided to carry out her IVF in Spain for this reason: “In France, PGD-A is not authorized. But as we age, chromosomal abnormalities increase. This increases the risk of miscarriage as well as medical termination of pregnancy in the case of late detection of a Down syndrome.“
Other biomarkers independent of the oocyte also make it possible to ensure the good performance of IVF, such as the recent (and French) discoveries on free DNA present in blood or biological fluids. As well as deep learning offered by the massive development of artificial intelligence.
Artificial intelligence at the service of IVF success?
Predicting IVF success while avoiding eugenic excesses which consist of deciphering the DNA of an embryo (blue eyes, sex, etc.), that is the challenge for today’s embryologists. Their mission? Reduce the “time to pregnancy”that is to say the number of implantation cycles necessary for a pregnancy, and thus select the best embryos among those available. And with the possible help of artificial intelligence.
In any case, this is the mission of the French company Im-Vitro, founded by Dr. Alexandra Boussommier-Calleja : generalize AI assistance when selecting the best embryo in the clinic in order to avoid miscarriages. The strength of this AI is based on a substantial database from multiple clinics over five years, which associates each embryo implantation with two success metrics : pregnancy then birth. Thanks to deep learning of artificial intelligence, the algorithm thus developed makes it possible to more accurately predict the best embryo among those available:
« For each embryo candidate for injection, the AI will analyze images from the microscope which evolve over time and thus issue an inference, a prediction. More than a precise percentage of success, it determines above all a difference in relative potential en the embryos available, and therefore a classification of them. » explains Dr. Alexandra Boussommier-Calleja.
To establish its classification, artificial intelligence relies not only on the appearance of the embryo, but also the evolution of its development as well as the biological data of the patient (age, BMI, smoking, etc.). The most surprising thing? If AI can predict the best embryo, it does not yet clearly explain its selection process.
Alexandre Boussommier-Calleja specifies: “ It’s very hard to ask the algorithm on which variables its ranking is based. What matters is its effectiveness and therefore its result. We use the technique, but the variables are not clearly communicated to the AI. »
Although the reduction of implantation errors during IVF is progressing, these new technologies cannot significantly push back the biological clock. And a woman over 40 sees her probabilities greatly reduced compared to that of 30.
A more radical solution would be to abolish medical intrusion into investment in cellular rejuvenation, particularly that of oocytes. Studies are already underway to create oocytes in vitro from stem cellswith encouraging success on mice.
Dr. Aubin Garcia specifies that the application for humans is not for tomorrow: “For the moment, cellular rejuvenation therapies remain experimental. And then this may raise other questions tomorrow, notably on the age limit for motherhood.“
While waiting to ask this question, natural fertilization remains today the safest path to a peaceful pregnancy even if scientific advances open up new possibilities. Future mothers must therefore deal with the vagaries of time passing, cells degenerating and the body tiring.
But for how much longer?
