Why Doctor: The film Joy traces the years of research by British doctors Dr Patrick Steptoe and Dr Robert Edwards as well as nurse embryologist Jean Purdy, who developed In Vitro Fertilization (IVF) and enabled the birth of the first test tube baby in the world in 1978. How did IVF arrive in France?
Professor Frida Entezami, reproductive biologist and co-head of department : French scientists became interested in IVF when research began to take place in England. It is the maternity ward of the Antoine-Béclère hospital in Clamart – which, in collaboration with gynecologist René Friedman and biologist Jacques Testard – managed to have the first French test tube baby. This is Amandine who was born in 1982, 4 years after Louise Brown who is talked about in the film Joy.
Professor Nathalie Massin, gynecologist and co-head of department : In fact, there were several French teams working on In Vitro Fertilization at that time. The first pregnancy was not achieved in Clamart. As I recall, it took place at the Clinique Marignan, a private structure which no longer exists today. The latter did not come to an end. In reality, there were several miscarriages before Amandine was born.
What must be remembered is that several teams entered into “the competition” to succeed in implementing an innovative technique to give people who were unable to conceive the opportunity to have a child. It is still extremely valuable.
“Today, in France, medically assisted procreation represents 3 to 4% of annual births”
More than 40 years after the birth of Louise Brown and Amandine, how many babies have seen the world thanks to IVF and Medically Assisted Reproduction (AMP) in France?
Professor Nathalie Massin : 40 years after Amandine's birth, it is estimated that more than 400,000 children have been conceived by IVF in France. In its latest report published in 2023, the Biomedicine Agency identified 158,826 ART attempts (including intrauterine inseminations, IVF and thawing of frozen embryos with gametes and embryos whether or not donated, Editor’s note) for the year 2022.
So today, in France, medically assisted procreation represents 3 to 4% of annual births. It's a lot.
Moreover, if I look at those around me, I know many couples who have had to follow an Assisted Reproduction program to have a child. Is it a coincidence or is there, in fact, an increase in consultations for infertility?
Professor Nathalie Massin : We are slowly seeing the number of annual MPAs progress, but we tend to see a plateau in recent years. This impression of a significant increase in cases comes, in part, from the fact that people are also talking about it more. PMA, miscarriage… The word is spreading around infertility disorders. Couples share their difficulties more easily with those around them. It's a less taboo subject than a few years ago.
But, are there more cases of infertility? The answer is yes. On the one hand, because women postpone their conception plans until later. This is a very important factor for the chances of conception.
Pr Frida Entezami : The other element is a continuous decline in sperm quality over the last 30 years. The sperm concentration dropped by 50%. The share of male infertility is actually only increasing in the indications for medically assisted procreation.
Added to this are the environmental conditions with all the endocrine disruptors that we have around us in the water, in the food, and in the air too. The household products and cosmetics we use. These three causes join hands and lead to greater recourse to medically assisted procreation.
In reality, between the societal causes which lead to a real decline in the desire to have a family and infertility, our population will decrease steadily in the near future.
IVF: “In the laboratory, we really went from night to day”
How does IVF work now? This must have changed a lot over the last 40 years?
Professor Nathalie Massin : For the clinical part, there has been little evolution. There have been improvements in the protocols we use. But overall, the basis remains the same. That is to say, the woman must take several days of injection. Then she must undergo surgery before she can have an embryo transfer. Overall, there haven't been a lot of changes.
Pr Frida Entezami : There was a fairly important one, all the same. At the start of IVF, eggs were retrieved by laparoscopy. Now, it’s truly a minimally invasive procedure. It is done vaginally. This is a huge improvement. In addition, until 1991-92, patients whose eggs had to be retrieved had numerous blood tests because ovulation could not be triggered correctly. They could, for example, take their dosages at 3 a.m. Depending on when they had their peak of ovulation, they had to go to the operating room for laparoscopy in the middle of the night. There has been a real paradigm shift since 1995. Gynecologists have managed to better stimulate and better control ovulation and collection.
And what about the laboratory part and the fertilization of the collected eggs?
Pr Frida Entezami : In the laboratory, we really went from night to day. At the very beginning of In Vitro Fertilization, at the end of the 1970s, embryo culture was done in salt water. Whereas today, our culture media are enriched with nutrients to closely mimic the natural conditions of a woman's body.
In 1992, a revolutionary technique called ICSI arrived. This involves the injection of a sperm selected under a microscope into an egg. This has revolutionized the management of male fertility disorders when sperm quality is very low.
The third most notable point at the laboratory level was the improvement in embryo freezing techniques, particularly with the arrival of vitrification. This is important because casually, we no longer have to place all the embryos in the uterus. This limits as much as possible the risk of multiple pregnancies which can cause risks for the mother or the babies.
Infertility: “There is also research on ovarian aging and oocyte rejuvenation”
What are the next challenges for research in terms of IVF?
Pr Frida Entezami : Our next challenge in terms of biology is to obtain – as far as possible – the ability to choose the embryo so well that there is no failure. This will certainly involve metabolic and genetic analyzes which will make it possible to very precisely select the best embryos.
There is also a lot of research on ovarian aging and oocyte rejuvenation. You should know that in women, fertility declines enormously from the age of 37. If we could find a way to stop this time – other than by freezing oocytes – or to rejuvenate an egg that has already aged, we could restore fertility to women of advanced age.
For men who have absolutely no sperm production, we are looking for a way to transform either cells found in their testicles or somatic cells (i.e. body cells) into sperm.
Assisted reproduction: “a bit like in Welcome to Gattacathe question of the best compatibility could be asked”
And the challenges for the clinical aspect?
Professor Nathalie Massin : Ovarian aging is also a challenge in the clinic, since we see patients arriving with increasingly late requests. As the success of our treatments is essentially based on the number of oocytes or sperm that we will recover, if we have only one oocyte, we will not necessarily be able to do things well. We must therefore progress in this area.
Genetics will likely be at the heart of this system. She will be able to help us determine which treatment protocol will be most suitable for a patient and her gametes. Choices can also be made based on the spouse's gametes. We are not yet at the stage of being able to say whether two people are compatible or not. But actually, a bit like in Welcome to Gattacathe question of the best compatibility could be asked.
Progress is also expected in treatment. When we do In Vitro Fertilization. The patient must have at least 3-4 blood tests, 3-4 ultrasounds. She moves every time. There is therefore more and more development of “At-home monitoring” projects, that is to say connected objects which follow patients and simplify the journey a little.
The question of clinical profiling also arises. All our patients are not the same: between those who have endometriosis, those who have polycystic ovarian syndrome, or even obesity problems… However, today, we apply almost the same protocols to everyone. world. Thanks to big data and artificial intelligence, we will move towards increasingly personalized precision medicine.
Desire for a child: “We are moving towards a reproduction of choice whether we like it or not”
What do you think the future holds for progression?
Pr Frida Entezami : In 1998, upon release of the feature film Welcome to Gattaca, uOne of my teachers told us: “Go see this film, it’s our future”. I only finally saw it in 2022 and I was amazed. It is truly prescient. In 150 years, humanity will almost only reproduce using IVF, that's for sure.
Indeed, many countries which are not regulated such as France, in particular China and the United States, have already started to offer embryo choices. It started with gender and the latest option is IQ. There is also the possibility of avoiding this or that disease, which can be understood. However, current projects show that we are moving more and more towards choices of appearance as well. These selections will be difficult to avoid because people who can afford them will engage in medical tourism to take advantage of these devices.
Professor Nathalie Massin : There is a need for a real ethical discussion around this question. We cannot consider that we will be able to block it, because there is a real demand. We must be careful about blocking the principle, because society evolves regardless. We are moving towards a reproduction of choice whether we like it or not.
Finally, it is interesting to put the film Joy, which traces the creation of IVF, into perspective with what we do today, and to question what we could go next with artificial intelligence and new technologies. We will certainly not accept being treated tomorrow as we are today, whether for cancer, PAD or metabolic disorders.
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