Female reproductive health researchers analyze an egg in Germany in 2020.picture alliance (dpa/picture alliance via Getty I)
Like much of medicine, that which deals with reproduction has a lot to do with fighting the passage of time.
In the last 30 years, IVF success rates have multiplied, but societal changes threaten to outpace technological progress.
According to data from the Spanish Fertility Society (SEF), in 2020, with the most widely used techniques, 35.5% of the attempts led to delivery in women under 35 years of age, 25.3% for those between 35 and 35 years of age. and 39 and 11.8% when the woman was over 40, an age at which more and more couples want to have children.
Despite the prolongation of life expectancy, the programming of the fertile years seems practically immovable.
This week, the journal
Science
dedicates a special issue to various review articles on the present and future of reproductive medicine, from the moment of fertilization to the birth of a healthy person, and among other more specific conclusions it is recognized that " Despite recent advances in understanding the causes of human infertility, our basic understanding of its complex mechanisms is still limited” or that “the development of therapies to treat pregnancy-related ailments is, for now, inadequate”.
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Most of the failures that prevent delivery after in vitro fertilization are due to genetic failures in the ovum or sperm or in the embryo that they produce when they unite.
Juan Antonio García Velasco, scientific director of IVI, acknowledges that now "many things are done by trial and error" in the selection of these protagonists.
“The ability to sequence the exome [the part of the genome where most disease-causing mutations are found] and correlate it with the phenotype [the visible result that the result of that sequencing will produce] is going to be very important for making diagnoses more precise and shorten the path of treatments, which are sometimes years of agony”, he points out.
This technology "will help us to understand what we do today and thus be able to act with more precision and avoid failed cycles," he adds.
An accurate genetic diagnosis
In an article signed by Lei Wang, from Fudan University, in Shanghai (China), examples of the precision diagnoses that can begin to be applied with the proliferation of genetic studies are given.
In some cases of male infertility due to the absence of sperm in the ejaculate, one solution is biopsies known as TESE, in which tissue is extracted from a testicle through a small incision in search of sperm for in vitro fertilization.
A recent study found that there are some genetic defects that can always be linked to a negative biopsy result, so accurate genetic diagnosis would avoid these types of invasive tests when they are not needed.
In addition to the selection of eggs, sperm or embryos, the path for the personalization of fertility treatments is opening new avenues.
Recent studies suggest, for example, that the polycystic ovary, which makes pregnancy difficult, can be caused by the presence of the bacterium
Bacteroides vulgatus
in the intestinal microbiota.
This interaction between the balance of the ecosystem of microbes that inhabits us and fertility is already used in some clinics for people who have repeated abortions because the embryos do not adhere to the internal wall of the uterus, the endometrium.
“This has to do with aging, and that is something very difficult to reverse”
Juan Antonio García Velasco, scientific director of IVI
"For these people, there is a personalized diagnosis that analyzes the presence of pathogenic bacteria in the endometrium or imbalances of good bacteria such as lactobacillus," explains Lydia Pilar, a gynecologist at the San Carlos Clinical Hospital.
“Chronic endometritis, which are infections of the uterus, cause the embryo implantation rate to decrease by up to 27%,” she says.
In addition to treating these microbial imbalances, the molecular study of the endometrium in search of dozens of genetic variants, "allows us to decide the optimal day, and even the hours, to carry out the transfer at the best time," adds Pilar, who highlights the importance of endometrial analysis to improve the chances of success.
Despite being a vital process, an important part of human reproduction is still shrouded in mystery.
14 days after the union between the ovum and the spermatozoon, gastrulation begins, a process in which the cells begin to organize themselves in a scheme on which the human being will be built.
The ethical barriers to using embryos in these phases of development or the biological differences with some common animal models make it difficult to advance in the knowledge of our first moments of existence.
A week ago, Chinese researchers managed to create macaque pseudo-embryos in the laboratory and implant them in three monkeys.
This model, according to its creators, can help reveal the origin of some congenital defects or explain why one in four human pregnancies ends in abortion.
Another of the works presented today and led by Sarah Stock, from the University of Edinburgh (United Kingdom), points to the possibilities offered by organoids as a model to better understand the pregnancy process.
These simplified and miniature versions of human organs have already been used to produce mini-kidneys, but they have also been used to create mini-placentas in which to study pregnancy problems such as preeclampsia, a complication that increases with age and poses a risk to health. life of the pregnant
For the future, García Velasco states, "the dream would be to restore oocyte function", which is the great limitation for women to have children after the age of 40, when oocyte DNA damage is excessive.
Beyond freezing the eggs, "what we do does not work, for the moment",
adds the scientific director of the IVI.
"This has to do with aging, and that is something very difficult to reverse," he concludes.
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