Boys look for girls; sperm rush to meet the egg. This was the routine history of human reproduction, until Professor Robert Edwards, a physiologist at the University of Cambridge , in England, materialized the miracle of conception in a test tube. In November 1977, Edwards’ team succeeded in having an egg taken from Lesley, a Bristol woman with a lesion in the fallopian tubes that prevented her from being a mother, was fertilized in a well – a glass container used in the laboratory. by a sperm provided by her husband John Brown.
On the 10th of that month, the resulting embryo was transferred to Lesley’s uterus. After an uneventful pregnancy, little Louise was born at Oldham General Hospital on July 25. The first test tube baby in history had come into the world. Professor Edwards knew that childbirth was a milestone in the history of medicine, but never imagined that it had opened the doors to an unpredictable era of human reproduction. Since Louise, more than a million test tube babies have been born around the world; 80,000 of them in our country. Let us remember that the first Spanish test tube baby, Victoria Ana, was conceived by in vitro fertilization (IVF) at the Dexeus Clinic in Barcelona, 19 years ago.
Today, the majority of men and women with fertility problems have a high possibility of being parents thanks to the list of assisted reproduction techniques that has emerged in the last 30 years and that allows solving previously unimaginable situations of sterility. Without going any further, scientists have learned to freeze oocytes -immature eggs- and ovarian tissue from women at high risk of undergoing early menopause, of those who may become infertile due to medical treatment, such as chemotherapy; or those who simply want to postpone motherhood. This cryopreserved material has already been used to harvest more than a hundred pregnancies around the world, five of them in Spain.
And in certain male sterilities, specialists can recover spermatids – sperm precursor cells – from the testicles of sterile men and microinject them into an egg. But scientific advances in the field of assisted reproduction are also creating unusual situations that pose serious bioethical and legal dilemmas, and unleash feelings of indignation and rejection on the part of certain sectors of society. For example, last July a lesbian couple from the United Kingdom became the first to generate a baby with semen acquired online and, around the same time, the press reported the birth at the Fertility Clinic in Ghent, in Belgium, of a child whose sex had been chosen at the express wish of the parents – the choice of sex in Spain and other European countries is only authorized for medical reasons.
Uterus rental
The rental of uteruses, the screening of embryos by means of genetic tests, the artificial pregnancy of menopausal women and those over 60 years of age, the cloning of embryos, the same freezing of eggs, the so-called post-mortem pregnancies of widows with frozen semen of their partner and the conception of babies to save the life of a sibling constitute acts that are observed by society in general and by the scientific community in particular with more concern than admiration. Undoubtedly, the continuous advances in assisted reproductive techniques (ART) have been welcomed by the population as commendable advances in helping that 15 percent of couples who have a problem conceiving children. But, as mentioned, a part of society looks at this type of treatment with suspicion, perhaps because of the specter of abuse of a new technique; or perhaps because of religious ideas that collide head-on with the handling of a biological material such as the embryo or with a fact as sacred as reproduction within the marriage institution. Without fear of misunderstandings, these and other facts have notoriously influenced legislators and scientific committees when it comes to channeling and setting limits to artificial reproduction. Legislation on this matter is uneven in different countries, which is creating a situation that is becoming known as reproductive tourism. On occasions, the regulations make waters in some sections and leave the doors open to controversial practices; and many experts complain that laws lag behind advances in reproductive medicine.
Certain proposals do not help to clear the picture: the announcement by a sect of the generation of children by cloning, a technique whose harmlessness for the future baby has not been verified, has provoked reactions of repudiation; and the recent experimental creation of a hermaphroditic embryo from male and female cells by Professor Norbert Gleicher of the Chicago Reproductive Medicine Foundation in the USA has been fiercely criticized by many reproductive scientists.
On the other hand, dissonant voices warn that some of the artificial insemination techniques in use, such as the so-called intracytoplasmic sperm injection (ISCI), the use of cryopreserved oocytes, the transfer of frozen embryos and the recent appearance of in vitro maturation of oocytes (IVM), have not been sufficiently evaluated. Certain controversial studies suggest that these procedures could lead to chromosomal alterations in embryos. Nor should we forget that ovarian stimulation practiced to optimize fertility is not harmless: it increases the risk of carrying twins or triplets and, therefore, the risk of premature childbirth. In addition, the TRAs themselves generate a surplus of embryos that ends up being cryopreserved for a time limit of between 1 and 8 years, depending on the country. In ours, the Law of Assisted Human Reproduction of 1988 established a maximum period of five years, but did not specify the fate of the expired embryos.
Frozen embryos
Official figures speak of the existence of some 35,000 frozen embryos: 18% of these have exceeded the legal term for cryopreservation. The reform of the Law put into operation introduces measures that try to alleviate this accumulation. Thus, except in exceptional cases, only a maximum of three embryos can be transferred – until now there was no limit – per cycle, while the maximum number of oocytes that can be fertilized in said cycle is restricted to this same number. On the other hand, the legal modification specifies that the surplus embryos “will be kept cryopreserved for a period equivalent to the fertile life of the woman, in order to be transferred to her in subsequent attempts.” But what will be the future of those so far preserved in the freezers of the reproduction clinics?
The modification contemplates that their owners will be able to choose voluntarily between these three options: keep the embryos frozen until they are transferred, donate them for reproductive purposes to other couples who are on the in vitro fertilization waiting list or allow the biological material obtained after Thawing can be used in research for therapeutic purposes. At this point, it must be emphasized that the human embryo has become an object of desire for so-called regenerative medicine, since it constitutes a source of stem cells. Also known as stem cells, these cells have the virtue of being able to become any of the 220 cell varieties that make up our body.
This capacity, which is total in embryos of just a few days -totipotent cells-, appears limited in the later stages of embryonic development -pluripotent cells- and very restricted in adult life -multipotent cells-. Medical trials with stem cells clearly constitute a glimmer of hope for those who suffer from now incurable pathologies. For example, injecting stem cells into the liver would produce new hepatocytes that would rejuvenate the organs affected by cirrhosis and hepatitis. Stem cells could also be forced to differentiate to regenerate infarcted hearts, repair the pancreas of diabetics, weld the spinal cord of tetraplegics, and tackle neurodegenerative disorders, such as Parkinson’s and Alzheimer’s disease. They could even restore sight to the blind.
Reproductive medicine
Reproductive medicine itself would benefit from stem cells from embryos left over in IVF, according to specialist Alan Trounson, from the Monash Institute for Reproduction and Development, in Ritchmond (Australia). For example, stem cells could make parents to certain couples who are unable to produce their own gametes or reproductive cells. “In the future, we will be able to get hold of a handful of cells and rebuild from them the equivalent of eggs and sperm,” predicts Dr. Trounson. The first trials in this direction are already in the making.In Tokyo, Toshiaki Noce, from the Mitsubishi Kagaku Institute of Life Sciences, has cultivated stem cells extracted from mouse embryosso that they spontaneously transform into different cell lines and collect only those aimed at the production of male gametes. This work is still unpublished, but Noce assures that male primordial germ cells (CGPs) have appeared in the culture, which arise in the first stages of spermatogenesis, that is, the production of sperm. These CGPs do not go any further in a culture medium, but when the Japanese scientist transplanted them into the testicles of a rodent, he found that after three months they had matured into cells capable of fertilizing eggs. Now, the litmus test is to determine whether healthy mice are born from the embryos. ? We cannot know to what extent these sperm are normal, since even morons can activate the eggs ,? warns Noce. Another trial led by George Daley of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, points in the same direction.
This expert stem cell biologist claims that he has obtained spermatocytes – a post-CGP stage in sperm formation – from mouse embryonic stem cells. The results of the trial have not been published either, although Daley tells us that his team “is trying to see to what extent it can isolate sperm with the ability to fertilize the female sex cell.” Despite the therapeutic promises of stem cells from embryos – specifically, from surpluses in assisted reproduction – different anti-abortion associations and religious groups oppose their therapeutic destiny, since it implies their destruction. They argue that the human embryo, even in its zygote state – the cell resulting from the fusion of the sperm and the egg – is a new individual of the human species. Many scientists disagree and respond that in the blastocyst stage -64 cells-, the embryo still does not meet two essential requirements to be considered a new human being: that of uniqueness -being unique and unrepeatable- and that of unity -being one. ?
This is one of the problems of the so-called status of the human embryo that has been discussed for many years and that will take time to resolve. The application of stem cells for therapeutic purposes and especially in the area of reproductive medicine is only the tip of the iceberg of the new bioethical dilemmas that lie ahead. These emerge in an incessant trickle from the work being done by biologists engaged in the artificial synthesis of sex cells, that is, concocted outside the testes and ovaries. The interest is clear: the incipient therapeutic cloning will require a collection of human oocytes to transform the patient’s own cells into tissues that will replace those lost due to age, disease and trauma.
Assisted reproduction
And some experts in assisted reproduction are optimistic for the first time to use laboratory-grown eggs and sperm to make sterile couples happy. The aforementioned embryonic stem cells constitute an artificial source of gametes, but it is not the only one. During the XIX Annual Conference of the European Society for Human Reproduction and Embryology, which was held last July in Madrid, Tal Biron-Shental, of the Meir Hospital, in Kfar Saba (Israel), perplexed the attendees while describing his attempt to grow eggs from ovaries from aborted fetuses.
The scientists took cells from the fetal ovaries and kept them in a culture broth for a month. This allowed them to verify that the oocytes – the precursor cells of the ovules – that normally evolve towards maturity during puberty, began their development when they were sprayed with a cocktail of hormones. Will aborted fetuses become a source of eggs for IVF? What would public opinion think of the origin of this biological material? The answer could be captured in a headline in the British press: “Your real mother was an aborted baby.” But even overcoming moral conflicts, the cultivation and production of gametes in the laboratory is extremely complex. One of the biggest limitations is in convincing sex cells to cut their chromosome makeup in half – a normal cell has two sets of chromosomes – an activity that involves a form of cell division known as meiosis.
Another complication is that sex cells do not grow or mature by themselves under natural circumstances : sperm need the collaboration of so-called Sertoli cells; and the precursors of the ovules are clothed and nourished by the so-called granule cells. But science never bows to adversity. In December 2002, John Eppig of the Jackson Laboratory in Bar Harbor, Maine, USA, announced in an online publication the birth of 59 mice out of a total of 1,160 embryos conceived with cultured oocytes. These were matured in a culture medium containing a soup of nutrients and hormones. A few months later, the Japanese Izuho Hatada, from Gunma University, obtained similar results with oocytes from ovaries of mouse fetuses sacrificed in the meridian of their gestation. As of today, it remains to be known if the rodents are completely normal or if, on the contrary, they carry some genetic defect .
Patricia Hunt of Case Western Reserve University in Cleveland, Ohio, has already detected certain chromosomal aberrations in mice sired with cultured oocytes. To avoid the abrupt handling of gametes, some researchers try to trick normal cells in the body into behaving like sperm and eggs. For example, Orly Lacham-Kaplan, a biologist who works at the same Australian institute as Trounson, has succeeded in making mouse oocytes -even with the double set of chromosomes- begin to multiply like a zygote after injecting into their interior adult cells from a male specimen. No less fascinating is the experiment carried out by Gianpiero Palermo , an IVF expert at Cornell University in New York. He has injected the nuclei of adult cells into ovules devoid of their chromosomes to see how these nuclei can reduce the number of chromosomes by half. This species of egg can then be fertilized to become a thriving embryo, according to Palermo.
Enrique M. Coperías
