Bioethics and development embryonic
Gonzalo Herranz.
department Bioethics Department, University of Navarra.
Course on Tubal Physiopathology.
department Obstetrics and Gynaecology.
University Clinic, School of Medicine, University of Navarra.
21 May 1999.
The two models of ethical analysis
Embryofetal Medicine and Pharmacology
The ethics of counter-management
The obligation to speak out about the embryo
Greetings and thanks
The whole course revolves around the reproductive function of the tube. The tube is, after all, an oviduct. Michel Idoate and Fernando de la source have already said enough about this. What I want to do in my talk is to draw attention to the ethical aspects of a few basic facts: that fertilisation usually takes place in the tubal ampulla, and that the first hours and days of the embryonic development take place here and in the isthmus.
These well-known facts have very important medical-ethical implications. The main one concerns who the human embryo is that is engendered in the fallopian tube and lives in it for four or five days. But no less important is the ethical relationship to be established between the doctor and the woman in whose fallopian tube an embryo floats.
It does not seem, from entrance, to pose us many problems to trace the coordinates, in time and space, in which the brief tubal phase of the human embryo takes place. Its life is measured in hours and days from the zero moment of fertilisation. Its existence takes place in the lumen of the tube, in its ampullary, isthmic and interstitial segments.
We know that in those days, the embryo experiences a few days of vertigo. We should never tire, in renewed amazement, of the fact that we are begotten in the tube: that is where the gametes are found and that is where the zygote is formed. And this is no accident: the tube is an active structure that captures and receives the gametes, nourishes them, matures them, and directs them to meet.
In the tube, the sperm complete their process training. In the tube, the oocyte, after fertilisation, has to eliminate half of the charge Genetics that it contains, thanks to the completion of the second meiotic division, asymmetrical, which expels the second polar corpuscle. In the tube, syngamy takes place and the accelerated process of zygote segmentation begins, leading, by the end of the third day, to a morula of 12 or 16 cells. At the end of the stay in the tube, with the embryo still enveloped in the pellucida, the process of compaction takes place, in which the cells establish special adhesion systems (with tight junctions at the periphery; intercellular communication links and desmosomes in the deepest portions) that set the stage for the rapid transition to blastocyst and the denudation of the pellucida on the fifth day, with the embryo's entry into the endometrial cavity.
While these very visible things are happening, a strong activation of the embryonic genome itself is taking place at the molecular level. With each passing year, the old idea that the young embryo is inert in terms of genome activation and that in its first days it lives off the abundant ribosomal heritage inherited from the mother is being demolished. The activation of the native embryonic genome is very early and takes place as early as the two-blastomere stage.
In the tube, wrapped in the pellucida, the embryo lives its individual life, and begins to babble its dialogue, for the moment only molecular, with its mother. We do not know very well the molecular interactions that depend specifically on the presence of an embryo, and not a mere oocyte, in the tube, but we do know that there is a veritable cascade of reactions and adaptations, of the release of growth factors by the tubal epithelium that influence the initial development of the embryo and that, little by little, we will learn the messages that the embryo sends to this epithelium.
Clinically, however, the tubal embryo makes very little noise. It goes unnoticed. It is there, but its presence is only suspected later, when it is a couple of weeks old and has become sufficiently loud for that molecular babble to become an explicit hormonal language, when the chorionic gonadotropin it secretes is capable of transforming the mother's physiology, mutating the process of menstruation into the process of gestation.
But despite this silence, the tubal embryo exists. What relevance should the doctor give to the embryo? This is an important question. If by patient we mean a human being who, regardless of his or her state of health or illness, enters into a professional relationship with the physician, the physician has always perceived the possibility, though not always the reality, that an embryo may be present in the womb of a fertile, sexually active woman. Thus, the question must be asked: who are the patients to be seen when attending to a woman who is a potential mother?
In the medical internship and until not so long ago, the dominant answer was that only one. In the clinical context, the human embryo was, from the beginning of time until two or three decades ago, an unknown, silent, hidden being. Its presence could only be indirectly suspected and confirmed when, as a foetus of about four months, it gave the first unmistakable signs of its presence through its active movements. The comparison between perceived foetal movements, foetal life and a certain awareness of gestation has left traces in morality, law and general culture that have not been erased.
This is why, in the past, the doctor, because of his enforced lack of certainty, felt a mixture of respect and perplexity towards the woman of childbearing age, as he could never be sure whether she was pregnant or not. Unable to establish a direct professional dialogue with the embryo, he tended to regard the fertile woman as his only patient, a complex patient, of which the embryo might be an integral but unperceived part.
The research and new technologies are changing the landscape and will change it more and more. More and more importance is being given to knowledge and medical applications aimed at the periconceptional period. It is true that we cannot visualise the tubal embryo in the clinical examination. But more and more data are accumulating thanks to the research, carried out in this ethically ambiguous field, on the in vitro embryo.
The embryo, even before implantation, will be increasingly known and taken into account, thus creating new professional relationships and ethical responsibilities between embryo and doctor. And this, even with the civil service examination of an extremely radical feminist sector, which considers that medicine brings with it the risk of devaluing the subjective, naturist experience of pregnancy and the whole maternal-fetal relationship.
The two models of ethical analysis 
In American medical ethics, so closely tied to the legal, so dependent on what judges say, two models, the unitary and the maternal-fetal dyad, have been constructed as framework for reference letter of obstetric ethics. The two models offer different options for determining the extent to which the woman's genital tract is, so to speak, a "public space", a place of human interaction, in which judges, lawyers, philosophers and politicians, and above all doctors, can assess whether or not certain interventions are justified to protect the future child from the risks arising from the mother's illness, way of life, work or leisure. Or, on the contrary, if it is a private and exclusive place where only the woman reigns with almost absolute power.
In the American ethico-legal perspective, the models are used to discuss when and under what conditions it is possible to order a necessary treatment to cure or prevent a disease of the foetus itself, to protect it from maternal diseases (diabetes, infections) or against damage resulting from pathogenic lifestyles of the mother (alcohol, illegal drugs, sexual activity), or to save it from high-risk obstetric situations (caesarean section); even to grant or deny the capacity to conceive.
The two models have usually been used for situations involving the foetus in late gestation or immediately prior to delivery. It is worth reflecting on their relevance for the doctor's relationship with the pregnant woman and her embryo.
Let's start by taking a look at the more general features of each model.
For the unitary model , there is only one capable and competent patient before the doctor: the woman. The embryo is in her, as part of her body. She determines the importance given to the embryo. She regulates the flow of information that circulates between embryo and doctor and filters through her agency the decisions that are made regarding the maternal-embryonic unit. The relationship is linear. The doctor has an ethical obligation to promote the well-being of this unit, advising and prescribing to the woman, but he does not enter, so to speak, into a direct dialogue with the embryo, because the mother speaks for herself and her embryo. The doctor has no rights or responsibilities that bind him directly to the embryo. Rather, they are mediated, indirect and subordinate through the organic whole that is the pregnant woman.
In the unitary model , scientific data and evidence-based criteria play a secondary role, because they do not determine the final decision to be taken. The skill to decide is concentrated in the sole autonomous agent with the capacity to decide, which is the pregnant woman. The doctor must respect what the woman decides and, out of professional loyalty to her, should not, in critical situations, allow his capacity for committee and persuasion to be limited to the private sphere, and not be replaced by the coercive intervention of a judge. At the very least, the doctor, in this model, should not take the initiative for apply for the intervention of the public prosecutor's office. In a typical interpretation of this ideology, the American Medical Association association states: "If he were to seek a court order, the physician would be depriving the pregnant woman of her right to accept personal risk and substituting his own judgement staff about the amount of risk that is acceptable for her. Such a course of action undermines the very foundation of free and informed consent.
In contrast, at model of the maternal-fetal dyad, the embryo and foetus tend to be seen as a genuine, individual patient, whose welfare and rights appeal directly to the physician. Obviously, because his relationship is now established with two particularly related patients, the physician cannot be blind to the welfare and rights of the pregnant woman. He must take them into account, for they are necessary for him to be able to treat the mother, who is always one of his two important patients. Now, however, the doctor can no longer consider only the overall effect of his treatment on the combined unit of mother and embryo, but must consider individually what is best for each of his two unique patients.
The elevation of the embryo to the status of patient can enrich in an extraordinary way, and also complicate, the decision-making process, because it doubles the doctor's responsibilities, and makes them much more explicit, both when they coincide and when they conflict. At model of two patients, situations in which the autonomy of the mother and the benefit of the embryo clash do not have a predetermined solution, but must be source of much reflection and constructive solutions.
Doctors in the Hippocratic-Christian tradition usually subscribe to the model of two patients, as it allows them to advocate more strongly in favour of the embryo, which is, in addition to an imperative of charity, a very strong professional argument to refute abortion.
The future works in favour of the model of two patients. As we learn more about what happens in the very young embryo, the doctor's responsibility towards it becomes clearer. There are already many signs that point in this direction: the labour right of a woman to be protected from the genetic risks of her offspring, the requirement of reliability of pre-implantation genetic diagnosis, the limitation of the issue number of embryos that can be implanted in the uterus in assisted reproduction interventions, the repression of iatrogenic damage caused in the early period of the embryo's development . The future connects, on the model of two patients, with the tradition of periconceptional care aimed at preventing alterations of the development neural tube and teratogenic damage induced by drugs or physical agents.
As is well known, the peculiar biology of the embryo creates, so to speak, a specific pharmacology, very closely linked to the dyadic model : a pharmacological action beneficial to the mother may provoke undesired effects on the embryo.
Fortunately, in contrast to what happens in the following weeks, the relationship of the tubal embryo with drugs is not very important. In the first two weeks, the embryo is relatively refractory to malformation disorders.
The young embryo has not yet developed, or possesses only in a very rudimentary state, the mechanisms by which, in later prenatal or postnatal life, drugs are managed to exert their effects. The embryonic organism itself has not developed some of the molecular and cellular Structures for the uptake, metabolisation and elimination of many drugs. They cannot exert their specific actions on effectors that have not yet developed or have not matured sufficiently at Degree .
Embryofetal Medicine and Pharmacology
The spectrum of pharmacodynamic reactions in the embryo is very narrow. Either the drugs have no effect on the embryo, often because the placenta is impermeable to them, or, if they are active, they interfere, not with highly differentiated functions, but with the basic functions of the embryonic organism, which are cell proliferation and differentiation of the outlines of organs. The consequences are easy to understand: some are general and non-specific, such as embryo death and miscarriage, or global growth deficiency with reduced birth weight; others are focal and specific, constituting the many different types of malformations or local disorders of development. This is teratogenic toxicity.
Under the effects of drugs that harm it, of anti-cancer agents given to the mother, for example, the tubal embryo can suffer cell losses which, if they do not exceed a certain level, can be compensated without consequences thanks to the formidable repair capacity of its toti- or pluripotent cells; if the damage exceeds a certain threshold of intensity, it can cause irrecoverable lesions leading to its death. They can, however, cause damage.
This suffices to support the conclusion that, in the context of respect for nascent life, there are, in the mother-embryo dyad, certain professional-ethical duties of the physician when prescribing medicines to women of childbearing age. The physician must refrain from prescribing potentially teratogenic drugs and offer them alternative, non-teratogenic drugs that are similar in efficacy and safety. If there is no alternative and the maternal disease, because of its severity, must be inexcusably treated with a teratogenic drug, it must be given at the most effective dose leave, as many teratogenic effects are dose-dependent. In cases where teratogenic drugs are of only marginal benefit or where the nature of the disease permits deferral of treatment, it is ethically obligatory to defer therapy until organogenesis has been completed and there is no longer an appreciable risk of inducing malformations. For diseases that require continued treatment, non-teratogenic drugs should be used before conception and during the first trimester and switched to other drugs during the remainder of the pregnancy.
However, despite all due caution, it will not always be possible to avoid a few cases of inadvertent, accidental or unavoidable exhibition to teratogenic drugs. There are drugs, such as some vitamin A analogues, isotretinoin, for example, that maintain their teratogenic action for months. If their administration is suspended, it is possible to avoid some of their adverse effects. And there are drugs that cannot be discontinued continuously, such as some anti-epileptic drugs, as fail treatment could have serious effects. In these cases, the imperative to do no harm obliges the doctor to seek the right balance between the treatment of the mother's illness and the preservation of the life and health of the embryo, as he or she has a moral responsibility to protect the embryo and to avoid serious harm resulting from exhibition to these drugs.
Physicians and, to the extent that it is their duty, pharmacists must always be guided by sound scientific data , not by anecdotal data which may induce an unfounded anti-therapeutic attitude. Even today, the sombre memory of the thalidomide tragedy continues to exert a pessimistic effect on the general assessment of drug teratogenicity.
We must bear in mind that, in the context of the maternal-embryonic dyad, it is not only the mother who can become ill. The embryo can. If the embryo becomes ill, it must be treated. The Code of Medical Ethics and Deontology of the Spanish Medical Association states in its article 25.2 that "The sick embryofetal human being should be treated agreement with the same ethical guidelines, including the informed consent of the parents, that inspire the diagnosis, prevention, therapy and research applied to other patients". The doctor must advise the pregnant woman, when the prevention or cure of an embryonic disease so requires and for the good of the embryo, the application of medicinal treatments, the adoption of dietary measures or the modification of lifestyle, even if this requires some renunciations and sacrifices. It should not be forgotten that most mothers are usually willing to sacrifice some of their safety, lifestyle and health for the well-being and safety of their children.
However, there is no shortage of those who believe that the autonomy of the pregnant woman should not be sacrificed in order to satisfy the health needs of the embryo. They use much more legal than ethical arguments to argue that the mother is under no obligation to suffer so that the necessary medical care can be provided to the embryo or foetus. If she did, they say, she would be reduced to the passive role of a foetal container, which she opens in order to gain access to the child, even at the risk of damaging the container. Enthusiasm for nascent embryo-fetal medicine has also been criticised as offering strong support for the right to life of the unborn, a right that may collide, especially when the mother has taken certain risks, with the legally recognised right to abortion.
Fortunately, mother-embryo relations remain a more endearing and humane field of gravitation than the cold analysis of conflicting rights by the cult of death. Undoubtedly, the future development of embryofetal medicine and surgery, both curative and preventive, will increase opportunities and conflicts. It is to be hoped that the more or less important servitude that the protection of the health and wellbeing of the embryo or the treatment of its illnesses requires of the pregnant women will be rendered with the love and availability of a mother. Let us not forget that in our language, to gestate is to carry and sustain the mother in her womb the living fruit from fertilisation to the moment of delivery.
This time, from conception to delivery, tends to be extended to include the preconception period, the days immediately preceding fertilisation. This time has become a time of high pharmacological temperature. It is the time when drugs that try to prevent the onset of certain errors of the development and in particular neural tube closure disorders must be used. But it also, and paradoxically, includes the days when counter-gestational drugs or poisons act, which try to destroy the newly conceived embryo, either by intercepting the mechanism of nidation or by acting as abortifacients of the embryonic phase.
The ethics of counter-management
The history of the pharmacology of hormonal contraception points to a clear evolutionary trend: its point of action has been shifting from the woman to the embryo. It started out as anovulatory: the first generation pill tried to prevent ovulation with the clear aim of preventing fertilisation, purpose , and achieved this at the cost of its high hormonal content. Now it does not exclude interceptive action: it is no longer of interest to interfere with ovulation, as it is more effective to prevent the nidation of the embryo. And if nidation has already taken place, it can be eliminated by means of the abortion pill, which is most effective against embryos of less than 8 weeks. From contraception we have moved on to contraception.
When Baulieu coined the term counter-management, he did not do so to designate the action of RU 486 in a new way. He was trying, with the neologism, to banish the idea of abortion: "My purpose - he wrote - is to eliminate the word abortion, because this word is as traumatic as the fact of abortion itself". But he was also interested in highlighting the fact that the abortion pill is not, as an abortifacient, a novelty in the field of birth control. Many methods of fertility control," he said, "are not contraceptive in the common and accepted sense of the term. In the case of intrauterine devices, hormonal contraception based on gestagens and postcoital contraception, we are dealing with a post-fertilisation interruption, which would have to be considered as abortifacient. [...] For this reason, we have proposed the term 'contragestation', a contraction of 'contra-gestation', to include most methods of fertility control.
In a sense, the contraceptive arc is now closed. A very recent work on the contraceptive efficacy of mifepristone states: "A dose leave of mifepristone, which does not inhibit ovulation, significantly reduces fertility by altering the endometrium". Endometrial contraception is seen as a promising and very attractive way forward, as it will leave ovarian function intact and will hardly disturb the course of the menstrual cycle. The cost of contraception will be entirely borne by the embryo position and will be physiologically free of charge for the woman. In the social-ethical field, people talk about endometrial contraception, as if it had nothing to do with the embryo. But it should not be forgotten that the pharmacology of endometrial contraception seeks to alter the endometrium minimally as far as the woman is concerned, but makes it inhospitable as far as the embryo is concerned. Taking advantage of the increasingly precise knowledge of the continuous and sophisticated molecular dialogue between mother and embryo, the aim is to specifically alter the expression of certain factors that are necessary for implantation. The result is the inhibition of blastocyst implantation.
The obligation to speak out about the embryo
Are you pregnant or could you be pregnant? Please speak to the nurse. So says a warning posted in the cubicles of the Radiodiagnostic Services.
I would like to conclude by referring to a significant aspect of the doctor's relationship with the embryo: to take it into account when talking about it with its mothers.
They should refer to him or her as a human being when informing their patients in antenatal consultations, and especially when prescribing and dispensing. It is important to talk about the safety and risks of medicines in the first two months of pregnancy.
But this is rarely done. There seems to be, in many medical circles, on the professional internship and on research, a conspiracy of silence around the young embryo in the mother's womb, especially the embryo not yet nested. The preference is to forget it or cancel it out. We do not know much about it. It is also of little interest to know too much, because it is good to have an escape to download from the ethical tension of embryonic destruction of contraception and assisted reproduction.
To achieve this, a redefinition of concepts and the circulation of a new language has been used, which "refutes the misconceptions and misinformation that, in the past, have obfuscated the whole question of the mechanisms of contraception". The light that sheds light on the problems comes with the precise (re)definition, based on scientific data , of the terms 'gestation' and 'abortion', redefinitions that are endorsed by illustrious political-scientific corporations, probably more interested in dressing up professional routines with apparent dignity than in clarifying the reality of the facts.
We refer, for example, to the authority of the ACOG (the American College of Obstetrics and Gynecology), which defines conception as the implantation of the blastocyst. Conception is therefore not synonymous with fertilisation. Gestation is defined as the woman's state extending from conception (implantation) to the termination of pregnancy. These new definitions received the blessing of FIGO (the International Federation of Gynaecology and Obstetrics), which had been commissioned by the World Health Organisation in 1985 to develop a precise definition of gestation. It offered this one: "Gestation is established only with the implantation of the fertilised egg".
From agreement with the (re)definitions of conception and gestation, abortifacient agents are only those that act to terminate gestation after implantation has been completed.
The pre-implantation period of the embryo is not taken into consideration, it has been hidden from us. This deprives obstetrics of the very important chapters of fertility and sterility, of fertilisation and its disorders, of the tubal course of the human embryo, of the fascinating process of nesting.
What is serious is that the lexical redefinition is not established as a matter of politically correct language, but is elevated to the status of a hard and unappealable biological fact: "The biological fact is that gestation begins with implantation and not with fertilisation. When a fertility regulation procedure works before implantation, it is ethically and medically important to explain to patients that the method is not abortifacient. We understand that there may be different opinions about when gestation begins, but [...] these beliefs cannot change the biological process involved.
The human embryo in its first week is thus cynically relegated to the sad status of the "disappeared". Their destruction does not appear in the official catalogue of ethical conduct. This is an aggressive, unscientific, manipulative attitude, because it is not based on observation of the facts, but on their partial, capricious and wilful suppression.
It would be good, then, if we can no longer speak of abortion, or even, as Baulieu wanted, of contragestation, to redefine contragestative embryo elimination in precise terms. We should speak of embryocide.
Nothing is said about what happens to the embryo between fertilisation and nesting: neither its biological entity nor its ethical status. The experts, the official authorities have decided to ignore its existence. The naïve frankness with which the pre-implantation embryo is officially volatilised is disturbing. Official science disregards it, ignores it: it is a non-existent.
With the support of organised science, it has become official doctrine that the crucial biological time between fertilisation and nesting is of no interest to clinical embryology, to the physiology or pharmacology of reproduction, and, not surprisingly, to ethics as well.
This is clearly an unscientific, manipulative attitude, because it is not based on observation of the facts, but on their partial, capricious and voluntaristic suppression. By redefining conception and gestation, a window of moral irresponsibility is created: the destruction of the pre-implantation embryo cannot be called abortion, nor can the agents that kill them or make the nesting of the pre-implantation embryo impossible be called abortifacients. But the reality is clear and undeniable: many contraceptive agents act through the destruction of human beings in the days of their floating existence from fertilisation to nesting.
But it has not been necessary to wait for development for contraceptives with abortifacient action to understand the continuum that contraception and abortion form. More than twenty years ago, when abortion laws were taking their first steps in advanced countries, Emily Campbell wrote in the International Inventory of Information on Induced Abortion: Abortion and contraception should be considered conceptually as complementary elements that apply in a total system of birth planning and fertility control. Abortion is often described as the most frequently used mode of birth control and possibly also as the procedure by which most births have been prevented issue . Induced abortion has played a more prominent role than contraception in the fertility decline experienced in the developed Western world.
What a great pity that the knowledge we have of the human embryo is so often scorned, even banned! In my view, one of the greatest miscarriages of justice of all time was the decision of the Supreme Court of the United States when, in 1983, in the lawsuit of a reproductive health centre against the municipality of Akron, Ohio, ruled that showing a woman seeking an abortion a photograph of an embryo the age of the one she intended to destroy or showing her a live ultrasound image of the living embryo she was carrying was not only an illegitimate way of providing information for consent to abortion, but an assault on liberty, a parade of atrocities, a sample of ideological torture. Never have the data that science is capable of revealing been more brutally disregarded.