Análisis de la disforia de género en el ámbito pediátrico. Revisión científica y bioética de la terapia / Analysis of gender disphoria in the pediatric field: scientific review and bioethics of therapy

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[Transsexualism: a Brain Disorder that Begins to Known]. / Transexualidad: Una Alteración Cerebral que Comienza a Conocerse.

Transsexualism describes the condition when a person's psychological gender differs from his or her biological sex. People with gender identity disorder suffer persistently from this incongruence and they search hormonal and surgical sex reassignment to the desired anatomical sex. This review, from an ethical perspective, intends to give an overview of structural and functional neurobiological correlations of transsexualism and their course under cross-sex hormonal administration. Several studies demonstrate an increased functional connectivity between cortex regions reaffirming psychosocial distress of psychologicalbiological sex incongruity. Such distress can be ascribed to a disharmonic body image due to changes in the functional connectivity of the key components of body representation network. These brain alterations seem to imply a strategic mechanism dissociating bodily emotions from bodily images. For a number of sexually dimorphic brain structures or processes, signs of feminization or masculinization are observable in transsexual individuals, who during hormonal administration seem to partly further adjust to characteristics of the desired sex. These changes allow a reduction of psychosocial distress. However, a model leading to a ″gender affirmation″ does not solve the problem, since brain disorders causing it are not corrected. This is a serious medical ethics issue. Prejudices should be left aside. To know what happens in the brain of transsexuals is a medical need, both to define what is and what is not, and so to choose an adequate treatment, and to decide and guide legal actions.

Transexualidad: una alteración cerebral que comienza a conocerse / Transsexualism: a brain disorder that begins to known

La transexualidad describe la condición de una persona cuyo sexo psicológico difiere del biológico. Las personas con trastorno de identidad de género sufren de forma persistente por esta incongruencia y buscan un cambio de la anatomía sexual, mediante tratamiento hormonal y quirúrgico. Esta revisión, desde una perspectiva ética, ofrece una visión de las correlaciones neurobiológicas estructurales y funcionales de la transexualidad y los procesos de cambio cerebrales por la administración de las hormonas del sexo deseado. Varios estudios demuestran un aumento de la conectividad funcional entre regiones de la corteza cerebral, que son huellas de la angustia psicosocial generada por la discordancia entre el sexo psicológico y el biológico. Tal angustia se puede atribuir a una imagen corporal incongruente debida a los cambios en la conectividad funcional de los componentes clave de la red de representación del cuerpo. Parte de los cambios de la conectividad suponen un mecanismo de defensa puesto que disocia la emoción sentida de la imagen corporal. Las personas transexuales presentan signos de feminización o masculinización de estructuras y procesos cerebrales con dimorfismo sexual y que durante la administración hormonal se desplazan parcialmente aún más hacia las correspondientes al sexo deseado. Estos cambios permiten una reducción de la angustia psicosocial. Sin embargo, un modelo de 'reasignación del sexo' no resuelve el problema, puesto que no se trata la alteración cerebral que lo causa. Se trata de una grave cuestión de ética médica. La liberación de los prejuicios para conocer lo que ocurre en el cerebro de los transexuales es una necesidad médica, tanto para definir lo que es y no es un tratamiento terapéutico, como para guiar las acciones legales

Transsexualism describes the condition when a person’s psychological gender differs from his or her biological sex. People with gender identity disorder suffer persistently from this incongruence and they search hormonal and surgical sex reassignment to the desired anatomical sex. This review, from an ethical perspective, intends to give an overview of structural and functional neurobiological correlations of transsexualism and their course under cross-sex hormonal administration. Several studies demonstrate an increased functional connectivity between cortex regions reaffirming psychosocial distress of psychologicalbiological sex incongruity. Such distress can be ascribed to a disharmonic body image due to changes in the functional connectivity of the key components of body representation network. These brain alterations seem to imply a strategic mechanism dissociating bodily emotions from bodily images. For a number of sexually dimorphic brain structures or processes, signs of feminization or masculinization are observable in transsexual individuals, who during hormonal administration seem to partly further adjust to characteristics of the desired sex. These changes allow a reduction of psychosocial distress. However, a model leading to a 'gender affirmation' does not solve the problem, since brain disorders causing it are not corrected. This is a serious medical ethics issue. Prejudices should be left aside. To know what happens in the brain of transsexuals is a medical need, both to define what is and what is not, and so to choose an adequate treatment, and to decide and guide legal actions

Neuroética: la dotación ética del cerebro humano / Neuroethics: ethical endowments of human brain

Los procesos neurobiológicos que subyacen al juicio ético es el foco de atención de la Neuroética. El conocimiento, desde las neurociencias, de qué áreas cerebrales se activan y cuales se silencian mientras las personas deciden cómo actuar ante un dilema moral, ha permitido conocer los correlatos cerebrales que subyacen a los actos humanos y ofrecer una explicación de cómo está impresa en la dinámica del cerebro la dotación ética de cada hombre y común a todos los hombres. De interés central es el papel causal que desempeñan las emociones en el juicio ético y en paralelo las áreas cerebrales relacionadas con las emociones. La finalidad de las inclinaciones naturales del hombre están fuertemente atadas, por hundir sus raíces en los sistemas instintivos de la supervivencia animal, sensible a las emociones básicas; y al mismo tiempo, e inseparablemente, la vida de cada hombre está liberada del automatismo de tales leyes, es decir, regido por la ley de la libertad. El juicio ético es propiedad innata de la mente (AU)

The neurobiological processes underlying moral judgement have been the focus of Neuroethics. Neurosciences demonstrate which cerebral areas are active and inactive whilst people decide how to act when facing a moral dilemma; in this way we know the correlation between determined cerebral areas and our human acts. We can explain how the 'ethical endowments' of each person, common to all human beings, is 'embedded' in the dynamic of cerebral flows. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion-related areas of the brain contribute to moral judgement. The outcome of man’s natural inclinations is on one hand linked to instinctive systems of animal survival and to basic emotions, and on the other, to the life of each individual human uninhibited by automatism of the biological laws, because he is governed by the laws of freedom. The capacity to formulate an ethical judgement is an innate asset of the human mind (AU)

[Neuroethics: Ethical Endowments of Human Brain]. / Neuroética: La Dotación Ética del Cerebro Humano.

The neurobiological processes underlying moral judgement have been the focus of Neuroethics. Neurosciences demonstrate which cerebral areas are active and inactive whilst people decide how to act when facing a moral dilemma; in this way we know the correlation between determined cerebral areas and our human acts. We can explain how the ″ethical endowments″ of each person, common to all human beings, is ″embedded″ in the dynamic of cerebral flows. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion related areas of the brain contribute to moral judgement. The outcome of man's natural inclinations is on one hand linked to instinctive systems of animal survival and to basic emotions, and on the other, to the life of each individual human uninhibited by automatism of the biological laws, because he is governed by the laws of freedom. The capacity to formulate an ethical judgement is an innate asset of the human mind.

El consejo genético prenatal / Prenatal genetic counseling

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Principios éticos básicos / Universal ethical principles

Entre el universalismo y el caso particular se necesitan unos principios básicos que den cabida al juicio ético del médico. Si no se tiene en cuenta la experiencia ética del médico, se podría acabar desarrollando una actitud pasiva. El médico es siempre un estudioso. La falta de rigor científico deja el juicio ético poco racional. De ahí que sea importante recuperar la racionalidad de la ciencia biomédica para aumentar la sensibilidad a dos principios éticos básicos: el respeto al débil y la no discriminación

Some basic principles are needed between universalism and particular case, which accommodates the ethical judgment of the doctor. If the ethic experience of the doctor is not taken into account, a passive attitude could be developed. The doctor is a researcher. The lack of scientific rigor makes ethical judgment less rational. So, it is important to take back the rational aspects of biomedical science in order to uphold two of the basic principles of ethics: respect for the weak and non-discrimination

[Biology and ethics of bioethics: an urgent need of realism]. / Biología y ética de la bioética: la urgente necesidad de realismo.

Tenets and recommendations of bioethics should be based on a profound knowledge of biological processes and at the same time deeply integrated with their human significance. Integration has been usually distorted by those implied in disciplines involved with human nature. Biology of fertilization and embryo development have been often fodder of science fiction, when considering that techniques can achieve any aim without acknowledging natural limits, and often handling data, and accepting without any critical attitude pseudoscientific dogma. In the middle of that pseudo-biology bioethics has suffered the onslaught of the ideology of man believing himself autonomous and claiming he is the only one who dictates the rules of reality of world and man, and leading development and progress with this technological power in his hands. The profoundly different response to this deep question of whether what is properly human and essential to each man emerges as a consequence of his own construction and development or, on the contrary, is inherent to the constitution of each man, has caused the splitting of bioethics into two really irreconcilable bioethics. And that because of their different reasoning and criteria. The Ethics of Bioethics requires a new thinking on this crucial point allowing it to grow as an unprejudiced Science. Serious consequences derive from taking one perspective or another. Adopting one or another perspective confront us with a serious problem. Is human life disposable? Or should it be elegantly preserved?

Biología y ética de la bioética: la urgente necesidad de realismo / Biology and ethics of bioethics: an urgent need of realism

El juicio ético de las intervenciones biotecnológicas se realiza mediante la integración interdisciplinar del sentido natural de los procesos biológicos con el significado humano de esos procesos. La integración se ha distorsionado por los cultivadores de las disciplinas implicadas en lo que se refiere a la constitución del hombre. La Biología de la fecundación y desarrollo embrionario ha sido pasto de la ciencia ficción al considerar que la técnica podrá lograr lo que se proponga y al no reconocer la existencia de límites naturales; y pasto, también, de la manipulación de los datos y de la aceptación acrítica de dogmas pseudocientíficos. Sobre esa pseudobiología, la Bioética ha sufrido la embestida de la ideología del hombre autónomo, que se arroga dictar las normas sobre la realidad del mundo y del hombre y dirigir su desarrollo y progreso en base al poder tecnológico. La respuesta dispar a la cuestión esencial sobre si lo propio humano emerge dela construcción y desarrollo de cada hombre o, por el contrario, es inherente a la constitución de cada uno, ha causado la separación de la Bioética en dos bioéticas irreconciliables en su fundamentación y criterios. La Ética de la Bioética exige una nueva reflexión sobre este punto crucial que parta de una Ciencia libre de prejuicios. Las graves consecuencias que hoy se derivan de asumir una perspectiva u otra, en relación con la disponibilidad o no de la vida humana, parecen exigirlo (AU)

Tenets and recommendations of bioethics should be based on a profound knowledge of biological processes and at the same time deeply integrated with their human significance. Integration has been usually distorted by those implied in disciplines involved with human nature. Biology of fertilization and embryo development have been often fodder of science fiction, when considering that techniques can achieve any aim without acknowledging natural limits, and often handling data, and accepting without any critical attitude pseudoscientific dogma. In the middle of that pseudo-biology bioethics has suffered the onslaught of the ideology of man believing himself autonomous and claiming he is the only one who dictates the rules of reality of world and man, and leading development and progress with this technological power in his hands.The profoundly different response to this deep question of whether what is properly human and essential to each man emerges as a consequence of his own construction and development or, on the contrary, is inherent to the constitution of each man, has caused the splitting of bioethics into two really irreconcilable bioethics. And that because of their different reasoning and criteria. The Ethics of Bioethics requires a new thinking on this crucial point allowing it to grow as an unprejudiced Science. Serious consequences derive from taking one perspective or another. Adopting one or another perspective confront us with a serious problem. Is human life disposable? Or should it be elegantly preserved? (AU)

[Select embryos: preimplantation genetic diagnosis]. / Selección de Embriones Humanos. Diagnóstico Genético Preimplantación.

The ability to detect chromosomal or genetic defects in embryos in vitro, associated with assisted human reproduction techniques before his possible transfer to the uterus to complete its development was presented as an alternative to eugenic abortion. And an option for older women to procreate, to avoid pregnancy of embryos with chromosomal defects. Genetic diagnosis before implantation (PGD) and screening of embryos in vitro (by the acronym, PSC), offers the image of the disabled person as an individual excluded from society. It assumes a direct human experimentation without therapeutic purposes or to manipulate the embryo that is chosen or discarded according to diagnosis or for advancement in perinatal medicine. Because these techniques can have multiple embryos, eugenics has also generated a ″positive eugenics″ that seeks to select embryos according to a third party, having certain characteristics, sex, or lack of predisposition to disease. Several issues demand unavoidable ethical duty to report on this form of eugenics, in addition to be directly and intentionally directed to destroy human life in its early stages, and does not meet the minimum requirements of rigorous scientific research or biotechnology. There have been no previous animal tests to validate the techniques so that there are serious errors in diagnosis with false positives and false negatives. Recently it has been shown that some discarded embryos can eliminate their detected defects two days after the biopsy. Moreover, the study about what may or may not be diagnosed is retrospective and unrecoverable damage. And, of particular importance is the fact that it is not known with certainty the effects that an embryo biopsy may cause to those diagnosed.

[Delay the age of procreation, decline in fertility and increased use of assisted reproduction: risk of birth defects]. / Retraso de la Edad de la Procreación, Incremento de la Infertilidad Y Aumento del Recurso a la Reproducción Asistida. Consecuencias en la Salud de los Hijos.

In recent years there has been a progressive decline in fertility, originated mainly on women by the aging of ovules and on man through changes in genetic material of sperm due to cumulative environmental factors over time. Infertility treatments and techniques of assisted reproduction, IVF or insemination, consist of, or preceded by ovarian stimulation treatment aimed to obtain a large number of mature ovules in one cycle. This stimulation does not resolve the crucial issue of changing the pattern of chemical modification, parental imprinting, which occurs in the epigenetic process of oogenesis. Ovules induced to mature and / or forced to fertilization, do not to provide a fresh genome to be passed in each generation passes from parents to children. These changes affect the regulation of expression of a gene cluster (known as imprinted genes) during embryonic development of the child, give him a predisposition to rare diseases that originate precisely in the chaos of such genes. Some factors that cause infertility can be traced to early stages of development. Therefore, infertility is already a generational issue. It is therefore necessary to inform and alert to important factors, and ways of life, giving rise to emerging problems.

[Estrogens and feminine brain maturation during adolescence: emergency contraceptive pill]. / Estrógenos y Desarrollo del Cerebro Femenino en la Adolescencia: Anticoncepción de Emergencia.

In the period between puberty and maturity takes place the process of brain maturation. Hormone levels induce changes in neurons and direct the architecture and structural functionality thus affecting patterns of development of different brain areas. The onset of puberty brings with it the invasion of the female brain by high levels of hormones, cyclic surges of estrogen and progesterone in addition to steroids produced in situ. Control centers of emotions (amygdala), memory and learning (hippocampus) and sexual activity (hypothalamus) are modified according to the cyclical concentrations of both hormones. Sex hormones stimulate multimodal actions, both short and longer terms, because neurons in various brain areas have different types of receptors, membrane, cytoplasmic and nuclear. The composition of emergency contraceptive pill (postcoital pill) with high hormonal content raises the urgency of a thorough knowledge about the possible effect that the lack of control of the menstrual cycle in a time of consolidation of brain maturation, can bring in structuring and development of brain circuitry. Changes in the availability of sex steroids during puberty and adolescence underlie psychiatric disorders whose prevalence is typically feminine, such as depression, anxiety disorders. It is a fundamental ethical duty to present scientific data about the influence of estrogen in young female brain maturation, both for full information to potential users, and also to induce the appropriate public health measures.

El cigoto de nuestra especie es cuerpo humano / The zygote of our species is the human body

Este artículo muestra cómo la palabra de la ciencia aporta un conocimiento directo e indiscutible acerca del comienzo de la vida de cada concebido de nuestra especie: dice cuándo estamos en presencia de un cuerpo humano en los procesos temporales de transmisión de la vida. Aporta también conocimiento directo acerca del carácter personal del embrión por la continuidad de su desarrollo, ya que lo decisivo no es que tenga lugar una continuidad desde el inicio, las etapas embrionarias y fetales, y el nacimiento, sino que esa continuidad suponga continuidad del cuerpo, que siempre es personal. Y un conocimiento indirecto del origen de cada ser humano, al mostrar qué es un cuerpo humano y cómo este tiene ese carácter peculiar exclusivo de los hombres, el carácter personal. En definitiva, la ciencia pone de manifiesto la presencia de una potencia real, distinta de la fuerza de la vida, involucrada en el origen de cada ser humano. El entrelazamiento en la vida única de cada hombre de la dimensión personal y la dimensión biológica es manifestación inequívoca de que existe un único sujeto personal con dos dinamismos. Un ser personal de naturaleza humana.

This article clearly shows science offers us direct and indisputable knowledge about the beginning of human life. It tells us when we are in the presence of a human body in the temporal processes involving the transmission of life. It also gives us direct information about the personal nature of the embryo through the continuity of its development. The decisive fact is not that there is an uninterrupted sequence from the start; that is, from the early embryonic and fetal stages and birth, but that this continuity assumes the continuity of a body, which is always personal. Science offers us indirect knowledge about the origin of each human being, showing it has a human body and every human body has a trait exclusive to man: that of being a person. Science definitely demonstrates the presence of a real power, one that is different from the living force and is involved in the origin of each human being. The intertwining of biological and personal dimensions in the life of every man is a clear sign that every human being exists as one subject with two dynamisms: a personal being that is human in nature.

Este artigo mostra como a palavra da ciência oferece um conhecimento direto e indiscutível sobre o início da vida de cada ser concebido de nossa espécie: dize quando esperamos na presença de um corpo humano nos processos temporais de transmissão da vida. Também fornece conhecimento direto sobre o caráter pessoal do embrião em seu desenvolvimento, já que o fator decisivo não é a continuidade desde o início, as etapas embrionárias e fetais e o nascimento, mas que a continuidade assumir a continuidade do corpo, que é sempre pessoal. Assim mesmo, o artigo provê conhecimento indireto da origem de todo ser humano, mostrando que é um corpo humano e como ele tem a natureza peculiar dos homens, o caráter pessoal. Em suma, a ciência revela a presença de uma potencia real, diferente da força da vida, envolvida na origem de todo ser humano. O entrelaçamento da dimensão pessoal e a dimensão biológica na vida de cada homem é a manifestação clara de que existe um único sujeito pessoal com duas dinâmicas. Um ser pessoal de natureza humana.

[Communication between mother and embryo or foetus]. / Comunicación materno-filial en el embarazo.

Molecular interactions and cellular exchanges between mother and foetus or embryo in pregnancy generate an intimate symbiosis of two different lives. Interpersonal communication is an established requirement in the life of each man to reach personal plenitude. Initially on a biological basis, each person is open to others and his surroundings. While the body of the child is developing in the womb of the mother, the mother prepares the "last finish", which will allow him to assimilate and adapt to his peculiar world. In parallel, the brain of the mother, stimulated by hormones and pregnancy factors, becomes ready for a rich and complex behaviour.

[From the totipotence of the zygote to mature stem cells and reserve cells]. / De la totipotencia del cigoto a las células troncales maduras y de reserva.

In the process of life-transmission, when could we say that we are in the presence of a developing human body? A new human being starts with conception, after the specific gametes of father and mother recognize and fuse with each other; inherited genetic information is fed back reciprocally between the two "pronuclei", during a number of hours, and the resulting egg cell is more than the sum resulting from the fusion of the gametes. It is a living being in its totipotent unicellular stage, a body indeed, with corporal axes assigned, and ready to develop following a "continuum", a marked-out sequence. Divisions initiated in the totipotent fertilized egg give rise to diverse stem cells: pluripotent, multipotent and germinating cells; these latter cells maturing in special niches. Space-cellular organization of each organ and tissue has a precise site in the early, developing organism following a process with precise starting and finishing times and always preserving the individual as a unit. At precisely linked stages the individual temporarily activates potentialities proper of his biological identity. The fact, being tracked through human biology, that each human body is a manifestation of its owner, offers a clear response to the debated question of the connection between the temporal beginning of each man as a zygote or fertilized egg and the origin of his specifically human capacities.

[Lack of biological exchange in assisted reproductive techniques]. / Carencias de la comunicación biológica en las técnicas de reproducción asistida.

There is a clear dividing line in the group of actions aimed at solving sterility, and the techniques aimed at generating embryos to be transferred to a womb. The dividing line is now clearly established by science. The growing alarm among paediatricians raised by the higher risk of malformations and diseases in children when generated in vitro, with respect to those normally engendered, is leading to the need to clearly establish the consequences of in vitro technologies and informing society in an honest way. Two types of lack of exchange of information, cellular and molecular, cause the detected defects. In the fi rst place it is clear that both gametes should recognize each other when adequately mature and in the appropriate natural environment. In vitro technologies force these conditions and either one or both gametes might be impaired and consequently negative effects for the child might be caused. In the second place both embryo and maternal womb are deprived of that early mother-child communication facilitating implantation.

[Does 2009 mark a revival of embryonic stem cells?]. / ¿Resucitan al inicio del 2009 las células troncales procedentes de embriones?

The legal possibility of using federal funds to work with embryonic cells and destroy embryos started on March 2009 in the USA. It has nothing to do with regenerative therapies. It is directed to create banks with human cells, banks directed by a few scientists involved in biotechnology enterprises connected with centers of in vitro reproduction. They pursue the use of ad hoc human embryos for biomedical research. The idea of using cell lines derived from embryos is quite spread, and even the idea of obtaining new lines of this type to validate reprogrammed somatic pluripotential cells, the so called iPS cell (induced pluripotent stem), without destroying embryos or using ovules. This type of cells is indeed of great value in medical research and it is opening new possibilities in Cell Therapy. Recent data are analyzed and considerations are advanced encouraging rational alternatives to eliminate embryonic cells in the evaluation of iPS cells.

Specific protein nitration in nitric oxide-induced apoptosis of human monocytes.

The sustained overproduction of nitric oxide (NO) observed in inflammatory conditions can contribute to cell demise by affecting apoptosis. Nitration of tyrosine residues occurs in a range of diseases involving macrophage activation. Since NO induces apoptosis in monocytes/macrophages, we tested the hypothesis that nitration of specific proteins could result in apoptotic cell death. The peroxynitrite generator SIN-1 promoted apoptosis in monocytes based on oligonucleosomal DNA fragmentation, caspase-3 and -9 activation, Bcl-2 depletion and accumulation of Bax and p53 proteins. We also found that the signaling pathway triggered by SIN-1 was initiated through tyrosine kinase and Rac activation and resulted in increased JNK and p38 activities. Among the tyrosine-nitrated proteins, Rac and Lyn were identified. Using specific inhibitors for different signaling and effector molecules involved in the apoptotic process we demonstrate that NO, via protein-nitration, could play an important role in controlling the inflammatory response by regulation of monocyte homeostasis.

[Ethical principles in research related to regenerative therapy]. / Etica de la Investigación en Terapia Regenerativa.

Recently published data on the function and properties of stem cells are examined and analyzed. This knowledge enhances our understanding of human development: stem cells follow a precise hierarchical pattern both in time and space, and they are part of the symbiosis of fetus and mother. The data do not support the idea of the existence of an early stage of the embryo development lacking a personal character. It has been suggested that an early embryo lacks an entity of sufficient ontological autonomy, which would be acquired with organogenesis at later stages. It is an ethical commitment of the scientific community to provide serious and precise information about the advances, problems and solutions involved an regenerative therapy. The use of autologous or heterologous human cells in this field demands of rules which determine their use and commercial potential. The induced reprogramming of adult cells to an embryonic stage (iPS) opens up new important perspectives both in basic research and for clinical treatments. The ethical commitment of Yamanaka, developer of this technology, with regard to its use in clinical treatments, is an example of the researcher's responsibility of the researcher, and, at the same time, an illustration of how that science may render a service to mankind only through ethical principles.

Maternal antigen presenting cells are a source of plasmatic HLA-G during pregnancy: longitudinal study during pregnancy.

The aim of this work was to investigate the longitudinal evolution of plasmatic soluble HLA-G (sHLA-G: shed HLA-G1 plus HLA-G5) during pregnancy, and if peripheral maternal antigen presenting cells (APC) can be a source of sHLA-G. Blood samples were obtained from 45 volunteers during normal pregnancy, 8 of them monthly; from 8 pregnant volunteers in the first weeks of pregnancy who had later a miscarriage, and from 14 healthy nonpregnant control women. Monocytes obtained during pregnancy showed a moderately HLA-G cell surface expression and stimulation with interferon (IFN)-gamma increased this expression. Monocytes-derived dendritic cells obtained from pregnant women during the first and third trimester of pregnancy secreted more sHLA-G than those obtained from nonpregnant women. Plasmatic sHLA-G concentration in pregnant women was significatively higher than in nonpregnant women, with a peak in the third month. We can conclude that maternal APC are a source of sHLA-G. Women who experienced miscarriage had previously very low or undetectable plasmatic sHLA-G levels in the second month of pregnancy. Data suggest that undetectable sHLA-G could be a risk of complications.