Autonomy in the Development of Stem Cell-Derived Embryoids: Sprouting Blastocyst-Like Cysts, and Ethical Implications.

The experimental production of complex structures resembling mammalian embryos (e.g., blastoids, gastruloids) from pluripotent stem cells in vitro has become a booming research field. Since some of these embryoid models appear to reach a degree of complexity that may come close to viability, a broad discussion has set in with the aim to arrive at a consensus on the ethical implications with regard to acceptability of the use of this technology with human cells. The present text focuses on aspects of the gain of organismic wholeness of such stem cell-derived constructs, and of autonomy of self-organization, raised by recent reports on blastocyst-like cysts spontaneously budding in mouse stem cell cultures, and by previous reports on likewise spontaneous formation of gastrulating embryonic disc-like structures in primate models. Mechanisms of pattern (axis) formation in early embryogenesis are discussed in the context of self-organization of stem cell clusters. It is concluded that ethical aspects of development of organismic wholeness in the formation of embryoids need to receive more attention in the present discussions about new legal regulations in this field.

Deseados pero abandonados: el incierto destino de los embriones criopreservados / Desired but abandoned: the uncertain fate of cryopreserved embryos

La reproducción asistida, de la mano de ciencias afines como la genómica y la criobiología, ha transformado de modo vertiginoso el abordaje de la fertilidad, no solamente por los avances científico-técnicos, sino por la coyuntura social contemporánea. Como es conocido, en la actualidad se ha elevado el porcentaje de mujeres y parejas que deben recurrir a estas técnicas biomédicas y, con ellas, se han diversificado las etiologías de la infertilidad. El continuo avance por superar los obstáculos biológicos y ofrecer nuevas opciones con las que solventar la infertilidad, lleva también asociados interrogantes y dilemas éticos y normativos. Entre esos dilemas nos encontramos los usos y destinos de los embriones criopreservados sobrantes de las técnicas de reproducción asistida (TRA). Tras más de cuatro décadas de fecundación in vitro (FIV), la problemática surgida a raíz de la criopreservación embrionaria y la incesante acumulación de embriones parece no haber alcanzado su fin. Así, las diferentes opciones contempladas por la normativa vigente no acaban de satisfacer a los pacientes y profesionales para poder responder a la situación existente de almacenamiento de un número importante de embriones criopreservados en los biobancos de los centros de reproducción asistida, sin destino definido (AU)

La reproducció assistida, de la mà de ciències afins com la genòmica i la criobiologia, ha transformat de manera vertiginosa l'abordatge de la fertilitat, no solament pels avanços cientificotècnics, sinó per la conjuntura social contemporània. Com és conegut, en l'actualitat s'ha elevat el percentatge de dones i parelles que han de recórrer a aquestes tècniques biomèdiques i, amb elles, s'han diversificat les etiologies de la infertilitat. El continu avanç per superar els obstacles biològics i oferir noves opcions amb les quals solucionar la infertilitat, porta també associats interrogants i dilemes ètics i normatius. Entre aquests dilemes ens trobem els usos i destinacions dels embrions criopreservats sobrants de les tècniques de reproducció assistida (TRA). Després de més de quatre dècades de fecundació in vitro (FIV), la problemàtica sorgida arran de la criopreservació embrionària i la incessant acumulació d'embrions sembla no haver aconseguit la seva fi. Així, les diferents opcions contemplades per la normativa vigent no acaben de satisfer als pacients i professionals per a poder respondre a la situació existent d'emmagatzematge d'un nombre important d'embrions criopreservats en els biobancs dels centres de reproducció assistida, sense destinació definida (AU)

Assisted reproduction, hand in hand with related sciences such as genomics and cryobiology, has vertiginously transformed the approach to fertility, not only because of scientific and technical advances, but also because of the contemporary social context. As is well known, a high percentage of women and couples who have to resort to this biotechnology and, with them, the aetiologies of infertility have diversified. The continuous progress in overcoming biological barriers and provide new therapeutic options to address infertility also raises ethical and regulatory questions and dilemmas. Among these dilemmas are the uses and purpose of cryopreserved embryos left over from assisted reproduction techniques. After more than four decades of in vitro fertilization (IVF), the concern arising from embryo cryopreservation and the incessant accumulation of embryos do not seem to have reached an end. Thus, the different options contemplated by the current regulations do not satisfy users and professionals to be able to respond to the existing situation of storage of a significant number of cryopreserved embryos in the biobanks of assisted reproduction clinics, with no defined destination (AU)

Análisis del término reproducción asistida / No disponible

Las técnicas de Reproducción Asistida son una práctica cada vez más común y habitual en la sociedad actual, y especialmente en la cultura occidental. Se suele hablar con cierta frecuencia de las técnicas que se someten las mujeres que quieren concebir un hijo, pero en pocas ocasiones nos planteamos las repercusiones de dicho procedimiento, junto con las implicaciones envueltas. Existen dos terminologías que utilizamos a diario y en algunos casos se emplean como sinónimos, nos referimos a la Reproducción Asistida y la Procreación Asistida. Sin el deseo de imponer un término sobre el otro, pero con la aspiración de conocer las extensiones e implicaciones que conlleva su uso, se valorarán los efectos de cada una, donde no solo existe una diferencia etimológica, sino también, filosófica, ideológica y cultural

The embodiment of assisted reproduction techniques is an increasingly common practice in European society. We usually talk with female patients, who want to conceive, regarding techniques that they undergo but rarely do we consider the impact of such a procedure, along with the implications involved. There are two terms we use every day and in some cases are used simultaneously such as Assisted Reproduction and Assisted Procreation. Without wishing to impose a term over the other, but with the desire to know the extensions associated with each term, the effects of each, where there is not only an etymological difference, but also philosophical, ideological and cultural are valued

Nuevos perfiles jurídicos del acto médico: responsabilidad derivada del screening genético / No disponible

El screening de enfermedades genéticas en donantes viene enmarcado dentro del proceso de selección y evaluación de los donantes de células reproductoras en procesos de técnicas de reproducción asistida, derivado de la necesidad reconocida por todas las sociedades científicas relacionadas con la donación de gametos, de realizar una historia clínica al donante que recoja sus antecedentes personales y familiares. El presente trabajo analiza las obligaciones legales y la responsabilidad derivada del mismo

The screening of genetic diseases in donors is framed within the process of selection and evaluation of donors of reproductive cells in processes of assisted reproduction techniques, derived from the need recognized by all scientific societies related to gamete donation, making a donor medical history to collect their personal and family history. This paper analyzes the legal obligations and liability arising the refrom

Human embryos cultured in vitro to 14 days.

We know a great deal about the development of the mammalian embryo until the time that the blastocyst implants into the uterus. With model organisms such as the mouse, we have also developed a considerable understanding of development immediately around gastrulation as embryos can be recovered at this stage for short-term in vitro culture. However, the intervening period of development remained a 'black box' because it takes place as the blastocyst is implanting into the uterus. Over the past 6 years, techniques pioneered and developed in Magdalena Zernicka-Goetz's laboratory for the in vitro culture of embryos through these implantation stages have opened up this box, affording the first glimpse of embryonic development through these previously hidden stages. Remarkably, the techniques developed with mouse embryos are equally applicable to human embryos, ushering the very first opportunities for studying our own development throughout this time. Here, I outline how the culture methods were developed, paving the way to culture of the human embryo to the point of gastrulation, an accomplishment recognized as the People's Choice for the Scientific Breakthrough of 2016 in Science magazine. I also discuss the new ethical challenges raised by the possibility of extending the time limits for human embryo culture.

Valoración de la adopción de embriones humanos congelados desde el punto de vista de la filosofía moral, la ética laica y dos religiones monoteístas / Valuating frozen human embryo adoption from a moral philosophical point of view, lay ethics and two monotheist religions / Valoração da adoção de embriões humanos congelados do ponto de vista da filosofia moral, a ética laica e duas religiões monoteístas

La búsqueda de la eficacia en la fecundación in vitro hace que se produzcan más embriones que los que se implantarán, lo que produce un excedente de embriones, que es congelado. Esto hace que ineludiblemente el número de embriones humanos congelados aumente. Entre las soluciones para dichos embriones humanos congelados está la donación/adopción de los mismos. Ineludiblemente esta práctica conlleva objetivos problemas éticos. En este trabajo se evalúa la eticidad de la donación/adopción de embriones humanos congelados desde la perspectiva de la filosofía moral, lo que podríamos llamar una "ética laica" y dos de las religiones monoteístas: la musulmana y la judía.

The search for IVF efficacy leads to a higher embryo production than it is necessary for implantation; this results in an excess of embryos which are kept frozen. This amount of frozen embryos inevitably increases. The donation/adoption are among the possible solutions for these frozen embryos. However, this practice has objective ethical problems. This article considers the ethical aspects of the donation / adoption of frozen human embryos from the point of view of moral philosophy, from what we could call "secular ethics" and from two monotheistic religions: Muslim and Jewish.

A busca da eficácia na fecundação in vitro faz com que se produzam mais embriões dos que se implantarão, o que produz um excedente de embriões, que é congelado. Isto faz com que inquestionavelmente o número de embriões humanos congelados aumente. Entre as soluções para os ditos embriões humanos congelados está na doação/adoção dos mesmos. Ineludivelmente esta prática implica objetivos problemas éticos. Neste trabalho se avalia a eticidade da doação/adoção de embriões humanos congelados a partir da perspectiva da filosofia moral, o que poderíamos chamar uma "ética laica" e duas religiões monoteistas: a mulçumana e a judia.

Embriones supernumerarios en las técnicas de reproducción humana asistida. ¿Qué hacer con ellos? Análisis jurídico y ético de las opciones legales en España / No disponible

La FIV puede llevar aparejada ia acumulación de embriones humanos excedentes. Aunque la ley prevé varios posibles destinos, las clínicas de reproducción asistida, que con frecuencia han de decidir qué hacer con ellos, buscan criterios para hacerlo de la forma más razonable posible. Este trabajo pretende aportar razones jurídicas y éticas que ayuden a esa decisión (AU)

IVF may entail the accumulation of surplus human embryos, Although Spanish law provides several possible destinations, assisted reproduction clinics, that of-ten have to decide what to do with them, look for criteria to help them to make their decisions as reasonably as possible. The aim of this paper is to provide legal and ethical reasons to help them to decide (AU)

Bioderecho y sujeto de derechos. Recategorización jurídica de la manipulación genética no terapéutica en estado embrionario pre-implantacional y del concepto de existencia legal de la persona / No disponible

El rasgo jurídico inédito que la manipulacion genética no terapéutica en estado embrionario despliega, exige un abordaje jurídico-procedimental, hasta ahora inexplorado que, a la vez, demanda la redefinición y ampliación de la estatura legal vinculante de categorías tradicionales del derecho positivo y que alcanzan las fronteras del derecho constitucional, de familia, reparatorio y penal. En este artículo busco demostrar la necesidad de definir un marcojuridico para regular la manipulación genética no terapéutica en estado embrionario preimplantacional que introduce desmejoras o discapacidades que redundan en perjuicios objetivos para un nuevo sujeto de derechos que debiera ser considerado en el mapa juridico: la persona futura. Por ello, pretendo subsanar el vacio legal existente, proponiendo actualizar, ampliar y profundizar los ordenamientos jurídicos iberoamericanos, a través de la recategorizacion jurídica de la manipulación genética no terapéutica y la emergencia de un nuevo sujeto de derechos: la persona futura (AU)

The unprecedented legal implications that non-therapeutic genetic manipulation in pre-implantation embryonic state points out demand a, until now, unexplored approach, which, at the same time, requires the redefinition and extension of legal-binding status of traditional categories of law related to constitutional, restorative, criminal and international law. ln this paper, l will identify and define a juridical framework to regulate non-therapeutic genetic manipulation in pre-implantation embryonic state, specifically when that manipulation introduces deteriorations, disabilities or illnesses, which imply objective harms for a new subject of rights who should be considered in the juridical map: the future person. ln addition, I intend to remedy the existing legal vacuum and loopholes in this matter by proposing to update, expand and deepen international legal systems through the juridical re-categorization of non-therapeutic genetic manipulation and the concept ot legal existence of the person (AU)

El inicio de la vida: discurso bioético-jurídico en la Legislación Mexicana / The beginning of life: bioethical and legal discourse in Mexican Legislation

De acuerdo con el artículo 124 de la Constitución mexicana, todas aquellas facultades no reservadas a la federación se entienden concedidas a los estados de la república así, la materia civil está reservada a los estados mientras que en temas de salud coexiste una concurrencia competencial. Como sabemos, la mayoría de los temas bioéticos tienen por un lado implicaciones civiles o familiares y por el otro implicaciones relacionadas con temas de salud. En consecuencia, dependiendo del enfoque que se le dé a los temas bioéticos encontraremos resultados diferentes. En México, se ha privilegiado la perspectiva civil, lo que ha ocasionado que surjan diversas expresiones jurídicas que terminan siendo dispares y en algunos casos contradictorias. En nuestra opinión, las implicaciones jurídicas de la biotecnología deberían ser abordadas desde una perspectiva nacional, mediante una legislación especializada, a fin de evitar, lo que ahora ocurre, es decir las contradicciones y/o absurdos jurídicos entre las diferentes legislaciones locales. En este trabajo se analizan, precisamente, las inconsistencias y absurdos que se han generado en diversas legislaciones locales, en virtud de esta visión civilista de los temas bioéticos (AU)

In accordance with Article 124 of the Mexican Constitution, all powers not reserved to the federation are understood to be granted to the states of the Republic, and in accordance with the federal pact, civil matters are reserved to the states while in issues health coexists concurrence competence. As we know, most of bioethical issues have civil or family implications as well as other implications related to health issues. Therefore, depending on the approach that is given to bioethical issues, we will find different results. In Mexico, the civil perspective has been privileged, resulting in the appearance of different legal expressions that end up being dissimilar and sometimes even contradictory. In our opinion, the legal implications of biotechnology should be addressed from a national perspective by a specific legislation, in order exactly to avoid what is now occurring, that is to avoid the contradictions and/or legal absurdities among the different local legislations. This paper analyzes the inconsistencies and absurdities that have been generated under this civil perspective in different local legislations regarding bioethical issues (AU)

El lenguaje bioético en la normativa y jurisprudencia sobre problemas biojurídicos / Bioethical language in the law and jurisprudence about bioethical problems

Se analiza el impacto que sobre el Derecho español relativo a cuestiones bioéticas —como la Ley sobre reproducción artificial, la Ley sobre investigación biomédica, y la Ley sobre salud sexual y reproductiva— puede tener la concepción de embrión humano enunciada por el Tribunal de Justicia de la Unión Europea en su sentencia de 18 de octubre de 2011, considerándolo como todo óvulo fecundado con independencia del grado de desarrollo alcanzado (AU)

The impact is analyzed that on the Spanish Law relative to questions bioethics —as the Law on artificial reproduction, the Law of biomedical investigation, and the Law on sexual and reproductive health— can have the conception of human embryo enunciated by the Court of Justice of the European Union in his judgment of October 18, 2011, considering it to be any ovum fertilized with independence of the degree of reached development (AU)

Patients' conceptualization of cryopreserved embryos used in their fertility treatment.

BACKGROUND: Although IVF treatments using cryopreserved embryos are offered by most infertility centres, little is known about patients' opinions regarding treatment using these embryos. The objective of this study is to describe how patients think about (treatment with) cryopreserved embryos. METHODS: In-depth interviews based on the method of interpretative phenomenological analysis were conducted with patients undergoing IVF/ICSI treatment at the Department of Reproductive Medicine of the Ghent University Hospital between May and July 2006. Seven couples (one couple considered as one participant) and 11 female patients who attended the clinic without their partner were interviewed. RESULTS: Most participants knew little about medical-technical procedures involved in treatment with cryopreserved embryos. This was compensated by a high confidence in the medical team. However, seven of the eighteen participants thought the quality of cryopreserved embryos diminished during the storage period. A lack of knowledge about medical-technical procedures was compensated by metaphors related to other domains of experience, especially kitchen metaphors: this might add to the belief that frozen embryos have an expiry date. However, none of the patients who considered treatment with cryopreserved embryos as less effective ever thought of refusing this type of treatment or discussed this with medical staff. In addition, patients rarely discussed the moral status of their cryopreserved embryos. CONCLUSIONS: The beliefs of infertile patients about (the effectiveness of treatment with) cryopreserved embryos encompass misconceptions, and doubts and fears which may influence their decision-making but which are seldom discussed with the medical staff.

Ethics report on interspecies somatic cell nuclear transfer research.

This report considers whether research involving the creation of human-animal interspecies somatic cell nuclear transfer (iSCNT) embryos raises new ethical issues, and if so, whether it requires additional or special criteria and oversight distinct from research on human-animal chimeras.

[The progressive legal vulnerability of embryonic human life in Spain: the law 35/1988 to 14/2006 and law 14/2007]. / La progresiva desprotección jurídica de la vida humana embrionaria en España: de la ley 35/1988 a las leyes 14/2006 y 14/2007.

This article examines the Laws on Human Assisted Reproduction and Biomedical Research in Spain. The Laws permit the use of human ovules, embryos and fetuses. Close to the technical and ethical problems that carry the research on embryonic stem cells, the detection of induced reprogramming of adult cells to an embryonic stage (iPS) opens up new perspectives in regenerative medicine. It makes unnecessary the use of frozen embryos or produced by nuclear transfer. These reasons would involve a review of the Spanish Legislation in this matter, in order that the human life is an ethical barrier and a fundamental to actual biomedical research.

[The juridical desprotection of the human embryos post the new law of human assisted reproduction and the law of biomedical investigation]. / La desprotección jurídica del embrión humano tras la nueva ley de reproducción humana asistida y la ley de investigación biomédica.

This research try to analyse the juridical statute of the human embryos in accordance with two recent laws which contain ordesr what affects him: the new Law of assisted reproduction technology -Law 14/2006, of 26 may (LRA)-, and the law of biomedical investigation -Law 14/2007, of 3 july (LIB)-, because the embryos in vitro is considered devoid of the quality what give the human dignity, why is allowed not only to research and to test with the remaining preembryos of assisted reproduction, but also to clone embryos with therapeutic purposes and to make a embryonic selection in order to cure other sons of the woman that recourse to fertilization in vitro through the donation of genetic material from the future baby.

[Some remarks on the protection of human embryo in the Spanish law]. / Breves anotaciones sobre la protección del embrión en el ordenamiento jurídico español.

We study in this article the Spanish legislation regulating the juridical status of the human embryo, in a comparative analysis with the International Right and the legislation in other countries of our cultural environment, leading to the conclusión that ours contradicts the international compromises of Spain and is less protective with the unborn human life than the juridical systems which advocate for the human being from the very moment of conception.

Unsuccessful derivation of human embryonic stem cell lines from pairs of human blastomeres.

Human embryonic stem cells (hESC) that differentiate into all three primordial germ layers have been established. Differentiation of these cells into desirable lineages offers hope for future transplantation therapies. Currently, hESC lines are derived from the inner cell mass (ICM) of blastocysts, leading to destruction of the embryo, and thus the process is ethically controversial. Successful attempts at deriving hESC lines from blastomeres without destruction of the ensuing embryo have not been reported. One or two blastomeres are routinely biopsied from 8-cell embryos for preimplantation genetic diagnosis. In this study it was therefore attempted to derive hESC lines from paired blastomeres. Of 66 pairs of 8-cell stage blastomeres, four pairs produced two morula and two blastocyst-like structures. When plated on mitomycin-C-treated mouse embryonic fibroblasts, one morula and one blastocyst-like structure separately produced small colonies containing hESC-like cells with prominent nucleoli and high nuclear-cytoplasmic ratios. When these colonies were detached and plated onto fresh feeders, there was no further colony formation or ensuing hESC lines. The results showed that it might not be possible to derive hESC lines directly from paired blastomeres. A minimum number of blastomeres in close contact with one another may be required to successfully generate an hESC line as blastomeres, like ICM and hESC cells, may be 'social' cells.

Ethical issues in deriving stem cells from embryos and eggs.

Human embryonic stem cell (ESC) research has attracted wide media coverage. It has been headline news for the past several months, revealing the complex case of Professor Hwang Woo-Suk and the scientific fraud where he purported to have created the first human patient-specific stem cell lines generated by cell nucleus replacement (CNR). To ethically obtain the raw materials (eggs, sperm and embryos) for human ESC research is an enormous challenge, yet essential if this research is to proceed in its quest to try to deliver some of the expectations placed upon it: developing treatments and possible cures for a range of serious diseases. This article examines some of the ethical issues surrounding human ESC research using the four principles frequently applied to healthcare and medical research; autonomy, beneficence, non-maleficence and justice. The author strives to ask questions throughout which will encourage debate and discussion.