Análisis bioético (subjetivismo moral) desde la percepción de los clínicos sobre la situación de los embriones sometidos a fecundación in vitro. Quito-Ecuador / Bioethical analysis (moral subjectivism) from the perception of clinicians on the situation of embryos subjected to in vitro fertilization. Quito-Ecuador / Análise bioética (subjetivismo moral) a partir da percepção dos médicos sobre a situação dos embriões submetidos à fertilização in vitro. Quito-Equador

Resumen: Objetivo. Analizar las percepciones y prácticas de los clínicos en relación con el manejo del embrión sometido a técnicas de fecundación in vitro. Metodología. Cualitativa (subjetivista y fenomenológico). Se realizaron 15 las entrevistas semiestructuradas aplicando un muestreo por saturación dirigidas a personal clínico que haya participado en procedimientos de fecundación in vitro. Los datos se analizaron con el programa Atlas Ti 8.0®. Resultado. Los clínicos consideran al embrión como un ser humano o futuro ser humano y, además, merecedor de respeto y consideración, proponiendo incluso mejoras en los procesos de manipulación y almacenaje. Conclusión. Los embriones no son considerados como entes susceptibles de recibir daño, desde argumentos no solo técnicos sino éticos. Desde la corriente principialista, se describe la necesidad de promover actitudes de responsabilidad y prudencia para evitar el dogmatismo (objetivismo moral) proponiendo una postura deliberativa.

Abstract: The objective of this paper is to analyze the perceptions and practices of clinicians in relation to the management of embryos subjected to in vitro fertilization techniques. Methodology is Qualitative (subjectivist and phenomenological). A total of 15 semi-structured interviews were conducted using saturation sampling for clinical personnel who have participated in vitro fertilization procedures. The data is analyzed with the Atlas Ti 8.0® program. Results: Clinicians consider the embryo as a Human being or future human being, in addition, deserving of respect and consideration even proposing improvements in the processes of handling and storage. Conclusion. Embryos are not considered as entities susceptible of damage from not only technical but ethical arguments. From the principialist current, the need to promote attitudes of responsibility and prudence to avoid dogmatism (moral objectivism) is described, proposing a deliberative position.

Resumo: Objetivo. Analisar as percepções e práticas dos médicos em relação ao manejo do embrião submetido a técnicas de fertilização in vitro. Metodologia. Qualitativo (subjetivo e fenomenológico). Foram realizadas 15 entrevistas semiestruturadas por amostragem de saturação para pessoal clínico que participou de procedimentos de fertilização in vitro. Os dados são analisados com o programa Atlas Ti 8.0®. Resultado. Os médicos consideram o embrião como um ser humano ou futuro, além de merecer respeito e consideração, propondo até melhorias nos processos de manuseio e armazenamento. Conclusão. Os embriões não são considerados como entidades suscetíveis a receber danos não apenas de argumentos técnicos, mas éticos. A partir da corrente principialista, descreve-se a necessidade de promover atitudes de responsabilidade e prudência para evitar o dogmatismo (objetivismo moral), propondo uma posição deliberativa.

Liability for embryo mix-ups in fertility practices in the USA.

PURPOSE: To study recent legal cases involving the transfer of the incorrect embryo into patients and learn how fertility clinics can better serve clients, protect themselves financially, and safeguard their physicians' personal assets. METHODS: The Nexis Uni database was used to review legal cases, news, and business publications of previous cases of embryo mix-ups. County and district courthouse dockets were also queried for filings and court documents related to lawsuits involving embryo mix-ups using Public Access to Court Electronic Records (PACER). Emphasis was placed on court decisions, awarded damages, and legal and media coverage related to embryo mix-up events. RESULTS: A case law review of US legal databases and courthouse dockets was conducted for cases between 2000 and 2020, focusing on lawsuits against reproductive endocrinologists and in vitro fertilization (IVF) facilities offering embryo transfer (ET). Improper labeling and ineffective communication led to errors in the cases reviewed. CONCLUSION: It is prudent for clinics to protect themselves from embryo mix-ups, which can subsequently lead to undesirable clinical outcomes, as well as lawsuits stemming from these errors. This article emphasizes following labeling guidelines when storing embryos, employing a two-step read back method prior to ET, and offering genetic testing when a discrepancy is found in the record. In the case an embryo mix-up does occur, it is recommended to protect personal assets through business organizing procedures and consider settlement offers for policy limits.

Medical research and reproductive medicine in an ethical context: a critical commentary on the paper dealing with uterine lavage published by Munné et al.

A recent study published in Human Reproduction claimed that uterine lavage offers a non-surgical, minimally invasive strategy for the recovery of human embryos from fertile women who do not want or need IVF for medical reasons but who desire preimplantation genetic testing (PGT) for embryos. To prove this hypothesis, the researchers recruited dozens of young Mexican women. The prospective oocyte donors underwent ovarian stimulation to induce the production of multiple mature oocytes. Subsequently, these women were inseminated by donor semen. A few days later, the developing embryos were collected by uterine lavage (uterine flushing) and subjected to genetic testing for aneuploidies (PGT-A). Oocyte donors with persistently elevated hCG levels, indicating the implantation of one or more embryos after uterine lavage, had to undergo uterine curettage and/or treatment with methotrexate. A critical opinion paper discussing the aforementioned study was published by De Santis and colleagues and has raised critical issues that are largely technical in nature. However, this opinion paper neglects-from our point of view-critical issues of the Mexican study regarding ethical principles and moral standards in human research. These aspects are summarized below.

Compassionate transfer: patient requests for embryo transfer for nonreproductive purposes.

A patient request to transfer embryos into her body in a location or at a time when pregnancy is highly unlikely to occur is deemed a request for "compassionate transfer" and often reflects the patient's deeply personal, strongly held preferences and values. It is ethically permissive for physicians to honor or decline such requests if they do so in a nondiscriminatory manner.

A moral argument for frozen human embryo adoption.

Some people (e.g., Drs. Paul and Susan Lim) and, with them, organizations (e.g., the National Embryo Donation Center) believe that, morally speaking, the death of a frozen human embryo is a very bad thing. With such people and organizations in mind, the question to be addressed here is as follows: if one believes that the death of a frozen embryo is a very bad thing, ought, morally speaking, one prevent the death of at least one frozen embryo via embryo adoption? By way of a three-premise argument, one of which is a moral principle first introduced by Peter Singer, my answer to this question is: at least some of those who believe this ought to. (Just who the "some" are is identified in the paper.) If this is correct, then, for said people, preventing the death of a frozen embryo via embryo adoption is not a morally neutral matter; it is, instead, a morally laden one. Specifically, their intentional refusal to prevent the death of a frozen embryo via embryo adoption is, at a minimum, morally criticizable and, arguably, morally forbidden. Either way, it is, to one extent or another, a moral failing.

Preimplantation genetic testing for more than one genetic condition: clinical and ethical considerations and dilemmas.

STUDY QUESTION: Which clinical and ethical aspects of preimplantation genetic testing for monogenic disorders or structural rearrangements (PGT-M, PGT-SR) should be considered when accepting requests and counselling couples for PGT when applied for more than one condition (combination-PGT; cPGT-M/SR)? SUMMARY ANSWER: cPGT is a feasible extension of the practice of PGT-M/SR that may require adapting the criteria many countries have in place with regard to indications-setting for PGT-M/SR, while leading to complex choices that require timely counselling and information. WHAT IS KNOWN ALREADY: Although PGT-M/SR is usually performed to prevent transmission of one disorder, requests for PGT-M/SR for more than one condition (cPGT-M/SR) are becoming less exceptional. However, knowledge about implications for a responsible application of such treatments is lacking. STUDY DESIGN, SIZE, DURATION: Retrospective review of all (40) PGT-M/SR applications concerning more than one genetic condition over the period 1995-2018 in the files of the Dutch national PGT centre. This comprises all relevant national data since the start of PGT in the Netherlands. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Data regarding cPGT-M/SR cases were collected by means of reviewing medical files of couples applying for cPGT-M/SR. Ethical challenges arising with cPGT-M/SR were explored against the background of PGT-M/SR regulations in several European countries, as well as of relevant ESHRE-guidance regarding both indications-setting and transfer-decisions. MAIN RESULTS AND THE ROLE OF CHANCE: We report 40 couples applying for cPGT-M/SR of which 16 couples started their IVF treatment. Together they underwent 39 IVF cycles leading to the birth of five healthy children. Of the couples applying for cPGT, 45% differentiated between a primary and secondary condition in terms of perceived severity. In the light of an altered balance of benefits and drawbacks, we argue the 'high risk of a serious condition' standard that many countries uphold as governing indications-setting, should be lowered for secondary conditions in couples who already have an indication for PGT-M/SR. As a consequence of cPGT, professionals will more often be confronted with requests for transferring embryos known to be affected with a condition that they were tested for. In line with ESHRE guidance, such transfers may well be acceptable, on the condition of avoiding a high risk of a child with a seriously diminished quality of life. LIMITATIONS, REASONS FOR CAUTION: We are the first to give an overview of cPGT-M/SR treatments. Retrospective analysis was performed using national data, possibly not reflecting current trends worldwide. WIDER IMPLICATIONS OF THE FINDINGS: Our observations have led to recommendations for cPGT-M/SR that may add to centre policy making and to the formulation of professional guidelines. Given that the introduction of generic methods for genomic analysis in PGT will regularly yield incidental findings leading to transfer requests with these same challenges, the importance of our discussion exceeds the present discussion of cPGT. STUDY FUNDING/COMPETING INTEREST(S): The research for this publication was funded by the Dutch Organization for Health Research and Development (ZonMw), project number: 141111002 (Long term safety, quality and ethics of Preimplantation Genetic Diagnosis). None of the authors has any competing interests to declare.

'Compassionate transfer': an alternative option for surplus embryo disposition.

Compassionate transfer is a procedure wherein in vitro-created embryos are placed in a patient's cervix, vagina or uterus at an infertile period in the menstrual cycle where they are expected to perish. Patients report that they feel this procedure is a more natural means of disposition and provides them with the opportunity to grieve the loss of a potential child. However, some have argued that the procedure is an unnecessary, and illogical, addition to fertility treatment and that it detracts resources from medical care. Here, we introduce compassionate transfer as an alternative disposition option and argue that, for certain patients, it may constitute an ethical extension of fertility care that respects patient autonomy and psychosocial health.

Disclosure of sex when incidentally revealed as part of preimplantation genetic testing (PGT): an Ethics Committee opinion.

Clinics may develop a policy to disallow selecting which embryos to transfer based on sex and choose to use only embryo quality as selection criteria. Clinics may also develop a policy to use randomization to select those embryos for transfer if more embryos suitable for transfer are available than can be transferred.

Dealing with treatment and transfer requests: how PGD-professionals discuss ethical challenges arising in everyday practice.

How do professionals working in pre-implantation genetic diagnosis (PGD) reflect upon their decision making with regard to ethical challenges arising in everyday practice? Two focus group discussions were held with staff of reproductive genetic clinics: one in Utrecht (The Netherlands) with PGD-professionals from Dutch PGD-centres and one in Prague (Czech Republic) with PGD-professionals working in centres in different European countries. Both meetings consisted of two parts, exploring participants' views regarding (1) treatment requests for conditions that may not fulfill traditional indications criteria for PGD, and (2) treatment and transfer requests involving welfare-of-the-child considerations. There was general support for the view that people who come for PGD will have their own good reasons to consider the condition they wish to avoid as serious. But whereas PGD-professionals in the international group tended to stress the applicants' legal right to eventually have the treatment they want (whatever the views of the professional), participants in the Dutch group sketched a picture of shared decision-making, where professionals would go ahead with treatment in cases where they are able to understand the reasonableness of the request in the light of the couple's reproductive history or family experience. In the international focus group there was little support for guidance stating that welfare-of-the child considerations should be taken into account. This was different in the Dutch focus group, where shared decision-making also had the role of reassuring professionals that applicants had adequately considered possible implications for the welfare of the child.

Current experience concerning mosaic embryos diagnosed during preimplantation genetic screening.

The concept of embryos containing multiple cell lines (mosaicism) is not new, but much attention has been paid to this concept recently owing to recent advances in molecular techniques to analyze human embryos. Mosaicism in embryos has been known and reported for some time, originally in early cleavage-stage embryos diagnosed with the use of fluorescence in situ hybridization (FISH). However, the early data have come under attack owing to the limited ability of FISH to reliably detect the actual copy number count of chromosomes as well as potential ascertainment bias of those early studies, which were all performed on already analyzed embryos found to be aneuploid. More recent molecular techniques for analyzing embryos have allowed scientists to really begin to understand mosaic embryos, and to now transfer and follow this class of embryo. Indeed, it could be said that three classes of embryos now exist after preimplantation genetic screening: euploid, aneuploid, and mosaic aneuploid. This paper attempts to bring to light the latest data on mosaic embryos and to understand how clinicians and others will deal with this issue today and in the future. Finally, an attempt is made to look to other fields of genetics to understand how this important issue can be dealt with as a group much better than any one individual group may be able to.

Transferring embryos with genetic anomalies detected in preimplantation testing: an Ethics Committee Opinion.

Patient requests for transfer of embryos with genetic anomalies linked to serious health-affecting disorders detected in preimplantation testing are rare but do exist. This Opinion sets out the possible rationales for a provider's decision to assist or decline to assist in such transfers. The Committee concludes in most clinical cases it is ethically permissible to assist or decline to assist in transferring such embryos. In circumstances in which a child is highly likely to be born with a life-threatening condition that causes severe and early debility with no possibility of reasonable function, provider transfer of such embryos is ethically problematic and highly discouraged.

Introduction: To transfer or not transfer a mosaic embryo, that is the question.

This issue's Views and Reviews section aims to offer readers a 360° view of the knowledge accumulated regarding the transfer of mosaic embryos by experts from around the world, as well as an in vitro fertilization worldwide survey on the topic.

Oncofertility: Fertile Ground for Conflict Between Patient Autonomy and Medical Values.

Oncofertility is a unique, multidisciplinary field that serves to bridge the gap between available fertility resources and the special reproductive needs of cancer patients. Oncofertility is a growing field due to the increasing number of survivors, development of new oncologic therapies, extension of duration of therapies, and development and refinement of reproductive therapies. While the technologies and demand for services expand, clinicians need to be appropriately prepared for dealing with various clinical scenarios that may require ethical deliberation. Three real cases are presented in which the patient wishes to pursue reproductive assistance, but her decision is met with hesitance or uncertainty by her care team. Discussion of these clinical scenarios highlights ethical implications of oncofertility practice and serves to highlight the need for the establishment of multidisciplinary care teams and guidelines to support both clinicians and patients. IMPLICATIONS FOR PRACTICE: The growing field of oncofertility is ripe for conflict between patient autonomy and medical values due to the nature of cancer and associated threat on an individual's health and survival, as well as the personal significance of childbearing. Cases are presented and ethical implications are discussed to further explore the inherent difficulties in oncofertility practice and guide clinicians in similar situations. Developing guidelines and establishing multidisciplinary teams to facilitate oncofertility discussions and care, as well as training of clinical team members, may improve patient safety, well-being, and satisfaction within the context of fertility decision making, care, and outcomes.

Principles guiding embryo selection following genome-wide haplotyping of preimplantation embryos.

STUDY QUESTION: How to select and prioritize embryos during PGD following genome-wide haplotyping? SUMMARY ANSWER: In addition to genetic disease-specific information, the embryo selected for transfer is based on ranking criteria including the existence of mitotic and/or meiotic aneuploidies, but not carriership of mutations causing recessive disorders. WHAT IS KNOWN ALREADY: Embryo selection for monogenic diseases has been mainly performed using targeted disease-specific assays. Recently, these targeted approaches are being complemented by generic genome-wide genetic analysis methods such as karyomapping or haplarithmisis, which are based on genomic haplotype reconstruction of cell(s) biopsied from embryos. This provides not only information about the inheritance of Mendelian disease alleles but also about numerical and structural chromosome anomalies and haplotypes genome-wide. Reflections on how to use this information in the diagnostic laboratory are lacking. STUDY DESIGN, SIZE, DURATION: We present the results of the first 101 PGD cycles (373 embryos) using haplarithmisis, performed in the Centre for Human Genetics, UZ Leuven. The questions raised were addressed by a multidisciplinary team of clinical geneticist, fertility specialists and ethicists. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixty-three couples enrolled in the genome-wide haplotyping-based PGD program. Families presented with either inherited genetic variants causing known disorders and/or chromosomal rearrangements that could lead to unbalanced translocations in the offspring. MAIN RESULTS AND THE ROLE OF CHANCE: Embryos were selected based on the absence or presence of the disease allele, a trisomy or other chromosomal abnormality leading to known developmental disorders. In addition, morphologically normal Day 5 embryos were prioritized for transfer based on the presence of other chromosomal imbalances and/or carrier information. LIMITATIONS, REASONS FOR CAUTION: Some of the choices made and principles put forward are specific for cleavage-stage-based genetic testing. The proposed guidelines are subject to continuous update based on the accumulating knowledge from the implementation of genome-wide methods for PGD in many different centers world-wide as well as the results of ongoing scientific research. WIDER IMPLICATIONS OF THE FINDINGS: Our embryo selection principles have a profound impact on the organization of PGD operations and on the information that is transferred among the genetic unit, the fertility clinic and the patients. These principles are also important for the organization of pre- and post-counseling and influence the interpretation and reporting of preimplantation genotyping results. As novel genome-wide approaches for embryo selection are revolutionizing the field of reproductive genetics, national and international discussions to set general guidelines are warranted. STUDY FUNDING/COMPETING INTEREST(S): The European Union's Research and Innovation funding programs FP7-PEOPLE-2012-IAPP SARM: 324509 and Horizon 2020 WIDENLIFE: 692065 to J.R.V., T.V., E.D. and M.Z.E. J.R.V., T.V. and M.Z.E. have patents ZL910050-PCT/EP2011/060211-WO/2011/157846 ('Methods for haplotyping single cells') with royalties paid and ZL913096-PCT/EP2014/068315-WO/2015/028576 ('Haplotyping and copy-number typing using polymorphic variant allelic frequencies') with royalties paid, licensed to Cartagenia (Agilent technologies). J.R.V. also has a patent ZL91 2076-PCT/EP20 one 3/070858 ('High throughout genotyping by sequencing') with royalties paid. TRIAL REGISTRATION NUMBER: N/A.

Counselling considerations for chromosomal mosaicism detected by preimplantation genetic screening.

The evolution of preimplantation genetic screening (PGS) for aneuploidy to blastocyst biopsy and more sensitive 24-chromosome screening techniques has resulted in a new diagnostic category of PGS results: those classified as mosaic. This diagnosis presents significant challenges for clinicians in developing policies regarding transfer and storage of such embryos, as well as in providing genetic counselling for patients prior to and following PGS. Given the high frequency of mosaic PGS results and the wide range of possible associated outcomes, there is an urgent need to understand how to appropriately counsel patients regarding such embryos. This is the first commentary to thoroughly address pre- and post-test genetic counselling recommendations, as well as considerations regarding prenatal screening and diagnosis. Current data on mosaic PGS results are summarized along with embryo selection considerations and potential outcomes of embryos diagnosed as mosaic.

Current regulatory arrangements for assisted conception treatment in European countries.

Infertility is a condition affecting an increasing number of individuals all over the world. In recent years, this phenomenon has spread across both western countries and developing countries, thus developing the features of a pandemic. For this reason, the World Health Organization (WHO) acknowledged that infertility should be considered a disease to all intents and purposes, as it diminishes the health and wellbeing of the individuals who suffers from it. At present, the most effective means to contain the spread of infertility are essentially prevention and Assisted Reproductive Technologies (ART). With reference to the latter, although most of these techniques are routinely used in the majority of countries, they are still subject to medical, ethical and political debates. There are huge variations noted when the regulatory legislation adopted by different countries to govern infertility treatment in various countries all over the world are reviewed. In fact, it has to be recognized that ART legislation depends on a variety of factors, such as social structure, political choices, ethical issues and religious beliefs. This makes it apparently impossible to create a standard regulation for different countries, especially in case of controversial issues like gamete and embryo donation, embryo cryopreservation or surrogacy.

Recommended Ethical Safeguards on Fertilization of Human Germ Cells Derived from Pluripotent Stem Cells Solely for Research Purposes.

Production of human fertilized embryos by using germ cells derived from pluripotent stem cells (PSCs) entails ethical issues that differ fundamentally depending on the aim. If the aim is solely to conduct research, then embryo generation, utilization and destruction must respect for the human embryo as having the innate potential to develop into a human being. If the aim is human reproduction, this technology must never be used to manipulate human life, confuse social order, or negatively affect future generations. Researchers should distinguish the aims and then accordingly establish a consensus on the safeguards needed to proceed with scientifically significant and socially accepted research, or otherwise set a moratorium. Currently, in Japan, germ cell production from human PSCs is permitted, whereas fertilization of these germ cells is not. The Japanese Expert Panel on Bioethics in the Cabinet Office has proposed that all of the following conditions must be met to approve fertilization for research purposes: (1) the research is significant for the life sciences and medicine; (2) the benefits or anticipated benefits are socially accepted; (3) human safety is assured; and (4) safeguards are put in place. If fertilization is ethically approved, I recommend the following safeguards: limitation of the purpose to improving conventional ART as an initial step; permitted culture of human embryos until the appearance of the primitive streak; restriction of the number of embryos produced to the minimum necessary; prohibition of transplantation into a human or animal uterus; and provision of human-derived ova that are not required for ART treatment.