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.

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.

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': 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.

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.

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.

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.

A case report of embryo donation: ethical and clinical implications for psychologists.

Third-party reproduction is a growing field, and an increasing body of literature considers the ethics of embryo donation. Due to the psychosocial complexities that generally accompany the donation and/or use of donor embryos, psychologists can play a pivotal role in these specialised fertility cases. While laws in the USA are in place to regulate the medical procedures involved in embryo donation, only unenforceable guidelines exist for psychologists specialising in fertility cases. The presentation of this case study aims to: (1) clarify the ethical concerns that fertility psychologists should consider in similar situations by assessing whether American Society of Reproductive Medicine (ASRM) and the American Psychological Association (APA) guidelines compete or complement one another within this case of embryo donation and (2) consider the interests, obligations and rights of all parties involved. Several principles, standards and guidelines that must be considered are described. Overall, the APA Ethics Code and the ASRM Guidelines appear to complement one another for most aspects of this case. Fertility psychologists should consider the clinical implications of the interests, rights and duties of all involved parties, including themselves.

To transfer or not to transfer: the case of comprehensive chromosome screening of the in vitro embryo.

The screening of in vitro embryos resulting from in vitro fertilization (IVF) treatment for chromosomal abnormalities (aneuploidies) has as a primary aim to help patients achieve a successful pregnancy. Most IVF centers will not transfer aneuploid embryos, as they have an enhanced risk of leading to implantation failure and miscarriage. However, some aneuploidies, such as trisomy-21, can lead to viable pregnancies and to children with a variable health prognosis, and some prospective parents may request transfer of such embryos. I present two cases where the testing for and detection of trisomy-21 can lead to conflicts between IVF professionals and patients and argue that in most such cases respect for choices of patients should prevail.

[The Cryopre-servation: history and the ethical issue of storing embryos]. / Kryokonzervace: historie a etická problematika skladování embryí.

This review article deals with the technique which is called cryopreservation. Text describes the principle of this method, history and ethical problems in assisted reproduction.

ESHRE task force on ethics and Law22: preimplantation genetic diagnosis.

This Task Force document discusses some relatively unexplored ethical issues involved in preimplantation genetic diagnosis (PGD). The document starts from the wide consensus that PGD is ethically acceptable if aimed at helping at-risk couples to avoid having a child with a serious disorder. However, if understood as a limit to acceptable indications for PGD, this 'medical model' may turn out too restrictive. The document discusses a range of possible requests for PGD that for different reasons fall outwith the accepted model and argues that instead of rejecting those requests out of hand, they need to be independently assessed in the light of ethical criteria. Whereas, for instance, there is no good reason for rejecting PGD in order to avoid health problems in a third generation (where the second generation would be healthy but faced with burdensome reproductive choices if wanting to have children), using PGD to make sure that one's child will have the same disorder or handicap as its parents, is ethically unacceptable.

Adoption first? The disposition of human embryos.

Anja Karnein has suggested that because of the importance of respect for persons, law and policy should require some human embryos created in vitro to be available for adoption for a period of time. If no one comes forward to adopt the embryos during that time, they may be destroyed (in the case of embryos left over from fertility medicine) or used in research (in the case of embryos created for that purpose or left over from fertility medicine). This adoption option would increase the number of embryos available for couples looking for help in having children, but that effect is less important--Karnein argues--than the observance of respect for human persons. As possible persons, she holds that embryos ought to be treated, as if they will become children, if only for a while. If enacted as a matter of law and policy, an 'adoption option' would wrongly interfere with the dispositional rights women and men ought to have over embryos they create in the course of trying to have children. Karnein's proposal would also deprive researchers of certainty that the embryos they create for research would actually be available that way, leading to increased burdens of time and money and maybe even to more embryos than would otherwise be produced. Karnein's analysis does not show, moreover, that any duty of rescue applies to embryos. No woman is required to adopt any embryo, which significantly undercuts the justification for an obligatory adoption period.

Opinion of obstetricians and gynaecologists on ethical issues in the practice of in-vitro fertilisation and embryo transfer in Nigeria.

The objective of this study was to bring ethical issues in the practice of in-vitro fertilisation (IVF) in Nigeria to the fore, to determine and articulate the views of Obstetricians and Gynaecologists on treatment modalities and to drive regulation of this specialised field. A plenary session was organised by The Bridge Clinic at the 2010 Society of Gynaecology and Obstetrics of Nigeria (SOGON) annual general meeting. Participants self-administered a 33-point questionnaire on their views on ethical issues in IVF. The results buttress the conclusions of an earlier publication, clearly indicating that even amongst specialised medical professionals; there are varying views which really cannot be challenged as being either right or wrong as they represent the individuals' position and his culture. Within the context of our society, ethics and morality especially as they affect patient care can and must be hinged on a code or framework which should be developed, implemented and its implementation monitored by a legally bound regulatory body for the protection of the rights and safety of our patients, their unborn children and for the integrity of our health care systems.

Ethical concerns for maternal surrogacy and reproductive tourism.

Reproductive medical tourism is by some accounts a multibillion dollar industry globally. The seeking by clients in high income nations of surrogate mothers in low income nations, particularly India, presents a set of largely unexamined ethical challenges. In this paper, eight such challenges are elucidated to spur discussion and eventual policy development towards protecting the rights and health of vulnerable women of the Global South.

Cryopreserved embryos and Dignitas personae: another option?

Many of the thousands of human embryos currently in cryogenic storage will sooner or later be discarded, often after being experimented upon. Others will remain in storage indefinitely, left there by parents who have no plans either to bring them to term or to offer them for adoption. These facts, coupled with a commitment to the basic moral equality of all human beings at all stages of development, generate a pressing question: What should be done for these embryos whose vital activities have been suspended and whose futures look so bleak? This paper offers a case that allows some of these cryogenically stored embryos to thaw and die, allows disposal of their remains in a manner that reflects their status, and is morally acceptable in that it is consistent with the principles that many accept as governing the removal of life-sustaining treatment in end-of-life cases.

Donation of 'spare' fresh or frozen embryos to research: who decides that an embryo is 'spare' and how can we enhance the quality and protect the validity of consent?

This paper analyses elements of the legal process of consent to the donation of 'spare' embryos to research, including stem-cell research, and makes a recommendation intended to enhance the quality of that process, including on occasion by guarding against the invalidity of such consent. This is important in its own right and also so as to maximise the reproductive treatment options of couples engaged in in vitro fertilisation (IVF) treatment and to avoid possible harms to them. In Part 1, with reference to qualitative data from three UK IVF clinics, we explore the often delicate and contingent nature of what comes to be, for legal purposes, a 'spare' embryo. The way in which an embryo becomes 'spare', with its implications for the process of consent to donation to research, is not addressed in the relevant reports relating to or codes of practice governing the donation of embryos to research, which assume an unproblematic notion of the 'spare' embryo. Significantly, our analysis demonstrates that there is an important and previously unrecognised first stage in the donation of a 'spare' embryo to research, namely: consent to an embryo being 'spare' and so, at the same time, to its disuse in treatment. This is not explicitly covered by the Human Fertilisation and Embryology (HFE) Act 1990, as amended by the HFE Act 2008. Having identified this important initial stage in the process of consent to the donation of a 'spare' embryo to research in conclusion to Part 1, in Part 2 we analyse the idea of consent to an embryo's disuse in treatment on the basis that it is 'spare' with reference to the legal elements of consent, namely information as to nature and purpose, capacity, and voluntariness. We argue that there are in fact three related consent processes in play, of which the principal one concerns consent to an embryo's disuse in treatment. If the quality of this first consent is compromised, in turn this will impact on the quality of the consent to the donation of that 'spare' embryo to research, followed by the quality of consent to future cycles of assisted reproduction treatment in the event that these are needed as a result of a donation decision. The analysis overall is of central relevance to the debate as to whether, and if so when, it should be permissible to request the donation of fresh embryos for research, as opposed to those that have been frozen and, for instance, have reached the end of their statutory storage term. This has a particular bearing on the donation of embryos to stem-cell research since there is a debate as to whether fresh embryos are most useful for this.