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Current ethical issues in IVF.

This article has briefly reviewed the range of public policy issues and ethical questions raised with respect to IVF. It then discussed selected issues that are now under policy debate and decision. Given the wide acceptance of IVF as a medical procedure for married couples, what variants might also be ethically defensible? IVF for unmarried couples appears defensible under specific conditions that are equally applicable to married couples. Involvement of third parties (gamete donation and gestational surrogacy) is more complex and needs case by case examination. Sperm donation appears to generate little that is ethically new when coupled with IVF but requires the same care and concern as AID. Egg or embryo donation, however, does raise new ethical questions that need close attention and continuing analysis. Freezing of human embryos also breaks new ethical ground, particularly in the options it generates beyond a narrowly defined medical domain. Certain of these options are better not undertaken without further public policy decision. Improvement of current procedures and techniques through effective clinical trials can be ethically carried out in terms of scientific and medical perspectives. However, efforts in this direction will be more effective if undertaken within a public policy framework that clearly defines acceptability during a transitional period of confidence-building.

Adoption↗

Increased risk of lethal graft-versus-host disease-like syndrome after transplantation into NOD/SCID mice of human mobilized peripheral blood stem cells, as compared to bone marrow or cord blood.

We tested the ability of human cells from different hematopoietic tissues to generate graft versus host disease-like syndrome (GVHD) in sublethally irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Tissue sources of human hematopoietic cells were: (1) bone marrow (BM), (2) nonmobilized peripheral blood (PB), (3) mobilized peripheral blood stem-progenitor cells (PBSC), and (4) cord blood (CB). To avoid interindividual donor variation, part of this study was done using BM, PB, and PBSC donated by a single healthy adult volunteer. A total of 179 NOD/SCID mice received graded human hematopoietic cell doses [5-500 x 10(6) mononuclear cells (MNC), containing 2-325 x 10(6) CD3(+) T cells, per mouse] from individual donors. Mice were observed for the development of GVHD and sacrificed 60 days after transplantation (earlier if ill). Mice were analyzed quantitatively by flow cytometry for human hematopoietic cell types and histologically, especially for human T lymphocytes infiltrating BM. No mouse transplanted with the tested doses of human CB or BM cells developed GVHD (experimentally defined as >10% human T lymphocytes infiltrating the mouse BM). For PB and PBSC, the frequencies of death, death with GVHD, and GVHD were directly related to the dose and source of human cells. Because PB cells contaminate harvested BM, the results from infused BM and PB were next combined for further analysis (BM/PB). The relative risks (hazard ratios estimated from the proportional hazards model) for death with GVHD, for each 10 human T cell dose increase, were 1.15 for BM/PB (p < 0.0001) and 1.47 for PBSC (p < 0.0001). In this in vivo xenogeneic model, the average T cell from human PBSC generated GVHD more potently than did the average T cell from human BM/PB, and the average CB T cell had a much lower GVHD potential. These results suggest that the potential for clinical GVHD from an HLA-disparate donor graft is likely to be quantitatively dependent both on the total number of T lymphocytes in the donor graft and the tissue source of the graft. Quantitative criteria for optimal T cell content of allogeneic donor hematopoietic grafts from different sources are discussed.

Animals↗

Ethical issues in critical care and cardiac arrest: clinical research, brain death, and organ donation.

Cardiac arrest results in global hypoxic-ischemic brain injury from which there is a range of possible neurological outcomes. In most cases, patients may require a surrogate to make decisions regarding end-of-life care, including the withdrawal of life-sustaining therapies. This article reviews ethical considerations that arise in the clinical care of patients following cardiac arrest, including decisions to continue or withdraw life-sustaining therapies; brain death determination; and organ donation in the context of brain death and cardiac death (so-called non-heart-beating donation). This article also discusses ethical concerns pertaining to the design and conduct of resuscitation research that is necessary for the development of effective therapies to prevent anoxic brain injury or promote neurological recovery.

Advance Directives↗

Do incentives matter? Providing benefits to families of organ donors.

Whether the number of organs available for transplant would be positively or negatively affected by providing benefits to families of organ donors has been debated by policymakers, ethicists and the transplant community at large. We designed a telephone survey to measure public opinion regarding the use of benefits in general and of five types in particular: funeral benefits, charitable contributions, travel/lodging expenses, direct payments and medical expenses. Of the 971 adults who completed the survey (response rate = 69%), all were from Pennsylvania households, 45.6% were registered organ donors, and 51.7% were nonwhite. Although 59% of respondents favored the general idea of incentives, support for specific incentives ranged from 53% (direct payment) to 84% (medical expenses). Among those registered as donors, more nonwhites than whites supported funeral benefits (88% vs. 81%; p = 0.038), direct payment (63% vs. 41%; p < 0.001) and medical expenses (92% vs. 84%; p = 0.013). Among those not registered as donors, more nonwhites supported direct payment (64% vs. 46%; p = 0.001). Most respondents believed that benefits would not influence their own behavior concerning donation but would influence the behavior of others. While benefits appear to be favored, their true impact can only be assessed through pilot programs.

Adolescent↗

Financial incentives for cadaver organ donation: an ethical reappraisal.

A panel of ethicists, organ procurement organization executives, physicians, and surgeons was convened by the sponsorship of the American Society of Transplant Surgeons to determine whether an ethically acceptable pilot trial could be proposed to provide a financial incentive for a family to consent to the donation of organs from a deceased relative. An ethical methodology was developed that could be applied to any proposal for monetary compensation to elucidate its ethical acceptability. An inverse relationship between financial incentives for increasing the families' consent for cadaver donation that clearly would be ethically acceptable (e.g., a contribution to a charity chosen by the family or a reimbursement for funeral expenses) and those approaches that would more likely increase the rate of donation (e.g., direct payment or tax incentive) was evident. The panel was unanimously opposed to the exchange of money for cadaver donor organs because either a direct payment or tax incentive would violate the ideal standard of altruism in organ donation and unacceptably commercialize the value of human life by commodifying donated organs. However, a majority of the panel members supported reimbursement for funeral expenses or a charitable contribution as an ethically permissible approach. The panel concluded that the concept of the organ as a gift could be sustained by a funeral reimbursement or charitable contribution that conveyed the appreciation of society to the family for their donation. Depending on the amount of reimbursement provided for funeral expenses, this approach could be ethically distinguished from a direct payment, by their intrusion into the realm of altruism and voluntariness. We suggest that a pilot project be conducted to determine whether this kind of a financial incentive would be acceptable to the public and successful in increasing organ donation.

Cadaver↗

Structural and functional comparison of polysaccharide-degrading enzymes.

Sugar molecules as well as enzymes degrading them are ubiquitously present in physiological systems, especially for vertebrates. Polysaccharides have at least two aspects to their function, one due to their mechanical properties and the second one involves multiple regulatory processes or interactions between molecules, cells, or extracellular space. Various bacteria exert exogenous pressures on their host organism to diversity glycans and their structures in order for the host organism to evade the destructive function of such microbes. Many bacterial organism produce glycan-degrading enzymes in order to facilitate their invasion of host tissues. Such polysaccharide degrading enzymes utilize mainly two modes of polysaccharide-degradation, a hydrolysis and a beta-elimination process. The three-dimensional structures of several of these enzymes have been elucidated recently using X-ray crystallography. There are many common structural motifs among these enzymes, mainly the presence of an elongated cleft transversing these molecules which functions as a polysaccharide substrate binding site as well as the catalytic site for these enzymes. The detailed structural information obtained about these enzymes allowed formulation of proposed mechanisms of their action. The polysaccharide lyases utilize a proton acceptance and donation mechanism (PAD), whereas polysaccharide hydrolases use a direct double displacement (DD) mechanism to degrade their substrates.

Amino Acid Sequence↗

[Spanish public opinion concerning organ donation and transplantation].

BACKGROUND: Information, beliefs, attitudes and the motivations of the Spanish population regarding organ donation and transplantation were studied to facilitate possible programs directed at the promotion of organ donation. METHODS: The Psychosocial Aspects of Donation Questionnaire (PADQ) was applied by personal interview to a representative sample of the Spanish population (n = 1,288). RESULTS: Sixty-five percent of the population was found to be in favor of donating their own organs while only 6.1% had an organ donation card. The main reasons inducing those questioned to be donors were solidarity (47%) and reciprocity (29%). The fundamental reasons hindering donation were not knowing how to be a donor (34%) and the fear of the possibility of an only apparent death (24%). Ninety-three percent would donate the organs of a dead relative if they knew that this person was in favor of donating. Only 52% would donate if they did not know the will of the departed relative. The younger subjects with a higher level of education, higher socioeconomic status, and better informed evaluated donation and transplantation favorably and those with direct experience showed a more favorable inclination to the donation of their own organs. CONCLUSIONS: Educational programs directed at the population should provide information on the efficacy and the profitability of transplantation presenting real cases and emphasizing the quality of life obtained by the receptors. Incentives to organ donation should be directed at reasons of solidarity and reciprocity. Family debate of the matter should be promoted as should the establishment of clear and accessible procedures for the obtaining of a donor card and thereafter the communication of the holders as to their decision to their respective relatives.

Adolescent↗

Is it ethical to prioritize patients for organ allocation according to their values about organ donation?

Because the supply of deceased donor organs fails to meet demand, patients needing a transplant frequently have lengthy waits or die while waiting. In an effort to reduce waiting times, the concept of "preferred status" has emerged. In the United States, preferred status has taken the form of a community of individuals called LifeSharers. Using directed donation, this group aims to facilitate priority organ allocation to its members-people who have agreed to be organ donors. Such preferred status programs increase societal awareness about organ donation and transplantation, but they are not without ethical controversy, as some term them "clubs." In the case of LifeSharers, the potential to increase the pool of deceased donor organs is a worthy goal that would benefit the community of patients awaiting transplantation, not just LifeSharers members.

Attitude to Health↗

[Physiopathologic changes in brain death. Their importance for management and organ donation decisions].

Technological advances in the medical area have allowed for development of useful techniques to treat patients with diverse diseases. For example, at intensive care units this technology allows maintenance blood flow and tissue oxygenation even when brain death (BD) is already established and the individual cannot function. The function of heart, lungs, and other organs can be maintained with different devices, but maintenance of cerebral functions is not not yet possible. Therefore, when a subject fulfills legal and medical requirements for BD, we must be clear that any patient procedure will not keep him alive, although the subject looks alive due to support devices; when BD is present, death must be accepted. Obviously, death is a difficult process to accept, including for health personnel. We consider that it is very important for medical and nursing personnel directly responsible for patient care to receive knowledge on BD and recognize the alternatives with regard this situation, to be able to provide specific orientation when it is required. This paper is a review of the BD concept, main physiopathologic changes, and some possible treatment alternatives to maintain the patient as a potential organ donor.

Brain Death↗

Oculoleptomeningeal amyloidosis associated with a new transthyretin variant Ser64.

BACKGROUND: A Canadian family with oculoleptomeningeal amyloidosis with both central and peripheral nervous system disorders was described in 1988. Death of affected family members resulted from recurrent cerebral hemorrhage. OBJECTIVE: To determine if oculoleptomeningeal amyloidosis is caused by a mutation in transthyretin (prealbumin). METHODS: DNA isolated from peripheral blood and archival tissues of affected members of the kindred was studied by direct DNA sequencing and restriction fragment length polymorphism analysis. RESULTS: Direct DNA sequencing identified a thymine-to-cytosine transition at the second base of codon 64, which resulted in a replacement of serine for phenylalanine. This mutation, which creates an additional HinfI site was detected by restriction fragment length polymorphism analysis in each affected individual. CONCLUSION: In this kindred, oculoleptomeningeal amyloidosis is related to a mutation in transthyretin (Phe64Ser).

Adolescent↗

[Oocyte donors. Psychological aspects].

This study concerns 63 oocyte donors who were investigated after a semi-directed interview. In our procedure all "personalized anonymity" donation took place on two levels: symbolic donation for close recipient, real donation for unknown recipient. All donors agree with anonymity without which some would not have preceded. Narcissic weakness often linked with recent trauma (death...) is often seen in patients who do not achieve the gift. Oblativity and happy motherhood are the most important reasons for oocyte gift.

Adaptation, Psychological↗

Organ donation terminology: are we communicating life or death?

The continued functioning of organ transplantation depends on obtaining the permission of the next of kin. This communication process between medical or transplant professionals and a donor family hinges heavily on the understanding of certain critical terms like brain dead, life support, and transplantation. Communication issues in obtaining organ donation consent were examined, with particular focus on what are literally life-and-death decisions. Using an experimental simulation methodology, data are offered in support of the claim that much miscommunication occurs in such situations. Directions for improving such communication by allaying latent fears and more carefully defining crucial terminology are offered.

Adolescent↗

Non-heart-beating organ donation: a reply to Campbell and Weber.

In the preceding commentary, Campbell and Weber raise two valid and important issues concerning non-heart-beating organ donation (NHBOD). First, because the procedure links withdrawal of life support and the potential for subsequent organ donation, the desire for organs may create a situation in which care of the dying individual has relatively less importance and the dying may receive suboptimal care. Second, even if concerns about care of the dying were dealt with adequately, there will not be enough non-heart-beating donors to significantly decrease the organ shortage that exists, making the procedure not worth the risk. We agree that attention to the important details of caring for the dying are, and must be, the primary concern of all health care workers caring for those individuals. Ensuring the patients' comfort, dignity, and autonomy, and providing for family and social support are the mainstays of this care. All policies for NHBOD should clearly support and mandate these concepts. Regarding the second concern, we agree that NHBOD is currently rare; however, evidence is increasing that this type of donation has great potential. Continued growth of the practice in this country will depend largely on public acceptance, which we believe will be directly influenced by whether the public perceives that care of the dying is not compromised by this procedure.

Cadaver↗

[Status of organ donation in Iceland].

According to Icelandic law, since 1991 the medico-legal criterion of death has been the cessation of brain function. Yet another law regulates the harvesting of organs for transplantation. A living donor must be at least 18 years of age, be fully informed, and not exposed to direct risk. Cadaver organs may be harvested provided the deceased has given consent in advance, or failing this if the next of kin gives consent. In the absence of explicit consent (i.e., presumed non-consent), no organ may be harvested.

Adult↗

Provision of transplant services.

To a large extent the success of any transplant programme depends ultimately on the expertise, skills and experience of the team of doctors, nurses and other health-care professionals. However, the logistics associated with the service will be the major factors determining the success of the programme. The service should be provided on the basis of epidemiological need, concentrating provision in an optimal number of units so that benefit is gained from the 'experience curve' effect of a relatively high throughput. The availability of the key resource for the programme, namely organs, depends on the willingness of the public to donate, and on the co-operation of other health-care professionals, not directly involved in transplantation, in identifying potential donors, encouraging relatives to consent and ensuring that the donor is maintained in an optimal condition. There are not many medical treatments that require such wide-ranging participation and co-operation as those needed for organ transplantation. All these factors have to be addressed for an organ transplant programme to be successful.

Humans↗

Organ transplantation in Latin America.

Organ transplantation is currently a form of treatment for end-stage organ disease in Latin America for which enthusiasm appears to be growing both in individual countries as well as in the whole region. The Latin-American Transplant Registry has been a factor in the development of communication among the different countries of the region and a focus for unification. Both renal and extra-renal organ transplantation have increased significantly during 1999 and for kidneys the activity is currently 12% of the world renal transplant statistics. Important evidence for the continuing development and maturity of transplantation in the region includes the number of new transplantation societies, the increase in the number of renal and extra-renal transplant programs, the development of national organ transplant registries, efforts towards analyzing costs and administration in transplantation and the incorporation of new immunosuppressants. The development of cardiac transplantation in Bolivia, Cuba, Paraguay, Perú, Puerto Rico and Uruguay, intestinal transplantation in Argentina, and liver transplantation in Bolivia all reflect a marked interest in organ transplantation in the different countries. Similarly, liver and cardiac transplantation are increasing at a very fast rate. End-stage organ disease is recognized as a growing health priority and organ donation as a critical limiting factor. Governments are directly and indirectly supporting transplantation initiatives. The return of trained transplant practitioners to their countries of origin also accounts for part of the increase in activity and for the organizational aspects of transplantation. The statistics presented in this report signify increasing maturity in the transplantation activities of Latin America.

Government Programs↗

Trypanosoma cruzi in Los Angeles and Miami blood donors: impact of evolving donor demographics on seroprevalence and implications for transfusion transmission.

BACKGROUND: Trypanosoma cruzi, the agent of Chagas' disease, continues to be a concern for blood safety, as demonstrated by recent transfusion-transmitted cases in the United States and Canada. The chronic nature of Chagas', coupled with increasing numbers of immigrants from T. cruzi-endemic countries, suggests that Chagas' is a long-term public health problem. Herein, we report on a multiyear epidemiologic study of T. cruzi in Los Angeles and Miami blood donors. STUDY DESIGN AND METHODS: From May 1994 to September 1998, blood donors in Los Angeles and Miami were queried regarding birth or time spent in an endemic country. Donations of "yes" respondents were tested by EIA, confirmed by radioimmunoprecipitation assay, and if confirmed as seropositive, enrolled in look-back investigations. RESULTS: A total of 1,104,030 Los Angeles and 181,139 Miami donors were queried regarding risk; 7.3 and 14.3 percent, respectively, responded yes. Seropositive rates were 1 in 7,500 Los Angeles and 1 in 9,000 Miami donors. In Los Angeles, seroprevalence rates increased significantly from 1996 to 1998 and were significantly higher for directed donors than nondirected donors. Look back identified 18 recipients, all of whom were seronegative for T. cruzi. CONCLUSION: Significant numbers of T. cruzi-seropositive donors contribute to the U.S. blood supply. The incidence of seropositivity is enhanced by minority recruitment efforts necessitated by donor demographic shifts. Similarly, high rates among directed donations in Los Angeles are attributable to a disproportionate number of at-risk directed donors. Current look-back data likely underestimate the frequency of transfusion- transmitted T. cruzi. These results indicate that continued evaluation of transfusion as a mode of T. cruzi transmission in the United States is needed.

Adult↗

Embryos created for research purposes.

The creation of embryos for research use has drawn a great deal of criticism. It is difficult to defend an ethical distinction between what one can do to "spare" embryos and what one can do to "research" embryos. The strongest ground on which to argue against the creation of embryos for research is a symbolic one, having to do with respect for human life. Ronald Dworkin's work in Life's Dominion on the symbolic meaning of the abortion debate throws a helpful light on this dispute. By understanding the basic question to be, Does the creation of research embryos weaken or insult our communal respect for the sanctity of human life in some way that in vitro fertilization (IVF) or the experimental use of "spare" embryos does not?, the debate can move in a more constructive direction.

Abortion, Eugenic↗