The newly issued International Society for Stem Cell Research (ISSCR) guidelines for human embryonic stem cell research (G. Q. Daley et al. , Policy Forum, 2 Feb., p. 603) include worthy goals and lofty language about truth and transparency in biomedical research, dissemination of research benefits “to humanity at large on just and reasonable terms,” and discussion of enhancing the informed consent process for the procurement of tissues and gametes ([1][1]). But the guidelines would in fact weaken important ethical standards that have already been established. We are particularly concerned about the recommendation that decisions about paying women for their eggs should be left to mostly local oversight committees. This is a complex social and ethical question. Many who have examined the issue closely, including ourselves, have concluded that researchers should compensate women only for their direct expenses, to avoid inducing economically vulnerable women to accept the significant risks of egg retrieval when they would not otherwise be willing to do so. This perspective has been adopted as law in California and a number of countries, and it is recommended in the U.S. National Academies guidelines. In other words, the ISSCR is now suggesting that governments and agencies abdicate their role to protect the health and safety of women in favor of a patchwork of inconsistent and opaque decisions made by local committees. Members of the ISSCR group justify weakening the rules on egg procurement by citing “cultural and political differences” ([2][2]). This is an unhelpful relativism that could all too easily endorse a kind of “tissue tourism,” in which researchers arrange to obtain women's eggs wherever the rules are most lax. This prospect, and emerging inconsistencies among standards for stem cell research, point to the need for binding rules to ensure that stem cell and other biotechnologies are developed and used in ways that truly support, rather than actually undermine, health and well-being. 1. 1.[↵][3]See ISSCR guidelines at [www.isscr.org/guidelines/index.htm][4]. 2. 2.[↵][5]1. A. Pearson , “New international guidelines for stem cell science,” NewScientist.com news service, 1 Feb. 2007 (see [www.newscientist.com/article.ns?id=dn11084&feedId=online-news_rss20][6]). # {#article-title-2} As evidenced by the Policy Forum “The ISSCR guidelines for human embryonic stem cell research” (G. Q. Daley et al. , 2 Feb., p. [603][7]), countries with public policies on the donation of surplus embryos for stem cell research broadly agree on the need for a fully informed consent and the avoidance of conflicts of interest. Quality assurance, therapeutic purpose, transparency, confidentiality, traceability, and ethics review are also common ground. However, there is less agreement regarding the retrieval and use of human oocytes for stem cell research. The recently released ISSCR guidelines attempt to fill this gap, but, in an attempt to reach consensus, it resorted to a vague, unclarified prohibition of “undue inducement” regarding compensation of oocyte donors. The use of financial incentives to obtain human oocytes to be used in stem cell research is a contentious issue. Are participating women vendors, providers, or donors? That depends on the type of compensation. Currently, there are five models of compensation: free market, pure gift, fixed compensation, minimum wage, and reimbursement of expenses. The free-market model is likely to prevail in the absence of sufficient debate and decision-making by governmental authorities around the world. Its obvious advantage is the high rate of recruitment given the increasing scarcity of access to human oocytes. Yet, this approach can result in commodification, undue inducement (if not coercion of the vulnerable), and commercialization. At the opposite extreme is an altruistic gift, which is likely to be rare, considering the invasive procedures involved and the unknown long-term health risks of ovarian hyperstimulation. International debate is sorely lacking for the other three models. The fixed compensation model provides for a standardized amount irrespective of the financial costs to the donor, socioeconomic status (i.e., need), or time and inconvenience. This model prevents monetary inducements as a primary motivation and minimizes financial loss to the donors, but ignores individual expenses. Although arbitrary, it has the advantage of certainty and, in a societal sense, fairness. The minimum-wage approach takes into account the number of hours donated. In all likelihood, providing a minimum wage would result in a higher rate of payment than the fixed compensation model. Reimbursement of expenses seems to be a more individually tailored approach. This depends, however, on whether reimbursement is for inconvenience, time, pain, and discomfort, or is limited to actual receipted expenses such as travel, lodging, parking, meals, and daycare. There are limited incentives for donors and, in practice, the administrative proof required is burdensome. A narrower receipted expenses-only policy will in the long term further reduce the availability of these materials. This could result in commercial importation or a black market. Some would see the current “exceptional” case in the U.K. of egg donation for research in exchange for access to fertility treatment as a variation of the reimbursement model. This approach, however, is akin to providing access to drugs or treatments in clinical trials and does not parallel the healthy volunteer guidelines in international guidelines for biomedical research. Perhaps a more equitable solution would be to develop a mixed model in which a standard amount of compensation would be determined by a competent authority, but would also include reimbursement for time and effort expended for procurement. Were such an approach to be adopted internationally, the additional issue of forum shopping (selecting a procurement site on the basis of the particular laws in effect there) may be lessened. The International Stem Cell Forum Ethics Working Party maintains that this approach respects altruism and solidarity. The amount will still largely remain a symbolic recognition of the true value of such participation in stem cell research. It provides a feasible solution to an issue that needs to be examined within the larger context of the participation in and ethical oversight of biomedical research. FOR THE INTERNATIONAL STEM CELL FORUM ETHICS WORKING PARTY: # Response {#article-title-3} Darnovsky and Fogel raise appropriate concerns that oocyte donation should not fall disproportionately on economically vulnerable women and that research guidelines should prohibit “tissue tourism.” The ISSCR guidelines directly address these concerns. The introduction to section 11 (“Procurement of materials”) clearly states: “Consistent with well-established principles of justice in human subject research, there must be a reasonable relationship between those from whom such materials are received and the populations most likely to benefit from the research,” and section 11.5b reads: “There must be monitoring of recruitment practices to ensure that no vulnerable populations, for example, economically disadvantaged women, are disproportionately encouraged to participate as oocyte providers for research.” Furthermore, the guidelines articulate the core principle that there be a “rigorous review to ensure that reimbursement of direct expenses or financial considerations of any kind do not constitute an undue inducement.” Research that is subject to a rigorous oversight process at the local, regional, or national level—as stipulated in the ISSCR guidelines—and conducted in accordance with these guiding principles will avoid the exploitation of women that is our shared concern. The Letter from the Ethics Working Party (EWP) of the International Stem Cell Forum acknowledges that women should be free from “undue inducement” when making decisions regarding the donation of oocytes for research, and outlines a proposal that if approved through a rigorous process of review and subject to appropriate oversight would be consistent with ISSCR guidelines. The EWP Letter correctly highlights the difficulties in defining what constitutes allowable expenses and the need to guard against the disproportionate recruitment of economically disadvantaged women, and illustrates the complexity of the deliberations required to arrive at a reasonable policy for engaging women in research. The ISSCR task force comprised scientists, ethicists, and legal experts from 14 countries. Despite the inevitable political, cultural, and religious differences that shape research policy internationally, our task force reached consensus on guiding principles for the conduct of human embryonic stem cell research. The ethical principles pertaining to oocyte donation are particularly challenging and continue to prompt debate and inquiry. The ISSCR guidelines encourage an open and ongoing dialogue concerning ethical procurement of human materials for stem cell research, and will be subject to review and refinement as more information becomes available. [1]: #ref-1 [2]: #ref-2 [3]: #xref-ref-1-1 "View reference 1. in text" [4]: http://www.isscr.org/guidelines/index.htm [5]: #xref-ref-2-1 "View reference 2. in text" [6]: http://www.newscientist.com/article.ns?id=dn11084&feedId=online-news_rss20 [7]: /lookup/doi/10.1126/science.1139337