Oöcytes for research: inspecting the commercialization continuum

Abstract

Using human oöcytes for research purposes is a controversial subject, but although much has been written on the ethical issues of the practice, there is comparatively little empirical knowledge of the practice itself. This article analyzes the scope, infrastructure, and dynamics of oöcyte procurement for research in Europe and California and identifies some major trends and shifts in the field. Our research shows that oöcyte procurement strategies have evolved out of close institutional integration with the IVF sector, that there has been a shift from “poor quality” oöcytes to “good quality” oöcytes – which implies a shift to ethically more problematic procurement practices – and that we see a variety of crypto-commercial strategies, which enable monetary transactions while avoiding confrontation with non-commercialization policies. Finally, there has been a move to more commercial models of procurement, which can be interpreted as a strategy to release the infrastructural requirements that tie researchers to the IVF sector.

Keywords:

• oöcyte procurement
• stem cell research
• commercialization

In June 2009, the New York Empire State Stem Cell Board decided it was appropriate for women to be compensated for giving their oöcytes to stem cell research and that payments of up to $10,000 should be reimbursable as an allowable expense under New York State Stem Cell Science (NYSTEM) contracts.1 To be sure, there had long been a market for oöcytes in the state of New York and elsewhere in the United States, but it had been restricted to transactions in oöcytes for purposes of in vitro fertilization (IVF). The practice of using another woman's egg for IVF, usually called “egg donation,” began in the mid-1980s and has since evolved into a growing industry. In the US, about 16,000 women used another woman's egg for IVF in 2005 (Levin 2010). In Europe, 12,685 so-called “egg donor cycles” were reported to the European Society for Human Reproduction and Embryology (ESHRE) in 2006.2 However, at least as a generic term, “egg donation” is a misnomer, inasmuch as women often receive money for giving their eggs to others. The average price in the US in 2005–2006 was estimated at $9,000 per cycle. Prices vary greatly depending on donor characteristics such as ethnicity, age, level of higher education, or fertility record. The maximum offered in the US in 2005–2006 was $50,000 (Levin 2010). In Europe, in contrast, there is no open market for oöcytes. The Council of Europe's Convention on Human Rights and Biomedicine of 1997 (Oviedo Convention) prescribes in Art. 21: “The human body and its parts shall not, as such, give rise to financial gain.”

Similarly, the Charter of Fundamental Rights of the European Union of 2000 postulates in Art. 3 para. 2 “the prohibition on making the human body and its parts as such a source of financial gain.” However, while both instruments seem to rule out payment to the woman from whom the oöcyte is retrieved, the concept of “financial gain” is not clearly defined. In addition, all European countries where research cloning is legal have some non-commercialization provisions in place that apply to oöcyte donation. In California too, vending oöcytes to research is prohibited, unlike vending oöcytes for IVF purposes. Still, as we will show, various forms of material incentives have developed that amount to more or less hidden forms of payment. In this article, after outlining the main concerns and arguments about oöcytes for research, we will give an overview of the practice in Europe and California. We will point out that access to good quality oöcytes is a decisive logistic factor for the development of the practice, which has largely been managed through establishing tight connections between the IVF sector and research – what Sarah Franklin (2006) termed the IVF–stem cell interface. We further show that we can observe two main, interrelated trends in the past few years: a shift from “surplus” oöcytes to “good quality” oöcytes, and a shift towards using material incentives. The IVF–stem cell interface, we argue, has formed on the one hand an infrastructural precondition for acquiring oöcytes for research. On the other hand, however, it also acts as a restriction from the point of view of research. More commercial forms of organizing access to human oöcytes, such as lump sum compensation or open payments, would allow researchers more direct access to good quality oöcytes and give them more independence from the IVF sector and thus are quite attractive from this point of view.

Concerns and controversies

When the practice of somatic cell nuclear transfer (SCNT), also known as research cloning or therapeutic cloning, began in the late 1990s, it reinforced concerns among feminists about the emergence of a new biotech industry that would rely on access to women's bodies and bodily materials and might bring about new forms of exploitation. In SCNT, the nucleus of a somatic cell is transferred into a denucleated egg, which then is induced to develop into an embryonic stage of a blastocyst. Ideally, researchers would then derive stem cells and genetically customized cells, tissue or even organs from that blastocyst that would not be rejected by the recipient's body. In 2008, the Californian biotech firm Stemagen announced that it had managed to create the first cloned human blastocyst.3 However, at the time of writing, no stem cell lines resulting from SCNT have been reported, and no patient-specific tissue has been created through SCNT.

Parthenogenic stem cells are the subject of another research strategy to generate customized stem cell lines that also requires human oöcytes. Here, embryonic-like stem cells are derived from an unfertilized oöcyte, which has been activated without sperm and induced to divide as if it had been fertilized. In January 2009, the International Stem Cell Corporation (ISCO), another Californian biotech firm, announced that it had created tissue, namely layers of retinal progenitor cells, from human parthenogenic stem cells and had transplanted it into animals for testing.4

Much has been written on oöcytes for research, in particular during the years following the so-called Hwang scandal in 2005 (Gottweis and Triendl 2006). As is well known today, Hwang claimed he had managed to generate 11 human stem cell lines via SCNT – which would have made him the first in the world to do so. While these lines never existed, the scandal also triggered an international debate about oöcyte procurement for research. Hwang declared that he had used 185 human oöcytes to produce his stem cell lines. The South Korean Bioethics Committee, however, gives a much higher number, namely 2221, derived from 121 women (Leem and Park 2008). Of these, 85 women had received payment. Of the women who were not paid, two were junior researchers on Hwang's team and thus stood in a relationship of dependence to him.

These events fueled concerns about a new industry relying on women's body materials on a large scale. Feminists and bioethicists entered into a controversy on the risks and benefits of this type of research and debated the commercialization of the female body, health risks for women, limits of informed consent, concepts of women's reproductive autonomy and/or ownership of the body, new forms of exploitation of women, and questions of regulatory responses.5 Feminists are divided on the issue. Some are concerned about health risks related to hormonal ovarian stimulation, which is used to raise the number of eggs retrieved per cycle from the normal one or two up to eight, 10, 20 or more. Critics emphasize the risk of severe ovarian hyperstimulation syndrome (OHSS) and the uncertainty about possible long-term risks of ovarian hyperstimulation. Additionally, they point out that egg retrieval is an invasive intervention into the woman's body, the justification for which rests not on her own medical needs nor on the tangible benefit of concrete others, but on the highly speculative prospect of future advances in biomedical research. Furthermore, they argue, the interests of researchers in obtaining large numbers of oöcytes, as well as exaggerated expectations raised not only by researchers, but also by the mass media and society at large, are likely to create a situation in which risks are downplayed or denied. In this context, “choice” or “informed consent,” these authors argue, are not meaningful concepts and should not form the basis of policy decisions (Norsigian 2005, Beeson and Lippman 2006, Sexton 2006, Dickensen and Alkorta Idiakez 2008). On these grounds, the California based feminist network “Hands Off Our Ovaries” (HOOO) campaigns for a moratorium on egg extraction for research purposes, at least “until such time as global discourse and scientific research yields information sufficient to establish adequate informed consent.”6 In the absence of long-term studies and scientific certainty about possible long-term effects for women, research demands, they argue “will place undue burdens on young, poor women.”7

Celia Roberts and Karen Throsby, for instance, object: “This nomination of all women as the objects of biotech research is misleading in the UK context” (Roberts and Throsby 2008, p. 161). Rather than women in general, or young, poor women, they argue, the groups affected by research demands for oöcytes are infertile women or women in infertile couples undergoing IVF. Therefore, they scrutinize the ways in which the demands of research affect these particularly vulnerable groups of women.

Others argue that women should not be denied the capacity and the right to make free and informed decisions about their bodies and their lives and advocate a combination of payment and informed consent procedures. Allowing the development of a regular, formal market for oöcytes would foreclose the emergence of “black” informal, unregulated markets and thus prevent exploitation of women (Thompson 2007). From a different perspective, Catherine Waldby and Melinda Cooper (2010) emphasize the productivity of the female body in this new sector. They conceptualize egg “donation” as a new form of women's labor, which they term “regenerative labour.” Providing bodily substances, which in this case are indispensible resources for regenerative medicine, is an onerous, time consuming and risk-laden productive activity, through which women actively participate in the production of biovalue. Although the productivity of their bodies is employed by stem cell research and made profitable, it is not recognized as such. It is rather naturalized and rendered invisible. In order to make women's participation in the production of biovalue visible, they argue, women, as regenerative laborers, should be entitled to bargain for social rights such as healthcare and safety, and payment. The model could be the organization of women as “sex workers” (Waldby and Cooper 2008). “Sex workers,” Waldby and Cooper suggest,

have organised on this basis, and successfully lobbied (in some countries at least) for regulation of sex work as labour, with rights not only to sufficient wages but also medical care, occupational health and safety, natural justice, work security and rights to set limits on the demands made by clients. (Waldby and Cooper 2008, p. 68)

The purpose of this article is not to discuss the issue of payment in a purely normative manner, reconstructing the different arguments pro and con, the premises and analogies on which they are built – not because we deem this discussion to be idle or futile, but because we think it would be useful to have some additional empirical background knowledge about the matter. Considering the volume of argument, surprisingly little is known on an empirical level about oöcyte procurement for research. A good portion of the literature focuses on normative and/or theoretical questions related to issues of commercializing the (female) body, ethical permissibility of oöcyte procurement for research, or optimizing regulation. Existing empirical knowledge about oöcyte procurement largely refers to procurement for IVF purposes (Waldby 2008, Ikemoto 2009). Some studies have critically analyzed particular models of oöcyte procurement and individual policy debates. Kate O'Riordan and Joan Haran, for instance, provide a critical analysis of the public consultation on “Donating Eggs for Research: Safeguarding Donors,” which the UK Human Fertilization and Embryology Authority (HFEA) conducted in 2006. They argue that the rhetoric and discursive framing of the consultation foreclosed a more fundamental problematization of egg “donation” for research (O'Riordan and Haran 2009). Celia Roberts and Karen Throsby have studied the egg sharing for research scheme at Newcastle, which, as they argue, forms a departure from the previous non-payment policy in the UK. By approving the scheme, the HFEA created the possibility of IVF patients being “paid to share” their oöcytes with stem cell research. This policy shift, as Roberts and Throsby show, was managed through representing the egg sharing scheme both as an ordinary continuation of existing practices (pointing out that egg sharing schemes existed already, albeit for IVF purposes) – and as extraordinary at the same time (pointing out that the research for which the oöcytes were obtained was extraordinarily promising and egg procurement therefore extremely urgent and important). These studies take a close look at individual schemes and related policy activities, and more specifically at the respective rhetorical strategies to make women's oöcytes accessible for research, and both address the situation in the UK. This article will focus not so much on rhetoric but on the infrastructure and logistics of oöcytes for research. Further, it seeks to complement the existing micro-analyses of particular procurement schemes or related policy measures by a broader European perspective on the field. From this perspective, we would qualify Robert and Throsby's argument that not “young, poor women” but infertile women, and women in infertile couples are the object of biotech research's demands. This is the situation in the UK – for now. In other places, notably Spain, the picture looks different, as we will show below. Moreover, in the UK too, there are discussions about adopting the Spanish compensation system, which would assimilate the UK situation to that in Spain.

We suggest that we need more empirical knowledge, particularly about the scope, logistics, and dynamics of the practice in order to assess what is going on. The aim of this article, therefore, is primarily to contribute to the empirical picture of oöcyte procurement practices in order to inform the ongoing discussion on oöcytes for research. The article is based on fieldwork we did between November 2008 and February 2010 in Europe and California. We visited research sites where SCNT or research on parthenogenic stem cells was being done or had been done until recently. We also did over 40 interviews with researchers, regulators, NGO representatives, IVF doctors, and biotech entrepreneurs, in order to establish where the practice is done, how it is organized and whether transactions take place between women and researchers, and if so, what forms of transactions. We will present four significant findings.

First, stem cell research strategies that require human oöcytes have evolved on the basis of close institutional and personal integration with IVF facilities. Thus, the existence of an IVF–stem cell interface (Franklin 2006) forms the infrastructural basis of these research strategies – and brings about structural conflicts of interests between research and reproductive medicine.

Second, we see a move in research from “spare” oöcytes to “good quality” oöcytes. This implies a shift from less to more controversial practices of oöcyte procurement, insofar as good quality eggs from IVF patients are also of interest for the IVF patient herself, or they come from non-patients who had been offered material incentives to undertake a risky and difficult procedure.

Third, there is a trend from less to more commercial models of oöcyte procurement. This trend, however, cannot adequately be grasped within a conceptual framework that opposes commercial to non-commercial relations. In this respect, we agree with Klaus Hoyer that “commodification of the body” is too crude a concept to grasp the dynamics that drive the “establishment of exchange systems for human biological material” (Hoyer 2007, p. 327). We prefer to describe the field in terms of a commercialization continuum, characterized by a variety of crypto-commercial strategies that enable more or less monetary transactions, while at the same time avoiding open clashes with existing non-commercialization provisions. Thus, our research confirms Waldby's point that today we see a multiplicity of forms of remuneration and transactions concerning human body materials, rather than a dichotomy between gift relationships and transactional economies (Waldby and Cooper 2010).

Fourth, however, the trend towards the commercial end of the spectrum can be interpreted as a strategy to release the infrastructural requirements that tie researchers to the IVF sector. Being able to offer money or material incentives makes researchers less dependent on the goodwill of IVF patients and clinics and thus offers a way to loosen the IVF–stem cell interface.

Contested benefits – contested risks

Some scholars, such as Heidi Mertes and Guido Pennings (2007) suggest that women who give their eggs to stem cell research are like human research subjects. Both, they argue, take certain risks in order to promote medical research, both should give informed consent, both should be protected by certain protocols, and receive material compensation for their service. One of the problems with this analogy, however, is that research on human subjects usually takes place at an advanced stage, when the drug or procedure at stake has already undergone preliminary testing, the likely benefits of research are clear, and it is therefore possible to establish a risk–benefit ratio. For both SCNT and parthenogenesis, however, it is hard to relate the risks for women as egg givers in any meaningful way to future benefits of the research. These are still very basic research programs, and at the moment, nobody can tell whether there will be any safe, applicable cures based on these technologies at all. The health risks to women involved in egg retrieval, on the other hand, are relatively well known.8 Risks are related to each step of the process.

First, the woman is given hormones to shut down her normal cycle. This is done basically for reasons of timing and coordination, not for medical reasons. Adverse effects, including nausea, depression, hypertension, abdominal pain, or liver function abnormality, have been reported to the American FDA in connection with one of these hormone drugs (Lupron) (Norsigian 2005).

Second, the woman takes hormones to stimulate her ovaries in order to mature more than one or two egg follicles per cycle. The most severe complication related to hormonal ovarian stimulation is ovarian hyperstimulation syndrome (OHSS). Effects of OHSS can be mild, such as nausea or a bloated stomach, or severe, ranging from respiratory distress or blood clotting disorders to pulmonary embolism or renal failure. Five deaths from OHSS have been reported for the UK (Spar 2007). Estimates of the risk of severe OHSS range from 0.1%–0.2% (US Institute of Medicine cited in Guidice et al. 2007), or 0.2–1% (based on a WHO report, see Hugues 2002), to 0.2–5% (based on an evaluation of a number of studies, see Delvigne and Rozenberg 2002) – but there is no dispute that it can occur and that it can be very serious or even fatal.

Third, from a research perspective, procurement practices that entail higher risks for women are more attractive. Researchers are particularly interested in access to younger women's eggs because they are of better quality. However, while some of the risks associated with extraction are known to be higher in younger women (Jayaprakasan et al. 2007), most research on risks has focused on women undergoing IVF, who are usually in their 30s or over. Furthermore, health risks increase with the number of eggs retrieved: the more eggs, the higher the risks. The extraction itself is onerous and also bears some risks; it is an invasive procedure that requires anesthesia and carries risks of bleeding or infection. Again, from the perspective of research, it is desirable to retrieve more eggs, but this implies riskier procurement practices.

Finally, relatively little is known about the possible adverse effects of ovarian hyperstimulation and egg extraction in the long term. Some studies report statistical correlations with increased rates of cancer and infertility, but there are few studies and results are conflicting (Beeson and Lippman 2006, Pearson 2006). Yet, regarding the existing scientific uncertainty, some feminists such as Diane Beeson and Abby Lippman or “Hands Off Our Ovaries” call for a moratorium on egg retrieval until more scientific knowledge is available about the long-term risks of the practice.9

Importantly, a number of recent studies suggest that so-called “mild IVF,” that is, IVF that does without or with only minimal doses of hormones, is less onerous, less risky, less costly, but nearly as efficient as conventional IVF in terms of “baby-take-home rates.”10 This is relevant in our context since here women's health interests and research interests again collide: whereas potential IVF patients have an interest in less risky and more affordable treatment, research has an interest in the existence of “spare” eggs – the number of which would be drastically reduced if mild IVF became standard practice.

Ethico-logistic constraints and infrastructural requirements

We found that in Europe, SCNT research requiring human oöcytes is rare. Yet this situation might change if changes occur among the vectors that determine demand and supply for oöcytes in the field of stem cell research. For instance, many stem cell researchers, according to several of our interviewees, have switched from SCNT research to induced pluripotent stem cells (iPS), viewing them as an alternative source of patient-specific stem cells without the logistical and ethical problems of using human oöcytes or embryos. However, if iPS11 turn out to be too difficult and unsafe to deal with, this situation may change again.

At the time we concluded fieldwork in February 2010, three research facilities were still doing research on SCNT in Europe: the Centro de Investigación Príncipe Felipe (CIPF) in Valencia, the Centro de Medicina Regenerativa de Barcelona (CMRB) in Barcelona, and the North East England Stem Cell Institute (NESCI) in Newcastle upon Tyne. Two further research facilities, Ghent University and the Karolinska Institute near Stockholm, had been doing it until recently but then abandoned the strategy.

We also did interviews and visited research sites in California in order to map out the regulatory and technoscientific landscape concerning oöcytes for research there. The idea of including Californian research sites in our survey was not so much to do a strict comparison but to alert ourselves to the possibility that things may be different elsewhere, particularly in a stem cell “hot spot” outside Europe. Thereby, we sought to avoid mistaking the European situation for the global one. We examined two biotech firms engaged in research using human oöcytes: Stemagen in La Jolla/San Diego and ISCO (International Stem Cell Corporation) in Oceanside, the latter active in research on parthenogenic stem cells. The stem cell research center we approached at University of California in San Francisco (UCSF) at the time had already abandoned its research on SCNT.12

One of the most significant reasons why this type of research is relatively rare and many research projects have been abandoned, is the enormous logistic difficulty of acquiring sufficient numbers of human eggs, in particular of “good quality” eggs. Good quality eggs, from the point of view of research, are mature, “fresh,” recently extracted eggs – in contrast to immature eggs or so-called failed-to-fertilize eggs left over from IVF. Further, good quality eggs mean eggs from younger women. Since the majority of IVF patients are already in their 30s, oöcytes from so-called non-patient “donors” are far more interesting for research purposes than those from the average IVF patient. In terms of suitability for research purposes, even fresh and mature eggs from IVF patients are less preferable than those from young non-patient women. We will come back to this.

Logistic difficulties, however, do not exist in isolation from institutional and cultural contexts. The institutional and cultural embeddedness of procurement logistics becomes most obvious with regard to non-payment provisions and mechanisms of healthcare coverage. On the subject of non-payment provisions, many researchers we talked to emphasized that very few women were willing to go through oöcyte extraction and hormone stimulation without being offered material incentives. Offering direct payment would immediately increase the number of women willing to undergo egg retrieval, as the development of the US reproductive oöcyte market has shown. However, paying women for yielding their oöcytes to research is prohibited all over Europe as well as in California. Regarding healthcare coverage, it is noteworthy that some research projects have turned to the model of “egg sharing” in order to provide incentives, meaning that women undergoing IVF give some of their eggs to other IVF patients – or to research. In return, they will receive a discount on their own IVF treatment. The attractiveness of egg sharing for patients, thus, depends on the costs of their IVF treatment and who covers them. In the UK, with a maximum of three IVF cycles covered by the National Health Service, and mostly after long waiting periods, most IVF is done as a private service, in which context egg sharing is attractive for many IVF customers. In Belgium, by contrast, egg sharing has become rare since Belgian IVF couples were granted up to six free cycles of IVF in 2003 (Pennings 2006). Public coverage thus diminishes the attractiveness of egg sharing for patients and thus the number of “spare” eggs available for research.

The air of unease or ethical concern that surrounds oöcytes for research has an informal influence on how many and which categories of oöcytes are available to researchers. We found that ethico-logistic constraints are among the reasons why there were so few SCNT projects in Europe, meaning constraints that result from researchers' own ethical concerns or the anticipation of ethical concerns of others such as legislators, the public, or the global scientific community. Outi Hovatta from Karolinska Institute, for instance, explained to us that she had a license to ask IVF patients whether, in case more than 20 mature eggs were extracted, they would leave two to research. Yet she decided not to do it:

It has been difficult for us to get it through because our midwives are unwilling to ask for the consent, and I don't want to push them. […] I have not regarded it so important.

Similarly, Björn Heindryckx from Ghent University told us his team did not work with recruited egg givers:

Theoretically and legally it's possible to do so, recruit patients, but we have never done it because, yes, there is also a negative atmosphere around it and, yes, we don't like the negative surroundings so much.

In both cases, a certain unease about asking women for eggs they could have used for themselves contributed to the discontinuation of research cloning and the decision to switch to iPS instead.

Another hugely important vector is the infrastructural connection between stem cell research and IVF facilities, the IVF–stem cell interface (Franklin 2006). In our field, this interface took the form of personal overlaps and close spatial proximity. More often than not, the leading clinician at the facility where the oöcytes were obtained was also the researcher who led the respective SCNT project. Anna Veiga was leading researcher at the Centro de Medicina Regenerativa de Barcelona and leading clinician at Dexeus, a private hospital, also in Barcelona, from where the eggs were obtained. Alison Murdoch was a leading researcher at the North East England Stem Cell Institute and a clinician at Newcastle Fertility Centre at Life, from where the eggs were obtained, with both facilities located literally under the same roof. Similarly, Outi Hovatta, a leading researcher at the Karolinska Institute, was also a clinician at the Department of Obstetrics and Gynaecology at Karolinska University Hospital from where the oöcytes were obtained, both located in the same building complex. Björn Heindryckx was both a leading researcher and clinician at Ghent University Hospital, from where the oöcytes were obtained, and again research and fertility treatment took place in the same building complex. Samuel Wood, finally, was founder of Stemagen, the biotech firm in California engaged in SCNT research, and a medical director at the Reproductive Sciences Center that provided the oöcytes for Stemagen's research, and founder of The Select Surrogate, an egg and surrogate brokering agency, with all three facilities being located in the same building complex in La Jolla/San Diego.

The background for this integration is, among other things, that after retrieval, the quality of the egg deteriorates by the hour. As Samuel Wood explained to us:

This side is the Reproductive Sciences Center and the other side of the wall is Stemagen. […] So they're adjacent to each other because that's critical for Stemagen's work. […] we know we need to get the eggs immediately – we have to start the procedure within two hours after the eggs are retrieved. […] It's critical. There has to be seamless integration between the fertility center and the stem cell laboratory.

Thus, it is extremely important for researchers to have the research site located as close as possible to the egg retrieving facility.

From “spare” to “good”

There are two main categories of oöcytes that are comparatively easy to obtain but not quite efficient as a resource: immature oöcytes harvested in the course of IVF treatment along with mature ones, and oöcytes left over from IVF because they have failed to fertilize. Looking at the dynamics within the field, we see that nearly all research projects that had initially used oöcytes of non-optimal quality switched either to alternative categories of oöcytes or to alternative strategies of stem cell research altogether.

Table 1

As Table 1 shows, three research teams who had worked with failed-to-fertilize or immature oöcytes (Karolinska Institute, Ghent University, UCSF) did not switch to other types of oöcytes but abandoned this strand of stem cell research altogether. As Björn Heindryckx from Ghent University explained:

The biggest problem in our group is to have access to good quality oöcytes. We mostly used spare oöcytes, immature oöcytes that we matured in the lab and that we used, but we know that the quality of these oöcytes is much less than in vivo-matured oöcytes. So, actually I have seen that blastocyst development was not possible. We have stopped this research for the moment.

Likewise, the team at the Karolinska Institute had worked with immature eggs and phased out SCNT. The teams at NESCI, CMRB and UCSF initially used failed-to-fertilize eggs but switched to other procurement strategies, or, in the case of UCSF, abandoned research cloning.

Of the other projects in that column (CIPF, CMRB I, NESCI I), two switched to better quality types of oöcytes while only one project (at CIPF) continued to use failed-to-fertilize eggs, in addition to fresh, mature eggs from IVF patients. For a while, the team at CIPF had also obtained some oöcytes from non-patients through a private fertility clinic.13 Interviewees in California told us that ISCO had plans to establish an egg sharing scheme too, which however had not yet materialized at the time we concluded fieldwork. The CMRB in Barcelona switched from failed-to-fertilize eggs to eggs from non-patient “donors” who had received financial compensation for undergoing this procedure. We will come back to this. ISCO in California also had plans to establish a scheme for recruiting non-patient donors. They are interesting, because they show a model for getting access to good quality oöcytes which would rely not on the usual IVF–stem cell interface but on cooperation between a research site and a commercial egg brokering agency. The idea here was that ISCO would establish a commercial relationship with an agency-to-be, Stem Cell Options. The prospective head of this agency, Terri Royal, an experienced egg broker, told us the plan was to work with women who had sold eggs for IVF purposes before, to a previous commercial egg “donation” agency of hers called Options National Fertility Registry. Some of these women, she told us, were willing to donate again – without payment – for research purposes, motivated by the idea of contributing to an extremely promising branch of research. In the long run, however, she was hoping for a revision of the California non-payment provision on eggs for research, as she told us:

And so that is the best we can do for now. You know, I am very much looking forward to when the laws are lifted from these restrictions [the Californian non-payment provision, SSCH] and we are able to do a lot more.

Hence, once the appropriate infrastructure, in the form of the agency, was in place, it would be able to shift smoothly on to a commercial basis. In the long run, this model might manage both the shift from “spare” eggs to “good quality eggs” and from “donation” to transaction. It would essentially outsource the functions of contacting and mobilizing potential egg “donors” that elsewhere are performed by the IVF–stem cell interface to a commercial service enterprise. At the time of writing, we do not know whether the plan has been implemented.

Good quality, that is, fresh and mature oöcytes are preferable from a research point of view but more problematic to obtain for both ethical and logistic reasons. There are two ways of obtaining fresh and mature, “good quality” oöcytes, and both are fraught with significant ethical issues: asking IVF patients to give some of their “good” eggs before fertilization, or obtaining them from so-called non-patient “donors.” In case of the former, the woman gives up eggs she might have used for herself and it is controversial whether this practice diminishes her chances to get pregnant. From an IVF patient's point of view, “‘fresh’ eggs are never ‘spare,’” as Roberts and Throsby (2008, p. 161) put it. Unlike frozen embryos, which can be donated after successful IVF treatment the decision about giving or not giving fresh eggs has to be made prior to pregnancy, namely prior to conception. For these reasons, many of our interviewees from private clinics had qualms asking their customers for eggs, even if they had more than 10, 12 or even 14. Montserrat Boada Palá, for instance, chief of the biology section of the reproductive medicine department at Dexeus, a private fertility clinic in Barcelona, declared quite categorically:

We would never ask her for fresh eggs before fertilization; she needs them for herself.

Of the research sites we looked at, there was only one where research cloning continued14 and fresh oöcytes defined as “surplus” were used without the offer of any form of material incentive, such as subsidized treatment, namely the Centro de Investigación Príncipe Felipe (CIPF) in Valencia. The team there, led by Mirodrag Stojkovic received eggs from the division of reproductive medicine at the Hospital La Fé in Valencia. Here, “surplus” was defined as more than eight or 10 oöcytes.15 Notably, the Hospital La Fé is a public hospital. It would take more empirical fieldwork to establish the motivations of these women to give some fresh eggs to research. Yet, it seems that private clinics were more reluctant to even ask their – usually more well-off and self-confident – customers for such a contribution.

In the case of so-called non-patient “donors,” the woman undergoes a risky, invasive procedure without any personal medical indication or benefit. For this reason, several researchers told us that they preferred oöcytes obtained within IVF treatment. Mirodrag Stojkovic, for instance, leading the research on SCNT at the Centro de Investigación Príncipe Felipe at the time, told us that for ethical reasons he preferred working with “surplus and donated” eggs. Undergoing ovarian stimulation, he pointed out, may seriously damage a woman's health16 and was therefore not acceptable if the woman did not need the eggs for her own IVF treatment.

From donation to transaction

Another move in the field was a shift towards economic incentives. Most researchers we talked to stated quite clearly that, according to their experiences, very few women were willing go through hormone stimulation and egg extraction without achieving a material benefit. If we conceive the spectrum of transactions taking place in the field as a commercialization continuum, we can clearly see a move towards the commercialization end of the spectrum.

Table 2

Again, we see that three projects (bottom left), that had used failed-to-fertilize eggs from women who received neither compensation nor subsidized treatment, discontinued their research into SCNT altogether. NESCI I continued this strand of research but switched from unpaid, failed-to-fertilize eggs to subsidized treatment (egg sharing); ISCO had plans to do so as well. The CMRB team switched from failed-to-fertilize eggs to fresh, mature eggs from women who did not undergo IVF but received a certain amount of compensation within a procurement strategy we term reallocation of IVF oöcytes and will explain below. CIPF continued to use uncompensated failed-to-fertilize eggs, in addition to fresh, mature eggs defined as surplus from IVF patients at the Hospital La Fé. For a while they had also received fresh oöcytes from non-patients within a reallocation model, but these were immature and not really suitable for research.17

In the following, we will explain the two main models that have evolved over the past few years to allow researchers to offer economic incentives while circumventing non-payment provisions: egg sharing and the reallocation of compensated or paid-for oöcytes.

Egg sharing has already been mentioned. Initially, it meant that women who in the course of an IVF treatment had relatively many eggs, due to superovulation, were asked whether they would give some of them to other women who wanted IVF but could not use their own eggs for some reason.18 The Newcastle team applied for a license to introduce an egg sharing for research program when it turned out that they had obtained only a small number, namely 66, of fresh, mature eggs from IVF patients in the course of 2005 for their research on SCNT. In July 2006, the HFEA approved the application and the scheme was launched in September 2007. Private IVF customers can receive a £1500 reduction in treatment costs if they give about half of their eggs to NESCI for purposes of stem cell research.19 The £1500 will be covered by the Medical Research Council that funds the research project. Egg sharing has been approved by the HFEA although it forms an exception to the general HFEA non-payment policy concerning gametes and embryos.20 Logically, this is somewhat incoherent, since, as expert member of HFEA Emily Jackson told us, it is payment, payment in kind, but offered only to “women who happen to also be infertile.” The reasons it nevertheless exists, she explained, are purely pragmatic:

So one of the reasons I think it's still there isn't because it makes any intellectual sense, but because taking it away would mean two significant cohorts of women wouldn't be able to have babies […].

This incoherence notwithstanding, the HFEA reasoned it could not deny approval to egg sharing for research when it had already approved egg sharing for IVF purposes.

At ISCO in California, when we concluded our fieldwork in February 2010, they also had plans to introduce a program of egg sharing for research. Their proposed strategy differed from the Newcastle model in that the recruitment of participants would be outsourced to private fertility clinics located nearby, which had been contacted by a new brokering agency, Stem Cell Options.21 Previously, ISCO had obtained oöcytes from a clinic in Moscow for their research into parthenogenic stem cells, which took place in an ISCO laboratory in Moscow. Not least for ethico-logistic reasons, however, they gave up this cooperation, as ISCO vice president Janus explained to us:

I think there's more regulatory overhead in the United States than there is in Russia so you have to be very diligent when you go to Russia to make sure that the processes that you put in place are acceptable in the West.

At the time of our fieldwork, it was unclear whether and when the ISCO egg sharing program would actually be launched, how much reduction of treatment costs it would offer to women and whether it would be politically accepted in California.22 By reason of proposition 71, egg selling in California is not allowed for purposes of research.

Reallocation of paid-for eggs is another model for negotiating non-payment provisions. Here, researchers use oöcytes obtained from non-patient “donors,” meaning women who had their eggs retrieved for the purposes of receiving some money and not for the purposes of getting pregnant. However, they had originally yielded these eggs to IVF clinics or IVF couples, not to research projects. A number of these oöcytes would then be diverted to stem cell research instead, with the consent of the egg giver and the recipient IVF patient or couple.

In Spain, it is legal to receive so-called compensation in return for oöcytes both for research and for IVF purposes. While article 5 of law 14/2006 on human assisted reproduction states that donation must not be of a commercial or profitable nature, the law does not rule out compensation payments. They are constructed not as financial gain, but as a means to make good for expenses and inconvenience caused. However, inconvenience and expenses do not need to be documented or quantified. Thus, in contrast to the reimbursement of documented expenses or lost earnings, these compensation payments form a real financial gain for the women involved. In the thriving private IVF sector in Spain, so-called compensaciones of up to €1,000 or even more per cycle are the rule and form an important motivation for women to undergo egg extraction (Orobitg and Salazar 2005, Clua Obrado, personal communication). Most of them are students, workers and, increasingly, migrants from Latin America and Eastern Europe. According to Elisabeth Clua Obrado, who is responsible for the egg donation program at Dexeus hospital, financial incentives play an ever-increasing role for these women. She told us:

The profile of donors is changing very much, depending for instance on the current economic crisis. Unfortunately, some girls come to see us for donation because they need the money – much more often than in former times. There is always, or in many cases, there is an economic motivation.

Thus, here it is mainly “young, poor women” who provide the IVF and biotech industry with the resource of human oöcytes, undergoing the risky procedure of hormone stimulation and egg extraction in exchange for money. Yet, when it comes to oöcytes for research, the compensation model is rarely used in a straightforward way. Indirectly, however, compensation was also applied by the CMRB in Barcelona. Anna Veiga, leading SCNT researcher at CMRB in Barcelona, had initially applied for permission from the relevant research review board to recruit non-patient “donors” and offer them €900 compensation for their service. The commission declined on the grounds that it considered €900 an undue incentive and suggested offering a maximum of €600 instead. Javier Arias Díaz, chair of the commission, explained:

However, one of them [of the proposed research projects] in particular wanted to use healthy donors solely for research purposes […] and this was rejected at first because the economic incentives they proposed for performing oöcyte extraction were very high. They proposed €900 per donor. […] Hence, the commission deemed that this was a type of incentive that would be against the spirit of the law. The law allows for reimbursement of costs but no economic incentives. Therefore, it was initially rejected and the commission suggested to offer only €600 maximum.

Although €600 was the limit for compensation that had been recommended by the Spanish National Commission for Reproductive Medicine for the IVF service sector in 2000,23 private fertility clinics offer higher amounts. Dexeus, the private clinic that cooperated with CMRB, usually pays €1,000 compensation to women who give eggs and who are not themselves IVF patients.24 With permission to offer only €600 compensation per cycle while the private fertility clinic at the same time offered €900–1,000 to “donors” for reproductive purposes, Veiga decided against this model and chose to work with failed-to-fertilize eggs from IVF treatments instead. This resource, however, turned out to be inefficient. In 2009 Veiga approached the commission again, who recommended that she reapply for permission to offer more than €600, on the grounds that failed-to-fertilize eggs had turned out unfit. Following this advice she was granted permission to use oöcytes that had originally been obtained by Dexeus, a private fertility clinic, for IVF purposes, in return for the usual amount of compensation of some €900–1,000. Some of these oöcytes would then be reallocated to Veiga's research project at CMRB. Within this model, she argues, women are not paid for selling their eggs to research, since the process of egg retrieval and the monetary transaction have already been completed when the reallocation takes place. The advantage of this model from a research point of view is that, in comparison to egg sharing, it allows access to the eggs of women who are younger than the average IVF patient. Also in Spain, the CIPF in Valencia has already obtained a small number of oöcytes from women who received between €300 and €700 compensation in a private fertility clinic, Instituto Bernabeu, in Alicante.25 In a similar vein, the California biotech firm Stemagen applied the reallocation model when they created the cloned blastocyst they presented in 2008. Stemagen obtained oöcytes from an agency called The Select Surrogate that brokers eggs for reproductive purposes and “surrogate” mothers.26 Both Stemagen and Select Surrogate were founded by Samuel Wood. Select Surrogate, as Wood explained to us,27 obtains oöcytes from women who do not undergo IVF but sell their eggs in return for money. The usual price they can achieve is about $5,000–10,000 per cycle. This is common and legal practice in California as long as the eggs are sold for reproductive purposes. Wood then selects those women whose oöcytes he deems most suitable for research cloning, namely women age 18–25, and, preferably, women whose eggs had already been used to successfully establish an IVF pregnancy. “… [t]he source of the eggs,” Wood explained, “would be critical and so we picked the cream of the crop in terms of eggs.” He asks them and the receiving couple whether they would consent to reallocate some of the eggs to research if more than 12 or 14 are derived. Nevertheless, Stemagen proclaims on its website that

The oöcytes used in this study were donated, without compensation, by egg donors and intended parents undergoing egg donation cycles for reproductive purposes at the Reproductive Sciences Center in La Jolla […].28

This is partly true in so far as these oöcytes were re-dedicated for research purposes in a separate transaction, after having been procured by the fertility clinic for reproductive purposes – in return for money.29

Thus, while the Spanish model of granting lump sum compensation as such already circumvents legal non-payment-provisions, the reallocation of compensated oöcytes from IVF to research purposes additionally circumvents existing provisions to prevent (California) or at least contain (Spain) the commercialization of oöcytes for research. This is not to say, however, that existing non-payment regulation has largely failed due to a general application of the reallocation strategy. For now, we rather find few approaches that test the limits of existing non-payment provisions, one of which, however, may serve as a model in the future.

In the UK, in contrast, sperm, egg or embryo providers may receive reimbursement only for documented costs, including compensation for loss of earnings up to £250.30 This rule applies both to the IVF sector and to research. However, the Human Fertilization and Embryology Authority in the UK has just concluded a public consultation that started in January 2011, on “The changing landscape of donation.” The purpose of the consultation was to discuss whether the HFEA should revise its current compensation scheme for egg and sperm donors and if so, how. The fact that in Spain oöcyte “donors” are compensated €900 is mentioned in various consultation materials,31 signaling that this might be a possible way to go for the UK, too. The HFEA has announced that it will make a decision on the issue of compensation and payment in kind in October 2011. If regulation switches to allowing considerable lump sum compensation in the IVF sector, we predict that it will probably not be long before similar compensation will be offered for research oöcytes as well, either directly or through the reallocation strategy.

Conclusion

Taken together, two trends emerge from our empirical research: a shift from “poor quality” to “good quality” oöcytes – which tends to involve a shift towards ethically more problematic procurement practices, and a trend towards crypto-commercial forms of transaction. Good quality oöcytes are ethically more problematic in so far as they are not “spare” in the sense that they could not be used for IVF as well. Reserving them for research means there are fewer eggs available for IVF. Further, “good quality” oöcytes are often obtained from young, non-patient women, but statistical evidence suggests that the risks involved in hormone stimulation are higher for younger women. Related to the quest for good quality oöcytes, there is a tendency to circumvent existing non-payment provisions through introducing material incentives in a legal grey zone between outright payment and strict non-payment. Research teams have switched from no payment, or reimbursement for documented expenses only to egg sharing or reallocating paid-for oöcytes from IVF to research purposes. The point is that offering material incentives is a way not only to mobilize quantitatively more women to provide oöcytes, but also to get access to qualitatively better oöcytes, namely fresh, mature oöcytes from young women. Thus, there are very strong motives behind the trend towards material incentives. These procurement strategies amount to a crypto-commercialization in so far as they operate on the basis of material incentives but at the same time avoid open payment due to existing non-commercialization policies. Our survey shows that research is very unlikely to be satisfied with “spare” oöcytes but has developed different strategies to access good quality oöcytes. In the light of these empirical trends and shifts, we predict that research strategies that require the use of eggs, such as SCNT or parthenogenic stem cell research, will either cease (sooner rather than later) or we will see a shift from crypto- to outright commercialization of human oöcytes. The facts on the ground are changing rapidly, and we think such questions should be addressed politically before, and not after the fact.

Close personal connections and spatial proximity between stem cell research and the IVF sector have been and largely still are the prerequisite for research strategies requiring human oöcytes. Hence, the IVF–stem cell interface is critical for the resource of human oöcytes (Franklin 2006). Yet, at the same time, strategies of using material incentives in order to access women's oöcytes, mainly through egg sharing and the reallocation of compensated oöcytes, but in the long run maybe also through direct payment, can be interpreted as a way to release the IVF–stem cell interface. Good quality oöcytes are an object of fierce competition between research on the one hand and IVF patients and clinics on the other. Researchers rely on good relations with IVF clinics and the willingness of IVF patients to donate “spare” oöcytes – which is far from given. Introducing more commercial forms of mobilization would be a way for researchers to become more independent from the goodwill of patients and the cooperation of clinics and get access to larger numbers of better quality oöcytes. Yet, the rationale of non-payment regulation, namely to prevent material incentives from inducing women, particularly young women and poor women, to take risks they would otherwise have no reason to take, has not lost any validity. Whether this objective, to protect women from exploitation and undue risk-taking, is more likely to be achieved through non-commercialization policies or, on the contrary, as Waldby and Cooper suggest, through self-organization, better payment, occupational health and safety and other provisions along the lines of the “sex work” model is a valid question. To assess the prospects of the “sex work” strategy would, in our view, require more empirical research on whether, where and under which conditions it is likely that the model would work in the field of oöcyte procurement and whether it would prevent the emergence of a parallel, unregulated black market. What our empirical survey shows, however, at least for Europe, is that a biotech research sector that requires human oöcytes should not be taken for a well-established, extended, existing sector like prostitution. On the contrary, in Europe this strand of research is rare and has declined rather than increased in the past few years. The dynamics of its development seem to depend strongly on whether this research seems feasible, ethically acceptable, promising and rewarding in comparison to other research strategies, as for instance iPS. Its feasibility, however, partly depends on sufficient access to good quality oöcytes, which in turn could be created through models of commercialization or crypto-commercialization. In other words, payment schemes in this case would (hypothetically) form a solution to the problems of a sector that without these payment schemes would virtually not exist, and it seems to us at least questionable whether this strand of research is really worth it.

Acknowledgements

The research leading to these results has been conducted within the research project "Regenerative Medicine in Europe" (ReMediE) and received funding from the European Union's Seventh Framework Programme ([FP7/2007-2013] [FP7/2007-2011]) under grant agreement No. 217180. The authors wish to thank Donna Dickensen, Itziar Alkorta Idiakez, Judit Sandor and Catherine Waldby for helpful insights and discussions.

Notes

See http://stemcell.ny.gov/news.html [Accessed 22 November 2010].

Based on reports by 32 countries, see http://www.eshre.eu/01/ [Accessed 23 September 2010].

http://www.stemagen.com/17jan08.htm [Accessed 18 August 2010].

http://www.internationalstemcell.com/news2009.htm## [Accessed 18 August 2010].

See Norsigian (2005), Beeson and Lippman (2006), Gupta (2006), Schneider (2006), Baylis and Mcleod (2007), Mertes and Pennings (2007), Spar (2007), Dickensen and Alkorta Idiakez (2008), Waldby (2008), Steinbock (2009).

See http://www.handsoffourovaries.com/ [Accessed 7 June 2011].

Ibid.

See Magnus and Cho (2005), Norsigian (2005), Beeson and Lippman (2006), Guidice et al. (2007), Kramer et al. (2009).

See Beeson and Lippman (2006), Dickensen and Alkorta Idiakez (2008). What is seldom problematized in this context, is that such knowledge could only be achieved through more elongated and more comprehensive studies – on exactly the practice in question. Such studies would require comprehensive apparatuses of registration, data storage, data processing and mandatory lifelong follow-up monitoring – generating, storing and processing quite sensitive data such as information about abortions, miscarriages, mental health problems and so forth, with a host of confidentiality issues involved.

Baart et al. (2007), Heijnen et al. (2007), Nargund et al. (2007).

IPS cells form another strategy to create “patient specific” cell types, from which therapies could be developed. The procedure introduced by Shinya Yamanaka in 2006 consists of “reprogramming” somatic cells, for instance skin cells, by inducing viruses. The resulting cells are regarded as pluripotent and thus similar to human embryonic stem cells. Induced pluripotent stem cells are promoted by many as being more “ethical” than human embryonic stem cells or SCNT, because no eggs or embryos are needed for their generation. At the moment, however, it is not yet quite clear how strongly iPS cells actually resemble natural stem cells and how great the risk is that they cause tumors.

This is not to say that there are no other SCNT projects in California.

Interviewees told us that Stojkovic had for some time received oöcytes from the Instituto Bernabeu in Alicante, a private fertility clinic. Some of these eggs were derived from altogether 23 women who were not themselves undergoing IVF and had received compensation for undergoing egg extraction. However, the clinic only handed over immature eggs which could not be used for IVF treatment of their customers. Because of the low quality of the eggs Stojkovic abandoned cooperation with the clinic (R. Cervera, personal communication, 3 July 2009, J. Ten, personal email communication, 23 September 2009).

The reference date is February 2010 here.

J.M. Rubio (personal communication, 2 July 2009, our translation).

M. Stojkovic (personal communication, 3 July 2009).

See endnote 13.

According to M. Boada Palá (personal communication, 9 July 2009, our translation).

According to A. Murdoch (personal communication, 26 November 2008). See also http://www.nesci.ac.uk/news/item/egg-sharing-women-to-get-help-with-ivf-treatment-costs-for-donating-eggs-to-research [Accessed 16 March 2009], and Baylis and Mcleod (2007).

http://www.hfea.gov.uk/500.html#guidanceSection4582 [Accessed 24 August 2010].

J. Janus (personal communication, 5 August 2009, 11 February 2010), T. Royal (personal communication, 27 August 2009, 26 November 2009, 10 February 2010), and ISCO 2010.

For further information see Schultz (2010).

Arias Diaz and Victor Gonzales Rumayor from the Spanish Health Ministry (personal communication, 18 September 2009, our translation).

E. Clua Obrado (personal communication, 9 July 2009, our translation).

According to M. Stojkovic (personal communication, 3 July 2009), and J. Ten (personal communication, 29 September 2009, our translation).

http://www.selectsurrogate.com/ [Accessed 9 June 2011].

S. Wood (personal communication, 13 August 2009).

http://www.stemagen.com/17jan08.htm [Accessed 26 August 2010].

According to S. Wood (personal communication, 13 August 2009).

http://www.hfea.gov.uk/500.html?fldSearchFor=payment [Accessed 16 March 2010].

http://www.hfea.gov.uk/6177.html; http://www.hfea.gov.uk/docs/2011-01-13_Donation_review_background.pdf [Accessed 9 July 2011].