Department of Obstetrics and Gynaecology, Karolinska Institute, Huddinge University Hospital, S-141 86 Stockholm, Sweden
1 To whom correspondence should be addressed. e-mail: Kerstin.Bjuresten{at}hs.se
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Abstract |
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Key words: embryo research/embryonic stem cells/ethics/human/informed consent
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Introduction |
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Swedish law accepts embryo research up to the age of 14 days after fertilization, excluding cryopreservation time. We obtained approval from the Ethics Committee of the Karolinska Instute in April, 2000 to establish human ES cell lines from embryos which cannot be used in a couples infertility treatment, complemented in January, 2001 by approval to study early differentiation of these cells in vivo in immuno-incompetent mice, and in vitro in culture. Before approval, the application was discussed by the National Ethics Board of Sweden, and also by the Ethics Committee of the Swedish Medical Research Council. The approval was for establishing and characterizing human ES cells, not for using them in therapy. Since then we have succeeded in establishing several ES cell lines from donated blastocysts.
Numerous ES cell lines will be needed by scientists to study all the properties of these cells, particularly in the future, when these lines will possibly be used in clinical cell transplantation. The aim of our research team has been to establish a good number of lines for these purposes. Hence, we have to obtain many embryos for the project. Donating embryos for research, and particularly for establishing continuously growing stem cell lines, may be a sensitive issue for the couples involved.
In our unit we have a midwife with special training in counselling and stem cell issues. She has informed all the couples who have been potential embryo donors in these studies. We report here how frequently infertile couples treated at our IVF Unit during 20012002 gave their consent and donated their supernumerary embryos for stem cell research.
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Subjects and methods |
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The criteria for good embryo quality for single embryo transfer or cryopreservation are as follows, according to an original scoring system developed by Mohr et al. (1985) and described in detail by Fridström et al. (1999
). A maximal score of 3.5 is given to the embryo if no factor reducing embryo quality is observed. The score is reduced in increments of 0.5 for non-ideal numbers of blastomeres (four cells on day 2 and eight cells on day 3 are considered ideal), the presence of >10% fragmentation, non-spherical blastomeres, unequal size of blastomeres, unevenness of the cell membrane, cytoplasmic abnormalities and when the embryo fails to fill the zona pellucida. Embryos with multi-nuclear blastomeres are avoided for embryo transfer and cryopreservation, and are also not used for stem cell derivation. The decision as to which embryos are selected for transfer and cryopreservation is made in the IVF laboratory by an embryologist not involved in stem cell research, and the decision is made according to the criteria described above.
We give information regarding ongoing research projects in our unit to all couples during their first visit to the clinic. This information includes that on stem cell research, and the couples also receive a package of written information. When it becomes obvious, on the basis of the number of embryos obtained, and embryo quality, that there will be embryos which cannot be transferred or cryopreserved, the couple receives detailed information regarding the stem cell project, both written and oral. The midwife with counselling experience gives this information and asks for consent. If the couples agree to donate the embryo/embryos they sign an informed consent form. Any kind of pressure is avoided, and the couples are freely allowed to say no. In the case of any hesitance the interpretation is that the couple are not consenting.
During this counselling session the midwife uses a checklist. According to this list, the couples are informed in detail about the fate of all obtained oocytes from fertilization to embryo quality, transfer and those embryos which could not be used for treatment. They are informed of the possibility to donate the embryos for research as an alternative for destruction of these embryos, which cannot be transferred or cryopreserved. In addition to stem cell research, information regarding projects other than stem cell research, such as improving cryopreservation methods or preimplantation genetic diagnosis (PGD). Information is given of the permanent nature of the ES cell lines, and that these cells are used for research only, not for treatment, and that the embryos donated for research will never be transferred to the uterus of any other woman, and that the embryo will be destroyed by isolating the inner cell mass. The potential therapeutic value of ES cells in severe diseases is described. The couples are told that not donating does not affect their treatment in the unit. They are also informed that the possible ES cells will not be sold, but used in research. If they do not want to donate for any research purposes they are informed that the embryos will be immediately discarded. In Sweden, there is no legal option to donate embryos to other infertile couples.
If a couple have cryopreserved embryos, but they no longer wish them to be transferred, they are given the same information. The longest cryopreservation time allowed for embryos according to Swedish law is 5 years, and when the deadline is approaching, the couples are sent a letter reminding them of the fact that they have to decide what to do with their embryos.
The midwife who informed the couples recorded all the answers and classified the couples into those giving their consent, those who were unsure and those saying no. The couples saying no were not asked why, but some of them expressed their opinions spontaneously, and these opinions were also recorded. Attention was particularly paid to the couples view of the moral status of the embryo, and their possible religious considerations. No member of the team participating in stem cell derivation or culture was regarded as eligible to ask for consent.
During the summer and autumn of 2001, there was wide public discussion in the Swedish media regarding the potential of embryonic stem cells in the treatment of severe diseases, and ethical and political justification of such research and treatment. The public received information regarding the biology of the embryonic stem cells, and their possible therapeutic value in the future. Religious views on the status of human embryos were also discussed. We looked at the effect of this discussion as regards consent.
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Results |
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During the first 6 months of 2001, before the widespread media discussion, the percentage of consenting couples was 89, and subsequently it was similar, at 93%. It has been easier to inform couples after the media discussion, because the level of knowledge of human ES cells has been much higher.
The main reasons for saying no or for being unsure, and the corresponding numbers of couples giving the reasons, are shown in Table II. The majority of couples who said no did not specify why. Ethical concerns were expressed by three couples, who were not sure if it was right to use embryos in research. The view was related to the moral status of an embryo and the couples feeling regarding it. One couple had difficulties in communication. Overall, a very high proportion of couples, 92%, donated their supernumerary embryos for stem cell research.
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Discussion |
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The ethics committee approvals, which we have had to date, are to establish ES cells only for research, not for clinical treatment using cell transplantation. We have now obtained a further approval to establish lines, which can also be used in treatment, and the possible effect of such approval remains to be seen.
Although we received consent from many couples to use their supernumerary embryos in research, the number of blastocysts which we actually obtained was not as large. The donated embryos were all of sub-optimal quality, and only 10% of them developed to blastocyst stage in culture, compared with 33% of those in cases where blastocyst transfer had been planned. However, our results have shown that it is possible to obtain blastocysts and ES cells from such sub-optimal embryos. If there was the possibility to use donated oocytes and sperm to create embryos for research, better quality embryos might be available (EGE, 2000; McLaren, 2001
). The ESHRE Task Force for Ethics and Law (2001
; 2002) accepts creation of embryos for research if the information cannot be obtained by research on supernumerary embryos. For the time being this is not an option in Sweden. It is forbidden in the European Bioethics Convention, which Sweden has not ratified, but there is no permissive law or any guidelines either. For the same reason somatic cell nuclear transfer in order to obtain tailor-made ES cells for recipients is not acceptable in Sweden for the time being, in contrast with the situation in the UK (McLaren, 2001
).
Swedish couples undergoing IVF treatment appear to be altruistic and prefer donating their supernumerary embryos for research instead of letting them be discarded. Very few are against embryo research on ethical grounds. This positive attitude has made it possible to establish human ES cell lines. This is very good when we think of the large number of genotypically different ES cell lines needed, and the necessity for stem cell banking for research and treatment.
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Acknowledgements |
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References |
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EGE (2000) Ethical aspects of human stem cell research and use. European Commission nr 15, 14 November 200, rapporteurs Anne McLaren and Göran Hermerén. (http://europa.eu.int/comm/secreteriat_general/sgc/ethics/en/gee_en.htm
ESHRE Task Force on Ethics and Law (2001) I. The moral status of the pre-implantation embryo. Hum. Reprod., 16, 10461048.
ESHRE Task Force on Ethics and Law (2002) IV. Stem cells. Hum. Reprod., 17, 14091410.
Fridström, M., Carlström, K., Sjöblom, P. and Hillensjö, T. (1999) Effect of prednisolone on serum and follicular fluid androgen concentrations in women with polycystic ovary syndrome undergoing in-vitro fertilization. Hum. Reprod., 6 14401444.
Hovatta, O. (2002) A North European perspective in assisted reproduction new legislation is coming in Finland and in Sweden. RBM Online, 4, 197198.[Medline]
Hovatta, O. and Ährlund-Richter, L. (2001a) Culture of human embryonic stem cells the Huddinge experience. In The Ethical Issues in Human Stem Cell Research, Nordic Committee on Bioethics, Nord. Biotech., 21, 1520.
Hovatta, O. and Ährlund-Richter, L. (2001b) Etiska aspekter på stamcellsforskning. (Ethical reflections on stem cell research). Läkartidningen, 98, 35153519.[Medline]
McLaren, A. (2001) Ethical and social considerations of stem cell research. Nature, 414, 129131.[CrossRef][ISI][Medline]
Mohr, L.R., Trounson, A. and Freeman, L. (1985) Deep-freezing and transfer of human embryos. J. In vitro Fert. Embryo Transf., 1, 110.
Reubinoff, B.E., Pera, M., Fong, C.Y., Trounson, A and Bongso, A. (2000) Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nature Biotech., 18, 399404.[CrossRef][ISI][Medline]
Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swiergiel, J.J., Marshall, V.S. and Jones, J.M. (1998) Embryonic stem cells derived from human blastocysts. Science, 282, 11421145.