Spare embryos and stem cell research: consent issues.

Introduction

Embryonic stem cells are touted as a source of promising treatment for debilitating diseases such as Parkinsons, Alzheimers, diabetes, cardiovascular disease, and many others. (1) In order to exploit the therapeutic potential of stem cells, extensive research is required on the risks and benefits of their use. (2) Respect for ethical boundaries should be included in this risk-benefit evaluation.

Different sources of stem cells have different therapeutic potential. The four sources of stem cells are: embryonic stem cells (hESC), adult stem cells (ASC), stem cells of aborted foetuses, and finally, umbilical cord stem cells. hESC are either totipotent or pluripotent. Totipotent cells are found when the embryo is composed of eight cells or less. Each totipotent cell is capable of developing into a complete organism. (3) Pluripotent cells can differentiate into many cellular types but they cannot create an entire organism (i.e. an embryo), hESC that come from the blastocyst, an embryonic structure found six days post-fertilization, are pluripotent. (4) Spare embryos at the blastocyst stage can provide pluripotent hESC.

For their part, ASC are multipotent, that is, they can differentiate into certain specialized cellular types. (5) but most often are committed to a single function. (6) Their principal function is to replace differentiated cells in a particular tissue when it is damaged or old. (7)

Cells from aborted foetuses are multipotent. These cells can come, for example, from neural foetal tissue and be derived into neural stem ceils. Cells from the umbilical cord also form part of this multipotent cell type category. Haematopoietic stem cells can be extracted from the umbilical cord and represent an interesting alternative to bone marrow graft. (8)

The therapeutic potential of each of these stem cell types remains to be established. Each seems full of promise but only research will tell. The most controversial is that which requires the creation of embryos for the research. Indeed, current restrictions on the deliberate creation of embryos for research (9) have led researchers to go to another existing source of embryos: surplus embryos left over from in vitro fertilization (IVF). Access depends on the donation by the couple of embryos for research purposes. It is spare embryos of pluripotent potential that are the subject of this paper.

To date, donor consent to research on surplus embryos has been general in nature. Since March 4, 2002, however, the Human Pluripotent Stem Cell Research: Guidelines for CIHR-Eunded Research (hereinafter referred to as the "CIHR Guidelines") require a specific consent for stem cell research. The major reasons provided are as follows: immortalized cell lines will be created that will continue to divide indefinitely and could be used in different research projects for many years; these cell lines could have an important commercial value (10) (without profiting the embryo donors themselves) and such research necessarily requires the destruction of embryos.

In Canada, in the absence of the adoption of An Act Respecting Assisted Human Reproductive Technologies and Related Research (Bill C-13), (11) it is the CIHR Guidelines that govern the ethical review of stem cell research protocols. Since 1998, the Tri-Council Policy Statement: Ethical Conduct for Research Involving Human, (hereinafter referred to as "the Tri-Council Policy Statement") governs the process of ethical review of research. Obviously, the general common law and civil law principles and procedures governing consent also apply.

We will begin our study of the issue of consent to stem cell research with a brief analysis of Bill C-13, followed by the Tri-Council, Policy Statement and the CIHR Guidelines. We will then examine the conformity of the consent forms used in eight Canadian fertility centres prior to 2003 against these norms. Finally, we will argue that stem cell research on spare embryos is not really that unique. Research on tissues generally, as well as genetic research, raises many of the same issues. The requirement of re-consent in stem cell research may, however, set a precedent for doing likewise in other research. In conclusion, we will propose core elements for stem cell research on spare embryos that could be included in future consent forms and any accompanying explanatory materials.

1. Bill C-13: An Act Respecting Assisted Human Reproductive Technologies and Related Research

Since the creation of the Royal Commission on New Reproductive Technologies in 1989, Canada has been attempting to define the proper legislative and regulatory controls for the governance of assisted human reproduction. In November 1993, the Royal Commission produced its report entitled Proceed with Care, recommending immediate regulation to protect the interests of all Canadians. (12) In 1995, the federal Minister of Health announced an interim voluntary moratorium on several activities of concern, such as human cloning and payment of surrogate mothers. Bill C-47, the proposed Human Reproductive and Genetic Technologies Act that was introduced in Parliament in 1996, would have prohibited specified activities, but it would not have set out a clear mechanism for regulating other activities that could be carried out under prescribed conditions. This legislation later died on the Order Paper with the call of the 1997 federal election. (13) On May 3, 2001, the federal Minister of Health invited the House of Commons Standing Committee on Health to conduct a full review of the Government of Canada's Proposals for Legislation Governing Assisted Human Reproduction. In December 2001, the Health Committee tabled its report and, among its multiple recommendations, requested that legislation be introduced on a priority basis.

Bill C-13, the proposed Assisted Human Reproduction Act (short title), incorporates many but not all of the Committee's recommendations. One significant change recommended by the Committee and reflected in the proposed Act is the establishment of a regulatory body to license, monitor, and enforce the Act. The Act would also prohibit a range of activities deemed by many Canadians to run contrary to human dignity and societal values, while permitting certain other controlled activities to be carried out, subject to governmental regulation and oversight. (14)

Some requirements of Bill C-13 (15) will not only affect the consent process for stem cell research but also for research on embryos in general. The first requirement is not novel. Donors must provide written consent for the use of their in vitro embryos;(16) the same applies for gamete donors regarding the use of their gametes (17). The biggest impact of C-13 on consent to stem cell (18) research is in the creation of a personal health information registry:

17. The Agency shall maintain a personal health information registry containing health reporting information about donors of human reproductive material and in vitro embryos, persons who undergo assisted reproduction and persons conceived by those procedures.

According to the Bill, donors must consent to the disclosure of information controlled by the Agency:

18(2). Notwithstanding section 8 of the Privacy Act but subject to subsections (3) to (8), health reporting information under the control of the Agency relating to a donor of human reproductive material or an in vitro embryo, a person who has undergone an assisted reproduction procedure or a person who was conceived by means of such a procedure is confidential and shall be disclosed only with the written consent of the donor or that person, as the case may be.

There are some situations, however, where the Agency will disclose health reporting information without consent: (19) to comply with a subpoena; an order made by a court, body or person with jurisdiction to compel the production of information; and to the extent required by provisions of any federal or provincial law respecting health and safety. Furthermore, the Agency may disclose health reporting information for the purpose of the enforcement of the Act, to the extent required for the administration of a health care insurance plan and for the purposes of disciplinary proceedings. (20) The identity of a donor or sufficient elements that would permit identification of a donor may not be disclosed by the Agency for research purposes:

18(8). The Agency may disclose health reporting information to an individual or organization for scientific research or statistical purposes, other than the identity--or information that can reasonably be expected to be used in the identification of any person. (21)

In short, Bill C-13 affects the disclosure in the consent process of the limits and safeguards of confidentiality for both the donor of gametes and for the patients who undergo fertility treatment. Future consent forms will have to take into account the possible introduction of the federal bill.

2. Tri-Council Requirements for Embryo Research

Under the terms of section 9 entitled "Research involving Human Gametes, Embryos or Foetuses," the Tri-Council, Policy Statement outlines the conditions for research on embryos:

Article 9.4--It is not ethically acceptable to create human embryos specifically for research purposes. However, in those cases where human embryos are created for reproductive purposes, and subsequently are no longer required for such purposes, research involving human embryos may be considered to be ethically acceptable, but only if all of the following apply:

(a) The ova and sperm from which they were formed are obtained in accordance with Articles 9.1 and 9.2; [free and informed consent (9.1); no commercial transaction (9.2)];

(b) The research does not involve the genetic alteration of human gametes or embryos;

(c) Embryos exposed to manipulations not directed specifically to their ongoing normal development will not be transferred for continuing pregnancy; and

(d) Research involving human embryos takes place only during the first 14 days after their formation by combination of the gametes. (22)

Referring to article 9.1, the Tri-Council requires the consent of both gamete providers at the time of the initial gift.

Article 9.1.--Researchers shall obtain free and informed consent from the individual whose gametes are to be used in research. (23)

As summarized in the explanatory note of article 9.1,

   ... researchers have a duty to seek the free and
   informed consent of prospective subjects for
   research involving their reproductive cells.
   Consistent with general requirements of full
   disclosure, subjects should be informed of the
   purpose of the proposed research, such as
   research involving infertility or birth control. The
   requirement for free and informed consent
   applies, of course, if the gametes were originally
   provided for a purpose other than research. (24)

Thus, gamete providers have to consent to a category of research but not necessarily to a specific type.

3. Canadian Institutes of Health Research (CIHR) Guidelines

The Guidelines set out the conditions under which the CIHR "will fund human pluripotent stem cell research, as well as those types of research that are not eligible for funding" (25) from CIHR (e.g. research involving the creation of human embryos, (26) somatic cell nuclear transfer (27) or directed donation of stem cell lines (28)).

As mentioned, the CIHR applied the Tri-Council, Policy Statement to their study of the issues surrounding stem cells. At different levels, the CIHR refers to section 9 of the Tri-Council, Policy Statement entitled "Research Involving Human Gametes, Embryos or Foetuses". (29)

The Guidelines are based on the following principles found in the Tri-Council, Policy Statement: research undertaken should have potential health benefits for Canadians, (30) a free and informed consent should be provided following full disclosure of all information relevant to consent, (31) privacy and confidentiality should be respected, (32) and there should be no direct or indirect payment for tissue collected for stem cell research. (33) Incorporated into the CIHR Guidelines, they "apply to all proposals for human pluripotent stem cell submitted to CIHR". (34) At this time, they do not apply to research proposals to other public sector funding organizations or to the private sector. (35) To review proposed stem cell research projects, the CIHR recommend the creation of a national oversight committee (Stem Cell Oversight Committee (SCOC)). Furthermore, the CIHR Recommended to Health Canada that the evaluation of stem cell research be made by a unique review board (National Review Committee) for research emanating from both the public and the private sectors. (36) A subcommittee could evaluate embryonic and foetal stem cell research protocols and eventually replace the SCOC. (37) Whether it be included in, or separate from, the Agency proposed by Bill C-13 is unknown. Turning now to the consent process in stem cell research, we will see that it is essential not only for the respect afforded to the personal values of the donors but also for the ethical admissibility of a project.

3.1 Consent to Stem Cell Research

The duty to obtain free and informed consent from gamete or embryo donors is frequently cited in the CIHR Guidelines. However, the criteria to be met in order to obtain a valid consent differ between the two categories of donors.

3.1.1 Consent of a Gamete Provider

The situation of gamete donation occurs when a person donates gametes (sperm or ova) for use by IVF programs. Gamete providers can consent, prior to the donation of their gametes, not only to the creation of embryos but also to unrestricted research use.

Under guideline 7.1 Research eligible for CIHR funding, section 7.1.1 states:

   ... where "donor" gametes have been used to
   create the embryos, the gamete providers must
   have originally given free and informed consent
   to the unrestricted research use of any embryos
   created when these embryos were no longer
   required for reproductive purposes. (38)

Thus, gamete donors are not required to provide consent to any specific type of research but to research in general. Furthermore, according to the CIHR, the renewal of the consent of the gamete provider "is not required provided that appropriate consent for unrestricted research use of the embryos was given at the time of gamete donation". (39)

3.1.2. Consent of Embryo Donors

The consent, privacy and confidentiality provisions (40) of the Guidelines require consent to the use of spare embryos. The three options proposed by the CIHR under guideline 7.2.1 are: donation to another couple; destruction; or, donation for research purposes. These options should be discussed with the couple prior to the creation of embryos for reproductive purposes. (41)

The Guidelines specify the need to reconfirm this consent when the embryos are to be used for stem cell research. (42) This affirms the right to withdraw and is essential due to the delay between the original consent to research at the time of creation and their specific use for research purposes. (43) Other reasons given for the need to re-consent include immortalization, commercialization and destruction. (44)

3.1.3 Different Standards?

Contradictions exist between the consent requirements for gamete providers and those for embryo donors. First, consent for research in general is required at the time of donation of gametes. This means that a couple in need of a gamete provider can know in advance that if one day they want to donate their spare embryos for research purposes, they must have used a gamete donor who has already provided consent for research. Yet, is it reasonable to single out potential "research" gametes prior to infertility treatment? It goes without saying that couples needing a gamete donor(s) to have a child do not select gametes according to such a pre-selection criterion. Second, the further CIHR requirements of the confirmation of both the original consent of the couple to research and now specifically to stem cell research do not apply to the gamete donor. Third, no such reconfirmation is required for the destruction or donation of spare embryos themselves. Fourth, unlike what is required for gamete donation, the Guidelines detail the information that should be given to embryo donors in order to obtain an informed consent for the use of spare embryos for stem cell research purposes.

When an embryo is created from the gametes of two donors or from one donor plus the gametes of one member of the couple, the goal is to create a family. Should the consent of gamete providers then be limited to destruction, or to donation for the creation of embryos for any future use by an infertile couple? If not, should the research option for gamete providers be limited to research on their own gametes and not to unrestricted research on future embryos created with their gametes? We maintain that the choice in favour of stem cell research on spare embryos should be under the exclusive purview of recipient couples. This would be consistent with the fact that currently, neither the CIHR, nor the Tri-Council, nor Bill C-13 allow the deliberate creation of embryos for research.

In short, we would argue that if gametes are provided by a third party for use by others, once an embryo is created with donor gamete(s), the consent to embryo donation for research purposes should belong to the couple who has entered an infertility program and is using such embryos. To do otherwise will open the door to the consideration of the opinion of a third party years after the fact. Moreover, the result would be that only embryos with unrestricted research advance directives could be used in stem cell research. Are gamete donors or couples thinking of research when they want to overcome infertility? Once a gamete donor has consented to the creation of embryos using (in part) his or her gametes and has not chosen the eventual option of destruction, the long-term choices affecting the eventually created embryo should remain those of the couple.

3.2 Information Needed for a Free and Informed Consent

The indications contained in the CIHR guidelines constitute the minimum information potential embryo donors should receive about stem cell research, in addition to the basic information on the treatment of infertility. The minimum information for donation of embryos for stem cell research required by the CIHR is:

1. An explanation that the cell line(s) will be anonymized except if the research involves autologous donation;

2. An assurance that prospective research participants are free not to participate and have the right to withdraw at any time before an anonymized cell line is created;

3. An explanation that the result could result in the production of a cell line that could be maintained for many years and used for different research purposes;

4. An explanation that the research participants will not benefit directly financially from any future commercialization of cell lines; nor will there be any personal benefit in terms of dispositional authority over any cell lines created (i.e., there will be no directed donation of the cells or cell lines to particular individuals), except if the research involves autologous donation. (45)

Regarding project specific consent, the CIHR final report (46) states at Section 5 under "Free and Informed Consent" that at the time the couple has made a decision not to pursue further infertility treatment and has made an initial choice in favour of stem cell research:

   researchers shall provide prospective research
   participants or authorized third parties with the
   following information.

1. A description of the purpose of the research;

2. A description of the research procedures;

3. A description of reasonably foreseeable harms and benefits that may arise from research participation; ... (47)

These requirements underscore the fact that consent for research on spare embryos must be given for a particular research project.

4. Current Consent Forms and Conformity with the CIHR Guidelines

Does the actual documentation used by Canadian fertility centres meet these criteria? To highlight actual practices and their conformity with the Guidelines as concerns stem cell research, consent forms and information leaflets from different fertility centres across Canada were analysed. Even with the promise of anonymity, collection was difficult. (48) This may be due to the highly politicised nature and legal/ethical uncertainty surrounding this subject.

The elements used for our research matrix were those of the Guidelines:

* the timing of the decision regarding the disposition of surplus embryos;

* the confirmation of consent to research (but this time specific to stem cells);

* the right to withdraw prior to the commencement of research;

* the assurance that the cell lines obtained will be anonymized;

* the absence of direct benefit;

* the absence of authority and proprietary rights over the cell lines created; and

* the provision of simplified scientific information.

It is important to note that prior to the CIHR Guidelines of 2002, most infertility clinics, whether private or public, did not single out stem cell research within the general research option. Even so, most clinics did not even meet the general requirements of the Tri-Council Policy Statement, i.e. a consent process that adequately informs the participants concerning the type of research envisaged for spare embryos if that was their choice.

5. Results of the Analysis

The following table presents the results of our evaluation of the consent forms and leaflets according to the elements searched. Each element will then be studied in turn.

5.1 Timing

Articles 9.4 (a) and 9.1 of the Tri-Council, Policy Statement stipulate that for embryo research: "free and informed consent shall be obtained from the individual whose gametes are to be used in research". (49) Thus, consent must be solicited at the time of the collection of gametes and preceding the creation of the embryos. Likewise, according to CIHR requirements, the decision regarding the fate of spare embryos shall be taken prior to the collection of gametes, (50) i.e. at the beginning of fertility treatment procedures. As shown in the table above, this element is largely respected by the different fertility centres.

5.2 Re-Consent and Right to Withdraw

It could be argued that the need to re-confirm consent is also found in the Tri-Council, Policy Statement. Article 2.1 (a) provides that:

   [r]esearch governed by this Policy ... may begin
   only if (1) prospective subjects ... have been
   given the opportunity to give free and informed
   consent about participation, and (2) their free and
   informed consent has been given and is
   maintained throughout their participation in
   research. (51)

Does this imply requiring of researchers an active effort to "maintain," or, unless there is an explicit objection, or does the initial consent to research remain valid? Are these requirements transposable to stem cell research?

In contrast, the CIHR guidance on consent is clear on the need to re-confirm consent prior to the use of embryos in stem cell research. (52) This element was not present in the consent forms or information leaflets studied. However, bearing in mind that the confirmation of consent is linked with the participants' right to withdraw, which can be exercised at any moment prior to the use of spare embryos in research, can we assume that fertility centres presumed such consent if the right to withdraw was not exercised? Obviously, participants could also change their minds about destruction or donation as well. Not all clinics clearly indicated the opportunity to withdraw consent to research at any time prior to use of the gametes or embryos.

5.3 Anonymization

The anonymization of stem cell lines obtained from embryo research is not specifically mentioned in the Tri-Council Policy Statement but, at section 10 on "Human Tissue," the Policy Statement underscores the necessity to provide the following information to potential donors of "tissues":

Article 10.2--For the purpose of obtaining free and informed consent, researchers who seek to collect human tissue for research shall, as a minimum, provide potential donors or authorized third parties information about: ...

(f) Identifying information attached to specific tissue, and its potential traceability; and

(g) How the use of the tissue could affect privacy. (53)

Thus, it could be argued that unless the Statement specifically excludes the applicability of its norms on tissues generally to embryos, the identifiability and traceability considerations should be communicated prior to the decision to donate either gametes or embryos for research or fertility treatment. This is already the case with respect to the promised anonymity for the gamete provider and recipients on most consent forms. If the federal legislation is adopted, participants will now be informed about the proposed registry of the federal government. (54)

What the CIHR Guidelines add is the requirement of informing the couple that the eventual stem cell lines obtained will be anonymized. This means that the couple from whom the embryo comes cannot be identified and, vice versa, the recipient couple or the researcher will not be able to trace back through the cell lines themselves. Under the proposed legislation (Bill C-13), we have seen that even if the stem cell lines are to be anonymized, information about the donors will be kept in government registries.

In our research, one clime mentioned the confidentiality of the identity of the donor but did not specify the anonymizatiun of any products of research.

5.4 Personal Benefit and Commercialization

The possibility of absence of direct benefit from research is found in the Tri-Council Policy Statement:

   As noted earlier, human research is intended to
   produce benefits for subjects themselves, for
   other individuals or society as a whole, or for the
   advancement of knowledge. In most research, the
   primary benefits produced are for society and for
   the advancement of knowledge. (55)

Bill C-13, the Tri-Council Policy Statement and the CIHR Guidelines all require that the couple be informed that they will not benefit directly from research involving their embryos. (56)

Turning now to the issue of notification of possible commercialization, this basic requirement was not found in most of the consent forms and information leaflets analysed. The Tri-Council emphasizes the altruistic aspect of providing tissue in research:

   it is reasonable to draw the ethical conclusion
   that the use of tissue for research depends on an
   individual's altruism in donating the tissue with
   the expectation that social good will be advanced
   and human knowledge increased . (57)

Under the section on research involving human tissue, the Tri-Council Policy Statement at article 10.2 states:

   For the purposes of obtaining free and informed
   consent, researchers who seek to collect human
   tissue for research shall, as a minimum, provide
   potential donors or authorized third parties
   information about: ... (d) The potential uses for
   the tissue including any commercial uses; ... (58)

Likewise, the CIHR requires:

4. An explanation that the research participants will not benefit directly from any future commercialization of cell lines; nor will there by any personal benefit in terms of dispositional authority over any cell lines created (i.e., there will be no direct donation of the cells or cell lines to particular individuals), except if the research involves autologous donation. (59)

Due to the requirement of anonymization by the CIHR, possible commercial benefit from the cell lines obtained is also impracticable. (60)

5.5 Scientific Information

As shown by the Table, neither the consent forms nor the information leaflets analysed provided sufficient scientific information and this, even for general embryonic research. Indeed, very little scientific information (if any at all) was found in the information leaflet or consent forms. Yet, this information is the basis of free and informed consent and the information leaflets are often the only tool that the couple brings home and it serves to help them in their reflection. In the future, what basic elements should be found in any consent form?

6. Timing of Re-Consent

The establishment by the federal government of a central agency to deliver accreditation to fertility centres and to license controlled activities such as the use of embryos (61) for research purposes will create a need for uniformity in practice. A uniform policy of consent will ensure that fertility programs conform to ethical and legal standards. Every centre will have the possibility to adapt their forms and leaflets in order to reflect their community but the core elements should remain the same.

The timing of the decision to consent to all research is an important aspect of the consent process. The CIHR proposes that persons undergoing infertility treatment consent to eventual research prior to the creation of embryos (62) and re-consent when the embryos are to be used for research to derive hESC. (63) Obviously, at the time of the first consultation for treatment, or even when the embryos are created, the couple does not know if they will have any embryos at all, to say nothing of spare embryos for research one day. Yet, at this stage the couple has to make prior agreements that indicate in advance the "destiny" of the embryos in the eventuality of death, separation, divorce, or when the parental project is abandoned. The choices are donation of their embryos to another couple, discarding their embryos or donation for research. At this point, couples could consent to research in general, to the known types of research ongoing in the centre or even to stem cell research generally. Then, at the time they decide not to pursue further infertility treatment, they could be informed about stem cell research in particular.

Because of the delay between the first consent and the donation of embryos for research purposes, a new specific consent has to be obtained. (64) The CIHR Guidelines place the moment of this new consent at the time of the derivation of cell lines. (65) The moment for re-consent should be when the couple makes the final decision regarding the disposal of their spare embryos. At this time, an extensive explanation on hESC can be given to the couple on more specific research. There are other key moments in the treatment of infertility where consent can be obtained, but the concept of self-determination and the right to withdraw underscores the possibility for the couple to change their minds as often as they want. Usually, it is when the annual fee for storage is charged that couples may take the opportunity to reconsider their initial choices.

Conclusion

We have attempted to illustrate current difficulties and incongruencies surrounding the issue of consent to stem cell research on spare embryos in Canada. We have also discussed the core elements to be considered in the evaluation of the adequacy of consent to embryo research. It goes without saying that the accuracy and the comprehensibility the scientific information provided are key. At the same time, it is interesting to note that some of the reasons given for the "specificity" of re-consent in this area of research are germane to human tissue research, as well as to genetic research. Indeed, the issue of traceability (or not), the requirement to address such issues as the absence of direct benefit, of commercialization, of the possible creation of cell lines and of destruction are required ethical elements in such research as well. They also apply to all embryo research, whether involving stem cells or not, and therefore are not unique. Yet, only stem cell research requires a re-consent. This is due not so much to these common factors, but to the lapse of time between the desire to have a child using IVF and the proposed research. Concrete decisions on the eventual fate of spare embryos can only be made when the couple has completed their treatment. Should this model of re-consent for stem cell research be applied to all types of research involving spare embryos and to the decision to donate or destroy as well? If so, why then make it a requirement for stem cell research alone? There will always be a time lag between infertility treatment and the eventual disposition of spare embryos whether it be destruction, donation or research. In short, the wish to destroy, to donate or to give for other types of research might need reconfirming as well.

Irrespective of the uncertain "legislative" future of stem cell research in Canada, some guidance is needed for fertility treatment centres. We have shown that most consent forms and information leaflets do not meet the ethical requirements of either Bill C-13, the Tri-Council Policy Statement or the CIHR Guidelines. Perhaps a reworking of these tools will lead to an improvement of the consent process with respect to other forms of embryo research as well. As concerns the re-consent for stem cell research itself, we propose some ideas for the content of the consent form/information pamphlet:

Core Elements for Embryonic Stem Cell (ESC) Research

Purpose

* Describe areas of ESC research ongoing in your Centre

Consent

* Refer to prior consent to research at time of initial embryo creation for reproduction

* Refer to specific consent to ESC

What is an embryo?

* Describe stages of development and stage where ESC takes place

What happens to spare embryo(s)?

* Procedure/Technique

* Destruction

What is a cell line?

* Immortalization

* No withdrawal

* Duration of use

Will I receive any benefit?

* No personal benefit

* Possible commercialization

* No proprietary rights

Confidentiality

* Anonymization of cell lines

What if I have questions?

* Give phone number of contact person

Ethics Approval

* Local

* Nation (SCOC)

Consent to ESC

* Signature of both partners

* Representative of clinic

Table 1: Information provided in the consent forms and information
pamphlets of eight Canadian fertility centres:

Elements Provided             1    2    3    4       5

Timing of the decision        X    X    X    X    No
                                                  Research
Re-consent
Right to withdraw                  X
Anonymization of cells
Absence of direct benefit
Ownership
Simplified Scientific info

Elements Provided             6    7    8

Timing of the decision        X

Re-consent                    X
Right to withdraw             X    X
Anonymization of cells
Absence of direct benefit          X
Ownership                     X    X
Simplified Scientific info    X

Legend: X Element found in consent form/leaflets

The authors wish to thank Dr. Arthur Leader for his valuable assistance.

(1) United States, National Institutes of Health--Department of Health and Human Services, Stem Cells. Scientific Progress and Future Research Directions (June 2001), at ES-4, online: <http://www.nih.gov/news/stemcell/fullrptstem.pdf> (date accessed: 17 June 2002); Canadian Institutes for Health Research, Human Pluripotent Stem Cell Research: Guidelines for CIHR-Funded Research, (Ottawa, 2002) at Foreword, online: <http://www.cihr-irsc.gc.ca/publications/ethics/stem_cell/stem_cell_gu idelines_e.shtml> (date accessed: 17 June, 2002).[CIHR Guidelines].

(2.) See Medical Research Council of Canada, Natural Sciences and Engineering Research Council of Canada and Social Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (Ottawa: Public Works and Government Services Canada, 1998) at 9.1 [Tri-Council Policy Statement]; see also Diane Nicol, Donald Chalmers & Brendan Gogarty, "Regulating Biomedical Advances: Embryonic Stem Cell Research" (2002) 2 Macquarie L.J 31 at 31.

(3.) United Kingdom, Medical Research Council, Research in Focus: Stem Cell Therapy, (London), online: Medical Research Council <http://www.mrc.ac.uk /pdf_stem_cells.pdf> (date accessed: 2 October 2002).

(4.) Ibid.

(5.) United States, National Institutes of Health, Stem Cells: A Primer, (Bethesda, Maryland: National Institutes of Health, 2001), online: National Institutes of Health <http://www.nih.gov/news/stemcell/ primer.btm> (date accessed: 5 August 2001).

(6.) Supra note 3.

(7.) Ibid.

(8.) Aude Bertrand-Mirkovic, "Les cellules souches du cordon ombilical: aspects scientifiques, juridiques et ethiques" (juin-juillet 2002) [unpublished].

(9.) CIHR Guidelines, supra note 1; Bill C-13, An Act Respecting Assisted Human Reproductive Technologies and Related Research, 2d. Sess., 37th Parl., 2002 online: Government of Canada <http://www.parl.gc.ca/PDF/37/2/parlbus/chambus/h ouse/bills/govemment/C-13_2.pdf> (date accessed: 16 December2002) [Bill C-13].

(10.) American Society for Reproductive Medicine, "Donating Spare Embryos for Embryonic Stem Cell Research", (2002) 78 Fertility and Sterility 957 at 958, online: American Society for Reproductive Medicine <http://asrm.org/Media/Ethics/donatingspare.pdf> (date accessed: 25 November 2002).

(11.) Bill C.13, supra note 9.

(12.) Canada, Royal Commission, Proceed with Care: Final Report of the Royal Commission on New Reproductive Technologies (Ottawa: Minister of Supply and Services Canada, 1993).

(13.) Government of Canada, "Bill C-13 Assisted Human Reproduction Act--Legislative History of Bill C-13", at 1, online: Government of Canada <http://www. parl.gc.ca/37/2/parlbus/chambus/house/bills/summar ies/c13-e.pdf> (date accessed: 18 February 18 2003).

(14.) Ibid. at 2.

(15.) Supra note 6.

(16.) Ibid. at art. 8 (3).

(17.) Ibid. at art. 8(1).

(18.) Or other type of research involving embryos or gametes.

(19.) Bill C-13, supra note 9 at art. 18(5).

(20.) 20 Ibid. at art. 18(6).

(21.) 21 Ibid. at art. 18(8).

(22.) 22 Tri-Council Policy Statement supra note 2 at 9.2, art. 9.4.

(23.) Ibid. at 9.2, art. 9.1.

(24.) Ibid at 9.2.

(25.) CIHR Guidelines, supra note 1; note that the CIHR, like Bill C-13, does not foresee the deliberate creation of embryos for research purposes.

(26.) Ibid. at Guideline 7.4.1.

(27.) Ibid. at Guideline 7.4.2.

(28.) Ibid. at Guideline 7.4.3; unless the research involves autologous donation.

(29.) See Canadian Institutes for Health Research, Human Pluripotent Stem Cell Research: Recommendations for CIHR-Funded Research: Report of the ad hoc Working Group on Stern Cell Research (Ottawa: Canadian Institute of Health Research, 2002) online: Canadian Institutes for Health Research <http://www.cihr-irsc.gc.ca/publications/ethics/ stem cell/stem cell recommendations_e.pdf> (date accessed: 17 June 2002); see also Tri-Council Policy Statement, supra note 2 at 9.1.

(30.) Tri-Council Policy Statement, supra note 2 at i.6.

(31.) Ibid. at i.5.

(32.) Ibid. at i.5.

(33.) Ibid. at i.5.

(34.) CIHR Guidelines, supra note 1 at 6.0 "Application of the Guidelines."

(35.) Ibid.

(36.) Ibid.

(37.) Ibid.

(38.) Ibid. at Guideline 7.1.1 (2).

(39.) Ibid. at Guideline 7.2.2.

(40.) Ibid. at Guideline 7.2.

(41.) Ibid. at Guideline 7.2.1.

(42.) Ibid. at Guideline 7.2.2.

(43.) Ibid.

(44.) Supra note 10 at 958.

(45.) CIHR Guidelines, supra note 1 at Guideline 7.2.3.

(46.) Canadian Institute of Health Research, Ethics in CIHR: Human Pluripotent Stem Cell Research: Recommendations for CIHR-Funded Research (January 2002), online: Canadian Institutes for Health Research <http://www.cihr-irsc.gc.ca/publications /ethics/stem_cell/stem_cell_recommendations_e.sht ml> (date accessed: 19 February 2003).

(47.) Ibid at para. 5.4.

(48.) Eight centres responded out of 41 contacted. We wish to thank Dr. Arthur Leader for his help in contacting the centres.

(49.) Tri-Council Policy Statement, supra note 2 at 9.2.

(50.) CIHR Guidelines, supra note 1 at Guideline 7.2.1.

(51.) Tri-Council Policy Statement, supra note 2 at 2.1, art.2.1 (a) (2). [Emphasis added].

(52.) CIHR Guidelines, supra note 1 at Guideline 7.2.2.

(53.) Tri-Council Policy Statement, supra note 2 at 10.3, art. 10.2 (f),(g).

(54.) Bill C-13, supra note 9 at art. 17.

(55.) Tri-Council Policy Statement, supra note 2 at.i.7.

(56.) CIHR Guidelines, supra note 1 at Guideline 7.2.3 (4).

(57.) Tri-Council Policy Statement, supra note 2 at art. 10.1.

(58.) Ibid. at art. 10.2 (d).

(59.) CIHR Guidelines, supra note 1 at Guideline 7.2.3 (4).

(60.) Except for autologous donation.

(61.) Bill C-13, supra note 9 at 10 (1).

(62.) CIHR Guidelines, supra note 1 at Guideline 7.2.1.

(63.) Ibid. at Guideline 7.2.2.

(64.) Ibid.

(65.) Ibid.

Marie-Helene Regnier is a Research Associate at the Centre de recherche en droit public, Universite de Montreal, Montreal, and Bartha Maria Knoppers is a Professor in the Faculty of Law, University de Montreal.