1 Department of Obstetrics and Gynecology, Asahikawa Medical College, Hokkaido, Japan and 2 Utah Center for Reproductive Medicine, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, UT, USA
3 To whom correspondence should be addressed at: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, 2B200 SOM, 50 North Medical Drive, Salt Lake City, UT 84132, USA. E-mail: c.matthew.peterson{at}hsc.utah.edu
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Abstract |
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Key words: IVF/oocyte donation/organ donation/posthumous ovarian donation/premature ovarian failure
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Introduction |
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In the clinical arena, the accelerated loss of primordial follicles/oocytes resulting in infertility may occur through surgical castration for gynaecological conditions, autoimmune mechanisms, genetic programming, chemotherapy and/or radiation. As a result of these conditions, human oocyte donation, banking and in-vitro maturation protocols (both heterologous and autologous) for the restoration of fertility are current interests in reproductive medicine. While animal and human studies performed to date on the cryopreservation and in-vitro maturation of ovarian follicles/oocytes have provided a groundwork, future advances will be required for the clinical use of human follicles.
A unique source of follicles/oocytes for research and innovative fertility restoration therapy is the posthumous donation of ovarian tissues at the time of organ donation. While posthumous ovarian donation may be beneficial both clinically and for research purposes, ethical and societal concerns regarding the ethics of posthumous donation must be addressed prior to widespread implementation. This survey of a representative sample of the Utah population and individuals with an express interest in follicle/oocyte donation was conducted to assess the acceptability of posthumous ovarian donation.
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Materials and methods |
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To determine whether a group of individuals with a strong potential interest in posthumous follicle/oocyte donation (women and partners requiring oocyte donation for pregnancy) felt similarly to the survey population (group 1), patients with ovarian failure (Turners Syndrome, autoimmune, chemotherapy- and radiation-induced, and genetic causes) or ovarian removal for various causes were also polled using the same IRB-approved survey protocol (n = 50) (group 2) in 20002001. Interviewees were randomly selected from a list of potential recipients of oocytes receiving treatment at the Utah Center for Reproductive Medicine (n = 31) as well as individuals who responded to the survey posted on the Turners Syndrome Society website (n = 19). Standard descriptive statistics and confidence intervals were tabulated. In addition, chi square analysis was performed to determine differences between or among groups. Significant differences (P < 0.05) were reported.
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Results |
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The scientific study of oocytes without fertilization was acceptable for 77.1% (299/388; 95% CI 72.981.3%) of women, and 70.9% (210/296; 95% CI 65.776.1%) of men. A decreasing level of acceptance was noted when fertilization and potential pregnancies from individually donated or guardian-directed donations were proposed. As a legal guardian (surrogate decision maker), 70.1% (482/688; 95% CI 66.673.5%) were comfortable with donating oocytes for scientific study without fertilization. When asked regarding the acceptability of donating their own or partners oocytes for fertilization and allowing progression to the eight-cell stage without transfer, 58.3% (398/683; 95% CI 54.662.0%) were comfortable. As a legal guardian only 54.8% (375/684; 95% CI 51.158.6%) would allow such a donation. Finally, 57.4% (392/683; 95% CI 53.761.1%) were comfortable donating their own or partners oocytes for fertilization and transfer of the resulting embryos to a couple desiring pregnancy, with 52.1% (353/678; 95% CI 48.355.8%) willing to allow such donation as a legal guardian. Males acting as legal guardians were more likely to allow donation to achieve pregnancy than female guardians (58.1% versus 47.3%; P = 0.006). Muslims were opposed to posthumous donation (n = 2). The results of the survey are summarized in Figure 1.
The group 2 survey participants (40 women, 10 men) who had, or their partners had, premature ovarian failure (POF), demonstrated a high level of acceptance (84%; 95% CI 70.992.8%) for the study of oocytes without fertilization. This group had an age range of 1874 years (mean ± SEM, 44.9 ± 1.53). In this biased population, 90% had attended college or beyond. Religious affiliations were: 33% in The Church of Jesus Christ of Latter-day Saints and 63% in other Christian denominations (Catholic 22%, Greek Orthodox 6.6%, Episcopalian 6.6%, Lutheran 6.6%%, other 21%). Fertilization with study to an eight-cell stage as well as preembryo transfer to cause a pregnancy were accepted at a higher level than found in the random (group 1) population [80% (95% CI 66.390%) versus 58.3% (95% CI 51.162.0%), P = 0.0025; and 76% (95% CI 61.886.9%) versus 57.4% (95% CI 53.761.1%), P = 0.01), respectively. Additionally, fertilization with study of the preembryo to an eight-cell stage after guardian-directed donation was more acceptable in group 2 [74% (95% CI 59.785.4%)] than in group 1 [54.8% (95% CI 51.158.6%)] (P = 0.008). However, as with the state survey (group 1), decreasing levels of acceptability indicative of reservations were evident when fertilization and potential pregnancies from donation and guardian-directed donations were queried (Figure1).
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Discussion |
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A previous survey performed in the UK noted widespread acceptance of ovarian tissue donation for research and therapy (88% of their study population) (Kazem et al., 1995
). However, in contrast to the present study, only 28% of participants in the UK study found posthumous donations to be acceptable. The difference between the UK and Utah studies may be explained by a greater proportion of ethnic or religious groups in the UK population that view posthumous donation negatively. Alternatively, the strong inclinations of the Utah population towards building families, and their demonstrated willingness to participate in posthumous organ donation and support research endeavors, may also explain the greater level of acceptance of posthumous donation. The Utah results may not be generalizable to other populations; however, recent studies suggest similar rates of acceptability for oocyte donation to help another couple conceive a child. In a German study, 43.268.6% of various study populations were willing to donate oocytes for the purpose of conception (Schroder et al., 2004
). Similarly, reproductive tissue donation for research appears to be well accepted. For example, in Sweden, 92% of couples with supernumerary embryos from IVF chose donation for stem cell research rather disposal in a recent survey (Bjuresten and Hovatta, 2003
).
The lay publics general acceptance of posthumous ovarian donation for research in Utah, accompanied by significant reservations when the donation is intended for the creation of a pregnancy, supports the published ethical recommendations and practice regarding the donation of organs to prolong life compared with donations intended to create life. In the context of organ donation to prolong life, surrogates are asked to act in accordance with the potential donors wishes and value system. However, a higher level of authorization (prior written consent) has been recommended in situations intended to create life. The University of Washington addressed posthumous reproduction in the context of a request to harvest gametes after death (Assisted Reproductive Technology Committee and University of Washington, 1997; Soules, 1999
). Their consensus opinion stated that the posthumous donation of gametes for the creation of new life was different from tissue donations given with the intention of prolonging life (i.e. organ donation) or for research. For that reason, they advised explicit prior written consent by potential donors. The Ethics Committee of the American Society for Reproductive Medicine also suggests explicit prior consent for potential posthumous reproduction: A spouses request that sperm or ova be obtained terminally or soon after death without the prior consent or known wishes of the deceased spouse need not be honored (Ethics Committee and ASRM, 2004
).
Surrogate decision makers (guardian-directed) are expected to act according to the wishes of the patient, to the extent they are known or to use the patients value system in their decision (Barber v Superior Court, 1983; Harmon, 1990
). Unfortunately, surrogates are routinely inaccurate in understanding and executing a patients personal preferences (Emanuel and Emanuel, 1992
; Sulmasy et al., 1994
; 1998
; Coppolino and Ackerson, 2001
). Further complicating surrogate decision makers responsibilities, one legal analysis states that surrogates have the right to take into account other factors, such as the demands of morality and the best interests of the family as a whole (Morley, 2002
). Some have suggested that surrogates potentially could be authorized to make tissue donation decisions to prolong life if they: (i) can substantively enunciate the patients wishes; (ii) derive no benefit from the donation beyond the altruistic action; (iii) have documentation that the donation will not alter the clinical course; (iv) gain the ethical approval of all participants in the donation procedure; and (v) have had the proposed donation prospectively evaluated by an ethics committee (UCLA Medical Center Ethics Committee and URT Program, 2004
). At the present time, a general lack of awareness of the feasibility and utility of posthumous ovarian tissue donation make a clear understanding of the patients wishes, approval of participants in the donation process and prospective ethics committee considerations noted above highly problematic for both research and/or therapeutic uses of ovarian tissue.
In summary, this survey of the Utah population (group 1) revealed that both IVF and the posthumous donation of ovarian tissue for scientific investigation was acceptable in a majority of respondents (Figure 1). Donation of follicles/oocytes for scientific investigation, without fertilization, was acceptable in 74.4% of those asked on behalf of themselves or their partner, and in 70.1% of those who would be acting as a surrogate decision maker. When participants were queried regarding fertilization and growth to an eight-cell preembryo, without a resulting transfer of the preembryo, the percentages fell to 58.3% and 54.8% for their own or their partners versus guardian-directed donation, respectively. Finally, when fertilization and transfer to a couple desiring a child was proposed, the acceptance levels fell to 57.4% and 52.1% for these groups, respectively. A similar pattern of increasing concern and decreasing acceptance regarding fertilization and potential pregnancies from donation, as well as guardian-directed donations, was noted in a separate survey of those who had a personal interest in such donations (ovarian failure or surgical castration; group 2). This study of the general publics views on ovarian tissue donation is concordant with the published views of ethics committees regarding posthumous gamete donation: that explicit prior written consent of the donor is advisable when donations are procured with the intention of creating life and in this particular survey, to allow fertilization or transfer of preembryos to cause a pregnancy. Because of the general lack of knowledge regarding the potential utility of posthumous ovarian donation for research or therapeutic purposes, surrogates would have a difficult time authorizing such a decision based on the above criteria without explicit written consent. In light of the rapid technological advancements in follicle/oocyte cryopreservation and maturation for physiological studies and potential clinical uses, it may be time to provide potential organ donors the opportunity to specify their desires regarding ovarian tissues when registering for organ donation.
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Submitted on August 18, 2004; resubmitted on March 14, 2005; accepted on June 17, 2005.
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