Hum. Reprod. Advance Access originally published online on October 24, 2007
Human Reproduction 2007 22(12):3124-3128; doi:10.1093/humrep/dem287
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Changes in patient preferences in the disposal of cryopreserved embryos
1 Reproductive Endocrinology and Infertility, University Hospital, London Health Sciences Centre, London, Ontario, Canada N6A 5A5 2 Department of Obstetrics and Gynecology, University of Western Ontario, London, Ontario, Canada
3 Correspondence address. Tel: +1-519-685-8500; Fax: +1-519-663-3938; E-mail: christopher.newton{at}lhsc.on.ca
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Abstract |
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BACKGROUND: The disposal of unused cryopreserved embryos can be a difficult decision for patients and the existence of unclaimed embryos raises ethical concerns for clinics. This study examined changes in patients’ preferences for disposition of unused embryos and the relevance of a two-stage process for obtaining consent.
METHODS: Patients who had not returned for cryopreserved embryos for over 5 years were contacted and asked to specify their current preferences for embryo disposition. These preferences were compared with dispositional choices made at the time of embryo freezing.
RESULTS: Over one-third of patients had not returned for cryopreserved embryos within 5 years, and 31% of these declined to provide an updated directive. Those with a live birth through treatment were more likely to provide a new directive and more likely to choose to discard rather than donate embryos for research. Prior to IVF, the majority of non-returnees had elected to donate unused embryos for research, but 59% of all couples changed their minds after treatment.
CONCLUSIONS: Changes in preferences for embryo disposition was linked to treatment outcome and highlighted the need for a two-stage process to obtain fully informed consent. In this Canadian sample, patients’ affinity for research declined after treatment.
Key words: cryopreservation/consent/preferences/embryos
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Introduction |
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In the course of infertility treatment using in vitro fertilization (IVF), not all embryos produced can be safely transferred to the woman’s uterus for implantation. Instead, surplus embryos can be cryopreserved (frozen) for later use. Published reports of the number of frozen embryos in storage have ranged from 52 000 (UK, 1996), 71 000 (Australia, 2000) and 400 000 (USA, 2003) (Hoffman et al., 2003
). Due to the lack of a central registry and national regulations, it had been difficult to ascertain the number of frozen embryos stored in Canadian IVF clinics, although a recent estimate suggested approximately 15 000 (Baylis et al., 2003). Once embryos are frozen, options include thaw and transfer for a couple’s own use, donation to another infertile couple, donation for research purposes or discard. Most stored embryos are targeted for patient use, but many couples do not return for these embryos. In Sweden, 30% of couples did not return during a 3-year period (Skoog-Svanberg et al., 2001), and similar reports have come from France (Lornage et al., 1995) and Denmark (Bangsboll et al., 2004). In addition, some reports have suggested that a disturbing number of patients seemingly ignore clinic efforts to maintain contact (Brzyski, 1996). The extent to which Canadian patients choose not to return for frozen embryos has not been reported.
The existence of unclaimed embryos creates ethical and procedural challenges for IVF clinics. To avoid the accumulation of unclaimed embryos, many clinics ask couples to make dispositional decisions before beginning IVF treatment. However, such pre-agreements made before IVF treatment, a potential pregnancy, the birth of a child or other unforeseen life events, might be viewed as an uninformed decision and particularly problematic in terms of donating unused embryos either to another couple or for research purposes (Bankowski et al., 2005). In fact, a recent report suggested that many patients change their mind after completing IVF treatment (Klock et al., 2001). At least in Canada, a wide variation in the timing of completion of disposition agreements has been reported among IVF clinics. Agreements might be formalized before embryos are created, before embryo freezing or sometimes only after treatment if couples wish to dispose of unused embryos (Baylis et al., 2003).
Most North American patients choose to discard unused embryos, but patients’ preferences are of great interest because these embryos are a potentially important resource for embryonic stem cell research (VanVoorhis et al., 1999; Nisker and White, 2005). In Canada, there may be few cryopreserved embryos available for stem cell research and even fewer may be eligible due to inadequate clinic consent practices (Baylis et al., 2003). Guidelines of the Canadian Institutes of Health Research (CIHR) require that a directive for disposition of unused embryos be obtained prior to gamete collection, but in addition, consent of the embryo providers must be reiterated at the time when embryos are to be used for stem cell research (CIHR, 2005).
Finally, patient receptivity to donation of embryos to another infertile couple shows wide international variation. Estimates of patient interest range from 11% in the USA (VanVoorhis et al., 1999) to 17% in France (Lornage et al., 1995) and 39% in Belgium (Laruelle and Englert, 1995). In Canada, 12% of couples have expressed preliminary interest in donation to another couple (Newton et al., 2003), but there have been no reports of the proportion of couples choosing this option or of the number of embryos available.
The present study aimed to explore the final dispositional choices of Canadian patients and to investigate whether treatment outcome might influence patient choices for embryo disposition. Second, we explored the feasibility and potential relevance of a two-stage consent process, hypothesizing that it would be necessary to address potential changes in patient preferences over time.
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Materials and Methods |
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Cryopreservation of surplus embryos created during IVF treatment cycles at University Hospital began in 1985. In 1992, a disposition agreement was implemented, where prior to oocyte retrieval, couples chose one of two directives if their embryos remained unclaimed after a 5-year storage period: either embryo discard or donation for unspecified research purposes. Until 1999 (when an annual storage fee was implemented), couples were required to pay a one-time fee of $300.00 for storage. Initially, this approach seemed advantageous in requiring no need to re-contact or to bill patients on an ongoing basis, but subsequently proved problematic due to concerns that patients’ views might change during the period of storage and that pretreatment directives might no longer be valid. As a result, a two-stage process for disposition of unused embryos was implemented, where couples were re-contacted and allowed to reconfirm or change their original directives.
Participants
Over a 3-year period (2002–2005), couples with unclaimed embryos in storage for 5 years or longer were identified and contacted. To ensure that privacy of personal health information was protected, mailing addresses were first confirmed through telephone contact and then a reminder notice was sent indicating the date of freezing, the number of embryos in storage and noting that the agreed 5-year storage period had either expired or been exceeded. Couples were asked to complete and return an attached consent form by choosing one of four disposition options: discard of embryos, donation for research, donation to another couple or continued storage for personal use at an annual fee of $200.00. Couples failing to respond within 60 days were sent a second final notice by registered mail, informing them that stored embryos would be disposed of within 30 days in accordance with couples’ pretreatment directives, unless further instructions were received. Where a current mailing address could not be confirmed, a registered letter was sent to the last known address requesting the couple contact the hospital. Patients who responded were mailed the reminder notice and consent form and if necessary, a final notice. If patients did not respond within 60 days, embryos were disposed of according to pretreatment directives.
Analysis
Statistical analyses were performed using the Statistical Package for Social Sciences (version 12.0 for Windows, SPSS, Chicago, IL, USA). Pearson 
2 tests were used to assess the association between individual variables and the McNemar test was employed to compare nominal data at two points in time.
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Results |
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Between 1985 and 1999, a total of 607 couples utilized the option of embryo freezing and storage. Of these, 232 couples (38%) failed to return and a combined total of 886 embryos remained unclaimed. At the time of the study, 77% of couples had stored their embryos for between 5 and 8 years, 20% of couples had continued storage for 9–11 years and 3% had stored for 12–17 years. Of those couples failing to return, 10% (23/232) could not be located and 32% (75/232) failed to provide a final directive for embryo disposition. Among couples who did not return for embryos, 64% had experienced a pregnancy and 58% had a live birth following their last treatment cycle.
Of the couples who failed to return for their embryos, 90% (209/232 couples) were located and a current mailing address was confirmed. Two couples provided a telephone directive requesting continued storage. Of the remaining couples, only 41% (84/207 couples) responded to the first reminder notice by providing an updated directive. Of the remaining couples, 47% (58/123) responded to a second final notice. Therefore in total, 69% (144/209 couples) who were successfully located provided a new updated directive. Among the remaining 31% who elected not to provide an updated directive, 62% had selected the research option pretreatment and 32% had chosen discard.
A significant relationship was observed between response to contact and IVF outcome (2 = 3.9, P = 0.04). Of couples with a live birth from IVF treatment, 67% responded to contact notices by providing an updated directive. In contrast, only 33% of couples with unsuccessful treatment provided a new directive.
Table 1 shows the eventual disposition of unclaimed embryos, based upon either patients’ last updated directive, or on pretreatment directives, when no updated directives were provided. (There were eight couples who provide no pretreatment or updated directives and their embryos were ultimately discarded.) The majority of couples (82%) designated their embryos either to be discarded or for research purposes. Very few couples (8%) expressed interest in donating embryos to another infertile couple. An even smaller number wished to continue storage when faced with an annual storage fee.
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Table 2 contrasts couples’ initial intentions for their unused embryos pretreatment with the actual final destination of these embryos. The difference reflects several factors including a change in patients’ preferences, a decision to postpone disposition and continue storage, the availability of another option (donation to another couple) and the clinic decision to discard all embryos if both pretreatment and updated directives were lacking (eight couples). At pretreatment, the majority of couples had selected the research option, but less than one half of couples eventually had embryos destined for research purposes. By comparison, embryo discard was less favoured at pretreatment, but ultimately a nearly equal number of couples had embryos destined for research or for discard. The option of donation to another couple was never offered as an option at pretreatment. The remaining couples had given no pretreatment directive as none was routinely obtained prior to 1992. It is important to note that the actual proportion of couples whose embryos were made available for future scientific investigations was lower than shown in Table 2. Only 46% (47/102) of all the couples whose embryos were ultimately stored for research purposes had actually provided a final directive confirming their preference for this option. As a result, only 176/349 embryos (50%) were set aside for future research. For the remaining couples, research interest could only be inferred based upon pretreatment directives. Couples who failed to provide an updated directive would be unlikely to provide later direction to an investigator as required by Canadian guidelines. Therefore the remaining embryos from these couples were utilized for quality assurance purposes in the centre’s laboratory.
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To assess the extent to which patients changed their decision about embryo research versus embryo discard, we compared the pretreatment and final directives of those couples who actively provided instructions on both occasions. Since the options of donating embryos to another couple or continued storage were not offered before treatment, couples who switched to these options in their final directive were omitted from the analysis. Because only couples choosing embryo research or embryo discard as their final directive were included, this analysis actually underestimates the overall percentage of couples who changed preferences.
The McNemar test showed a significant difference between original and final active choices (n = 99, P < 0.001). Of 78 couples who originally chose research and gave a final directive, only 37(47%) selected research as their final option, whereas 41(53%) switched their choice to discard. In contrast, of 21 couples who originally chose discard and gave a final directive, 16 couples (76%) maintained this decision post treatment and 5 couples (24%) switched to research. In total, 59% of couples changed their directive after completing treatment.
To determine whether final dispositional choices might be related to treatment outcome, a 2 analysis was performed, comparing choices among couples who experienced treatment failure with those who had a successful live birth. The results indicated a significant relationship (2 = 5.6, P < 0.05). Couples who had experienced a live birth preferred to discard unused embryos (52%) rather than direct them for research purposes (30%) or donate them to another couple (18%). By comparison, couples experiencing treatment failure were evenly divided in their preferences for embryo discard (46%) or research (48%), but less receptive to donation to others (6%). No significant relationships were found between the length of the storage period or the number of embryos in storage and the final choice of either embryo discard or research.
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Discussion |
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A substantial number of couples did not return for their cryopreserved embryos, particularly if previous IVF treatment had been successful. Despite successful clinic efforts to contact them, almost one-third failed to provide a final directive concerning the disposition of their embryos. Among those who responded, a willingness to donate embryos for research purposes declined once couples had ended their participation in IVF treatment when compared with attitudes before treatment.
Remarkably, more than one-third of couples elected not to return for the transfer of previously frozen embryos. The fact that one half of these couples had experienced a live birth through their IVF treatment was not surprising, since couples most often claim: ‘satisfaction with current family size’ or ‘involvement in child care’, as primary reasons for not returning for further treatment (Lornage et al., 1995; Skoog-Svanberg et al., 2001; Newton et al., 2003). The non-return rate appears to be higher than that reported by European clinics (Lornage et al., 1995; Skoog-Svanberg et al., 2001; Bangsboll et al., 2004) and estimating from the present study, about 15% of all Canadian couples who utilize embryo freezing will not provide directives for disposition of their embryos after IVF treatment.
A two-stage consent process, whereby couples provide both a pretreatment directive and then a final confirmation of their wishes at the time of embryo disposition proved both feasible and highly relevant. Such a process is clearly more onerous for clinics, in terms of staff resources and record keeping required. However, despite the fact that no annual contact had been maintained with these couples, 89% were successfully located using different computerized databases and the Internet. Annual collection of storage fees and update of patient records would likely improve this rate. More importantly, a two-stage process revealed that more than one half of all couples (59%) who gave an updated directive changed their decision between the options of research and embryo discard. This finding is consistent with other international reports (Brinsden et al., 1995; Lornage et al., 1995; Klock et al., 2001) and highlighted the question of whether clinics have an ethical responsibility to reaffirm patients’ wishes. While it has been argued that responsibility rests with patients to notify the clinic of a change of mind, others have noted that people are imperfect decision makers who may neglect to communicate their wishes in part due to procrastination, particularly if the task is disagreeable and laden with negative emotions (Pennings, 2000).
Patient preferences for disposition before and during IVF treatment often reflected an altruistic desire to help others. Almost two-thirds of couples favoured the research option and only about one quarter preferred discard. However, 5 or more years after treatment, the preference for embryo discard almost doubled with a comparable reduction of interest in research. This shift was related in part to the experience of successful IVF treatment. Couples experiencing a live birth after treatment were more likely to favour embryo discard and less likely to favour research, whereas couples experiencing failed IVF treatment showed no preference. Quite possibly, the significance or meaning of frozen stored embryos might have been altered by the birth experience. Rather than simply representing a back-up option to achieve a pregnancy, the embryos might be seen as potential siblings to a child(ren) born through treatment (de Lacy, 2005). Other researchers have also reported that patient conceptualizations of their embryos figured large in disposition decisions (Nachtigall et al., 2005) and observed a similar shift in preferences away from altruistic options and towards embryo discard after successful IVF treatment (de Lacy, 2005). Together these findings lend support to the view that a fully informed decision about embryo disposition may not be possible until after treatment. In fact, it has been argued that contracts signed before or even during an IVF treatment cycle may be literally and ethically worthless (Lockwood, 2006). At the same time, a substantial number of patients seem unwilling to provide an updated directive.
Less than one half of the couples who selected the research option at pretreatment provided a final directive. Since many couples were unwilling to confirm their wishes for research with the clinic, it is possible but questionable whether a future principal investigator could gain further consent from these same couples for a particular study (as per Canadian guidelines). However, the couples who did provide a final directive, offering a total of 176 embryos for research purposes, might represent a conservative estimate of actual research interest.
Assuming that 50% of all available embryos will be used for stem cell research and 66% will survive the freeze thaw process, a recent survey of Canadian clinics concluded that only 98 embryos would be available across Canada for stem cell research (Baylis et al., 2003). By similar calculations, there would be at least 58 embryos available from our centre alone. Therefore, previous reports may have underestimated the number of embryos potentially available for use in Canadian stem cell research.
In contrast, only a small number of couples expressed an interest in donating a total of 88 unused embryos to another infertile couple. This proportion is quite consistent with other international estimates suggesting that from 4–18% (Hounshell and Chetkowski, 1996; Soderstrom-Anttila et al., 2001) of couples are willing to donate to other couples. Thus, there may be many more potential recipients than embryos available in the current climate and the utility of this option remains limited.
In the course of follow-up, a number of couples failed to provide a final directive concerning their embryos, despite two written requests and a 90-day time frame. A recent Italian study similarly reported that one quarter of couples failed to assume responsibility to designate a preference for the disposition of their embryos (Cattoli et al., 2005). The reasons are unclear, but in the present study, a non-response was significantly more likely following IVF treatment failure. Unsuccessful couples might have avoided further communication with the clinic because contact was psychologically difficult after treatment failure. By comparison, successful couples were more likely to participate in final decision-making, possibly because cryopreserved embryos had taken on a greater meaning. Alternatively, it has been suggested that some couples simply may wish to escape the moral responsibility for the destruction of their embryos (Skoog-Svanberg et al., 2001; Lockwood, 2006). Although this study involved a relatively large patient sample, patient behaviour and preferences reflect a single geographic area and might not be representative of other infertility patients. In addition, it is unclear from the findings, whether some patients failed to respond simply because they were aware of and satisfied with their default pretreatment directives.
In conclusion, clinics should anticipate that a substantial number of patients will not return for stored embryos, that many patients will not provide a final directive for embryo disposition and that others will change their views. Clinics need to address theses issues in developing an appropriate process to obtain fully informed consent. Future research is needed to explore more fully the reasons why some patients fail to provide updated consent or change their preferences after treatment.
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Submitted on May 8, 2007; resubmitted on July 24, 2007; accepted on August 6, 2007.
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