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Expanding Access to Testicular TissueCryopreservation: An Analysis by AnalogyTuua Ruutiainen a , Steve Miller b , Arthur Caplan c & Jill P. Ginsberg da Tulane University School of Medicineb The Johns Hopkins Hospitalc New York University Langone Medical Centerd Perelman School of Medicine at the University of PennsylvaniaPublished online: 21 Feb 2013.

To cite this article: Tuua Ruutiainen , Steve Miller , Arthur Caplan & Jill P. Ginsberg (2013) Expanding Access toTesticular Tissue Cryopreservation: An Analysis by Analogy, The American Journal of Bioethics, 13:3, 28-35, DOI:10.1080/15265161.2012.760672

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The American Journal of Bioethics, 13(3): 28–35, 2013Copyright c© Taylor & Francis Group, LLCISSN: 1526-5161 print / 1536-0075 onlineDOI: 10.1080/15265161.2012.760672

Target Article

Expanding Access to Testicular TissueCryopreservation: An Analysis

by AnalogyTuua Ruutiainen, Tulane University School of Medicine

Steve Miller, The Johns Hopkins HospitalArthur Caplan, New York University Langone Medical Center

Jill P. Ginsberg, Perelman School of Medicine at the University of Pennsylvania

Researchers are developing a fertility preservation technique—testicular tissue cryopreservation (TTCP)—for prepubescent boys who may become infertile as a result

of their cancer treatment. Although this technique is still in development, some researchers are calling for its widespread use. They argue that if boys do not bank their

tissue now, they will be unable to benefit from any therapies that might be developed in the future. There are, however, risks involved with increasing access to an

investigational procedure. This article examines four methods of expanding access to TTCP: (1) expansion of institutional review board (IRB)-approved research trials;

(2) offering TTCP as an innovative procedure in hospitals; (3) offering TTCP as a standard practice in hospitals; and (4) commercialization of TTCP. The ethical and

practical implications of each are evaluated through a comparison with umbilical cord blood banking (UCBB), a technology that has achieved widespread use based on

similar claims of future benefit.

Keywords: cancer, children and families, informed consent, medicine, pediatrics, reproductive technologies

Continuing improvements in the rates of remission andcure of childhood cancers have unveiled a new pressingproblem for the survivors of these diseases: infertility re-sulting from their treatment (Ginsberg 2011). The high-dosechemotherapeutic agents that are necessary to treat cer-tain cancers can also kill spermatogonial cells that are cru-cial to reproductive function in men, resulting in sterility(Meistrich 2009). Postpubescent boys can preserve their fer-tility through sperm banking, but there is no proven methodfor fertility preservation in prepubescent boys (Dillon andGracia 2012). Testicular tissue cryopreservation (TTCP) is animportant emerging experimental technology that seeks toaddress the need for fertility preservation in these patients.

TTCP involves freezing testicular tissue from pre-pubescent boys. The frozen testicular tissue contains sper-matogonial stem cells (SSCs), which could theoretically bereimplanted into the testicles to restore spermatogenesis(Brinster 2007; Clark et al. 2011). Alternatively, it may bepossible to grow sperm in vitro from testicular tissue sub-jected to specific culture media (Brinster 2007; Clark et al.2011). These therapeutic possibilities remain experimental,as the technology has yet to produce viable sperm in humanpatients (Brinster 2007; Clark et al. 2011).

At present, access to TTCP is limited. Institutional re-view board (IRB)-approved research protocols at a small

This work was generously supported by the St. Baldrick’s Foundation for Childhood Cancer Research (JPG). Tuua Ruutiainen and SteveMiller are joint first authors.Address correspondence to Tuua Ruutiainen, Tulane Univesity School of Medicine, New Orleans, LA 70118, USA. E-mail: tuua.ruutiainen@gmail.com

number of medical centers in the United States permiteligible children to undergo TTCP. Though TTCP remainsinvestigational, there have been calls to expand access.Some researchers argue that all prepubescent boys who arepreparing to undergo gonadotoxic cancer treatment shouldbe counseled about TTCP (Sadri-Ardekani et al. 2011). Oth-ers advocate for more “widely applied cryopreservation oftesticular tissue fragments” among high-risk cancer patients(Schlatt et al. 2009).

Those who favor expanding access to TTCP argue thatprepubescent cancer patients should bank their testiculartissue now so that they can later benefit from any success-ful therapies that may be developed (Sadri-Ardekani et al.2011; Schlatt et al. 2009). Boys who do not bank their tis-sue may lose the opportunity to have biological children(Murphy 2010). Although TTCP is still in development, thetechnology has made steady gains, with proponents point-ing to recent successes in animal models as evidence thathuman applications are not that far away (Clark et al. 2011).

Nevertheless, there are many countervailing argumentsagainst expanding access to TTCP. Some commentators cau-tion against sensationalism, arguing that questions of safetyand feasibility should be at the forefront of any discussion ofthe procedure (Clark et al. 2011). Since TTCP is a procedurewith uncertain benefits and more than minimal risk (Clark

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et al. 2011), restricting TTCP to IRB-approved research pro-tocols may be the best method for protecting patients untilfurther progress is made. It is possible that alternative tech-niques for maturing sperm from somatic cells will be devel-oped, obviating the need for the procedure entirely (Clarket al. 2011). In addition, were TTCP to be expanded outsideof research protocols, parents of cancer patients could beasked to share some of the costs of the procedure, whichcould place an additional burden on parents already in astate of emotional extremis (Ginsberg et al. 2010). In eval-uating these arguments, we compare TTCP to autologousumbilical cord blood banking (UCBB)— a technology thathas achieved widespread use based on similar theoreticalclaims of future benefit.

UCBB is the practice of harvesting, freezing, and bank-ing stem-cell-rich blood from the umbilical cords of new-born babies (American Academy of Pediatrics Section onHematology/Oncology et al. 2007). This article focusesspecifically on autologous UCBB—UCBB banking directedfor self-use. Parents bank autologous UCB as a form of “bio-logic insurance” for their children (Ballen et al. 2008). Autol-ogous UCB has an established use as a source of stem cellsfor children with cancer and other diseases requiring bone-marrow transplant (Ballen et al. 2008; Liao et al. 2011). UCBis also being studied as a source of tissue for “regenerativemedicine”—a field that seeks to use stem-cell technology totreat diseases such as diabetes and heart failure (Ballen et al.2008; Liao et al. 2011; Mimeault et al. 2007).

The likelihood that children will use their autologouscord blood (CB) for stem-cell transplant is extremely low,and regenerative medicine remains completely speculative(Kaimal et al. 2009). Many countries have banned or issuedrecommendations against autologous UCBB (EuropeanGroup on Ethics in Science and New Technologies to theEuropean Commission 2004; Fisk et al. 2005). The AmericanAcademy of Pediatrics issued a statement voicing oppo-sition to the practice (American Academy of PediatricsSection on Hematology/Oncology et al. 2007). Despitewidespread disapproval, autologous UCBB has becomewidely available in the United States through commercialbanks (Fisk et al. 2005).

UCBB provides both a cautionary tale and a guide thatmerits examination for the lessons that apply to TTCP. Thisarticle explores the ethical issues that will arise as hospi-tal administrators, researchers, and other stakeholders con-sider expanding access to TTCP through a comparison be-tween these two technologies. Issues within three majorareas—the state of research, the distribution of benefits, andinformed consent—are explored.

POSSIBLE ROUTES FOR EXPANDING ACCESS TO TTCP

Research Protocol Offered by Hospitals

The American Society of Reproductive Medicine (ASRM)and the American Society of Clinical Oncology (ASCO) cur-rently classify TTCP as an experimental procedure and rec-ommend that it only be conducted within IRB-approved

protocols (Ethics Committee of the American Society forReproductive Medicine 2005; Lee et al. 2006).

TTCP offered through research protocols may remainaccessible to patients at only a few hospitals. The CommonRule (45 CFR §46, Subpart A) requires institutional reviewboard (IRB) oversight of research receiving federal funding(Department of Health and Human Services 2005). IRB ap-proval involves bureaucratic hurdles (Eyadhy and Razack2008), and some hospitals lack IRBs altogether (ACOG Com-mittee on Ethics 2006). Research also requires grant funding,which serves as a barrier to access due to the limited num-ber of grants that are available. Funding constraints and IRBapproval make research protocols the most restricted formof access to TTCP.

Innovative Procedure Offered by Hospitals

According to the National Commission, innovative ther-apies are procedures “designed solely to enhance thewell-being of an individual patient or client” but lack “areasonable expectation of success” (Cowan 1985–1986;National Commission for the Protection of Human Subjectsof Biomedical and Behavioral Research 1977; NationalCommission for the Protection of Human Subjects ofBiomedical and Behavioral Research 1978b). Innovativetherapies differ from standard therapies because they “lacksuitable validation of [their] safety and efficacy” (Levine1979). Innovative clinical care, unlike clinical research, isoften nonstandardized (Eyadhy and Razack 2008).

If TTCP were offered as an innovative procedure, itmight be possible to expand access to the procedure. In-novative procedures do not have to meet the same typesof stringent IRB regulatory requirements as experimentalprocedures (ACOG Committee on Ethics 2006). In addi-tion, hospitals do not have to fund innovative procedureswith research grant money. The costs are shared betweenpatients, hospitals, and third-party payers (Stafinski et al.2010; Steinberg et al. 1995), potentially making access atsmaller institutions feasible.

Standard Practice Offered by Hospitals

The Belmont Report defines standard practices as “inter-ventions that are designed solely to enhance the well-beingof an individual patient or client and that have a reasonableexpectation of success” (National Commission for the Pro-tection of Human Subjects of Biomedical and BehavioralResearch 1978a). Standard practices must be “sufficientlytested to meet peer group or regulatory agency standardsfor acceptance or approval” (Levine 1978).

If TTCP were to become a standard therapy, then itwould be easier for physicians to offer the procedure. Stan-dard therapies, like innovative procedures, are not subjectto the same type of strict framework, oversight, and moni-toring as research. Third-party payers may be more likely tocover standard practices than innovative procedures, mak-ing them more affordable for patients. In addition, physi-cians and hospitals may be more inclined to offer standardpractices since the treatments have proven benefits. This

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approach would represent the widest possible expansion ofaccess.

Procedure Offered by Commercial Companies

Medical procedures that are commercialized are sold di-rectly by private companies. The procedures may be exper-imental, innovative, or standard practices. Commercializa-tion can broaden access to procedures since companies havea profit motive to disseminate their services as widely aspossible (Sugarman et al. 1997). However, a higher marketcost to patients could prove limiting.

STATE OF BASIC SCIENCE RESEARCH

TTCP

TTCP is being studied at several pediatric oncology centersin the United States. These centers are enrolling boys withsolid tumors and hematological conditions that requirestem-cell transplant (Ginsberg et al. 2010). For example, thecurrent protocol at the Children’s Hospital of Philadelphia(CHOP) is targeted toward boys undergoing treatmentwith high-dose chemotherapy that puts them at high riskof infertility (Ginsberg et al. 2010). Half of the testiculartissue that is excised from the boys is used for researchpurposes, while the other half of the tissue is stored for laterclinical use (Ginsberg 2011). Thus far, approximately 51patients have been offered the opportunity to bank TTCP atCHOP. The testicular tissue excision and cryopreservationprocedure is offered without cost to the patient.

Researchers are investigating two methods for preserv-ing fertility using cryopreserved tissue. The first involvesisolating and expanding populations of spermatogonialstem cells (SSCs) from testicular tissue (Brinster 2007). TheseSSCs could then be autotransplanted back into the seminif-erous tubules of the testicles to allow for spermatogene-sis to resume. Reimplantation of expanded populations ofSSCs has been demonstrated in animal models (Clark et al.2011; Sato et al. 2011). Expansion of SSCs isolated from tes-ticular tissue has also been preliminarily demonstrated inhumans, though the data await replication (Sadri-Ardekaniet al. 2011; Wu et al. 2009).

The second line of research involves in vitro maturationof spermatogonia from SSCs for use in in vitro fertilization(Brinster 2007; Clark et al. 2011). In vitro maturation of SSCsto sperm has been demonstrated in animal models but notyet in humans (Clark et al. 2011; Sato et al. 2011). Some esti-mates suggest that TTCP could become a usable technologywithin the next two decades, which would be well withinthe reproductive life span of the boys whose tissue is beingbanked now (Clark et al. 2011).

UCBB

Autologous UCBB studies are investigating the use of theUCB for stem cell transplantation and its potential use forregenerative therapy. The use of UCB for stem-cell trans-plant for hematological malignancies, bone-marrow failure,hemoglobinopathies, and inborn errors of metabolism is

well established (Ballen et al. 2008; Liao et al. 2011). Theapplication of UCB in regenerative medicine is in a veryearly stage of development (Butler and Menitove 2011). Re-searchers have succeeded in transforming cord blood stemcells into differentiated cell types (Butler and Menitove 2011;Liao et al. 2011). They are currently investigating the use ofumbilical stem cells for a variety of conditions, includingneurologic, endocrine, and cardiac diseases (Ballen et al.2008; Liao et al. 2011). Clinical applications remain purelytheoretical at this point (Ballen et al. 2008; European Groupon Ethics in Science and New Technologies to the EuropeanCommission 2004).

Practical Considerations

On a practical level, the path for expanding access to TTCPis likely to be somewhat different from that of UCBB. UCBBis a standard practice that has achieved widespread usethrough commercialization. Although autologous UCBB isgenerally not recommended, it is considered effective instem-cell transplantation (Liao et al. 2011). Companies havebeen able to successfully market UCBB because there are alarge number of concerned parents who wish to bank theirchildren’s UCB (ViaCord 2012). The companies argue thatevery child is at risk for developing one of the conditionsthat UCBB is designed to treat (Viacord n.d.).

TTCP, on the other hand, cannot be considered a stan-dard practice because it does not have a proven clinicalapplication (Clark et al. 2011). In addition, TTCP is unlikelyto be commercialized. Only a small number of children un-dergo gonadotoxic chemotherapy, making commercializa-tion unprofitable. TTCP will achieve widespread use if hos-pitals substantially increase the number of research trials orif they begin to offer TTCP as an innovative clinical practice.

Although the avenues for expansion are different, UCBBand TTCP raise many of the same ethical issues since inboth cases the arguments for expanding access are based ontheoretical claims of future benefit

Ethical Considerations

Three ethical considerations surrounding the state of basicscience research can help inform expansion: the lag timebetween banking and use, alternative procedures, and theavailability of raw material for research.

The long delay between the time of tissue banking andthe time of transplantation is one of the primary argumentsfor widening access to UCBB and TTCP. Proponents ofUCBB have argued, “No one has a second chance to collecttheir cord blood” (Fisk et al. 2005). If autologous UCBB stud-ies succeed and researchers discover that UCBB is an impor-tant source of stem cells for regenerative therapy, childrenwho did not bank their tissue at birth will have missed theopportunity to use the technology. A similar argument canbe made for TTCP. If TTCP research does come to fruition,all of the boys who are outside of the small research co-hort would miss the opportunity to preserve their fertility(Murphy 2010). This time lag is a unique feature of pedi-atric tissue banking technologies and is a strong argumentfor providing wider access to TTCP.

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The availability of alternative methods of treatmentcould provide an argument against expanding access toTTCP. Although autologous UCBB has been successfullyused for stem-cell transplantation, it is not the only sourceof stem cells for transplantation. Bone marrow and periph-eral blood are often adequate or preferable sources of stemcells for these conditions (Ballen et al. 2008; ViaCord n.d.).There are also alternative sources of stem cells for regen-erative therapy, including bone marrow, peripheral blood,embryonic tissues, and other adult tissues (Mimeault et al.2007).

Similar alternatives may become available for fertilitypreservation in prepubescent patients. Researchers are cur-rently investigating methods for acquiring transplantableSSCs or sperm from induced pluripotent stem cells derivedfrom somatic cells (Clark et al. 2011). This would make itpossible to restore fertility without the use of stored testic-ular tissue, giving cancer survivors the opportunity to con-sent to the fertility restoration procedure themselves. BeforeTTCP is further expanded, parents should be made awarethat alternative therapies could develop that may obviatethe need for the procedure.

In order for research on TTCP and UCBB to progress,patients must donate their tissue as raw material for theresearch effort. Expanding access to tissue banking outsideof research may increase the supply of tissue for research.Researchers who are investigating regenerative uses for au-tologous UCB obtain tissues either at birth from parentswho donate their children’s tissue directly to public banks,or by recruiting children whose tissue is stored in privatebanks (National Institutes of Health 2011). Private bankstherefore serve as an additional supply of raw material forresearch.

TTCP is currently only available through small researchtrials, so TTCP investigators do not have access to any ad-ditional sources of tissue. Just as with UCBB, if TTCP wereoffered outside of research protocols, a new source of tis-sue for research could emerge. If TTCP were offered as aninnovative clinical service by hospitals, parents could stillchoose to donate part of their children’s tissue to research.Comparison with UCBB shows that researchers could con-tinue to receive raw material for their work without beingthe sole providers of TTCP.

DISTRIBUTION OF BENEFITS

TTCP and UCBB

UCBB and TTCP provide different types of direct benefitsto the children who undergo these procedures. AutologousUCB can be used for lifesaving therapies, though it is highlyunlikely to ever be used for this purpose (Ballen et al. 2008).TTCP has the potential to prevent psychological morbidityassociated with infertility and preserve reproductive auton-omy for patients who undergo the procedure (Patrizio et al.2005; Schover 1999). The likelihood that those who banktesticular tissue will accrue benefits is high if the techniqueproves successful.

Ethical Issues

Those who advocate expanding access to TTCP should con-sider three factors related to the distribution of benefits: thepotential for direct benefit, the probability of direct benefit,and the specific risk group to whom the procedures shouldbe targeted.

The manner in which a technology directly benefits pa-tients should be a primary consideration for those who aredeliberating increasing access to TTCP. In the case of UCBB,the benefit of banking lies in its potential to provide a life-saving treatment both in its extant use as an alternativesource of stem cells for transplant and in its hypotheticalfuture use in treatment of deadly conditions such as heartfailure or diabetes (Ballen et al. 2008; Yanling 2011).

The benefit of TTCP lies in its potential to significantlyimprove quality of life. Several studies have demonstratedthe significant psychological morbidity of infertility for can-cer survivors (Schover 1999; Schover et al. 1999; Schoveret al. 2002). Survivors place high importance on havingchildren (Schover 2009) and on the provision of fertilitypreservation treatments (van den Berg et al. 2007). Maleadolescent survivors of childhood cancer in one study in-dicated that they were pleased to have been provided theoption to preserve their fertility, regardless of whether or notthe procedure was successful (Ginsberg et al. 2008). Whilechildren enrolled in TTCP studies are too young to havebeen surveyed, TTCP patients are likely to share many ofthe same views as other cancer survivors who value fertilitypreservation.

In addition to psychological benefit, fertility preser-vation helps patients maintain reproductive autonomy(Patrizio et al. 2005). The right to reproduce can be con-sidered a “right-in-trust” that adults must protect so thatchildren can have open futures in which they can maketheir own choices (Davis 1997; Feinberg 1980). These bene-fits argue for making TTCP more widely available, just asUCBB has been made widely available based on its potentialto reduce mortality.

The probability of direct benefit from TTCP shouldalso be considered. Comparison with UCBB is apropos.The likelihood that children will use banked autologousUCB for stem cell transplantation is between 1:2500 (0.04%)and 1:200,000 (0.0005%) in the first 20 years of life (Ballenet al. 2008; Kaimal et al. 2009). It is much more difficultto predict the potential for using UCB for regenerativetherapy. The low likelihood of using UCB for autologoustransplant coupled with the experimental nature of regen-erative medicine are part of the reason that the Ameri-can Academy of Pediatrics discourages UCBB directed forpersonal use (American Academy of Pediatrics Section onHematology/Oncology et al. 2007). Despite this official rec-ommendation, access to UCBB has been widely dissemi-nated by commercial companies. This underscores the needto more carefully regulate access to TTCP.

The probability of direct benefit from TTCP appearsto be much higher than that of UCBB. Almost all of thechildren who are currently banking testicular tissue have

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undergone treatment with high-dose cytotoxic chemother-apy and thus have a potent indication to undergo TTCP(Ginsberg et al. 2010). Unlike patients who bank UCB, pa-tients undergoing TTCP are likely to develop the conditionthat TTCP is designed to mitigate. A recent study showedthat male pediatric cancer survivors were approximatelyhalf as likely as their siblings to sire a pregnancy (Green2010). High-risk exposure to radiation and chemotherapywere the major factors that decreased their likelihood ofsiring a pregnancy (Green 2010). UCBB was made widelyavailable despite the low likelihood of benefit for an indi-vidual patient; consequently, the procedure may have beenprematurely disseminated. In contrast, the high risk of in-fertility among pediatric cancer patients may make TTCPmore ripe for dissemination.

One way to maximize the likelihood that TTCP willbenefit patients is to target it toward those who are at highestrisk. UCBB provides a cautionary example in this regard,since commercialization has mostly expanded access withina low-risk population (Ballen et al. 2008).

Research studies on TTCP, in contrast, are currently tar-geted toward children who are at high risk for infertility asa result of their cancer treatment. Allowing TTCP to be per-formed outside of research protocols and without stringentcontrols over the patient population could expose childrenwho are at low risk of infertility to the risks associated withbiopsy, general anesthesia, and delayed cancer treatment.UCBB was perhaps too liberally expanded within a low-risk group. Great care should be taken to ensure that thisdoes not occur with TTCP.

INFORMED CONSENT

TTCP

Informed consent for TTCP has two steps. The initial in-formed consent is for the harvesting and cryopreservationprocedure. It involves an explanation of the experimentalaims of the procedure and an explanation of risks and ben-efits (Ginsberg 2011). Since minor children cannot legallyconsent to the procedure, parents provide consent to this ini-tial step. The second stage of informed consent will occur ifthe science for using human testicular tissue is achieved andwhen the patient reaches the age of majority (Anonymous1995; Cohen 2009; Patrizio and Caplan 2010). The timelinefor the first stage of informed consent is highly compressed.Most parents are approached in the days following theirchildren’s cancer diagnosis but before the initiation of treat-ment with gonadotoxic chemotherapy (Ginsberg et al. 2010)

UCBB

The consent process for autologous UCBB in private banksis also divided into two steps. The initial consent informsparents about the potential use of the tissue, directions forbanking and harvesting the tissue, and risks of the pro-cedure (ViaCord n.d.). The second stage of the informedconsent, which would authorize future use of the tissuesby the child, is not mentioned in the consent form that is

given to the parents (ViaCord n.d.). Physicians have verylittle involvement with the informed consent process forUCBB. Instead, parents print the informed consent forms,and then send the signed forms to the company with theirpayment (ViaCord n.d.). Many parents learn about UCBBfrom direct-to-consumer advertising, rather than from theirphysicians (Annas 1999; Ballen et al. 2008; Lubin et al. 2009)

Ethical Issues

Two important ethical considerations arise when comparingthe informed consent process for TTCP and UCBB: the emo-tional state of the parents, and the risks of the procedure.

UCBB demonstrates why it is important to consider theemotional state of parental decision makers when broaden-ing access to experimental procedures. Parents consentingto UCBB are in an emotionally vulnerable state (AmericanAcademy of Pediatrics Section on Hematology/Oncologyet al. 2007; Annas 1999). During pregnancy, prospectiveparents may be especially susceptible to advertisementsby UCBB companies that offer “biologic insurance” fortheir children (American Academy of Pediatrics Section onHematology/Oncology et al. 2007; Ballen et al. 2008). Thistype of marketing is particularly problematic since UCBBis an expensive procedure that costs an average of $3,620with a very low likelihood of direct benefit (Kaimal et al.2009). Regulators should be wary of broadening access totechnologies such as UCBB that have the potential to exploitanxious parents.

Expanding access to TTCP is worrisome since it couldput parents in an even more stressful position. In the case ofTTCP, parents receive news that their children have cancerand then have a matter of a few days to make numerousmedical decisions. In this emotional milieu, it may be moredifficult for parents to make an informed decision regardingthe speculative costs and benefits of TTCP.

The emotional state of the parents could be particularlyproblematic if TTCP becomes an innovative procedure thatmust be paid for out of pocket, as is the case for UCBB. Stressand fear could cause parents to consent even when they donot have the financial means to pursue the procedure. Thismay impose an unfair and painful burden on parents whoare faced with life-and-death decisions about cancer treat-ment. If TTCP were to become an innovative clinical servicefor which patients were asked to pay, it would be importantto have financial support available through cancer advo-cacy groups or other payment sources (Fertile Hope 2012;Patrizio and Caplan 2010). In light of parents’ emotionalstate and the short time frame during which treatment de-cisions must be made, extreme care would need to be takenif TTCP were offered outside of free clinical research.

The level of risk should also inform expansion. Proce-dures that pose more than minimal risks must be intro-duced cautiously. UCBB is distinct from TTCP in that it isa minimal-risk procedure with risks arising chiefly fromthe maternal blood draw (ViaCord n.d.). Future use of thetissue for transplantation or regenerative medicine wouldhave risks, but these are not extensively addressed in the

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initial consent (ViaCord n.d.). The low risks of banking maybe one of the reasons why UCBB has been widely expandeddespite the fact that children are unlikely to benefit from theprocedure.

TTCP is a higher risk procedure, which requires a testic-ular biopsy with attendant risks of bleeding, infection, andsoreness (Ginsberg 2011). Patients undergoing TTCP mustalso undergo general anesthesia for the harvesting proce-dure, though research protocols currently require testiculartissue to be excised at the same time as some other med-ically required procedure that involves general anesthesia(Ginsberg et al. 2010). Future therapeutic use of the tissuewould carry additional risks. Some of these risks, such asthe possibility that the tissue would be unsafe to transplantdue to the risk of transmitting malignancy, are mentionedduring the initial informed consent process, but these risksremain speculative.

Additional risks may arise if TTCP is expanded out-side of research settings. Parents could opt to delay theirchildren’s cancer treatment in order to seek TTCP at a hos-pital where it is available. In addition, parents may wanttheir children to undergo TTCP even if they are not sched-uled to undergo general anesthesia. The risks of the TTCPprocedure in aggregate make expansion of access beyondresearch protocols challenging. Outside of research proto-cols, more children could be exposed to risks and the risksmay not be monitored as thoroughly. Great care needs tobe taken to continue to mitigate risks in whichever settingTTCP is offered.

CONCLUSIONS

Technologies with theoretical future benefits, such as UCBB,have been widely disseminated despite recommendationsto the contrary from governing bodies in medicine. Withoutcareful regulation, the same could occur with TTCP. Lessonslearned from the expansion of UCBB may help guide theexpansion of TTCP in a more organized manner. Access toTTCP could be expanded either by increasing the numberof clinical trials or by offering it as an innovative procedure.

Comparison with UCBB yields several strong argu-ments that favor adopting the broadest form of access toTTCP. Prepubescent cancer patients who miss the oppor-tunity to bank their testicular tissue would be unable tobenefit from TTCP if the technology matures in the nexttwo decades. Fertility restoration from TTCP would offersignificant psychological benefits to patients who bankedand would allow them to exercise reproductive autonomy.In addition, the patients are likely to use their banked tis-sue if new therapies develop, since they are at high risk forinfertility.

However, restricting TTCP to patients within researchsettings might be the only effective way to prevent the typesof problems that arose with UCBB. Since TTCP is an un-proven technology with no current therapeutic use andsome risk, the additional protections imposed by the IRBin a research setting could benefit patients. For example,IRB oversight would help ensure that TTCP is not offered

to cancer patients who are at low risk of infertility, andthat children do not undergo additional courses of generalanesthesia. Cost is perhaps the most compelling reason torestrict TTCP to research settings. Offering TTCP as an ex-pensive innovative procedure, rather than as a free proce-dure within a research protocol, could place parents in anextremely vulnerable position. In addition, it is possible thatalternative technologies will develop that will help patientsrestore their fertility without requiring them to bank tissueat an early age. The potential for these new technologiesprovides an argument for limiting access to TTCP at thisstage.

The arguments that disfavor expansion outside of re-search settings are potent. However, TTCP may ultimatelybe expanded outside of research, despite the recommenda-tion of expert panels and professional organizations. UCBBcan shed light on the ways that this expansion could best beguided. When an investigational procedure such as TTCPor UCBB is offered outside of a research protocol, it is im-portant to inform parents about alternative therapies thatare in development. UCBB provides an interesting exam-ple of how tissue banked outside of research studies canbe used as raw material for research. The same could oc-cur for TTCP, meaning that offering TTCP outside researchprotocols may benefit researchers by providing them withmore tissue to research. UCBB also illustrates how largelyunregulated investigational technologies can be dissemi-nated to low-risk populations. IRB oversight and bindingagreements with governing bodies could help ensure thatTTCP, unlike UCBB, is targeted toward those patients whoare most likely to benefit from the procedure. Most impor-tantly, UCBB demonstrates that worried parents may feelobligated use medical technologies that could give theirchildren a chance at a better life, regardless of cost. If TTCPis offered outside of research protocols, it will be crucial toprovide financial support to poor families. �

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