Gonadotoxic consequences of therapy can be a daunting prospect for newly diagnosed males with cancer. Sperm banking has become the gold standard for fertility preservation in pubertal males. However, because of the physiologic limitations of the immature testis, prepubertal males do not currently have an option for fertility preservation at diagnosis. Testicular biopsy and tissue cryopreservation holds promise for this cohort of patients. Additional scientific advances are still needed to translate successes in animal research to human clinical practice.
Because this study requires a testicular biopsy at the time of cancer diagnosis, parental desire and acceptability of testicular tissue cryopreservation as well as the safety of this procedure were of primary importance. Researchers have interviewed 318 parents regarding their acceptance of such an idea (van den Berg et al., 2007
): they asked parents to think hypothetically about the following scenario, ‘If there was an experimental procedure available at diagnosis, would you allow your sons to undergo a testicular biopsy in an attempt to collect SSCs?’, and asked them to imagine themselves back at the time of diagnosis when answering this question. At diagnosis, SSC collection by means of testicular biopsy was theoretically approved by 61% of these parents (van den Berg et al., 2007
). These data indicate that the transfer of methods used in current animal experiments on SSC collection and transplantation into clinical care is highly desired by parents of prepubertal boys with cancer. The high acceptance rate of our current prospective pilot protocol (76% chose to go through with the biopsy) affirms and surpasses the hypothetical acceptance shown in this earlier research. Families are interested in this option and are willing to undergo the procedure in real clinical practice, even when there are no clinical guarantees.
Although our current sample size is small, our first year of experience with this pilot protocol is highly encouraging. Development of the proper infrastructure and an interdisciplinary team is at the cornerstone of the pilot's success. This experimental protocol requires collaboration between clinicians and research scientists. It was important to identify experts who had the knowledge and the physical resources to support the proposed research. Prior to any patient enrollments, great care was taken to cultivate our relationships with these experts and to procure the appropriate equipment and media for both the laboratory aims of the study as well as storage of the specimens for future clinical use. With each patient enrolled on the study, the team learned how to improve our processes for identification and recruitment of eligible subjects who were at high risk for infertility, how to communicate both within our team and with other health care providers involved with the patient's care, and how to coordinate the acquisition and distribution of the tissue for clinical use and research. Flexibility was crucial, but we found that with the appropriate infrastructure and a committed interdisciplinary team, this type of approach can be successful.
Several barriers were encountered that merit consideration. First, oncology providers do not automatically consider fertility preservation options as part of the standard workup of a newly diagnosed prepubertal male. To ensure that this opportunity is offered to all eligible prepubertal boys who meet the proposal's selection criteria, our intake team must be diligent in screening patient lists and new patient referrals to the Division. Once identified, the team must contact the patient's caregiver as early as possible, making them aware of the study and finding the appropriate time to approach the family for consent.
An additional potential barrier to the success of this research is that a family is being asked to make a critical decision during an already stressful time about an additional surgical procedure that is experimental in nature. The questionnaire data from our pilot demonstrate that, although the time at diagnosis is stressful, families want to be presented with options and are able to make thoughtful decisions about fertility preservation.
From a safety perspective, there have been no acute adverse effects of the testicular biopsy, and this procedure is well tolerated. Although the long-term impact of testicular biopsy on newly diagnosed males with cancer is not currently known, there are long-term data on cryptorchid boys who have had testicular biopsies performed during orchiopexies (Patel et al., 2005
). In this cohort, a total of 112 patients who had previously undergone orchiopexy and a testicular biopsy at a mean age of 8.6 years were asked to return for long-term follow-up. The mean age at follow-up was 18.6 years. All patients underwent an exam and bilateral scrotal ultrasound. On ultrasound, no patient had evidence of testicular atrophy or testicular damage related to testis biopsy. Moreover, a semen sample was collected and 57 of the 112 patients underwent measurement of antisperm antibodies. None of the 57 semen samples showed evidence of antisperm antibodies. There was no evidence of additive testicular damage in prepubertal boys who had testicular biopsies (Patel et al., 2005
). The technique for testicular biopsy is the same as that used in the current research.
Over the last several decades, reproductive scientists have continued to make remarkable strides in developing fertility preservation options and expanding the cadre of assisted reproduction technologies that are available for achieving successful live births. If the pace of reproductive advances to date is any indicator of future successes, there is reason to be hopeful that the laboratory techniques developed for utilizing cryopreserved testicular tissue to restore fertility can be translated for use in human subjects.