An unfortunate consequence of the treatments currently used to treat pediatric cancers is infertility. An important issue to consider is whether a child's fertility status later in life is likely to be impacted by his treatment. Ideally, this should occur prior to the initiation of therapy, when a window of opportunity may exist to preserve the patient's future reproductive potential. For pubertal males, there are options available, specifically, producing sperm by masturbation and freezing the sperm for use later in life. For boys who have not gone through puberty, preserving fertility is more challenging. Prepubertal boys cannot produce semen by masturbation and they do not have mature sperm in their testes. The prepubertal testicle does, however, contain a small amount of the stem cells (parent cells) that, with the right signals and under the appropriate conditions, will eventually become mature sperm. Promising research with relevant animal models has shown that testicular tissue can be removed, and the stem cells can be extracted. These cells can then be reimplanted as is, or matured and increased in number outside of the body before reimplantation. Animal research has demonstrated that these cells will then go on to produce mature sperm once reimplanted in the body. The success of this research has created an exciting potential for translation to human clinical practice, particularly for patients who are facing cancer therapy that will leave them infertile. In the ideal scenario, boys could freeze testicular tissue at diagnosis. Then, when they are ready to start a family, the tissue could be thawed, the stem cells removed, expanded in number and put back into the testes to become mature sperm, thus restoring the young man's fertility. These cells could also be matured outside of the body and then specialized techniques for fertilization of an egg could be used. At this time, clinical applications of this science in humans are purely experimental. There are several key issues which require further inquiry before this can be successfully translated to human clinical practice. This study will explore the following: 1) To assess feasibility and acceptable to patients and families to offer freezing of testicular tissue for newly diagnosed prepubertal boys at risk for infertility 2) To evaluate the safety of the surgical procedure required to perform a testicular biopsy on these patients and 3) To determine what is the best way to handle the germ cells that are in the testicular tissue in the laboratory so the maximum number of sperm creating cells can be obtained.

Public Health Relevance

This protocol will examine the feasibility of offering testicular cryopreservation to prepubertal boys who are at risk for infertility from cancer therapy (a cohort who currently have no options for fertility preservation) and will advance the translational laboratory science that is required for in vitro expansion of human spermatogonial stem cells. A multidisciplinary infrastructure for the acquisition and storage of testicular tissue will be utilized, ultimately providing a benchmark for future protocols for the cryopreservation of human testicular tissue as a standard option for fertility preservation in prepubertal males with cancer.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-EMNR-L (50))
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Lamar, Charisee A
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Children's Hospital of Philadelphia
United States
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Pietzak 3rd, Eugene J; Tasian, Gregory E; Tasian, Sarah K et al. (2015) Histology of Testicular Biopsies Obtained for Experimental Fertility Preservation Protocol in Boys with Cancer. J Urol 194:1420-4
Ginsberg, Jill P; Li, Yimei; Carlson, Claire A et al. (2014) Testicular tissue cryopreservation in prepubertal male children: an analysis of parental decision-making. Pediatr Blood Cancer 61:1673-8
Ginsberg, Jill P (2011) New advances in fertility preservation for pediatric cancer patients. Curr Opin Pediatr 23:9-13
Ginsberg, J P; Carlson, C A; Lin, K et al. (2010) An experimental protocol for fertility preservation in prepubertal boys recently diagnosed with cancer: a report of acceptability and safety. Hum Reprod 25:37-41
Wu, Xin; Schmidt, Jonathan A; Avarbock, Mary R et al. (2009) Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules. Proc Natl Acad Sci U S A 106:21672-7