title: Histology of Testicular Biopsies Obtained for Experimental Fertility Preservation Protocol in Boys with Cancer.
abstract: OBJECTIVE
  Cryopreservation of testicular tissue with subsequent reimplantation after therapy has the potential to preserve fertility for prepubertal boys with cancer. We present the histology and feasibility of testicular tissue procurement for this novel approach.
  
  
  METHODS
  We performed a prospective cohort study of boys at significant risk for treatment associated gonadotoxicity who were eligible for an experimental research protocol between 2008 and 2011. Open testicular biopsy was performed while the patients were anesthetized for another treatment related procedure. Half of the specimen was reserved for cryopreservation, while the other half was used for research purposes. Semithin sections of the biopsy specimens were evaluated for histological features and compared to age adjusted reference values.
  
  
  RESULTS
  A total of 34 boys underwent biopsy between March 2008 and October 2011. Of the patients 29 had solid tumors and 5 underwent hematopoietic stem cell transplantation for benign disease. A total of 27 patients had adequate tissue for histological analysis. Median patient age was 8.7 years (IQR 2.2 to 11.5). All children had either normal (81.5% of patients) or increased (18.5%) numbers of germ cells per tubule for their age. However, 5 of 26 patients (19%) older than 6 months had no evidence of adult dark spermatogonia and 9 of 16 (56%) older than 6 years had no evidence of primary spermatocytes on biopsy, which would be expected based on age norms. These findings are suggestive of abnormal germ cell maturation.
  
  
  CONCLUSIONS
  The preliminary histological findings of abnormal spermatogenesis maturation in the testes of prepubertal boys with cancer warrants further investigation.
authors.affiliation: Division of Urology, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: eugene.pietzak@uphs.upenn.edu.
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Pietzak
authors.affiliation: Division of Urology, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Division of Urology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Center for Pediatric Clinical Effectiveness, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Tasian
authors.affiliation: Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Tasian
authors.affiliation: University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania.
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Brinster
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Cancer Survivorship Program, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Claire
authors.initials: C
authors.lastname: Carlson
authors.affiliation: Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Cancer Survivorship Program, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Ginsberg
authors.affiliation: Division of Urology, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Division of Urology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Kolon
mesh_terms: D000293:Adolescent; D001706:Biopsy; D017690:Cell Transplantation / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D015925:Cryopreservation; D005298:Fertility; D059247:Fertility Preservation / Q000379:methods*; D005500:Follow-Up Studies; D006801:Humans; D007248:Infertility, Male / Q000175:diagnosis / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D011446:Prospective Studies; D013076:Sperm Count; D013091:Spermatogenesis; D013737:Testis / Q000473:pathology*; D013997:Time Factors
keywords: biopsy; child; fertility preservation; spermatogenesis; testis