title: Establishing reference values for age-related spermatogonial quantity in prepubertal human testes: a systematic review and meta-analysis.
abstract: OBJECTIVE
  To collect published data on spermatogonial quantity in the testes of healthy children and calculate the reference values of spermatogonial quantities throughout prepuberty.
  
  
  METHODS
  Systematic literature search in PubMed and EMBASE focusing on the number of spermatogonia per transverse tubular cross section (S/T) and spermatogonial density per cubic centimeter (cm3) of testicular volume (S/V) throughout prepuberty.
  
  
  METHODS
  None.
  
  
  METHODS
  None.
  
  
  METHODS
  None.
  
  
  METHODS
  Polynomial meta-regression analyses of S/T and S/V of healthy boys from the ages of 0 to 14 years.
  
  
  RESULTS
  We found six papers describing original quantitative data on S/T and S/V of healthy boys (total n = 334 and 62, respectively) that were suitable for meta-analysis. Polynomial meta-regression analyses of S/T and S/V demonstrated a clear pattern of spermatogonial quantity throughout prepubertal life. This consisted of a decline during the first 3 years of life, a gradual increase until the ages of 6 to 7 years, a plateau until the age of 11 years, and a sharp incline reaching pubertal numbers at 13 to 14 years of age. The association between S/T and S/V allowed us to perform S/T to S/V extrapolation, creating reference S/V (rS/V) values throughout prepubertal life from a cohort of 372 boys.
  
  
  CONCLUSIONS
  Spermatogonial quantity varies during testicular development toward puberty. The values found in this study may serve as a baseline clinical reference to study the impact of diseases and adverse effects of gonadotoxic treatments on spermatogonial quantity in prepubertal testes. Spermatogonial quantity reference values may also help to evaluate the quality of testicular biopsy samples acquired for fertility preservation of prepubertal boys.
authors.affiliation: Center for Reproductive Medicine, Women's and Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Ieva
authors.initials: I
authors.lastname: Masliukaite
authors.affiliation: Center for Reproductive Medicine, Women's and Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Hagen
authors.affiliation: Department of Women's and Children's Health, Paediatric Endocrinology Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden; Division of Haematology-Oncology and Stem Cell Transplantation, Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Jahnukainen
authors.affiliation: Department of Women's and Children's Health, Paediatric Endocrinology Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: Jan-Bernd
authors.initials: JB
authors.lastname: Stukenborg
authors.affiliation: Center for Reproductive Medicine, Women's and Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Repping
authors.affiliation: Center for Reproductive Medicine, Women's and Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Fulco
authors.initials: F
authors.lastname: van der Veen
authors.affiliation: Center for Reproductive Medicine, Women's and Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Madelon
authors.initials: M
authors.lastname: van Wely
authors.affiliation: Center for Reproductive Medicine, Women's and Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: a.m.vanpelt@amc.uva.nl.
authors.forename: Ans M M
authors.initials: AM
authors.lastname: van Pelt
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011627:Puberty; D012016:Reference Values; D012044:Regression Analysis; D013076:Sperm Count / Q000592:standards*; D013093:Spermatogonia / Q000166:cytology*; D013737:Testis / Q000166:cytology*
keywords: Healthy boys; prepuberty; spermatogonial density; spermatogonial quantity; testicular development