Failure of a combined clinical- and hormonal-based strategy to detect early spermatogenesis and retrieve spermatogonial stem cells in 47,XXY boys by single testicular biopsy.

Background: Although germ cells in boys with Klinefelter syndrome (KS) are reduced in number as early as infancy, a severe germ cell loss occurs during mid-puberty. Therefore, we wanted to detect spermatogenesis at an early stage and investigate the strategy of preserving spermatozoa and/or testicular spermatogonial stem cells in adolescents with KS when signs of deteriorating spermatogenesis are observed.

Methods: Tanner staging, testicular size, serum inhibin B and spermaturia were assessed every 4 months before the attempt to procure gametogenic cells in seven non-mosaic 47,XXY adolescents, aged between 10 and 16 years.

Results: Despite an increasing testis volume in the youngest and a Tanner staging of more than three in the oldest patients, no spermaturia was observed. In two patients serum inhibin B increased gradually, while in all others a rather rapid but variable decline was observed at different ages. No spermatozoa were observed after electroejaculation. No spermatocytes or spermatids were found at microscopic examination of single biopsies, while spermatogonia were identified in four subjects, three of whom had measurable serum inhibin B. Massive fibrosis and hyalinization were observed in all biopsies.

Conclusion: No spermatogenesis was documented in non-mosaic 47,XXY adolescents either by spermaturia, electroejaculation or testicular biopsy. Neither clinical nor hormonal parameters were of value in determining the timing for optimal spermatogonial stem cell retrieval. More data are needed to elucidate the potential role of testicular tissue cryopreservation in adolescents with KS. Therefore, at present, the cryopreservation of testes tissue for clinical reasons should not be recommended.