Males with Klinefelter syndrome (KS) have impaired gonadal function due to sex chromosome aneuploidy (47,XXY), ultimately resulting in testicular atrophy and hypergonadotropic azoospermia, thus infertility. At what time serum testosterone (T) concentrations decline in affected individuals, thereby indicating lifelong replacement, is not predictable. An early testosterone treatment provides potential benefits with respect to body composition, neuro-muscular function and final height. However, exogenous sex steroids have suppressive effects on the patient´s central hypothalamo-pituitary-gonadal (HPG) axis, thereby opposing a possible wish for future paternity.
KS males may have some euploid spermatogonial stem cells in their testicles. With onset of puberty, these cells enter meiosis, resulting in focal spermatogenesis. The elongated spermatozoa may be harvested (either from semen of via microsurgical sperm extraction procedures (mTESE)) and cryopreserved for future use in assisted reproduction, specifically intracytoplasmic sperm injection (ICSI).
We investigated HPG axis hormones in 281 KS males aged 1025 years and 233 age-matched controls and analyzed semen in late pubertal subjects. In addition, the success of surgical sperm retrieval was determined in 50 late pubertal und 85 adult azoospermic KS patients.
Serum T concentrations of ≥10 nmol/L were achieved spontaneously in 62% of adolescent KS males and in 85% of controls (TKFS: 12.2 ± 5.4 vs. TC: 16.6 ± 7.2 nmol/L). LHKFS concentrations were above the reference range, i.e. >10 U/L in 84% of young KS males (LHKFS: 18.6 ± 12.2 vs. LHC: 3.5 ± 1.6 U/L). In 9/130 (7%) KS adolescents, few spermatozoa were found in semen, in contrast to normal adult sperm concentrations in 73% (46/63) of controls. The chances for successful surgical sperm retrieval decreased with age, with adolescents aged 15-25 having the highest chances (54%), if LH was ≤17.5 U/L and T ≥7.5 nmol/L.
There is a window of opportunity for harvesting and cryopreserving sperm in males with KS during late spontaneous puberty and young adulthood, potentially enabling future paternity. Testosterone replacement should rather not be started before exploration of the KS individual´s reproductive potential.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology