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JU INSIGHT Age, Sperm Retrieval, and Testicular Histology in Klinefelter Syndrome

By: Caroline Kang, MD, PhD, Weill Cornell Medicine, New York, New York, Atrium Health Carolinas Medical Center, Charlotte, North Carolina; Nahid Punjani, MD, MPH, Weill Cornell Medicine, New York, New York, Mayo Clinic, Phoenix, Arizona; James A. Kashanian, MD, Weill Cornell Medicine, New York, New York; Peter N. Schlegel, MD, Weill Cornell Medicine, New York, New York | Posted on: 19 Jan 2024

Kang C, Punjani N, Kashanian JA, Schlegel PN. Age, sperm retrieval, and testicular histology in Klinefelter syndrome. J Urol. 2024;211(1):163-169.

Study Need and Importance

Males with Klinefelter syndrome (KS) are typically infertile due to primary testicular failure and suffer from hypergonadotropic hypogonadism. Biologic paternity may be an option with surgical sperm retrieval using microdissection testicular sperm extraction which may identify small pockets of seminiferous tubules with mature sperm. The concern for progressive germ cell loss and initiation of exogenous testosterone therapy in KS males, both of which may put future sperm production at risk, has been used to recommend early sperm retrieval in adolescence. However, the optimal timing for surgical sperm retrieval in KS males has not been defined.

What We Found

We examined testis histology patterns and sperm retrieval rates in adolescent (<20 years) and adult (≥20 years) KS males who underwent microdissection testicular sperm extraction from 1995 to 2020 at our institution. Adult patients were further stratified into decades of age (20-29 years, 30-39 years, and ≥ 40 years). We found that the proportion of patients with germ cell–containing histology patterns in testis biopsy samples decreased with increasing age, and no males greater than 40 years had any foci of germ cell–containing histology. The sperm retrieval rate in adolescent KS males was 53% and was significantly higher in the 20 to 29–year cohort (71%) and lower in the ≥40-year cohort (13%; Figure). Multivariable analysis demonstrated hypospermatogenesis histology pattern on testis biopsy was associated with increased odds of successful sperm retrieval.

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Figure. Sperm retrieval rates in males with Klinefelter syndrome. Sperm retrieval rates (%) from microdissection testicular sperm extraction by age in deciles (adolescent [<20 years] and adults [20-29 years, 30-39 years, ≥ 40 years]) are shown. Chi-square statistics were used to determine differences in sperm retrieval rates between each group. Adult cohorts were compared to the adolescent group (referent group).

Limitations

Our study was limited by its retrospective nature, limited sample size of the oldest age cohort, and the fact that the vast majority of adolescent KS males were taking testosterone-related medications.

Interpretation for Patient Care

KS males in their twenties have the highest chance of sperm retrieval, not adolescent males. There is no clear benefit to attempted sperm retrieval in adolescent KS males unless exogenous testosterone supplementation is planned.

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