Age, Sperm Retrieval, and Testicular Histology in Klinefelter Syndrome

Abstract

Purpose:We sought to examine sperm retrieval and testicular histology in males of different ages with Klinefelter syndrome.Materials and Methods:We identified all males with Klinefelter syndrome who underwent microdissection testicular sperm extraction at our institution from 1995 to 2020. Patients were divided into adolescent (<20 years) and adult (≥20 years) cohorts. Histology and sperm retrieval were compared using chi-square statistics. Multivariable logistic regression models were used to examine factors associated with successful sperm retrieval.Results:We identified 217 males with Klinefelter syndrome, of whom 59 were adolescents and 158 were adults. Adults were stratified into 10-year groupings (20-29 years, n = 62; 30-39 years, n = 88; ≥40 years, n = 8). Approximately 17% of adolescents had testis histology containing germ cells compared with 15% of the 20 to 29–year cohort, 14% of the 30 to 39–year cohort, and 0% over 40 years. In comparison to adolescents (53%), the sperm retrieval rate was significantly higher in the 20 to 29–year cohort (71%, P = .04) and lower in the ≥40-year cohort (13%, P = .03). In multivariable analysis, the presence of hypospermatogenesis on testis biopsy (OR 5.8, P = .03) was associated with higher odds of successful sperm retrieval.Conclusions:Younger males more frequently had germ cell–containing testis histology, however this finding was not associated with a higher odds of sperm retrieval. Reproductive urologists should counsel azoospermic males with Klinefelter syndrome that sperm retrieval during adolescence for fertility preservation is not required and can be performed in young adulthood.

Letter: Age, Sperm Retrieval, and Testicular Histology in Klinefelter Syndrome

“…The authors aimed to confirm that higher serum T and higher serum dihydrotestosterone (DHT) levels at baseline would not increase the incidence of asymptomatic LUTS or exacerbate LUTS progression in symptomatic patients participating in the REDUCE study. 1 The final result of the study was consistent with the hypothesis that higher T and DHT are not associated to LUTS. We intend to discuss potential reasons to help readers understand the relationship.…”

“…To the Editor: We are writing in response to the recent article by Kang et al, addressing the controversial topic of fertility preservation in adolescents and young adult men with Klinefelter syndrome (KS). 1 Some have advocated for early testicular sperm extraction due to a concern for progressive testicular hyalinization and the transition to testis atrophy with uniform Sertoli-cell-only syndrome histology.…”

“…SRRs were significantly highest for adults in the age range of 20 to 29 years old (71%) compared to adolescents (53%) and adult patients of increasing age range (45% and 13% for 30-39 and 40, respectively). 1 While the findings shed light on the age-related differences in SRR, it's crucial to scrutinize the factors influencing these outcomes. Notably, the majority of adolescents with KS in the study were undergoing testosterone replacement therapy (TRT), a factor known to potentially impair spermatogenesis.…”

“…Our meta-analysis echoes similar trends, indicating that peripubertal/adolescent patients exhibit a higher rate of spermatozoa-negative and spermatogonia-positive status on histology compared to adult KS patients. 2,3 However, the existing literature, including Kang et al's work, 1 is clouded by the confounding influence of concomitant TRT in adolescent patients.…”

Editorial Comment

“…1 Kang et al echo these findings, with the highest SRR (71%) in those 20 to 29 years and the lowest in those ≥40 years (13%). 2 SRR in adolescents (53%) was similar to those 30to 39 years old (45%). It appears safe to wait until the patient can provide informed consent as an adult, though a decline in SRR is eventually noted.…”