Serum total testosterone and testicular histology help predicting positive sperm retrieval in nonmosaic Klinefelter patients undergoing testicular sperm extraction: real-life data from a large multicenter cohort.

OBJECTIVE

To study real-life rates and predictors of sperm retrieval (SR) in men with nonmosaic Klinefelter syndrome (KS) seeking medical help for primary male factor couples' infertility.

DESIGN

Multicenter, retrospective, cohort study.

SUBJECTS: Data analysis from 383 non-Finnish, White-European, nonmosaic KS men with nonobstructive azoospermia (NOA) undergoing testicular sperm extraction (TESE) between 2008 and 2024 at 12 tertiary referral centers in Italy.

EXPOSURE: All patients received a comprehensive diagnostic work-up, including hormonal/genetic tests and testicular ultrasound. Semen analysis followed 2021 World Health Organization criteria. Testicular histology was recorded. Either conventional testicular sperm extraction (cTESE) or microsurgical TESE (mTESE) was used, depending on surgeon's preference. Descriptive statistics and logistic regression assessed predictors of positive SR (+SR).

MAIN OUTCOME MEASURES: Positive sperm retrieval rate in nonmosaic KS men undergoing cTESE or mTESE for NOA, and the identification of clinical and histological predictors associated with +SR.

RESULTS

Median (inter quartile range) age was 31 years (25-36) and testicular volume was 3.8 mL (3-5) mL. Baseline follicle-stimulating hormone and total testosterone (tT) levels were 31.2 mUI/mL (21.5-41.8) and 3.6 ng/mL (2.7-5.1), respectively. Of 383, 50 (13.1%) patients have been on continuous testosterone therapy before surgery, which has been interrupted at least 6 months before c/mTESE. Of all, 246 (64.2%) men underwent cTESE and a bilateral c/mTESE procedure was performed in 345 (90.1%) men. Histologic reports showed Sertoli cell-only syndrome, maturation arrest, and hypospermatogenesis (HS) in 350 (91.4%), 20 (5.2%), and 13 (3.4%) patients, respectively. Overall, +SR was found in 114 (29.8%) men. Patients with +SR had higher tT values (3.8 vs. 3.6 ng/mL) than those with -SR. Sertoli cell-only syndrome histology was more frequently associated with -SR compared with both maturation arrest and HS. Multivariable logistic regression analysis confirmed that higher baseline tT values (odds ratio 1.1, 95% confidence interval: 1.02, 3.45) and HS histology (8.8, 95% confidence interval: 2.96, 15.76) were independently associated with +SR.

CONCLUSIONS

One third of men with nonmosaic KS had +SR at c/mTESE. Higher preoperative tT and testicular histology emerged as independently associated with SR outcomes. These findings can be clinically useful for tailored counseling before c/mTESE in nonmosaic KS men with NOA.