Predictive factors shaping fertility potential and reproductive outcomes in men with Klinefelter syndrome

Klinefelter syndrome (KS), marked by testicular heterogeneity, provides a rationale for testicular sperm extraction in azoospermic men, yet large-scale evaluations of predictive and reproductive outcomes remain limited. This retrospective study included 79 karyotype-confirmed KS patients who underwent conventional testicular sperm extraction (cTESE) and microdissection testicular sperm extraction (micro-TESE) between February 2001 and August 2024. Clinical, hormonal, histological, embryological, and reproductive data were analyzed, with successful sperm retrieval (SR) defined as the presence of at least one spermatozoon. SR was achieved in 40.5% of patients and was significantly associated with larger testicular volumes (left: P = 0.018; right: P = 0.028), lower follicle-stimulating hormone (mean ± standard deviation [s.d.]: 29.06 ± 14.49 IU l-1vs 38.22 ± 16.97 IU l-1; P = 0.016), and lower luteinizing hormone levels (mean ± s.d.: 16.41 ± 7.46 IU l-1vs 20.65 ± 9.59 IU l-1; P = 0.047). These parameters also correlated with the number of frozen sperm vials. Among those with SR, 46 embryo transfer cycles were conducted, involving 79 embryos. Fertilization, cleavage, and blastulation rates were 50.3%, 80.7%, and 40.2%, respectively. Good-quality embryos were observed in 45.1% on day 3 and 55.0% on day 5, with clinical pregnancy and live birth rates of 39.1% and 39.5% per transfer. These findings indicate that favorable hormonal profiles and testicular characteristics are predictive of SR success and that reproductive outcomes among KS patients with sperm retrieval are comparable to those in non-KS populations. Overall, the results support the continued use of testicular sperm extraction as a viable path to genetic parenthood in this population.