Does age affect sperm retrieval in patients with Klinefelter Syndrome?

In this video, Leila Momtazi-Mar, of Cleveland Clinic Lerner College of Medicine in Cleveland Ohio, discusses a systematic review and meta-analysis examining sperm retrieval outcomes in patients with non-mosaic Klinefelter syndrome (KS) who underwent either conventional testicular sperm extraction (cTESE) or microdissection testicular sperm extraction (mTESE).¹ The review encompassed 48 studies and 2815 participants, with a median sperm retrieval rate (SRR) of 44% across all procedures. Patients with successful sperm retrieval were, on average, 2.8 years younger than those with negative retrieval outcomes.

A key objective was to determine whether age at the time of sperm retrieval—adolescence vs adulthood—affects success rates. Adolescence was defined as an average age under 20 years, and adulthood as 25 years or older. The analysis found no significant difference between the 2 groups: adolescents had an average SRR of 45%, whereas adults had 42%. Furthermore, meta-regression analysis adjusting for testosterone levels, gonadotropins, and testicular volume showed that age did not significantly influence SRR.

The study also reviewed live birth outcomes, with 22 studies reporting data. The median live birth rate was 11.1%, underscoring the cumulative attrition throughout the assisted reproductive process. Momtazi-Mar emphasized that this information is vital for counseling patients and families about realistic expectations.

Regarding the timing of sperm retrieval, the findings suggest it is reasonable and safe to delay the procedure until adulthood. This approach allows patients to make reproductive decisions when they are better informed and ready to pursue parenthood. Delaying also avoids costs and potential quality loss from cryopreserving sperm retrieved during adolescence. However, Momtazi-Mar noted preliminary evidence suggesting lower retrieval rates after age 40, indicating that early to mid-adulthood may be the optimal window for sperm retrieval in men with Klinefelter syndrome.

REFERENCE

1. Momtazi-Mar L, Naelitz BD, Mucci A, Cannarella R, Lundy SD. Surgical sperm retrieval in patients with nonmosaic Klinefelter syndrome (47,XXY) may be safely delayed until adulthood: a systematic review and meta-analysis. Fertil Steril. 2025 Jul 19:S0015-0282(25)00594-1. doi:10.1016/j.fertnstert.2025.07.021