What factors influence sperm retrieval success in patients with Klinefelter syndrome?

In this interview, Leila Momtazi-Mar, of Cleveland Clinic Lerner College of Medicine in Cleveland, Ohio, discusses emerging evidence on factors that may influence sperm retrieval success, emphasizing both the potential clinical implications and the current limitations of available data.

She notes that although some studies suggest a decline in retrieval rates after age 40, this association remains preliminary. Because the evidence is neither robust nor consistent enough to guide clinical decision-making, she cautions against using age 40 as a strict cut-off. Instead, she suggests treating it as a general indicator that earlier pursuit of reproductive goals may be beneficial, while stressing that pursuing retrieval after 40 is still reasonable and supported by existing outcomes. She highlights the need for more targeted research involving patients over 40 to better understand whether age meaningfully affects success rates.

Momtazi-Mar also addresses the potential predictive value of baseline hormonal levels and testicular volume. Although clinicians often hope to use laboratory parameters—such as testosterone, gonadotropins, or testicular measurements—to forecast retrieval outcomes, the available data are limited because these values are inconsistently reported across studies. Among the cases where data were available, patients with successful retrieval tended to show slightly higher testosterone, slightly lower LH, and marginally larger testicular volume. However, these differences were small and unlikely to be clinically meaningful. Further, no differences were observed in FSH, estradiol, estrogen, or prolactin. Complicating interpretation, many studies did not reliably report prior or ongoing use of exogenous testosterone, which can significantly alter hormone levels and retrieval outcomes. Meta-regression also showed no predictive value for testosterone, FSH, LH, or testicular volume, reinforcing that these metrics should be viewed as contextual rather than determinants of management.

Finally, she reports that sperm retrieval rates were comparable between conventional TESE and microdissection TESE. Neither technique appeared superior, and the relationship between age and retrieval success was independent of surgical method. As a result, she concludes that procedural choice should be guided by surgeon expertise and resource availability rather than expectations of different success rates.