The FSHB -211 G>T polymorphism as predictor for TESE success in patients with unexplained azoospermia.

Busch, Alexander Siegfried; Tüttelmann, Frank; Cremers, Jann-Frederik; Schubert, Maria; Nordhoff, Verena; Schüring, Andreas N; Zitzmann, Michael; Gromoll, Jörg; Kliesch, Sabine

Abstract

Context: Testicular sperm extraction (TESE) followed by assisted reproductive techniques often remains the only therapeutic option for men with azoospermia due to spermatogenic failure. Reproductive parameters, such as gonadotropin levels and testicular volume or histopathology, contribute to the prediction of sperm retrieval rate (SRR) in TESE. However, there is an eminent lack of noninvasive predictive factors for TESE outcome. Objective: To clarify the impact of three common genetic variants affecting FSH and its cognate receptor on testicular histopathology patterns and SRR in TESE. Design: We evaluated the association of the single-nucleotide polymorphisms (SNP) FSHB -211G>T (rs10835638), FSHR -29G>A (rs1394205), and FSHR c.2039A>G (rs6166) with testicular histopathology and SRR in patients with azoospermia. Setting: Tertiary referral center for andrology. Patients or other participants: Men (n = 1075) with azoospermia who underwent TESE (grouped by clinical pathologies). Intervention(s): All participants underwent TESE. Main outcome measure(s): Testicular histopathology, SRR, and reproductive hormone levels. Results: FSHB -211G>T was significantly associated with reduced chances of sperm retrieval in patients with unexplained azoospermia. Indicating an additional mechanism, the association of the SNP with SSR could not be solely attributed to decreased FSH levels. Conclusion: A common genetic factor was significantly associated with SRR in TESE. In perspective, a calculator or score including the noninvasive parameters FSH level, testicular volume, and FSHB haplotype should be considered to estimate the chances for sperm retrieval in men with azoospermia.