Use of Hormonal Profiles to Predict Surgical and Medical Treatment Outcomes

Traditionally, elevated FSH has been considered a poor prognostic indictor for successful surgical sperm extraction. Perhaps this was due to the use of now defunct blind testicular sperm extraction techniques to obtain sperm from men with ASD, which did not account for the heterogeneous foci of spermatogenesis in the testes of such men. However, Tournaye et al., in 1997, published a series of random incisional testicular extraction procedures—stopping only once sperm was obtained—and demonstrated that FSH was not highly predictive of successful sperm retrieval.⁴⁵ Subsequently, Ramasamy et al. published a large single-institution series from Cornell of microsurgical testicular sperm extraction procedures and also found that FSH was a poor predictor of successful surgical sperm retrieval. Of 792 men in their series, three successful sperm retrievals were performed in men with FSH levels greater than 90 IU/mL. Interestingly, they found the subset of men with an FSH less than 15 IU/mL to have comparatively lower successful sperm retrieval rates. The authors hypothesized that the subset of men with diffuse maturation arrest may present with normal gonadotropins and normal size testes, making this small subpopulation of men with ASD quite difficult to accurately stratify preoperatively.⁴⁶ An expanded cohort from Cornell was subsequently used to formulate a neural computational model to predict surgical sperm retrieval rates from microsurgical testicular sperm extraction. Again, FSH was not a significant predictor of surgical outcome.⁴⁷

Gonadotropin assays may also be a useful guide to predict surgical outcomes among men with clinically significant varicoceles. Traditionally, patient counseling regarding fertility outcomes after varicocelectomy has focused only on varicocele grade and baseline seminal parameters. Kondo et al. performed a retrospective analysis of 97 men with oligozoospermia and a mixture of left and bilateral clinical varicoceles. On multivariate analysis, the authors found that a lower FSH was significantly associated with a positive response to varicocelectomy (odds ratio 0.881, 95% CI 0.779—0.997, P = 0.04).⁴⁸ Similarly, Yoshida et al., in a retrospective analysis of 168 infertile men with left-sided only varicoceles, demonstrated that an FSH cut-off of less than 11.7 mIU/mL was associated with improved postsurgical outcomes.⁴⁹ Although still controversial, varicocelectomy in the setting of ASD is more likely to subsequently produce sperm in the ejaculate—thereby avoiding testicular sperm extraction—if the preoperative FSH is less than 10.1 mIU/mL.⁵⁰ Thus, significantly elevated FSH values reflect severely impaired germinal epithelium, unlikely to recover after varicocelectomy surgery.