Spermatogenesis in the contralateral testis of patients with testicular germ cell cancer: histological evaluation of testicular biopsies and a comparison with healthy males

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Abstract
To assess histologically signs of testicular dysgenesis (TD) in the contralateral testes of patients with testicular germ cell tumours (GCTs) and to compare these findings with the spermatogenetic quality in healthy men, as the contralateral testis is considered to be involved with dysgenetic features such as poor sperm production, and accordingly, GCTs are hypothesized to be part of the 'TD syndrome' (TDS). One testicular biopsy is thought to represent spermatogenesis in the entire testis. We evaluated this view by using testicular two-site biopsies. 2318 patients with testicular GCT had a contralateral testicular two-site biopsy. Testicular biopsies taken on forensic autopsy from 1388 presumably healthy men served as controls. Spermatogenesis was rated histologically according to a modified Johnsen score. Clinical factors were recorded to explore associations with reduced spermatogenesis. Differences in spermatogenesis scoring results among two-site biopsies were noted. Statistical analysis involved Wilcoxon-Mann-Whitney and Jonckheere-Terpstra tests for comparing patients and controls, and for studying associations with clinical factors. Classification and regression-tree analysis was used to explore multivariate associations. Histologically, patients had significantly poorer spermatogenesis than healthy men. Clinically, hypospermatogenesis was significantly associated with testicular atrophy, undescended testes, male infertility, and advanced clinical stage; 5.4% of cases (95% confidence interval 4.43-6.27) had discordant findings of >2 points on double biopsy and 9.8% had differences of 1 point. Discordance was significantly associated with poor spermatogenesis and testicular atrophy. We confirmed histologically that there is markedly reduced spermatogenesis in the contralateral testes of patients with GCT. This result lends credence to the view that GCT is part of the so-called TDS. But as hypospermatogenesis is associated with advanced clinical stage, impairment of sperm production might at least partly be acquired secondary to the endocrine activity of GCT. There were clinically relevant discordant results on double biopsy in 5.4%, predominantly in infertile patients and in atrophic testes. Thus the histological evaluation of male infertility is best done by multiple biopsies.