Fertility versus infertility

In Klinefelter syndrome (KS) the topic of fertility vs. infertility is of major concern since that, until recent years, infertility was considered an untreatable condition in KS. Due to chromosome aneuploidy, KS children undergo a progressive testicular impairment leading to spermatogenic failure and infertility (Foresta et al., J Clin Endocrinol Metab 84:3807–3810, 1999). In prepubertal boys with KS a diminished number or complete absence of spermatogonia has been described despite a normal appearance of Sertoli and Leydig cells (Muller et al., Int J Androl 18:57–62, 1995). However, immunohistochemical studies demonstrated that, in early adolescence, the majority of boys with KS have germ cells in their testes despite a marked reduction in adult dark spermatogonia (Muller et al., Int J Androl 18:57–62, 1995; Wikstrom et al. J Clin Endocrinol Metab 89:2263–2270, 2004). Subsequently the onset of puberty is associated with accelerated and progressive depletion of testicular germ cells, which may precede elevation in serum gonadotropin levels (Mehta and Paduch, Fertil Steril 98:274–283, 2012). For these reasons fertility in KS is a major challenge: it is essential to locate the optimal timing to search spermatozoa in KS and the most appropriate technique and modality to give KS subjects the best chance to reach fertility.