Sperm retrieval in adolescent males with Klinefelter syndrome: medical and ethical issues.

Transl Pediatr 2016;5(2):104-106 tp.amegroups.com Many men with conditions linked to azoospermia were formerly considered infertile. However, over the last two decades advances in assisted reproductive technology (ART) have been devised and have permitted these men to become biological fathers. Foremost among these have been testicular sperm extraction (TESE) and a “microdissection” advance in which individual spermatic tubules are punctured and sperm extracted (microTESE). In the former multiple biopsies of the subject’s testes are taken and sperm retrieved as available (1). The micro technique originally noted by Schlegel and colleagues considers individual tubules for micropuncture using optical magnification (2,3). Sperm retrieval rates (SRR) are somewhat higher when performing the latter technique on men with non-obstructive azoospermia or men with Klinefelter syndrome (KS) or one of its variants (2,4,5). Previous investigators have reported that younger age was a factor for successful SRR [this report and (4)], although other investigators [see (6), for review] did not find age to be a significant factor for success of sperm retrieval in men with KS, ascertained through infertility clinics. In theory, the residual spermatogenesis that often exists in KS patients after puberty may potentially deteriorate further with age as a continuation of the process of hyalinization of seminiferous tubules that occurs during pubertal maturation. At that age most tubules degenerate totally and become ‘ghost tubules’ without Sertoli and germ cells. These reports were updated during a recent Workshop on Klinefelter Syndrome (Muenster, Germany, March 10–12, 2016). The conclusions of a Roundtable discussion chaired by Professor Eberhard Nieschlag at the end of the conference included: • TESE-ICSI provides similar results concerning SRR, pregnancy rate, miscarriage rate and children’s health. In men with KS as in men with nonobstructive azoospermia with normal karyotype; • The experience of the surgeon and the biologist is important for the success of TESE. MicroTESE performed by trained surgeons’ results on average in higher SRR than open biopsy; • The age range giving rise to higher chances of sperm retrieval is 15–35 years. Caution should prevail because at the younger age the adolescent boys may not be mature enough or not psychologically prepared to address the fertility issue. Conversely, some important issues remain to be investigated properly: • Whether previous testosterone treatment, even when withdrawn for at least 6 months at the time of TESE or microTESE is or is not deleterious for the SRR. This could be investigated, first retrospectively, by noting the modality of the previous testosterone treatment (type, dose and duration), and prospectively by randomizing young patients to different treatment modalities (usual treatment, lower dose treatment leaving the gonadotropin levels within the normal range, or no treatment). Such a study will resolve the question whether it is necessary to perform TESE before initiating testosterone therapy or is it safe to wait until paternity is wished? • Whether a treatment designed to increase intratesticular testosterone secretion (hCG, clomiphene, Commentary