Lecture* at the 13th. Eurasian Andrology Summit & 19th European Society of Sexual Medicine Joint Meeting, 2-4 February, 2017 - Nice
Fabrizio I. Scroppo1, Elisabetta M. COLPI2, Giovanni M. Colpi3,
1Urology Unit, Ospedale di Circolo e Fondazione Macchi, ASST Settelaghi, Varese (Italy);
2GyneCentro Ticino, Lugano (Switzerland);
3ProCrea Institute, Lugano (Switzerland) and Andrology & IVF Unit, Clinica San Carlo, PadernoDugnano / Milano (Italy)
*Text published in the Proceedings
INTRODUCTION
Non-Obstructive Azoospermia (NOA) is an unfavorable prognostic condition for male infertility, since spermatogenesis is disrupted and NOA men have no treatment options other than attempting testicular sperm retrieval coupled with intracytoplasmic sperm injection. The technique of testicular sperm extraction (TESE) via an open testicular biopsy was first described for Obstructive Azoospermia (OA) by Schoysman et al. as well as by Craft et al. (1,2), and subsequently by Silber et al. and Devroey et al. for NOA (3,4). The theoretical basis for the extraction of testicular tissue was founded on the early quantitative histological studies from testicle biopsies, showing occasional mature spermatids in the testicular histology of NOA men (5,6). This was subsequently confirmed by Silber et al., who showed how men with germinal failure have a mean of 0-6 mature spermatids per seminiferous tubule in contrast to 17-35 mature spermatids per tubule in men with normal spermatogenesis and OA (7).
conventional TESE
Conventional TESE (cTESE) is a common procedure, and the technique of choice in many infertility Clinics due to its simplicity and low cost. For cTESE, a standard open surgical biopsy technique is used to remove the testicular parenchyma without the aid of optical magnification. A 1-cm incision is made into the albuginea, and a fragment of approximately 5×5 mm is excised with sharp scissors and placed in sperm culture media (8,9). Others perform multiple smaller biopsies, and still others have reported excising a majority of the volume of the testis in an effort to sample enough tissue to extract spermatozoa (7). The initially reported sperm retrieval rate (SRR) following a first cTESE attempt in a well-defined NOA population was around 50% (10), while SRRs reported later in the literature were inconsistent ranging 30-60% of NOA men (11,12,13). The selection of patients may explain these inconsistencies: e.g., inclusion of patients without a proper histopathologic diagnosis could lead to inclusion of misdiagnosed OA subjects. Recently Vloeberghs et al. reported a 40.5% successful sperm retrieval (SSR) in a large series of 714 NOA men at their first cTESE (14). The most appropriate number of biopsies to be taken remains controversial: single testicular biopsy has been advocated as the best technique based on the finding that spermatogenesis in NOA is multifocal (7); otherwise some studies found a patchy distribution of regions with minimal spermatogenesis throughout the testis, thus suggesting taking multiple samples in an effort to increase the chances of finding islands of spermatogenesis in sampled tissue (15, 16, 17). Moreover in NOA patients the sperm retrieval is quite an unpredictable factor, given that FSH, testicular volume and other clinical characteristics have low sensibility and specificity when their predictive ability is individually evaluated, and there is general agreement that testicular histopathology is the best predictor of SSR in NOA patients, with best SSR obtained in hypospermatogenesis, while the worse results occur in Sertoli Cell Only Syndrome (SCOS) (10, 18).
MicroTESE
In 1999 Schlegel et al. reported a new technique of microdissection of testicular tubules (MicroTESE), in order to identify sperm-containing regions before their removal in NOA men, taking the advantage of an open excision technique without the need to remove large quantities of testicular tissue. The Authors used an operating microscope to identify regions containing spermatozoa in the testes of NOA men, and performed multiple biopsies while avoiding the subtunical blood vessels. In Schlegel's hands, this technique of microdissection resulted in an improvement of SRRs from 45 to 63%. Initially, the testes are observed under 6–8x magnification to allow optimal visualization of the blood vessels, and a single wide incision in an avascular region of the tunica albuginea is made to expose underlying testicular parenchyma. Next, under higher magnification (15–25x), the surgeon identifies potential sperm containing tubules and dissects them. Tubules with spermatozoa are presumed to be larger, thicker, and more opaque. Once testicular tissue samples are given to the biologist in 300-500 microliters of sperm transport media. The process begins in the operating room where tubules are initially mechanically disrupted and continues in the laboratory for an extensive search to yield sperm by tissue digestion and centrifugation of the sampled tissue (19,20). Main advantages of the microdissection are higher SRRs, less tissue removal and visualization end preservation of the subtunical vessels. On the other hand MicroTESE requires special surgical skills along with the need of magnification equipment, and it’s a time consuming procedure, thus making it more expensive and less accessible to all Centres (21). As well as for cTESE, testicular histology is currently the only known predictor of successful sperm retrieval, but since also in SCOS there is a good SRR, ranging from 22.5% to 42.8%, its utility is doubtful (22). In our recent experience, on 107 NOA patients with an overall SSR of 57% by MicroTESE, the SRR ranged from 100% in hypospermatogenesis to 31.4% in complete SCOS. Interestingly the SRRs were 92.6% and 42.4% respectively, when ‘dilated’ or ‘apparently dilated’ tubules were microscopically observed by the surgeon.
conventional TESE vs. MicroTESE
To date, no randomized controlled trial has compared the efficiency of cTESE and MicroTESE, and thus current recommendations are based on cumulative evidence provided by descriptive, observational and controlled studies. Donoso et al. reviewed seven controlled studies comparing cTESE and MicroTESE: by the mean of a subgroup analysis related to histopathological findings, he concluded that MicroTESE performed better than cTESE in SCOS, with a lower incidence of hemorrhagic complications (23). In a randomized controlled study, Colpi et al. reported a significant better SRR when the FSH serum concentration was > 3 fold the maximum value of normal range (24). In a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement, out of 62 papers comparing SRRs by cTESE vs MicroTESE, Deruyver et al. considered «eligible» only 7 of them. SRR resulted significantly higher in MicroTESE group in five eligible studies and the SRR ranged between 16.7% and 45% in cTESE group vs 42.9% and 63% in MicroTESE group. According to two studies in this series, SCOS predicted a significant better result versus Maturation Arrest in the MicroTESE group (25). In a more recent systematic review and meta-analysis, Micro-TESE resulted 1.5 times more likely to achieve a successful SR as compared with cTESE (26). MicroTESE is finally a good option when NOA patients have undergone previous negative SR with less exhaustive techniques (cTESE or TESA). In those cases the SRRs range between 46% and 30%, respectively (27).
Conclusions
The EAU (European Association of Urology) Guidelines state (grade A recommendation) that “men with NOA can be offered (c)TESE with cryopreservation of the spermatozoa to be used for ICSI”, and “To increase the chances of positive sperm retrieval in men with NOA, TESE (microsurgical or multiple) should be used”, because microsurgical TESE increases retrieval rates vs. conventional TESE, and should be preferred in severe cases of non-obstructive azoospermia (28). Furthermore
the AUA (American Urology Association) Best Statement Practice is more unclear about the type of sperm retrieval procedure considered the best and recommended for patients with NOA, underlining that “Open surgical testicular sperm retrieval with (=MicroTESE) or without (=cTESE) microscopic magnification is recommended for patients with nonobstructive azoospermia” (29). According to the Canadian Guidelines “The testicular sperm extraction procedure should be offered to all men with NOA, but should only be undertaken in a Centre with expertise in MicroTESE and where an ICSI Laboratory with expertise in handling these samples is available” (30). Randomized, prospective, controlled studies endorsing the superiority of MicroTESE versus cTESE are still lacking in terms of SRRs, side effects and complications, but we can reasonably state that MicroTESE (i.e. sparing testicular tissue) should be offered in selected Infertility Centers to NOA men with low testicular volume.
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