Outcomes of microdissection testicular sperm extraction in men with nonobstructive azoospermia due to maturation arrest

Capsule:
The sperm retrieval rate using microdissection testicular sperm extraction in men with maturation arrest is 52%; men with late maturation arrest and higher follicle-stimulating hormone levels have the highest rates.

Authors:
Aaron M. Bernie, M.D., M.P.H., Kalee Shah, B.A., Joshua A. Halpern, M.D., Jason Scovell, B.A., Ranjith Ramasamy, M.D., Brian Robinson, M.D., Peter N. Schlegel, M.D.

Volume 104, Issue 3, Pages 569-573

Abstract:

Objective:
To evaluate sperm retrieval in men with nonobstructive azoospermia and maturation arrest (MA) undergoing microdissection testicular sperm extraction (micro-TESE).

Design:
Retrospective chart review.

Setting:
Tertiary referral center.

Patient(s):
Men with nonobstructive azoospermia and MA who underwent micro-TESE.

Intervention(s):
Microdissection TESE.

Main Outcome Measure(s):
Sperm retrieval rate (SRR).

Result(s):
A total of 211 patients (13%) had a histologic finding of MA at the most advanced level. The overall SRR was 52%. A total of 146 patients were classified as having early MA (arrest at the primary spermatocyte stage), and 65 as having late MA (early spermatid stage). The SRR in men with early, vs. late, MA was 40% vs. 78%. Of the 211 men with MA, 51 had diffuse MA (100% of tubules showed MA). The SRR was significantly lower in men with diffuse vs. focal MA (35% vs. 57%). On multivariable analysis, late MA and higher follicle-stimulating hormone levels were positively associated with successful sperm retrieval.

Conclusion(s):
Sperm were successfully identified in up to one half of the men with MA after micro-TESE. Among men with MA, late MA seems to be the best predictor of successful sperm retrieval with micro-TESE.

  • Kubilay Vicdan, MD, PhD

    Other than the reported limitations of this study including its retrospective nature and also not wee established definition of diffuse vs.focal MA, I further believe that there are some more questions that should be explained;
    1-The pathologic information used in this study was from a single random intraoperative biopsy takenat the time of micro-TESE and biopsy slides were classified
    as either early or late MA. The authors stated that “Late MA on diagnostic biopsy clearly suggests that the more advanced the pattern seen on biopsy, the more
    likely there are to be areas of complete spermatogenesis elsewhere in the testicle”.So, it can easily be speculated that, because of the heterogeneity of the testis, some
    other areas of the testis can actually have a pattern of hypospermatogenesis”. Therefore, the SRR maybe increased from 40 % for cases with early maturation arrest to 78% for caseswith late MA, and if more biopsy specimens were available and studied, thediagnosis might have been the hypospermatogenesis instead of late MA. The evaluation of a single random biopsy might be the cause of the overdiagnosis of late MA, and the areas including spermatozoa which can lead to the diagnosis of
    hypospermatogenesis, might be overlooked. it is not always possible to find
    spermatozoa in all wet preparats during TESE or in all pathology spercimens evaluated thereafter in some severe forms of hypospermatogenesis.

    2- The authors claimed that men who had focal, early MA had better SRR outcomes than those who had diffuse, early MA (48% vs. 19%). However, this trend did not
    hold true for men who had late MA, as no difference in SRR was found among men with focal, late MA vs. diffuse, late MA (76% vs. 79%). They said that these findings suggest that the positive prognostic indicator of late MA overwhelms the negative predictor of diffuse MA in these men. But, in my opinion,, this may also support the
    idea of overdiagnosis of Late MA instead of the diagnosis of hypospermatogenesis in the other areas of the testis.

    3-I agree with the comment of the authors; ”Clinicians should be aware that men who have normal testicular volume and FSH, with NOA, may have particularly poor SRR outcomes, even with micro-TESE. If these men are found to have diffuse or early MA, then they can be appropriately counseled on the low likelihood of success of their micro-TESE”. But sperm recovery in this group is about 35%, and this rate is still not very low as these might be real cases of early MA with real focal spermatogenesis.

    4- If no spermatozoa are available after a TESE procedure carried out extensively, but the histopathologic evaluation shows round spermatid with a diagnosis of late MA, do we offer a second TESE trial for the same patient ? If the pathologic diagnosis of late MA increases the presence of areas of complete spermatogenesis elsewhere in the
    testis, is it still possible to find spermatozoa that they might not be encountered during current TESE procedure ?

    In conclusion, I think that the very high SRR of 78% with the Late MA in this study may be due to the inreased probability of having hypospermatogenesis elsewhere in the testis and the lower SRR of 40% with the early MA may be due to the more frequent occurence of focal spermatogenesis instead of widespread sperm production in these cases.

  • msamplaski

    This is an interesting study by Schlegels group, which provides valuable prognostic information for men with MA undergoing MT, and also underscores the importance of a thorough MT. The finding of high FSH having a positive predictive value is particularly unique. A multi-institutional study would be interesting. In addition, it will be interesting to see if hormonal stimulation changes the SSR in either of these groups.

  • High FSH has been predictive of sperm retrieval in both men with maturation and Sertoli-cell only histology (Berookhim et al. F&S) – it could be that high FSH would be associated with smaller testis and better sampling of the tubules with microdissection

  • Maturation arrest is one of the more frustrating NOA diagnoses to provide to a couple. It is very difficult to explain why all of the normal testicular architecture and components are present but that the assembly line for sperm production does not proceed to completion and produce a mature spermatocyte.

    This article provides prognostic factors that we can use to counsel our patients as to their chances in conceiving naturally if they are diagnosed with early vs late maturation arrest from a prior biopsy. It also stresses the importance of doing a thorough MicroTESE rather than a quick and haphazard standard TESE in order to give a couple undergoing fertility treatments the best chance of conceiving together.

    It is also very interesting that on multivariate analysis that a higher FSH level had better predictive value in finding sperm on microTESE. In fellowship, we tried looking at our maturation arrest data comparing sperm retrieval rates in early vs late maturation arrest as well as trying to see if FSH levels were predictive of sperm retrieval rates. Due to a smaller sample size, there was no difference.

    Job well done.

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