Prediction Models for Successful Sperm Retrieval in Patients with Non-Obstructive Azoospermia Undergoing Microdissection Testicular Sperm Extraction: Is There Any Room for Further Studies?

Abstract

Several prediction models for successful sperm retrieval (SSR) in patients with azoospermia due to spermatogenic dysfunction (also termed non-obstructive azoospermia—NOA) have been developed and published in the past years, however their resulting prediction accuracy has never been strong enough to translate their results in the clinical practice. This notwithstanding, the number of prediction models being proposed in this field is growing. We have reviewed the available evidence and found that, although patients with complete AZFc deletion or a history of cryptorchidism may have better probability of SSR compared to those with idiopathic NOA, no clinical or laboratory marker is able to determine whether a patient with NOA should or should not undergo microdissection testicular sperm extraction (mTESE) to have his testicular sperm retrieved. Further research is warranted to confirm the utility of evaluating the expression of noncoding RNAs in the seminal plasma, to individuate patients with NOA with higher probability of SSR.

Non-invasive molecular biomarkers for predicting outcomes of micro-TESE in patients with idiopathic non-obstructive azoospermia

“…Considering the disputable results on the predictive status of circulating total testosterone for micro-TESE outcomes, intratesticular testosterone may serve as a better indicator (Ref. 6). However, to bypass the invasive measurement of intratesticular testosterone, serum 17-hydroxyprogesterone level could reliably be used as a proxy for intratesticular testosterone level (Ref.…”

“…Such models allow clinicians to tailor personalised clinical practices for patients with NOA, predicting the success rate of micro-TESE (Ref. 6). Several candidate predictors have been proposed to evaluate success rates; for instance, the NOA aetiology is a key predictor for successful sperm retrieval (SSR).…”

“…Non-obstructive azoospermia (NOA), the most severe type of male infertility, is a condition in which spermatozoa are absent in the ejaculate due to spermatogenic dysfunction in the testes. NOA affects approximately 1% of men worldwide (Refs 4–6). Although several underlying causes are known, including chromosomal abnormalities, Y-chromosome microdeletions, cryptorchidism, hypogonadism, viral or bacterial orchitis, chemotherapy/radiation therapy, varicocele, etc., the exact aetiology of most NOA cases remains unclear, which is therefore referred to as idiopathic NOA (INOA) (Refs 7, 8).…”

“…SSR rates vary from 20 to 66% in NOA patients with Klinefelter syndrome (Refs 6, 25–28). However, no sperm can be retrieved by micro-TESE in patients with complete AZFa or AZFb deletions, although better chances of SSR are present in patients with AZFc deletions (Refs 6, 29–31). For patients with INOA, the SSR varies from 20 to 50.1% (Refs 32–36).…”

Update on the Management of Non-Obstructive Azoospermia: Current Evidence and Unmet Needs

“…Management of men with NOA would undoubtedly benefit from the identification of clinical and laboratory markers of spermatogenesis able to individuate those patients really suited for mTESE. The evidence from the literature in this field, reviewed by our group for this Special Issue [ 6 ], clearly shows that, although few factors, including complete AZFc deletion or history of cryptorchidism, were associated with better chances of successful sperm retrieval (SSR), no clinical or laboratory marker is able to predict the outcome of mTESE, due to the anatomic singularity of the testes of men with NOA, which may hide few loci of spermatogenesis. Moreover, the great impact of the surgeon’s skill and experience, together with the time and efforts dedicated to the search for sperm in the testicular specimens, may have an impact on mTESE outcome.…”