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

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.

Predicting the testicular function in non-obstructive azoospermia via targeted gene panel

Background Men with non-obstructive azoospermia constitute a challenging subgroup of male infertility patients in whom a genetic cause of defective spermatogenesis may be a contributing factor. The aim of this prospective observational cohort study was to determine whether assessment of meiotic nuclear division 1 (MND1) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression (MND1/GAPDH) in testicular tissue could be a prognostic indicator for sperm retrieval and ICSI outcome in patients with non-obstructive azoospermia. The study participants underwent clinical evaluation, conventional semen analysis, serum follicular stimulating hormone (FSH), testosterone assay, scrotal ultrasound examination, microsurgical testicular sperm extraction (mTESE), and assessment of MND1/GAPDH gene expression levels in testicular tissue via quantitative polymerase chain reaction (qPCR) techniques. Results The MND1/GAPDH level was associated with the likelihood of identifying sperm in testicular biopsies (odds ratio (OR) 1.25, 95% confidence intervals (CI) 1.14 to 1.34, p < 0.0001), which was confirmed by the pairwise comparison of high vs. low levels of MND1/GAPDH (OR 5.34, 95% CI 1.97 to 13.16, p = 0.0006). The level of FSH was inversely associated with a lower chance of finding sperm (OR 0.37, 95% CI 0.20 to 0.65, p = 0.001). Compared with small testicular volume, normal volume was inversely associated with the chance of sperm presence (OR 0.16, 95% CI 0.06 to 0.47, p = 0.0002). However, there was no correlation between MND1/GAPDH levels and ICSI outcome. Conclusion Gene expression analysis to predict the likelihood of sperm retrieval following mTESE in patients with non-obstructive azoospermia provides a new avenue for future research, diagnosis and treatment of male factor infertility. Before its wider clinical application, however, this proof-of-concept should be tested in a large multinational, multicenter observational study.