Nonobstructive azoospermia (NOA) is a condition affecting 5% to 15% of men undergoing infertility evaluations and accounts for nearly 60% of azoospermia cases. NOA can result from a variety of factors, including genetic abnormalities, congenital disorders, exposure to gonadotoxic agents, orchitis, and testicular trauma, although many cases remain idiopathic. Patients with NOA often exhibit varying degrees of Leydig cell insufficiency, which can reduce intratesticular testosterone (T) production and exacerbate spermatogenesis impairment. Testosterone plays a crucial role in spermatogenesis by working synergistically with follicle-stimulating hormone (FSH) to support the development of germ cells in Sertoli cells.
For men with NOA who are seeking to conceive, microdissection testicular sperm extraction (micro-TESE) is frequently recommended due to its higher sperm retrieval rates (SRR) compared to other methods. A study involving 616 consecutive NOA patients with hypogonadism (defined as total testosterone levels below 350 ng/dL) who underwent micro-TESE between 2014 and 2021 found important associations with sperm retrieval success. All participants had no prior sperm retrieval history and were aged 23 to 55, undergoing comprehensive evaluations for NOA before being categorized into two groups based on pre-SR hormonal stimulation.
A multivariable logistic regression analysis was performed to explore the relationship between patient characteristics and the success of micro-TESE, which was defined as the presence of viable spermatozoa in the extracted specimens. The analysis yielded adjusted odds ratios (aORs) and 95% confidence intervals (CIs) to evaluate the impact of various predictors on sperm retrieval success. The results showed an overall micro-TESE success rate of 56.6%. Key independent predictors included baseline FSH levels (aOR, 0.97; 95% CI, 0.94–0.99), pre-SR hormonal stimulation (aOR, 2.54; 95% CI, 1.64–3.93), presence of clinical varicocele (aOR, 0.05; 95% CI, 0.01–0.51), history of previous varicocelectomy (aOR, 2.55; 95% CI, 1.26–5.16), and findings from testicular histopathology.
Among patients who received hormonal treatment prior to micro-TESE, the pre-operative testosterone levels and the change in testosterone levels (delta T) were positively associated with sperm retrieval success. A testosterone level of 418.5 ng/dL (area under the curve value: 0.78) and a delta T of 258 ng/dL (area under the curve value: 0.76) were identified as optimal cut-off points for predicting successful outcomes. Notably, subgroup analysis revealed that hormonal stimulation prior to sperm retrieval was particularly beneficial for normogonadotropic patients compared to those who were hypergonadotropic.
The study concluded that in this large cohort of hypogonadal men with NOA undergoing micro-TESE, lower baseline FSH levels and a history of varicocelectomy were associated with increased odds of successful sperm retrieval. Conversely, the presence of clinical varicocele was linked to decreased odds. A higher percentage of patients who achieved successful sperm retrieval displayed either hypospermatogenesis or maturation arrest on testicular histopathology, while those with unsuccessful outcomes often exhibited Sertoli cell-only syndrome (SCO). The complication rate for micro-TESE was found to be 1.9%, with 10.3% of hormone-pretreated patients experiencing minor side effects.
These findings highlight the complex interplay between clinical factors and micro-TESE success in hypogonadal men with NOA, suggesting potential benefits from pre-surgical interventions such as hormonal stimulation and varicocele repair. While the results provide promising insights for enhancing fertility outcomes in this patient population, further research is needed to establish standardized treatment protocols and evaluate reproductive outcomes. Healthcare providers considering pre-surgical interventions should engage in comprehensive discussions with patients regarding the limited evidence, potential risks, and associated costs to ensure informed decision-making.
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