O-258 Clinical factors associated with sperm retrieval success in hypogonadal nonobstructive azoospermic males undergoing microdissection testicular sperm extraction
Authors: Achermann A , Esteves S , Miyaoka R , Verza S , Fregonesi A , Riccetto C 
Published: July 2024

Abstract

Study question
What factors are associated with sperm retrieval (SR) success through microdissection testicular sperm extraction (micro-TESE) in nonobstructive azoospermic (NOA) males with biochemical hypogonadism?

Summary answer
The SR success in hypogonadal NOA males is associated with FSH levels, pre-micro-TESE hormonal stimulation, presence of clinical varicocele, varicocelectomy history, and testicular histopathology results.

What is known already
Previous studies have investigated clinical predictors for SR success in NOA males, such as testicular volume, genetic status, and testicular histopathology, but these factors cannot be modified before SR. On the other hand, pre-SR hormonal stimulation and varicocele repair have shown potential for improving SR rates, although the evidence is inconclusive due to heterogeneity in patients and treatments. This lack of information makes it difficult for clinicians to determine whether medical or surgical interventions should be used before SR in NOA patients.

Study design, size, duration
This observational cohort study involved 616 hypogonadal NOA patients with primary spermatogenic failure who underwent micro-TESE at a University-affiliated center for male reproductive health between 2014 and 2021. Biochemical hypogonadism was defined as total testosterone (T) levels &lt;350 ng/dL, measured from morning venous samples. All patients were naïve concerning previous SR attempts and were categorized into two groups based on whether they received pre-SR hormonal stimulation with recombinant gonadotropins (hCG alone or combined with FSH).

Participants/materials, setting, methods
Patients aged 23-55 underwent comprehensive clinical, laboratory, and histopathological evaluations for NOA. Multivariable logistic regression analysis explored the associations between patient variables and micro-TESE success. Adjusted risk ratio (aRR) assessed the relationship between SR success and relevant predictors. SR rates were compared between patients receiving hormonal stimulation and those who did not. Logistic regression analysis evaluated the effect of baseline FSH levels, stratified by normogonadotropic (&lt;12 IU/L) and hypergonadotropic (≥12 IU/L) classes, on SR success.

Main results and the role of chance
The overall micro-TESE success rate was 56.6%. Independent predictors of SR success included baseline FSH levels (aRR 0.98, 95% CI 0.96-0.99, p = 0.04), pre-SR hormonal stimulation (aRR 1.52, 1.28-1.73, p = 0.0002), the presence of clinical varicocele (aRR 0.09, 0.01-0.66, p = 0.04), history of previous varicocelectomy (aRR 1.53, 1.14-1.84, p = 0.01), and testicular histopathology results (p &lt; 0.05). Patients who received hormonal stimulation achieved higher SR success rates than untreated patients (62.5% [182/291] vs. 51.4% [167/325], p = 0.006; aRR 1.52, 95% CI 1.28-1.73). Among patients receiving hCG-based hormonal stimulation, pre-micro-TESE T levels and Delta T (absolute increase in T levels from baseline) were associated with SR success (p &lt; 0.0001). A pre-micro-TESE T level of 418.5 ng/dL (AUC: 0.78) and a Delta T of 258 ng/dL (AUC: 0.76) distinguished treated patients with positive and negative SR outcomes. Subgroup analysis by baseline FSH levels showed that normogonadotropic individuals (aRR 1.41, 1.16-1.58, p = 0.002) benefited from hormonal stimulation, whereas hypergonadotropic subjects did not (aRR 1.20, 0.86-1.50, p = 0.23). The frequency of patients showing biochemical hypogonadism after hCG stimulation was reduced to 22.3% (65/291). The micro-TESE postoperative complication rate was 2.3% (14/616), while the frequency of patients exhibiting adverse effects presumably attributed to hormonal stimulation was 10.3% (30/291).

Limitations, reasons for caution
Limitations of the study include its observational nature and the absence of pregnancy data. The study focused on micro-TESE as the SR method and hormonal stimulation solely based on hCG (as monotherapy or associated with FSH), so results may differ with other treatments.

Wider implications of the findings
Our study underscores the complexity of counseling hypogonadal men with NOA, stressing the significance of assessing various factors. While our findings suggest potential benefits from pre-SR interventions, particularly hormonal stimulation and varicocele repair, none of the identified predictors can definitively determine the likelihood of successful SR.

Trial registration number
NCT05110391