Recent research published in Fertility and Sterility suggests that pre-sperm retrieval normogonadotropic hormonal stimulation could significantly improve outcomes for individuals with nonobstructive azoospermia (NOA). This condition affects up to 15% of men evaluated for infertility and often leads to the use of microdissection testicular sperm extraction (micro-TESE) as a treatment option. However, there has been limited data on factors influencing the success of sperm retrieval in these cases.
To explore these factors, researchers from Androfert, a Brazilian reproductive health center affiliated with a university, conducted an observational cohort study (ClinicalTrials.gov Identifier: NCT05110391). The study involved 616 men aged 23 to 55 with hypogonadal NOA who underwent micro-TESE between 2014 and 2021. Comprehensive clinical, histopathological, and laboratory evaluations were performed, categorizing participants based on pre-sperm retrieval hormonal stimulation and baseline follicle-stimulating hormone (FSH) levels.
The primary focus was on the correlation between sperm retrieval success and various patient data. Secondary outcomes included sperm retrieval rate, complications from micro-TESE, and adverse effects of hormonal therapy.
The median age of participants was 35 years, with a median BMI of 27.5 kg/m². Among the subjects, 70% had idiopathic NOA, 57.6% underwent bilateral micro-TESE, and 47.2% received pre-sperm retrieval hormonal stimulation. Sperm retrieval was successful in 56.6% of cases, with higher success rates among those who underwent unilateral micro-TESE and received hormonal stimulation.
In the fully-adjusted analysis, several factors were positively associated with sperm retrieval success:
- Biopsies showing hypospermatogenesis or Sertoli cell-only syndrome (adjusted odds ratio [aOR], 356.6; 95% CI, 253.3-522.0; P <.0001)
- Biopsies indicating hypospermatogenesis or germ cell maturation arrest (aOR, 182.0; 95% CI, 117.8-281.3; P <.0001)
- A history of varicocele repair (aOR, 2.55; 95% CI, 1.26-5.16; P =.01)
- Pre-sperm retrieval hormonal stimulation (aOR, 2.54; 95% CI, 1.64-3.93; P =.0002)
- Biopsies indicating germ cell maturation arrest or Sertoli cell-only (aOR, 1.99; 95% CI, 1.28-3.10; P =.001)
Conversely, factors negatively associated with sperm retrieval success included clinical varicocele (aOR, 0.05; 95% CI, 0.01-0.51; P =.04) and higher baseline FSH levels (aOR, 0.97; 95% CI, 0.94-0.99; P =.04).
When stratifying by hormone stimulation type, normogonadotropic stimulation was linked to higher micro-TESE success rates (aOR, 3.20; 95% CI, 1.59-6.44; P =.001), whereas hypergonadotropic stimulation did not show a significant association (aOR, 1.46; 95% CI, 0.74-2.88; P =.27).
The study identified optimal cutoff levels for predicting sperm retrieval success: FSH at 9.8 IU/L (AUC, 0.64; sensitivity, 0.46; specificity, 0.77), testosterone at 418.5 ng/dL (AUC, 0.777; sensitivity, 0.78; specificity, 0.71), and a testosterone change of 258 ng/dL (AUC, 0.761; sensitivity, 0.50; specificity, 0.92). The combined use of these cutoffs provided an AUC of 0.79, with a sensitivity of 0.79 and specificity of 0.68.
The study acknowledges limitations, including the lack of follow-up on fertility outcomes. The authors stress the importance of establishing standardized treatment protocols and further research to improve fertility outcomes for NOA patients. Healthcare providers are advised to discuss the limited evidence, potential risks, and costs associated with pre-sperm retrieval hormonal stimulation to facilitate informed patient decisions.
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