Men with non-obstructive azoospermia, the most severe and common form of azoospermia, face a stark reality: no spermatozoa appear in their ejaculate, confirmed on at least two separate semen analyses, and for roughly 10 to 15 percent of infertile men this is the diagnosis. A new retrospective study from eastern Algeria now offers a clearer picture of which clinical and biological factors can forecast whether surgical sperm retrieval will succeed in this difficult population, identifying testicular histology, serum follicle-stimulating hormone levels and testicular volume as the strongest independent predictors.
The research, conducted at the assisted reproductive technology center of the IBN ROCHD Clinic in Constantine, reviewed medical records from patients seen between 2018 and 2025. Of 323 patients who underwent testicular biopsy during that period, 128 men diagnosed with non-obstructive azoospermia and carrying complete clinical, hormonal and histopathological data formed the final study population. The mean patient age was 39.23 years, with a standard deviation of 7.179 years, and ages ranged from 26 to 62 years; 57.8 percent of the patients were under 40. Varicocele was absent in 97 cases, or 75.8 percent of the cohort.
The central finding is sobering but informative: sperm retrieval was successful in 38.3 percent of patients, meaning 49 of the 128 men had sperm recovered during conventional testicular sperm extraction. This figure underscores why non-obstructive azoospermia remains such a clinical challenge. In obstructive azoospermia, sperm retrieval rates approach 90.6 percent, while in non-obstructive cases success falls to around 57.6 percent in the broader literature cited by the researchers. For men with non-obstructive azoospermia, testicular sperm extraction followed by intracytoplasmic sperm injection represents the only viable fertility option, which makes predicting outcomes before surgery a matter of considerable practical importance.
Testicular histology emerged as the most powerful discriminator. The researchers classified testicular tissue into four main patterns ranked from most to least productive: hypospermatogenesis, where all stages of spermatogenesis are present but reduced in number; maturation arrest, in which spermatogenesis halts at a specific developmental stage, either early or late; Sertoli cell-only syndrome, marked by the complete absence of germ cells with seminiferous tubules containing only Sertoli cells; and tubular hyalinization, characterized by replacement of seminiferous tubules with fibrotic or hyalinized tissue. In the cohort, Sertoli cell-only syndrome was diagnosed in 57 patients, or 44.5 percent, while tubular hyalinization appeared in 12 patients, early and late maturation arrest in 24 and 20 patients respectively, and hypospermatogenesis in 15 patients.
The association between histological type and retrieval outcome was highly significant, with a p value below 0.001. The highest sperm retrieval rates were observed in patients with late maturation arrest and hypospermatogenesis, patterns in which some residual spermatogenic activity persists. Conversely, severe histological patterns were strongly linked to failure: testicular fibrosis and Sertoli cell-only syndrome carried odds ratios of 0.024 and 0.020 respectively for successful retrieval. In the multivariate logistic regression, which used hypospermatogenesis as the reference category because it most closely resembles normal spermatogenesis, early maturation arrest was also significantly associated with lower odds of success, while late maturation arrest did not retain statistical significance after adjustment. Early maturation arrest yielded successful retrieval in only 12.2 percent of affected patients.
Hormonal measurements added a second layer of prediction. Mean serum levels of follicle-stimulating hormone, luteinizing hormone and testosterone were 15.65, 9.49 and 5.75 units respectively, with most values falling within normal ranges. FSH showed a significant correlation with retrieval success, at p equal to 0.004. Logistic regression produced an odds ratio of 0.947 for FSH, with a cut-off value of 8.83 milli-international units per milliliter, indicating that lower FSH levels were associated with higher retrieval success. Receiver operating characteristic analysis determined this threshold with a sensitivity of 69.6 percent and a specificity of 59.2 percent. Patients with FSH above the reference value showed lower retrieval success and higher failure rates, while those at or below the threshold fared better.
Luteinizing hormone told a more nuanced story. A positive retrieval result was observed in 44.9 percent of patients with low LH levels, while the group with elevated LH showed the highest rate of negative outcomes. The univariate association between LH levels and retrieval outcomes was described as a trend toward significance at p equal to 0.05, indicating only a weak correlation. Yet multivariate analysis revealed a positive association between higher LH levels and retrieval success, with an odds ratio of 1.069 and a cut-off value of 5.75 milli-international units per milliliter, at a sensitivity of 64.6 percent and a specificity of 57.1 percent. The researchers concluded that LH is a weaker, dependent predictive factor compared with FSH and testicular volume, likely because LH primarily reflects Leydig cell function rather than the Sertoli cell activity on which spermatogenesis depends. Testosterone, meanwhile, showed no statistically significant association with retrieval outcomes.
Testicular volume completed the predictive triad. Normal testicular volume, defined as 10 to 15 milliliters, was observed in 63.6 percent of cases, with hypotrophic volumes of 5 to 10 milliliters in 31.3 percent and atrophic volumes below 5 milliliters in 3.3 percent. Patients with normal volume had the highest rate of positive retrieval, while those with hypotrophic and atrophic testes showed lower success. The authors note that volume reflects the functional mass and spermatogenic environment of the testis, and that reduced volume often signals germinal tissue loss or atrophy. Notably, the study also found significant associations between histological types and the hormonal and volumetric parameters measured, with FSH and LH linked to histology at p equal to 0.000, testosterone at p equal to 0.012, and testicular volume at p equal to 0.003.
The practical implications extend beyond prediction. Although histological evaluation is obtained only after biopsy, the authors argue it remains clinically valuable by guiding personalized patient management, including the selection of the most appropriate sperm retrieval technique, the initiation of hormonal therapy, and the prediction of outcomes in subsequent retrieval attempts. The FSH cut-off identified here, 8.83 milli-international units per milliliter, is lower than thresholds around 14 milli-international units per milliliter reported in other studies, a difference the researchers attribute to a broader range of histological patterns in their cohort, lower mean FSH levels in their population, and their use of conventional rather than microdissection TESE, the latter being known to increase retrieval likelihood.
The study carries important limitations that temper its conclusions. It was a single-center investigation with a relatively small sample size, which may limit generalizability. Microdissection TESE was not included because the technique had only recently been introduced into local protocols. Genetic analyses, including karyotyping, were unavailable or not routine, meaning some cases of Klinefelter syndrome may have gone undetected. Hormonal markers such as inhibin B and AMH could not be assessed due to restricted availability and high cost, and small hyperechoic foci on ultrasound were not systematically recorded. Despite these constraints, the researchers position the work as the first comprehensive study of its kind for eastern Algeria, addressing a documented gap in regional data and offering clinicians a framework for counseling men whose options depend on finding even rare sperm.
Subject of Research: Predictors of sperm retrieval success in men with non-obstructive azoospermia undergoing conventional testicular sperm extraction
Article Title: Predictive factors of c-TESE success in eastern algerian patients with non-obstructive azoospermia: role of histology, hormones, and testicular volume
Article References: Nourine, B. H. A., Ounis, L., Hamoul, M., Haddad, F. Z., & Zoghmar, A. (2026). Predictive factors of c-TESE success in eastern algerian patients with non-obstructive azoospermia: role of histology, hormones, and testicular volume. Basic and Clinical Andrology, 36(1), Article 12. https://doi.org/10.1186/s12610-026-00311-7
Image Credits: AI Generated
DOI: 10.1186/s12610-026-00311-7
Keywords: non-obstructive azoospermia, testicular sperm extraction, sperm retrieval, testicular histology, follicle-stimulating hormone, luteinizing hormone, testicular volume, Sertoli cell-only syndrome, hypospermatogenesis, maturation arrest, male infertility, Algeria
News Source: Ophelia Keating. (October 30, 2026). Histology, FSH and testicular volume predict sperm retrieval in Algerian men with non-obstructive azoospermia. Scienmag.
