Comparative Outcomes of Micro-TESE Following Preoperative Letrozole versus hCG+FSH Therapy in Non-Obstructive Azoospermia.

Abstract

Background

Preoperative hormonal optimization is variably used before microdissection testicular sperm extraction (micro-TESE) in non-obstructive azoospermia (NOA). Letrozole improves testosterone-to-estradiol (T/E2) ratio, whereas gonadotropin therapy (hCG+FSH) directly stimulates Leydig and Sertoli cells. Evidence comparing their clinical impact remains limited.

Objective

To compare sperm retrieval rate (SRR) and reproductive outcomes following micro-TESE in NOA patients receiving preoperative Letrozole vs hCG+FSH therapy.

Methods

A comparative observational study of 100 NOA patients: 50 received Letrozole (2.5 mg/day ≥12 weeks) and 50 received hCG (1,500–2,500 IU 2–3×/week) + FSH (75–150 IU 2–3×/week) for ≥12 weeks before micro-TESE. Primary outcome: SRR. Secondary outcomes: hormonal response, ICSI fertilization, and clinical pregnancy.

Results

hCG+FSH therapy resulted in significantly higher post-treatment testosterone levels (620 ± 115 vs 485 ± 92 ng/dL, p=0.01).The sperm retrieval rate was higher in the hCG+FSH group (48% vs 34%, p=0.048).ICSI clinical pregnancy rate was also higher but not statistically significant (22% vs 14%, p=0.21).On multivariable logistic regression, post-treatment testosterone (aOR 1.14; p=0.02) and testicular volume (aOR 1.09; p=0.03) independently predicted sperm retrieval.

Conclusion

Preoperative hCG+FSH therapy was associated with significantly higher sperm retrieval rates compared to Letrozole. While Letrozole improved the T/E2 ratio, the gonadotropin-driven increase in intratesticular testosterone appears more physiologically favorable for spermatogenesis in selected NOA men. Hormonal priming should be individualized based on endocrine profile and testicular reserve.