Azoospermia on TRT? hCG vs Clomid for Fertility—Why Sperm Recovery May Not Depend on FSH

[madman]

Abstract​

INTRODUCTION AND OBJECTIVES:​

To evaluate FSH recovery rates and sperm production in men with testosterone therapy (TTh)-induced azoospermia treated with hCG alone versus hCG combined with clomiphene citrate, focusing on men with severely suppressed baseline FSH.

METHODS:​

Retrospective study of 42 men (median age 39 years, IQR 33-43.8) with TTh-induced azoospermia treated with hCG alone (n=9) or hCG with clomiphene (n=33) following median 19.5 months (IQR 8-48) on TTh. Primary outcomes: FSH change from baseline to first total motile count (TMC) and FSH recovery rates (≥1.5 mIU/mL) in men with baseline FSH ≤1.49 mIU/mL. Secondary outcome: TMC by FSH recovery status. Fisher's exact test compared categorical variables; Mann-Whitney U test compared continuous variables (p<0.05).

RESULTS:​

Median treatment duration was 3.5 months (IQR 2-5). Both groups demonstrated FSH recovery: hCG with clomiphene median Δ FSH 0.73 mIU/mL (IQR 0-3.9); hCG alone median Δ FSH 1.3 mIU/mL (IQR 0.1-2). Median TMC was comparable (hCG with clomiphene: 13.5 million, IQR 2.6-24.6; hCG alone: 7.65 million, IQR 0.7-10.5; p=0.348). In the severely suppressed FSH cohort (n=34), 50% (13/26) with hCG and clomiphene achieved FSH ≥1.5 mIU/mL versus 37.5% (3/8) with hCG alone (OR 1.64, 95% CI 0.26-12.83, p=0.693). FSH recovery to ≥1.5 mIU/mL did not correlate with superior sperm production. Median TMC was 12.3 million (IQR 3.2-32.8) in those achieving FSH ≥1.5 versus 13.9 million (IQR 1.8-22.4) in those remaining <1.5 mIU/mL (p=0.852).

CONCLUSIONS:​

Men with TTh-induced azoospermia can achieve meaningful sperm production regardless of baseline FSH severity or degree of FSH recovery. The addition of clomiphene citrate to hCG showed a non-significant trend toward improved FSH recovery in men with severely suppressed baseline FSH but did not enhance sperm production outcomes. These findings suggest that FSH normalization is not a prerequisite for successful sperm recovery in this population, and hCG monotherapy may be sufficient for fertility restoration even in men with undetectable baseline FSH.