Can follicle stimulating hormone (FSH) levels be used to determine fertility status in nonazoospermic men?

FSH Cannot Reliably Determine Fertility Status in Nonazoospermic Men

FSH should not be used as a standalone test to determine fertility status in nonazoospermic men, as FSH thresholds between 2.9 and 9.3 IU/L perform poorly for predicting fertility (positive predictive values only 0.49-0.59), and only extreme values above the 95th percentile (>12.1 IU/L) achieve clinically useful predictability. 1

Why FSH Fails as a Standalone Fertility Test

The fundamental problem is that FSH levels show substantial overlap between fertile and subfertile nonazoospermic men:

• Median FSH in fertile men is 4.0 IU/L versus 6.0 IU/L in subfertile men—statistically different but with massive overlap 1
• The entire range of commonly used FSH thresholds (2.9-9.3 IU/L) demonstrates similarly poor predictive performance, with positive predictive values barely better than a coin flip (0.49-0.59) 1
• Only when FSH reaches the 95th percentile (12.1 IU/L) does the positive predictive value exceed 0.7, and the highest predictive value (0.84) occurs at FSH of 20.8 IU/L (99th percentile) 1

The Inverse Correlation Exists But Is Not Clinically Decisive

While FSH levels are negatively correlated with spermatogenesis—meaning higher FSH generally indicates decreased sperm production—this relationship is not absolute enough for clinical decision-making 2, 3:

• FSH levels alone cannot definitively predict sperm retrieval success in all cases 2, 4
• Men with maturation arrest on testicular histology can have normal FSH and testicular volume despite severe spermatogenic dysfunction 2, 3
• Up to 50% of men with non-obstructive azoospermia and elevated FSH still have retrievable sperm 2

When FSH Does Provide Useful Information

FSH testing remains clinically valuable in specific contexts 1:

Extreme Values

• FSH >12.1 IU/L (95th percentile) begins to have clinically useful predictive value for subfertility 1
• FSH >7.6 IU/L strongly suggests non-obstructive azoospermia rather than obstructive causes 2
• FSH >10.18 IU/L demonstrates excellent discriminatory ability for non-obstructive azoospermia (AUC 0.921) with a 38.93-fold increased risk 5

Discordant Results

• When FSH and semen analysis results don't match expectations, this warrants further investigation 1
• Elevated FSH with normal testicular size suggests a different pathophysiology than elevated FSH with testicular atrophy 2

The Correct Diagnostic Algorithm

Instead of relying on FSH alone, use this approach:

1. Perform at least two semen analyses separated by 2-3 months to confirm fertility status, as single analyses can be misleading due to natural variability 2, 3

2. Obtain complete hormonal evaluation including FSH, LH, and testosterone to understand the full endocrine picture 2, 3

3. Conduct physical examination focusing on testicular size and consistency—normal-sized testes with elevated FSH suggest better prognosis than atrophic testes 2, 3

4. Consider genetic testing if semen analysis confirms severe oligospermia (<5 million/mL) or azoospermia with elevated FSH:

   • Karyotype analysis to exclude Klinefelter syndrome 2, 3
   • Y-chromosome microdeletion testing (AZFa, AZFb, AZFc regions) if sperm concentration <1 million/mL 2, 3

5. Evaluate reversible causes such as thyroid dysfunction, metabolic stress, and medication effects that may temporarily elevate FSH 2, 3

Critical Pitfalls to Avoid

• Never use FSH cutoffs in the 2.9-9.3 IU/L range to make definitive fertility determinations—these thresholds have poor predictive value despite being commonly referenced 1
• Never prescribe exogenous testosterone to men desiring fertility, as it suppresses FSH and LH through negative feedback, potentially causing azoospermia that can take months to years to recover 2, 3
• Don't assume elevated FSH means zero sperm—even men with FSH >30 mIU/mL can have motile spermatozoa in testicular tissue 6

Clinical Context Matters

The relationship between FSH and fertility becomes more predictive at extremes:

• FSH 7.32-10.18 IU/L range: Associated with 8.51-fold increased risk of oligozoospermia 5
• FSH >10.18 IU/L: Associated with 38.93-fold increased risk of non-obstructive azoospermia 5
• FSH >7.5 IU/L: Five- to thirteen-fold higher risk of abnormal semen quality compared to FSH <2.8 IU/L 7

However, even these associations don't eliminate the need for direct semen analysis, as the overlap between groups remains substantial until FSH reaches truly extreme values (>12.1 IU/L) 1.