No First-Line Medication for Normal Semen Analysis
There is no first-line medication indicated to increase sperm count in men with normal semen analysis, normal hormonal profile, and normal scrotal ultrasound. This clinical scenario represents normal fertility status and does not warrant pharmacological intervention 1.
Why No Medication Is Indicated
Men with normal semen parameters (sperm concentration ≥16 million/mL per WHO reference limits) and normal hormonal profiles have adequate fertility potential and should not receive empiric medical therapy 1.
The medications used for male infertility—including clomiphene citrate, letrozole, and human chorionic gonadotropin (hCG)—are specifically indicated for men with documented abnormalities such as hypogonadotropic hypogonadism, elevated FSH with oligospermia, or low testosterone with impaired spermatogenesis 2, 3, 4.
Exogenous testosterone is absolutely contraindicated if fertility is desired, as it completely suppresses spermatogenesis through negative feedback on the hypothalamus and pituitary, potentially causing azoospermia that can take months to years to recover 1, 2.
When Medications Are Actually Indicated
Human Chorionic Gonadotropin (hCG)
- First-line for hypogonadotropic hypogonadism (low testosterone with low/normal LH and FSH) in men desiring fertility 2.
- Dosing: 500-2500 IU administered 2-3 times weekly subcutaneously or intramuscularly 2.
- Restores testosterone production while preserving spermatogenesis, unlike exogenous testosterone 2.
Clomiphene Citrate (Selective Estrogen Receptor Modulator)
- Indicated for men with oligospermia and low/low-normal testosterone 3, 5.
- Increases sperm concentration by mean difference of 8.38 × 10⁶/mL and total motility by 8.14% 3.
- Dosing: typically 25-50 mg daily 5.
- One-third of men with <5 million total motile count improved to >5 million, expanding reproductive options to include intrauterine insemination 5.
Letrozole (Aromatase Inhibitor)
- Indicated for men with severe oligozoospermia (sperm concentration <5 million/mL), particularly those with low testosterone-to-estradiol ratio 4, 6.
- Produces 5.5-fold increase in sperm concentration even in men with normal testosterone-to-estradiol ratios 6.
- Dosing: 2.5 mg daily for 4 months 4, 6.
- Side effects include loss of libido (54%), headaches (25%), and fatigue (21%), but no serious adverse effects 6.
Critical Pitfalls to Avoid
Never prescribe testosterone to men with current or future fertility desires—this is the most common and devastating error in male reproductive medicine 1, 2.
Do not treat normal semen parameters empirically—medications for male infertility have modest benefits even in appropriate candidates and are not indicated for men with normal baseline fertility 3, 7.
Avoid medication-induced FSH elevation—drugs like clomiphene, tamoxifen, and aromatase inhibitors can artificially elevate FSH through disruption of normal feedback mechanisms, potentially confusing diagnostic evaluation 1.
What To Do Instead
Optimize modifiable lifestyle factors: smoking cessation, maintaining healthy body weight (BMI <25), minimizing heat exposure to testes, adequate sleep, and regular exercise 1, 7.
Nutritional supplementation with proven benefit includes zinc, vitamin D (if deficient), L-arginine, and omega-3 fatty acids, though effects on testosterone are modest 7.
Reassure and counsel on natural conception probability—couples with normal male parameters and female partner under 30 have >90% chance of pregnancy within 2-3 years of trying 1.
Consider fertility evaluation only if no conception after 12 months of timed intercourse, or earlier if female partner has known fertility factors 1.