Treatment of Retrograde Ejaculation
For men with retrograde ejaculation seeking fertility, first-line treatment should be sympathomimetic medications (pseudoephedrine or imipramine), with pseudoephedrine 60-120 mg taken 120-150 minutes prior to ejaculation or imipramine 25-75 mg daily showing the highest success rates for converting retrograde to antegrade ejaculation. 1
Treatment Algorithm
First-Line: Sympathomimetic Medications
Pseudoephedrine is the most effective single agent:
- Dosing: 60-120 mg taken 120-150 minutes prior to sexual activity 1
- Success rate: 47.8-58.3% conversion to antegrade ejaculate in complete retrograde ejaculation 2, 3
- Alternative protocol: 60 mg every 6 hours the day before, plus two 60 mg doses on the day of planned ejaculation 3
- In partial retrograde ejaculation, 62.5% of patients achieve ≥50% increase in antegrade sperm count 3
Imipramine as alternative or second-line:
- Dosing: 25-75 mg daily, or 25-50 mg for 7 days prior to planned ejaculation 1, 4, 5
- Success rate: 38.5% conversion in complete retrograde ejaculation 2
- Side effects include dizziness, weakness, nausea, or sweating in approximately 50% of patients 4
Combination therapy (pseudoephedrine + imipramine):
- Most effective approach: 61.5% success rate for converting complete retrograde ejaculation 2
- Use when single-agent therapy fails 2
Second-Line: Alternative Sympathomimetics
Ephedrine:
- Dosing: 15-60 mg taken 1 hour prior to sexual activity 1
- Success rate of 17.6% in diabetic patients with retrograde ejaculation 2
- Only 12.5% success in post-retroperitoneal surgery patients 5
Midodrine:
- Dosing: 5-40 mg daily, taken 30-120 minutes prior to sexual activity 1
Adjunctive Measures for Fertility
Urine alkalinization to preserve sperm viability:
- Add sperm wash media into the bladder prior to ejaculation 6
- Alkalinize urinary pH with oral medications 6
- Perform urethral catheterization after ejaculation to retrieve sperm from bladder 1
When Medical Therapy Fails
Assisted reproductive techniques:
- Penile vibratory stimulation 1
- Electroejaculation 1
- Surgical sperm retrieval (testicular or epididymal extraction) 1
Etiology-Specific Considerations
Diabetic patients: Medical treatment should be first-line, with combination therapy offering the best outcomes (61.5% success) 2
Post-retroperitoneal surgery: Imipramine shows better efficacy (42.8% success) than ephedrine (12.5% success) in this population 5
Medication-induced: Consider dose reduction or medication substitution before adding sympathomimetics 7
Important Caveats
- Success rates vary significantly by etiology, with idiopathic causes responding better than post-surgical cases 5, 3
- Even partial improvement in antegrade ejaculation can enable spontaneous pregnancy or improve assisted reproduction outcomes 2, 4
- Two spontaneous pregnancies were achieved with imipramine treatment in patients with normal sperm concentrations 4
- Medical treatment preserves the possibility of natural conception, making it preferable to immediate surgical sperm retrieval 2