Our initial approach to the man with primary infertility is outlined in figure 3. Although some would advocate only treating men who are hypoandrogenic and have an abnormal semen analysis, given the variability of semen parameters and the inability of semen analyses to reliably predict pregnancy, we treat most men with hypoandrogenism and infertility.
Once the patient is on a stable dose of medication, we repeat a hematocrit, testosterone, and PSA every 3 months for a year and then annually for the duration of medical therapy. Clomiphene is generally well tolerated, but some patients do not respond or have a paradoxical response (~6%), hence the need for rechecking labs 2 weeks after each change in dosing. We have found that endocrine manipulation in men is a cost-effective first step in management along with lifestyle modification. We repeat a semen analysis 3 months after any intervention to assess the impact of our intervention. Additionally, we email a copy of the note in a HIPAA-secure fashion to the referring reproductive endocrinologist the day of referral to ensure timely evaluation.
We have seen that approximately 3% to 10% of hypoandrogenic men with azoospermic spermatogenic failure will have sperm return to their ejaculate after normalization of their male endocrine axis (BJU Int 2013; 111:E110-4). Further, this has been found to significantly improve sperm retrieval rates, which will further drive down costs for infertile couples. Although the absolute chance of significant motile sperm returning to the ejaculate is low, we have had patients who have gone from azoospermic to TMCs of >100 M and saved tens of thousands of dollars in microdissection testicular sperm extraction (TESE) and ART costs. Further, they have avoided the risk of surgery.