This study compares two medical treatments to see how well they improve sperm production in men with infertility due to low sperm counts (oligospermia) or no sperm in the semen due to non-obstructive causes (nonobstructive azoospermia). Some men with these conditions have limited nonsurgical treatment options, and current therapies do not work for everyone.

Participants in this study will be adult men ages 19 to 50 who have been diagnosed with oligospermia or nonobstructive azoospermia and do not have a correctable cause for infertility. Eligible participants will be randomly assigned to receive one of two treatments for three months: oral isotretinoin taken twice daily, or human chorionic gonadotropin (hCG) injections given three times per week. hCG is a standard hormonal therapy used in certain types of male infertility, while isotretinoin is being studied for its potential role in stimulating sperm production.

At the start of the study, participants will have blood tests to measure reproductive hormone levels and a semen analysis. Blood tests will be repeated at one month and three months, and a repeat semen analysis will be performed at three months, which corresponds to a full cycle of sperm development. The main goal of the study is to determine whether motile (moving) sperm appear in the semen after treatment. Additional goals include measuring changes in sperm count and hormone levels, as well as monitoring medication side effects.

Both study medications are FDA-approved and have known side effect profiles. Participants may or may not experience improvement in sperm production. The results of this study may help guide future treatment options for men with infertility due to low or absent sperm production.

Inclusion Criteria:

• Male participants aged 19 to 50 years
• Confirmed diagnosis of oligospermia (sperm concentration <15 million/mL), nonobstructive azoospermia, or hypogonadotropic hypogonadism (defined by low or normal FSH with low testosterone)
• Normal genetic evaluation if diagnosed with azoospermia
• No other identified and correctable cause of infertility
• Considered appropriate candidates for medical therapy for infertility in the clinical judgment of the investigators
• Willing and able to comply with study procedures, including laboratory testing, semen analyses, and follow-up visits
• Able to provide informed consent

Exclusion Criteria:

• Obstructive azoospermia (including vasal obstruction, ejaculatory duct obstruction, or prior vasectomy)
• Prior successful medical therapy for infertility
• Current or recent use of medications known to impair spermatogenesis, including exogenous testosterone or anabolic steroids, unless discontinued with adequate washout
• Current use of isotretinoin for any indication
• Contraindications to isotretinoin (including significant liver disease or uncontrolled hyperlipidemia)
• Contraindications to human chorionic gonadotropin (including hormone-sensitive malignancy)
• Significant medical or psychiatric conditions that, in the opinion of the investigators, would interfere with safe participation
• Inability to provide semen samples
• Inability to provide informed consent