Isotretinoin vs hCG for Male Infertility Due to Low or Absent Sperm

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.

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Key information

Conditions

Oligospermia Azoospermia, Nonobstructive Genital Diseases Genital Diseases, Male Infertility Infertility, Male Male Urogenital Diseases Urogenital Diseases

Age range

19 year–50 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

isotretinoin

Drug

Oral isotretinoin administered at a dose of 20 mg twice daily for 3 months as part of a randomized treatment arm evaluating effects on sperm production and reproductive hormone levels.

Human chorionic gonadotrophin (hCG)

Drug

Human chorionic gonadotropin (hCG) administered by subcutaneous injection at a dose of 2,000 units three times weekly for 3 months as part of a randomized treatment arm evaluating effects on sperm production and reproductive hormone levels.

Primary outcomes

Presence of Motile Sperm in the Ejaculate

Time frame: 3 months

Assessment of whether motile (moving) sperm are present in the ejaculate following treatment with isotretinoin or human chorionic gonadotropin (hCG), as determined by standard semen analysis

Sponsors and collaborators

Lead sponsor

University of Nebraska

Other

Registry information

Official study title

A Prospective Comparison of Isotretinoin and hCG Therapy in Males With Oligospermia and Azoospermia

Important dates

Study start: 2026
Primary completion: 2027
Study completion: 2027
First posted: Mar 18, 2026
Registry last updated: Apr 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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