By InvitationPhase 2

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

United States100 participantsStarted 2026-04-13

Plain-language summary

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.

Who can participate

Age range

19 Years – 50 Years

Sex

MALE

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Presence of Motile Sperm in the Ejaculate

Timeframe: 3 months

Trial details

NCT IDNCT07481370

SponsorUniversity of Nebraska

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2027-06-30

View on ClinicalTrials.gov More Oligospermia trials