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

April 14, 2026 updated by: Christopher Deibert, University of Nebraska

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University Of Nebraska Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Isotretinoin Treatment Arm
Participants in this arm will receive oral isotretinoin 20 mg twice daily for 3 months. Reproductive hormone testing will be performed at baseline, 1 month, and 3 months, and a semen analysis will be repeated at 3 months to assess treatment response.
Drug: isotretinoin
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.
Active Comparator: hCG Treatment Arm
Participants in this arm will receive human chorionic gonadotropin (hCG) injections at a dose of 2,000 units three times weekly for 3 months. Reproductive hormone testing will be performed at baseline, 1 month, and 3 months, and a semen analysis will be repeated at 3 months to assess treatment response
Drug: Human chorionic gonadotrophin (hCG)
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Nebraska

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Chris Deibert, MD, MPH, University of Nebraska

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 13, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 13, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 13, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 18, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 20, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 14, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0849-25-FB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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