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

Enrolling by invitation

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • 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 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

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
Intervention / Treatment
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

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

University of Nebraska

Investigators

  • 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)

April 13, 2026

Primary Completion (Estimated)

June 30, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

March 13, 2026

First Submitted That Met QC Criteria

March 13, 2026

First Posted (Actual)

March 18, 2026

Study Record Updates

Last Update Posted (Actual)

April 20, 2026

Last Update Submitted That Met QC Criteria

April 14, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID 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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