Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups (GONACLO)

April 13, 2026 updated by: Dr. Pásztor Norbert, Szeged University
Men enrolled in the study are assigned to each APHRODITE group. Group 2,3,4 are treated with either gonadotropin preparations or clompihene-citrate (except group 4). The type of the treatment (gonadotropin vs clomiphene) is randomized. After treatment, hormonal measurements, spermiogram and DNA fragmentation tests are repeated, allowing for analysis of the outcome.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

Our research involves male partners of couples suffering from male infertility. After a comprehensive andrological examination, based on the test results, the men are classified into so-called "APHRODITE" categories. Based on these categories, half of the patients are given so-called gonadotropin treatment (the exact treatment depends on the type of category), which involves subcutaneous injections several times a week for a total of 12 weeks. The other half of the patients are recommended oral tablets containing the active ingredient clomiphene citrate, also for 12 weeks. It is important that both types of therapy (gonadotropin and clomiphene citrate) are effective treatments in certain cases of male infertility, according to the literature, so all patients participating in the research receive effective treatment. However, it is decided who receives which treatment by randomization.

After the 12-week treatment, a control sperm analysis and a DNA fragmentation test are performed to determine the success of the treatment (changes in sperm analysis results and DNA fragmentation index).

The improvement in sperm parameters will be determined in the two treatment regimens, the rate of fertilized eggs in subsequent assisted reproduction cycles, the quality of the resulting embryos, and the rate of pregnancies and subsequent losses. The results of the two therapeutic modalities will be compared, so that it can be decided which treatment method is more effective.

The research process is essentially as follows:

  1. information, examination
  2. classification into the APHRODITE category based on the results
  3. randomization (gonadotropin or clomiphene citrate)
  4. injection treatment for patients in the gonadotropin group, with therapy according to the APHRODITE category for 12 weeks
  5. tablet treatment for patients in the clomiphene citrate group for 12 weeks
  6. control spermiogram and DNA fragmentation
  7. analysis of the results of subsequent assisted reproduction procedures

Study Type

Interventional

Enrollment (Estimated)

500

Phase

  • Phase 4

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

  • Hungary
      • Szeged, Hungary, 6724
        • Reproductive Medicine Centre, Department of Obstetrics and Gynecology, University of Szeged

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
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • abnormal sperm analysis result, APHRODITE 2,3,4 categories

Exclusion Criteria:

  • obstructive azoospermia
  • non-obstructive azoospermia due to genetical defects (Klinefelter-syndrome, AZFa, AZFb microdeletion syndrome etc)
  • problems with the administration of subcutaneous injections
  • disagreement

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: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: APHRODITE category 2 treated with gonadotropin
subcutaneous recFSH 3x150NE weekly for 12 weeks
Drug: recFSH
recFSH 3x150NE sc weekly for 12 weeks
Other Names:
  • recombinant FSH
Experimental: APHRODITE category 2 treated with clomiphene-citrate
per os 50mg clomiphene-citrate daily for 12 weeks
Drug: Clomiphene Citrate 50 mg
clompihene-citrate 50mg p.o. daily for 12 weeks
Other Names:
  • CC
Experimental: APHRODITE category 3 treated with gonadotropin
subcutaneous recFSH 3x150NE weekly and subcutaneous hCG 2x5000NE weekly for 12 weeks
Drug: recFSH
recFSH 3x150NE sc weekly for 12 weeks
Other Names:
  • recombinant FSH
Drug: HCG injection
hCG 2x5000NE sc weekly for 12 weeks
Other Names:
  • choriogonadotropin alfa
  • human chorionic gonadotropin
Experimental: APHRODITE category 3 treated with clomiphene-citrate
per os 50mg clomiphene-citrate daily for 12 weeks
Drug: Clomiphene Citrate 50 mg
clompihene-citrate 50mg p.o. daily for 12 weeks
Other Names:
  • CC
Experimental: APHRODITE category 4 treated with gonadotropin
subcutaneous hCG 2x5000NE weekly for 12 weeks, if FSH level drops below 1.5 IU/l, subcutaneous recFSH 3x150NE weekly added
Drug: recFSH
recFSH 3x150NE sc weekly for 12 weeks
Other Names:
  • recombinant FSH
Drug: HCG injection
hCG 2x5000NE sc weekly for 12 weeks
Other Names:
  • choriogonadotropin alfa
  • human chorionic gonadotropin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
sperm DNA fragmentation
Time Frame: 12 weeks of treatment
sperm DNA fragmentation Index (%), high DNA stainability (%) are measured and compared to the pretreatment values. Lower numbers mean improvement in this outcome.
12 weeks of treatment
ejaculate volume
Time Frame: 12 weeks of treatment
ejaculate volume (ml) after treatment are assessed and compared to the pretreatment values. Higher number means improvement in this outcome.
12 weeks of treatment
sperm concentration
Time Frame: 12 weeks
Sperm concentrations (million/ml) before and after the treatment are compared. Higher number means improvement in this outcome.
12 weeks
sperm motility
Time Frame: 12 weeks
Sperm total motility (%), progressive motility (%) after the treatment are compared to the pretreatment values. Higher numbers mean improvement in this outcome.
12 weeks
total sperm count, total functional sperm count
Time Frame: 12 weeks
Total sperm count (million) = ejaculate volume (ml) x sperm concentration (million/ml) and total functional sperm count (million) = total sperm count x progressive motility x 100 are compared before and after the treatment. Higher numbers mean improvement in this outcome.
12 weeks
Sperm morphology
Time Frame: 12 weeks
Percent of normal sperm morphology (%) is counted after the treatment and compared to the pretreatment result. Higher number mean improvement in this outcome.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
gonadotropin vs clomiphene - total sperm count, total functional sperm count
Time Frame: 12 weeks of treatment
in the APHRODITE 2 and 3 groups, the results of the gonadotropin and clomiphene-citrate arms are compared regarding the percent of patients with improvement in total sperm count (million) and total functional sperm count (million)
12 weeks of treatment
gonadotropin vs clomiphene - DNA fragmentation
Time Frame: 12 weeks
in the APHRODITE 2 and 3 groups, the results of the gonadotropin and clomiphene-citrate arms are compared regarding the percent of patients with improvement in DNA fragmentation Index (%) and high DNA stainability (%)
12 weeks
Gonadotropin vs clomiphene - sperm total motility, progressive motility
Time Frame: 12 weeks
in the APHRODITE 2 and 3 groups, the results of the gonadotropin and clomiphene-citrate arms are compared regarding the percent of patients with improvement in total sperm motility (%) and progressive sperm motility (%)
12 weeks
gonadotropin vs clomiphene - normal sperm morphology
Time Frame: 12 weeks
in the APHRODITE 2 and 3 groups, the results of the gonadotropin and clomiphene-citrate arms are compared regarding the percent of patients with improvement in normal sperm morphology (%)
12 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gonadotropin hormones
Time Frame: 12 weeks of treatment
serum FSH (IU/l), LH (IU/l) are measured after the treatment and compared to the pretreatment values.
12 weeks of treatment
Testosterone level
Time Frame: 12 weeks
Total testosterone (nmol/l) is measured after the treatment and compared to the pretreatment values.
12 weeks
Estradiol level
Time Frame: 12 weeks
Estradiol (pmol/l) are measured after the treatment and compared to the pretreatment results
12 weeks

Collaborators and Investigators

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

Sponsor

Szeged University

Investigators

  • Principal Investigator: Norbert Pásztor, MD, PhD, University of Szeged, Department of Obstetrics and Gynecology, Reproductive Medicine Centre

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)

September 1, 2024

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

March 28, 2026

First Submitted That Met QC Criteria

April 4, 2026

First Posted (Actual)

April 13, 2026

Study Record Updates

Last Update Posted (Actual)

April 16, 2026

Last Update Submitted That Met QC Criteria

April 13, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NNGYK943

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

IPD used in the results publication, especially general information (age, BMI, smoking habits, alcohol consumption of patients), sperm analysis results, hormonal results.

IPD Sharing Time Frame

Starting after publication

IPD Sharing Access Criteria

Researchers upon request by email (hirt78@gmail.com)

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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