Probiotics on Sperm Quality in Male Infertility Patients

January 8, 2026 updated by: Mackay Memorial Hospital

Effect of Probiotics on Sperm Quality in Male Infertility Patients

This randomized, placebo-controlled pilot study aims to evaluate the effects of probiotic supplementation on sperm quality in male patients diagnosed with infertility. Male infertility accounts for approximately 40% of all infertility cases and is closely related to abnormalities in sperm count, motility, and morphology. Factors such as oxidative stress, inflammation, and DNA fragmentation are known to impact sperm function and subsequent fertilization potential negatively.

Probiotics are microorganisms that confer health benefits by improving the intestinal microenvironment and regulating immunity. Emerging research suggests that probiotics may reduce oxidative stress and DNA fragmentation in men with asthenozoospermia; however, clinical data on human sperm remains limited. This study seeks to determine whether specific probiotic strains can improve sperm parameters and function in patients with unexplained oligozoospermia, asthenozoospermia, or oligoasthenoteratozoospermia.

The study will enroll 60 male participants aged 20 to 45 who meet specific inclusion criteria, including a sperm concentration of less than 50 million/mL, motility less than 40%, and normal morphology (Kruger) less than 4%. Participants will be randomly assigned to either an experimental group receiving probiotics or a control group receiving a placebo for approximately 100 days.

Semen samples will be collected and analyzed at three time points: before the intervention (Day 0), during the intervention (Day 60), and at the end of the study (Day 100). The primary objective is to assess changes in sperm concentration, motility, and morphology using the Computer-Aided Sperm Analysis (CASA) system. Secondary objectives include evaluating sperm DNA integrity using the Sperm Chromatin Structure Assay (SCSA) by flow cytometry and assessing sperm function via the acrosome reaction assay. The results of this pilot study will help determine the potential therapeutic role of probiotics in the management of male infertility.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Content: Male infertility accounts for approximately 40% of infertility cases and is often characterized by abnormalities in sperm count, motility, and morphology. Factors such as oxidative stress, environmental hormones, and inflammation can lead to sperm DNA fragmentation and mitochondrial dysfunction, ultimately affecting fertilization potential. While probiotics are known to improve gut microbiome balance and regulate immunity, limited studies suggest they may also improve sperm motility and reduce DNA fragmentation in men with asthenozoospermia.

This pilot study employs a randomized, placebo-controlled design to evaluate the efficacy of probiotic supplementation in improving sperm quality. A total of 60 male participants with unexplained infertility (specifically oligozoospermia, asthenozoospermia, or oligoasthenoteratozoospermia) will be recruited. Participants will be divided into two groups: an experimental group receiving probiotics and a control group receiving a placebo.

The study duration for each participant is approximately 100 days, with semen samples collected at three distinct time points:

  1. Day 0 (Start Test): Baseline sample collection.
  2. Day 60 (Mid Test): Interim sample collection.
  3. Day 100 (Final Test): Post-intervention sample collection.

Semen analysis will be conducted using the following methodologies:

  • Sperm Concentration and Motility: Analyzed using a Computer-Aided Sperm Assay (CASA) to measure parameters including total motility, progressive motility, VAP, VCL, VSL, Straightness, and Linearity.
  • Sperm DNA Integrity: Assessed via the Sperm Chromatin Structure Assay (SCSA) using flow cytometry. Sperm are treated with acridine orange; red fluorescence indicates single-stranded DNA (fragmentation), while green fluorescence indicates double-stranded DNA. Results are expressed as the DNA Fragmentation Index (DFI).

Sperm Function (Acrosome Reaction): Evaluated using Peanut Agglutinin (PNA) staining. The assay determines the percentage of sperm capable of undergoing the acrosome reaction, a necessary step for fertilization.

Inclusion Criteria

  • Gender: Male.
  • Age: 20 to 45 years old.
  • Diagnosis: Diagnosed with unexplained oligozoospermia, asthenozoospermia, or oligoasthenoteratozoospermia.

  • Semen Parameters:

    • Sperm concentration < 5×106/mL (Note: Source indicates "5x10/mL", contextually adjusted to standard unit for oligozoospermia).
    • Sperm motility < 40%.

    • Sperm morphology (Kruger strict criteria) < 4%. Exclusion Criteria

      1. History of hormonal disorders or epididymo-orchitis.
      2. Substance abuse, including drugs or excessive alcohol consumption.
      3. Diabetes mellitus.
      4. Kidney disease (defined as a doubling of creatinine levels or more).
      5. Chronic liver disease.
      6. Varicocele.
      7. Current use of medications that interfere with hormones.
      8. Occupational or environmental exposure to pesticides, heavy metals, or solvents.
      9. Intake of antioxidant supplements within the past three months.
      10. Body Mass Index (BMI) of 30 kg/m² or higher.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

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

  • Name: Sheng-Hsiang Li, PhD
  • Phone Number: 2357 886-2-28094661
  • Email: lsh@mmh.org.tw

Study Locations

  • Taiwan
      • New Taipei City, Taiwan, 25160
        • Recruiting
        • Mackay Memorial Hospital
        • Contact:
          • Sheng-Hsiang Li, PhD
          • Phone Number: 2357 886-2-28094661
          • Email: lsh@mmh.org.tw

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:

  • Males aged 20 to 45 years
  • Diagnosis of unexplained oligozoospermia, asthenozoospermia, or oligoasthenoteratozoospermia
  • Sperm concentration < 5 x 10^6/mL
  • Sperm total motility < 40%
  • Sperm morphology (Kruger strict criteria) < 4%

Exclusion Criteria:

  • History of hormonal disorders or epididymo-orchitis
  • Substance abuse, including drugs or excessive alcohol consumption
  • Diabetes mellitus
  • Kidney disease (defined as a doubling of creatinine levels or more)
  • Chronic liver disease
  • Varicocele
  • Current use of medications that interfere with hormones
  • Occupational or environmental exposure to pesticides, heavy metals, or solvents
  • Intake of antioxidant supplements within the past three months
  • Body Mass Index (BMI) of 30 kg/m^2 or higher

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental: Probiotics Group
The experimental group takes probiotics, two capsules a day, after meals.
Dietary supplement: Probiotics
The subjects take 2 probiotic capsules after each meal daily.
Placebo Comparator: Placebo Comparator: Control Group
The control group is given the same dosage form without probiotics (placebo), two capsules a day, after meals.
Dietary supplement: Placebo
The control group takes two placebo capsules (containing no probiotics) after meals daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Sperm Concentration Assessed by Computer-Aided Sperm Analysis (CASA)
Time Frame: Day 60, Day 100
Sperm concentration (million/mL) will be measured using the Computer-Aided Sperm Analysis (CASA) system. The change from Baseline (Day 0) to subsequent time points will be calculated.
Day 60, Day 100
Change From Baseline in Total Sperm Motility Percentage Assessed by Computer-Aided Sperm Analysis (CASA)
Time Frame: Day 60, Day 100
The percentage of total motile sperm will be measured using the Computer-Aided Sperm Analysis (CASA) system. The change from Baseline (Day 0) to subsequent time points will be calculated.
Day 60, Day 100
Change From Baseline in Percentage of Normal Sperm Morphology Assessed by Computer-Aided Sperm Analysis (CASA)
Time Frame: Day 60, Day 100
The percentage of sperm with normal morphology will be measured based on Kruger strict criteria using the Computer-Aided Sperm Analysis (CASA) system. The change from Baseline (Day 0) will be calculated.
Day 60, Day 100

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Sperm DNA Fragmentation Index (DFI) Assessed by SCSA
Time Frame: Day 60, Day 100
Sperm DNA integrity will be assessed using the Sperm Chromatin Structure Assay (SCSA) via flow cytometry. Sperm are stained with acridine orange. The result is expressed as the DNA Fragmentation Index (DFI), representing the ratio of red fluorescence (fragmented DNA) to total fluorescence (red + green). A lower DFI indicates better DNA integrity.
Day 60, Day 100
Change From Baseline in Sperm Acrosome Reaction Rate Assessed by PNA Staining
Time Frame: Day 60, Day 100
Sperm function will be evaluated by the acrosome reaction assay using peanut agglutinin (PNA) staining. The percentage of sperm that have undergone the acrosome reaction (indicated by specific staining patterns observed under a fluorescence microscope) will be calculated. This measures the sperm's physiological capability to fertilize an egg.
Day 60, Day 100

Collaborators and Investigators

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

Sponsor

Mackay Memorial Hospital

Collaborators

Grape King Bio Ltd.

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 16, 2023

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

May 7, 2025

First Submitted That Met QC Criteria

January 8, 2026

First Posted (Actual)

January 15, 2026

Study Record Updates

Last Update Posted (Actual)

January 15, 2026

Last Update Submitted That Met QC Criteria

January 8, 2026

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GP001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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