Maternal Inheritance of a Pathogenic MT-ND1 Mutation Causes Mitochondrial Dysfunction and Spermatogenic Failure in Men (MTND1-INA/C)

July 7, 2026 updated by: The Third Affiliated Hospital of Guangzhou Medical University

Study Protocol Used in Maternal Inheritance of a Pathogenic MT-ND1 Mutation Causes Mitochondrial Dysfunction and Spermatogenic Failure in Men

Idiopathic non-obstructive azoospermia and cryptozoospermia are severe forms of male infertility in which sperm production is absent or extremely low and the cause is often unknown. This retrospective observational study examined whether mitochondrial DNA variants, particularly the MT-ND1 m.3700G>A variant, are associated with impaired sperm production in Chinese men.

Existing clinical records and available biospecimens from affected men, eligible family members, and fertile controls were analyzed to assess familial inheritance patterns, the frequency of the variant, and its association with infertility phenotypes. No study-related treatment or intervention was provided to human participants.

Study Overview

Status

Recruiting

Conditions

Study Type

Observational

Enrollment (Estimated)

1200

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: Chen
Phone Number: 86-15918822529
Email: 15918822529@163.com

Study Locations

China
- Guangdong
  - Guangzhou, Guangdong, China, 510150
    - Recruiting
    - The Third Affiliated Hospital of Guangzhou Medical University
    - Contact:
      
      Chen Liao
      
      Phone Number: 86+15918822529
      
      Email: 15918822529@163.com

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

Child
Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

Participants were selected from men receiving care at the Reproductive Medicine Center of the Third Affiliated Hospital of Guangzhou Medical University. The study population included men with idiopathic non-obstructive azoospermia or cryptozoospermia identified through clinical records and available biospecimens; men with normal spermatogenic function or obstructive azoospermia who served as comparison participants; and, when needed, available first-degree relatives and spouses for family-based genetic analyses. Testicular tissue was obtained only from residual specimens following clinically indicated testicular biopsy, TESA, or micro-TESE procedures.

Description

Inclusion Criteria:

Men with idiopathic non-obstructive azoospermia or cryptozoospermia.
Male patients undergoing a clinically indicated testicular biopsy, testicular sperm aspiration (TESA), microdissection testicular sperm extraction (micro-TESE), or a related clinical procedure, when residual clinical specimens are available.
Comparison participants with normal spermatogenesis, including men with obstructive azoospermia and men undergoing sperm retrieval or testicular tissue evaluation for clinical reasons.
Selected relatives and spouses of enrolled patients, when needed for genetic segregation analysis and determination of variant origin.

Exclusion Criteria:

For the idiopathic non-obstructive azoospermia or cryptozoospermia cohort, azoospermia with an established alternative cause, including chromosomal abnormalities, Y-chromosome microdeletions, testicular tumors, severe trauma, prior radiotherapy or chemotherapy, or confirmed infection.
Incomplete clinical data or inability to obtain informed consent.
Biospecimens that do not meet quality requirements for the planned analyses.

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

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
INA/C Patients Men with idiopathic non-obstructive azoospermia or cryptozoospermia who were included in the retrospective clinical and genetic analyses.
Fertile Controls Fertile men who were included as comparison participants for mitochondrial DNA variant analyses.
Family Members Affected participants and available relatives who were included for pedigree, segregation, and maternal inheritance analyses of mitochondrial DNA variants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection and Familial Segregation of the MT-ND1 m.3700G>A Variant Time Frame: Baseline (single genetic testing assessment at enrollment)	Detection of the MT-ND1 m.3700G>A mitochondrial DNA variant by sequencing in available biological samples, with assessment of its distribution and maternal segregation among affected male family members, unaffected relatives, unrelated patients with idiopathic non-obstructive azoospermia or cryptozoospermia, and fertile controls.	Baseline (single genetic testing assessment at enrollment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Classification of Idiopathic Non-obstructive Azoospermia or Cryptozoospermia Time Frame: Baseline (single clinical classification based on pre-enrollment clinical records)	Affected participants were classified as having idiopathic non-obstructive azoospermia or cryptozoospermia according to the clinical diagnosis recorded after routine semen analyses and standard clinical evaluation.	Baseline (single clinical classification based on pre-enrollment clinical records)

Collaborators and Investigators

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

Sponsor

The Third Affiliated Hospital of Guangzhou Medical University

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 1, 2021

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

July 1, 2026

First Submitted That Met QC Criteria

July 7, 2026

First Posted (Actual)

July 9, 2026

Study Record Updates

Last Update Posted (Actual)