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

NCT07691827 | Recruiting

• 1 other identifier: 82471639
• Study Type: observational
• Target: 1,200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Azoospermia, Nonobstructive; Cryptozoospermia

Keywords

Male Infertility; MT-ND1; Maternal Inheritance

Outcome Measures

Primary Outcomes (1)

• Detection and Familial Segregation of the MT-ND1 m.3700G>A Variant

  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 Outcomes (1)

• Clinical Classification of Idiopathic Non-obstructive Azoospermia or Cryptozoospermia

  Baseline (single clinical classification based on pre-enrollment clinical records)

Study Arms (3)

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.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Third Affiliated Hospital of Guangzhou Medical University: lead

Study Sites (1)

The Third Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510150, China

RECRUITING

MeSH Terms

Conditions

Azoospermia, Nonobstructive; Oligospermia; Infertility, Male

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Infertility; Male Urogenital Diseases

Central Study Contacts

Chen

CONTACT

86-15918822529; 15918822529@163.com

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2026
• First Posted: July 9, 2026
• Study Start: April 1, 2021
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 9, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)