Evaluating Traditional Medicine Syndromes in Male Infertility With Oligoasthenoteratozoospermia

Characterization of Traditional Medicine Syndromes in Male Infertility With Oligoasthenoteratozoospermia Via Latent Tree Models

The goal of this observational study is to identify and evaluate the characteristics of Traditional Medicine (TM) syndromes in men aged 18 to 60 with male infertility and oligoasthenoteratozoospermia (OAT) syndrome. The main questions it aims to answer are:

• What are the common Traditional Medicine syndromes and symptoms associated with male infertility based on Traditional Medicine literature?
• What are the specific Traditional Medicine syndromes and symptoms found in men with OAT syndrome at Binh Dan Hospital when analyzed using Latent Tree Models?

The research will be conducted in two phases:

• Phase 1 (Literature Review): Researchers will collect and analyze Traditional Medicine texts to list the symptoms and syndromes related to male infertility. This phase will help create a standardized clinical survey.

• Phase 2 (Clinical Survey): Researchers will recruit 300 male participants with OAT syndrome.

  • Participants will answer a survey questionnaire about their Traditional Medicine symptoms.
  • Researchers will apply Latent Tree Models (a mathematical approach) to the collected data to objectively classify the TM syndromes.

Study Overview

• Status: Recruiting
• Conditions: Male Infertility With OAT

Detailed Description

• Study Rationale and Methodology Oligoasthenoteratozoospermia (OAT) is a significant contributor to male infertility, characterized by concurrent abnormalities in sperm concentration, motility, and morphology. While Traditional Medicine has been recognized by the World Health Organization (WHO) for its role in improving semen parameters, the classification of TM syndromes often relies on subjective clinical experience. This study utilizes Latent Tree Models (LTMs), a sophisticated probabilistic graphical model, to objectively identify the distribution and characteristics of TM syndromes in men with OAT.

• Phase 1: Literature-Based Framework Development The study begins with a systematic survey of classical and modern TM literature published between July 2025 and October 2025.

  • Source Selection: Literature includes classical texts recognized by the WHO/WPRO, textbooks from major medical universities in Vietnam and China, and expert consensus from Traditional Medicine associations.
  • Survey Tool Construction: Symptoms and syndromes related to male infertility are extracted and tabulated. Symptoms with a frequency of higher 30% in the literature are selected to build the formal clinical survey questionnaire.
  • Standardization: All Traditional Medicine terms are standardized according to WHO international terminologies.
• Phase 2: Clinical Implementation and Data Collection Clinical data will be collected at the Department of Andrology, Binh Dan Hospital, from November 2025 to August 2026.

Clinical Screening: Patients are first diagnosed with OAT by an andrologist based on the WHO Laboratory Manual (6th Edition).

Traditional Examination: Eligible participants undergo a non-invasive TM examination, including the "Four Examinations" (observation, listening/smelling, inquiring, and palpation).

Symptom Mapping: Symptoms are recorded as binary variables (presence or absence) to facilitate mathematical modeling.

*Statistical Analysis Using Latent Tree Models (LTMs) The core analysis employs the Lantern 5.0 software to discover the hidden (latent) structure of TM syndromes.

• Structure Learning: The Extension-Adjustment-Simplify-Transfer (EAST) algorithm is used to automatically group symptoms that frequently co-occur or are mutually exclusive.
• Parameter Estimation: The Expectation-Maximization (EM) algorithm estimates the probability of each patient belonging to a specific latent syndrome class.
• Syndrome Identification: Latent variables are interpreted and named as TM syndromes based on the symptoms that provide at least 95% Cumulative Mutual Information (CMI).
• Classification Algorithm: The study establishes a scoring threshold for each syndrome based on Naïve Bayes principles, allowing for a quantitative diagnosis of TM patterns in the OAT population.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Minh-Man Pham Bui, PhD; Phone Number: +84916080803; Email: bpmman@uhsvnu.edu.vn
• Study Contact Backup: Name: Dai-Nhan Tran, Medical Doctor; Phone Number: +84773478145; Email: nhantd97@gmail.com

Study Locations

• Vietnam
  • Ho Chi Minh City
    • Ho Chi Minh City, Ho Chi Minh City, Vietnam
      • Recruiting
      • Binh Dan Hospital
      • Contact: Dai-Nhan Tran, Medical Doctor; Phone Number: +84773478145; Email: nhantd97@gmail.com
      • Contact: Tien-Dung Mai Ba, PhD; Phone Number: +84913809110; Email: maibatiendung@yahoo.com
      • Principal Investigator: Dai-Nhan Tran, Medical Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population is a clinical cohort of men aged 18 to 60 years who seek medical consultation or treatment for reproductive health issues at the Department of Andrology, Binh Dan Hospital, Ho Chi Minh City. The specific population focuses on individuals diagnosed with male infertility and Oligoasthenoteratozoospermia (OAT) syndrome, characterized by a concurrent reduction in sperm count, motility, and normal morphology according to the World Health Organization (WHO) standards .

Description

Inclusion Criteria:

• Male patients aged between 18 and 60 years.
• Diagnosed with male infertility by an andrology specialist according to World Health Organization (WHO) standards.
• Semen analysis results meet the diagnostic criteria for Oligoasthenoteratozoospermia (OAT) syndrome.
• Voluntary agreement to participate in the research and signed Informed Consent Form.

Exclusion Criteria:

• Infertility caused by genetic or chromosomal abnormalities, including but not limited to: Klinefelter syndrome, Sandberg mosaic syndrome (46 XY/47 XXY), or XYY syndrome.
• Presence of structural abnormalities of the reproductive organs.
• Patients with Azoospermia (absence of sperm in the ejaculate) as defined by WHO 2021 standards.
• Use of medications affecting spermatogenesis within the last 3 months, including: cannabinoids, hydantoins, valproate, anabolic steroids, cimetidine, colchicine, spironolactone, nitrofurantoin, sulfasalazine, or calcium channel blockers.
• Inability to understand or answer survey questions due to physical or mental limitations (e.g., mutism, deafness, intellectual disability, coma, or being on a ventilator in the ICU).
• Lack of cooperation during the clinical examination and interview process.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Male Infertility Patients with OAT Syndrome; Men aged 18 to 60 years who are diagnosed with male infertility and present with Oligoasthenoteratozoospermia (OAT) syndrome. According to the World Health Organization (WHO) standards, OAT is defined by the following concurrent semen parameters:Oligozoospermia: Sperm concentration < 15 million/mL or total sperm count < 39 million.Asthenozoospermia: Progressive motility < 32%.Teratozoospermia: Normal morphology < 4%.; Participants are recruited from the Department of Andrology at Binh Dan Hospital, Ho Chi Minh City. The study excludes individuals with:Genetic or chromosomal abnormalities (e.g., Klinefelter syndrome, XYY syndrome).Structural abnormalities of the reproductive organs.Azoospermia (no sperm in the ejaculate).Recent use (within the last 3 months) of medications known to affect spermatogenesis, such as anabolic steroids or certain calcium channel blockers.Inability to communicate or participate in the survey.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Classification of Traditional Medicine Syndromes	The identification and classification of male infertility patients with Oligo-Astheno-Teratozoospermia into distinct TCM syndrome subtypes using the Latent Tree Model (LTM) and the Extension-Adjustment-Simplify-Transfer (EAST) algorithm. The analysis uses clinical symptoms and signs as features to cluster patients into groups.	At the time of enrollment in the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Traditional Medicine Syndrome Subtypes	The percentage distribution of each identified subtype within the study population.	At the time of enrollment
Statistical Characteristics of Clinical Symptoms per Syndrome	The occurrence probabilities of clinical indicators within each identified cluster. This provides quantitative evidence for the symptom profiles that define each syndrome.	At the time of enrollment

Collaborators and Investigators

• Sponsor: University of Medicine and Pharmacy at Ho Chi Minh City
• Investigators: Study Chair: Thi-Bay Nguyen, PhD, University of Medicine and Pharmacy at Ho Chi Minh City; Study Director: Minh-Man Pham Bui, PhD, University of Medicine and Pharmacy at Ho Chi Minh City; Study Director: Tien-Dung Ba Mai, PhD, Binh Dan Hospital; Study Director: Kim-Oanh Thi Ngo, University of Medicine and Pharmacy at Ho Chi Minh City; Principal Investigator: Dai-Nhan Tran, Medical Doctor, University of Medicine and Pharmacy at Ho Chi Minh City

Publications and helpful links

General Publications

• Zhang NL, Yuan S, Chen T, Wang Y. Latent tree models and diagnosis in traditional Chinese medicine. Artif Intell Med. 2008 Mar;42(3):229-45. doi: 10.1016/j.artmed.2007.10.004. Epub 2007 Dec 21.
• WHO laboratory manual for the examination and processing of human semen, 6th ed

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2026
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: March 28, 2026
• First Submitted That Met QC Criteria: April 9, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Male Infertility; OAT; Oligoasthenoteratozoospermia; Traditional Medicine Pattern
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Male Urogenital Diseases; Infertility; Infertility, Male; Oligospermia
• Other Study ID Numbers: 146/DHYD-HDDD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this study, after de-identification (including semen analysis parameters and Traditional Medicine clinical symptoms), will be shared with researchers who provide a methodologically sound proposal. The data will be available for the purpose of conducting meta-analysis or validating the Latent Tree Model (LTM) findings. Proposals should be directed to the Principal Investigator at nhantd97@gmail.com . To gain access, data requestors will need to sign a data access agreement and obtain approval from the study's scientific committee.
• IPD Sharing Time Frame: Beginning 6 months after publication and ending 3 years after publication.
• IPD Sharing Access Criteria: Requests should be directed to nhantd97@gmail.com . To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No