Clinical Characteristics, Semen Parameters, and Reproductive Hormone Profiles in Infertile Men with Testicular Microlithiasis: A Meta-analysis

Summary

This meta-analysis of 13 studies provides a descriptive synthesis of testicular characteristics, semen parameters, and reproductive hormone profiles in infertile men with testicular microlithiasis.

Abstract

Testicular microlithiasis (TM) is frequently observed in infertile men, but its clinical significance remains controversial. This study aimed to systematically summarize the testicular characteristics, semen parameters, and reproductive hormone profiles of infertile men with TM and to describe the differences across TM subtypes. A systematic literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science from inception to November 14, 2025. Eligible studies included infertile male patients with ultrasound-confirmed TM. Data on testicular history, semen parameters, and hormonal profiles were extracted. Pooled prevalence estimates or pooled mean values were calculated using fixed- or random-effects models. Subgroup analyses were performed based on TM classification: classical (CTM) and limited (LTM). Thirteen studies were included. The pooled prevalence estimates of cryptorchidism, testicular cancer, and varicocele in infertile men with TM were 10.0%, 7.0%, and 37.0%, respectively. The pooled prevalence estimates of cryptorchidism, testicular cancer, and varicocele in infertile men with TM were 10.0%, 7.0%, and 37.0%, respectively. The pooled mean sperm concentration was 20.17 × 10⁶/mL. Subgroup analysis showed that CTM was associated with significantly lower sperm concentration than LTM (P = 0.042), whereas no significant differences were observed between CTM and LTM for sperm morphology or gonadotropin levels.. In conclusion, this meta-analysis provides a descriptive synthesis of clinical findings, semen characteristics, and endocrine profiles in infertile men with TM.

Introduction

Testicular microlithiasis (TM) is an ultrasonographic finding characterized by multiple non-shadowing hyperechogenic foci within the seminiferous tubules, typically reflecting intratubular calcifications. The clinical significance of TM remains under debate, particularly because of its proposed association with testicular germ cell tumors (TGCTs)¹. Although the prevalence of TM in the general male population is relatively low, usually reported to be less than 5%^2,3, its prevalence appears to be higher among infertile men, with recent studies reporting rates exceeding 10%

Protocol

Search strategy and selection criteria

This study conducted a comprehensive literature search across four databases, including PubMed, Embase, Cochrane Library, and Web of Science, covering the period from database inception to November 14, 2025. The search strategy combined Medical Subject Headings (MeSH) and free-text terms related to male infertility and TM and was adjusted according to the indexing system of each database. Representative search terms included "testicular microlithiasis", "microlithiasis", " testicular", and "Infertility, Male". The complete search strategies are provided in Supple....

Results

Study details and demographics

A total of 684 records were initially identified through the database search. After screening and eligibility assessment, 13 studies published between 1998 and 2022 were included in the meta-analysis. The included studies covered multiple geographical regions, including Europe, Asia, the Middle East, and North America^{4,13,17,.......}

Discussion

To our knowledge, this is the first meta-analysis specifically focused on infertile men with TM that quantitatively synthesizes semen characteristics, coexisting testicular conditions, and reproductive hormone profiles. Compared with previous evidence syntheses that primarily focused on semen parameters, our study further extends the current evidence by providing pooled estimates of cryptorchidism, varicocele, testicular cancer, and reproductive hormone levels, together with subgroup analyses according to TM subtype

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Cochrane Library	Cochrane	N/A	Database searched for eligible studies.
Embase	Elsevier	N/A	Database searched for eligible studies.
Medical Subject Headings (MeSH)	U.S. National Library of Medicine	N/A	Controlled vocabulary used in the search strategy.
Newcastle-Ottawa Scale (NOS)	N/A	N/A	Tool used to assess the methodological quality of observational studies.
PubMed	U.S. National Library of Medicine	N/A	Database searched for eligible studies.
Stata 17.0	StataCorp LLC	N/A	Software used for statistical analysis.
Web of Science	Clarivate	N/A	Database searched for eligible studies.
WHO semen analysis criteria/manuals (1999 and 2010)	World Health Organization	N/A	Reference criteria used to extract semen parameters according to the versions reported in the original studies.