Testicular microlithiasis and male fertility: a dual perspective integrating imaging and physiological insights

Testicular microlithiasis (TM) is a pathological condition characterized by diffuse calcifications within the seminiferous tubules. Its clinical significance remains controversial. While some studies regard TM a benign imaging finding, others suggest potential associations with impaired fertility and an increased risk of testicular malignancy.

This study aims to systematically review the existing evidence regarding the relationship between TM and male fertility, incorporating both imaging and physiological perspectives.

A systematic review was conducted in accordance with PRISMA guidelines. We searched the PubMed, Embase, and CNKI databases from 2003 to 2025 using the keywords "testicular microlithiasis" in combination with "fertility," "spermatogenesis," and "semen analysis." The inclusion criteria comprised clinical studies evaluating TM in the context of male fertility, including imaging techniques, physiological mechanisms, case-control studies, cohort studies, cross-sectional studies, and narrative reviews. Conference abstracts and animal studies were excluded from the review. After rigorous screening, 66 high-quality studies were included for synthesis and analysis.

The prevalence of TM was significantly higher in infertile men (5.54%) compared to the fertile population (1.47%), reinforcing the potential link between TM and male infertility. Bilateral TM was strongly associated with reduced testicular volume, lower sperm retrieval rates, and abnormal semen parameters, indicating a more pronounced detrimental effect on reproductive function. Imaging and physiological data suggest that scrotal ultrasonography, used as the primary diagnostic tool, frequently reveals an elevated testicular resistive index (RI) in patients with TM. Concurrent findings include damage to the seminiferous tubules, aberrant expression of fertility-related genes such as KITLG and BMP7, and dysregulation of the testicular microenvironment, which may underlie impaired spermatogenesis. Additionally, in high-risk populations, TM has been linked to an increased risk of testicular germ cell tumors.

Individuals with bilateral TM and testicular atrophy should be classified as high-risk and closely monitored through routine ultrasound evaluations. Assisted reproductive technologies, such as microdissection testicular sperm extraction (micro-TESE), may be necessary to optimize fertility outcomes. Future research should prioritize large-scale prospective cohort studies and interdisciplinary approaches to elucidate the molecular mechanisms underlying TM and to advance personalized treatment strategies.