Multifactorial analysis of male infertility: sperm DNA damage, semen parameters, and genetic testing in Iranian...

Male infertility is a multifactorial condition influenced by genetic, physiological, and environmental factors. While semen analysis is the cornerstone of diagnosis, additional tests like sperm DNA fragmentation (DFI) assessment and genetic testing are increasingly recognized for their diagnostic and prognostic value. This study investigates the relationships between DFI, semen parameters, and genetic abnormalities in Iranian men.

A retrospective cross-sectional study analyzed 6,397 men (5,196 infertile and 1,201 fertile controls) at the MOM Infertility Center between December 2022 and August 2023. Semen analysis evaluated sperm concentration, motility, morphology, Y chromosome AZF microdeletion testing, and whole-exome sequencing (WES) on subsets of infertile men. Correlations between age, sperm parameters, and DFI were assessed, and logistic regression evaluated the likelihood of abnormal sperm conditions.

Infertile men showed significantly lower sperm concentration, motility, and morphology, along with higher DFI, compared to controls. DFI was negatively correlated with sperm concentration, motility, and morphology. Age was positively correlated with DFI and negatively correlated with motility and morphology. Genetic abnormalities, including chromosomal anomalies, AZF deletions, and WES-detected mutations, were identified in subsets of infertile men, underscoring the value of genetic testing.

This study highlights significant associations between DFI, age, semen parameters, and genetic abnormalities in male infertility. Incorporating advanced diagnostic tools, such as DFI assessment and genetic testing, into clinical practice can improve diagnostic accuracy and guide personalized treatment strategies for infertile men.