Pathophysiology-Based Classification of Male Infertility: Evidence from an 800-patient Prospective Cohort

Area of Science:

• Reproductive Medicine
• Endocrinology
• Urology

Background:

• Male factor infertility (MFI) is often labeled idiopathic due to reliance on basic semen analysis.
• This diagnostic gap overlooks crucial endocrine and pathophysiological factors.
• Targeted management for MFI is hindered by the lack of detailed phenotyping.

Purpose of the Study:

• To phenotypically define MFI through comprehensive evaluation.
• To develop a pathophysiology-based classification system for MFI.
• To reduce the incidence of idiopathic infertility diagnoses.

Main Methods:

• Prospective cohort study of 800 male partners of infertile couples.
• Standardized clinical, hormonal (testosterone, FSH, LH), semen, and ultrasound assessments.
• Included microbiological, transrectal ultrasound, and genetic analyses as indicated.

Main Results:

• Primary spermatogenic failure (56.0%) and infection/inflammation (22.4%) were the most common MFI categories.
• Hypogonadotropic hypogonadism accounted for 8.5% of cases.
• Idiopathic infertility was reduced to 5.3% post-comprehensive work-up, with distinct endocrine profiles observed.

Conclusions:

• Comprehensive phenotyping drastically lowers idiopathic MFI diagnoses.
• Identifies distinct, clinically relevant subgroups of male infertility.
• Supports integrated endocrine diagnostic strategies for targeted MFI management.