Contemporary Diagnostic Work-Up for Male Infertility: Emphasizing Comprehensive Baseline Assessment

Abstract

Infertility is a prevalent issue affecting many couples during their reproductive years, with a significant number facing challenges in conceiving despite regular unprotected intercourse. Male factor infertility (MFI) contributes significantly to these cases, with a significant proportion of men lacking an identifiable etiology. As such, a thorough assessment of MFI has become increasingly vital for personalized management. This position paper from the Andrology team at IRCCS Ospedale San Raffaele emphasizes a comprehensive and individualized approach to MFI work-up, addressing the evolving challenges encountered in clinical practice. Our approach involves a thorough diagnostic work-up to identify the underlying causes of MFI, integrating insights from extensive literature review and our proprietary data. Our data demonstrates that an extensive diagnostic assessment allows us to identify at least one underlying cause of MFI in most infertile men. However, challenges persist in diagnosing less severe phenotypes with unclear etiology. We discuss the importance of individualized MFI work-up and its implications for developing rational therapeutic protocols. Lastly, this paper highlights the necessity for a personalized diagnostic assessment, addressing the daily clinical challenges and emphasizing tailored approaches to try to improve outcomes among couples seeking first medical help for infertility.

Keywords: Diagnosis; Epidemiology; Infertility, male; Semen analysis.

Fig. 1. Diagnostic approach to MFI at IRCCS Ospedale San Raffaele. MFI: male factor infertility, OAT: oligoasthenoteratozoospermmia, TV: testicular volume, NOA: non-obstructive azoospermia, CFTR: cystic fibrosis transmembrane conductance regulator, NLR: neutrophil-to-lymphocyte ratio, HPV: human papillomavirus, PSA: prostate-specific antigen, FSH: follicle-stimulating hormone, LH: luteinizing hormone, PCa: prostate cancer, BMI: body mass index, SCSA: sperm chromatin structure assay.