Sperm DNA fragmentation and assisted reproduction: an umbrella meta-analysis

Area of Science:

• Reproductive Medicine
• Male Infertility Research
• Assisted Reproductive Technology (ART)

Background:

• Male infertility contributes significantly to global infertility issues.
• Conventional semen analysis offers limited insight into sperm function.
• Sperm DNA fragmentation (SDF) is a potential indicator of sperm nuclear quality, but its clinical utility in ART is debated.

Purpose of the Study:

• To perform an umbrella meta-analysis of existing meta-analyses.
• To evaluate the association between SDF and key ART outcomes: clinical pregnancy (CP), pregnancy loss (PL), and live birth rate (LBR).

Main Methods:

• Systematic literature search across major databases (PubMed, Embase, Web of Science, Scopus, Cochrane Library) up to July 2025.
• Inclusion of systematic reviews with meta-analyses on SDF in IVF, ICSI, and IUI.
• Assessment of evidence quality using AMSTAR-2 and GRADE frameworks.

Main Results:

• Eight meta-analyses covering over 25,000 ART cycles were analyzed.
• Elevated SDF correlated with reduced CP in IVF and IUI, and a borderline association in ICSI.
• High SDF showed a strong association with increased PL in ICSI cycles.
• Evidence regarding LBR was limited and inconclusive.
• Overall evidence certainty was low due to heterogeneity and methodological limitations.

Conclusions:

• Elevated SDF adversely impacts ART outcomes, particularly in IVF and IUI.
• A weak association was found for ICSI outcomes, but a strong link to miscarriage in ICSI was observed.
• Findings highlight the prognostic value of SDF but underscore the need for standardized assays and further prospective research for clinical integration.