Recurrent Pregnancy Loss: A Couple-Based Framework for Integrating Paternal Assessment.

Background/

Objectives

Recurrent pregnancy loss (RPL) has traditionally been investigated predominantly through maternal factors, while the clinical role of paternal assessment remains inconsistently defined. Current guidelines differ substantially regarding semen analysis, sperm DNA fragmentation (SDF), genetic testing, and referral for andrological evaluation. This review aimed to compare contemporary guideline recommendations, critically appraise the directness, prognostic value, and clinical utility of the supporting evidence, and classify paternal assessment strategies as routine, selective, or investigational.

Methods

A structured narrative review was conducted using PubMed and Scopus searches through June 2026. International RPL, obstetric, reproductive medicine, and andrology guidelines were compared. Evidence from systematic reviews, meta-analyses, clinical studies, and clinically relevant molecular investigations was evaluated according to its directness to RPL populations, diagnostic and prognostic value, and evidence that test-guided interventions improve miscarriage or live-birth outcomes.

Results

Routine paternal assessment should include age, reproductive and medical history, body weight, lifestyle, medication exposure, and relevant environmental or occupational risks. Conventional semen analysis is appropriate primarily when RPL coexists with infertility or suspected male reproductive disease. SDF is the most extensively studied advanced paternal biomarker and is frequently elevated in RPL cohorts, but findings vary by assay and comparator population, while prospective prediction of subsequent live birth and benefit from SDF-directed treatment remain unproven. Parental karyotyping has established counselling value but should be risk-stratified. Sperm aneuploidy testing, oxidative stress assays, seminal microbiome profiling, epigenetic biomarkers, and biomarker-directed interventions remain investigational.

Conclusions

Paternal assessment in RPL should be couple-based, clinically targeted, and evidence-informed. Current evidence supports routine clinical evaluation, selective use of semen analysis, SDF testing, genetic assessment, and reproductive urology referral, and restriction of unvalidated biomarkers and treatments to research settings.