The Impact of SARS-CoV-2 on Male Infertility: A Systematic Review and Meta-Analysis of Cohort Studies

This meta-analysis of cohort studies found statistically significant reductions in sperm concentration, count, motility, and DNA fragmentation index following SARS-CoV-2 infection.

Journal: Reviews in Medical Virology | Published: 2026-03 | Type: Systematic Review, Meta-Analysis | PMID: 41863427 Authors: Barzoki Mehdi Gholami, Farahmand Mohammad, Mahmodi Mohamad Javad, Amirjannati Naser, Malekshahi Somayeh Shatizadeh — Tarbiat Modares University (Virology), Tehran University of Medical Sciences, Avicenna Research Institute / ACECR (Reproductive Biotechnology) Funding/COI: Funded by Iran's National Institute for Medical Research Development. COI not disclosed.

Summary

This is the most current systematic review and meta-analysis on SARS-CoV-2 and male semen parameters, covering cohort data through December 2023 across PubMed, Scopus, Cochrane, and Web of Science. It uses two analytical frameworks: between-group comparisons (recovered men vs. uninfected controls) and within-subject comparisons (pre- vs. post-infection in the same individuals). The between-group analysis shows statistically significant reductions across five parameters — concentration, total count, total motility, progressive motility, and DNA fragmentation index — but the abstract reports only p-values, leaving effect size context absent. Whether "statistically significant" here translates to clinically meaningful impairment in real fertility outcomes is a question this paper raises but does not close.

Claims

• In single-arm studies (no control group), semen volume was significantly reduced post-COVID (p = 0.0023)
• In controlled cohort comparisons, recovered men showed statistically significant decreases in:
• Sperm concentration (p < 0.0001)
• Total sperm count (p = 0.0001)
• Total motility (p = 0.0009)
• Progressive motility (p = 0.0391)
• DNA fragmentation index (p = 0.04)
• Morphology was assessed but no significant finding is reported in the abstract
• Effect sizes were calculated as standardized mean differences (SMD) with 95% CIs using the DerSimonian-Laird method; specific SMD values are not reported in the abstract

Study Quality

The methodological framework is appropriate: PECO-structured research question, multi-database search, standardized effect size calculation (SMD), heterogeneity estimation via DerSimonian-Laird and Jackson methods, and publication bias assessment using both funnel plots and Egger's test. Splitting the analysis into controlled and single-arm cohorts is the right call — these are fundamentally different evidence tiers, and conflating them would obscure the signal. The controlled cohort findings are the ones that matter, and those p-values are strong.

The critical gap is that the abstract provides only p-values, not the SMDs themselves. Without knowing the magnitude of the effect — how many million/mL of sperm concentration were lost, or by how much DFI shifted — it is impossible to assess clinical relevance from the abstract alone. A statistically significant SMD can represent a trivial real-world change if confidence intervals are narrow and the underlying means differ by a fraction of a standard deviation. The literature cutoff is December 2023, and the paper was published in early 2026; that 26-month lag is notable and raises the question of why significant time elapsed before publication.

Red Flags

• Abstract reports p-values only — SMD effect sizes, which are the paper's primary outcome, are absent from the summary; clinical significance cannot be assessed without them
• COI is "not listed" — for a paper from an Iranian government-funded institution, potential publication pressure cannot be evaluated
• Literature cutoff December 2023; published March 2026 — the 26-month gap between data and publication is unexplained
• Single-arm studies lack controls by definition; the semen volume finding rests on this weaker tier
• "Compelling evidence" in the abstract is editorializing that overreaches what a meta-analysis of observational cohorts can establish
• Post-COVID recovered men may differ from uninfected controls in confounding ways (fever severity, hospitalization, concurrent medications, lifestyle changes during illness) that cohort design cannot fully control
• DFI p-value of 0.04 is marginal; at typical meta-analysis scales, this could flip with one additional study

Strengths

• Most up-to-date meta-analysis on this topic, covering literature through December 2023
• Four major databases searched, with PECO framework applied consistently
• Correct decision to separate controlled-cohort from single-arm analyses rather than pooling incompatible study designs
• Within-subject comparison design (pre/post same individuals) is the stronger causal frame and is included alongside the between-group analysis
• Publication bias formally tested with both Egger's test and funnel plots
• Clinically relevant parameter set: covers the full standard semen analysis panel plus DFI, which is not always included

Verdict

The finding that COVID-19 measurably disrupts multiple semen parameters is not surprising — viral illness, fever, and systemic inflammation are well-established insults to spermatogenesis, and earlier, smaller studies pointed in this direction. What this paper adds is a pooled, structured synthesis that strengthens the signal. The between-group controlled analysis is credible. The problem is that the abstract withholds the effect sizes that would let a reader judge whether "statistically significant" means "your semen analysis will look different" or "fertility clinics should be asking about COVID history." Read the full paper for the SMDs before treating this as definitive. Solid meta-analysis work on a question that warranted it; overstated in the abstract's conclusion.