Double-stranded sperm DNA fragmentation assessed using comet assay is associated with recurrent pregnancy loss


Drakeley, A ORCID: 0000-0002-8802-4706, Lunt, RL, Newton, E, Gregoire, RC, Watkins, L, Bambang, K, Ellard, AM, Ledgerwood, CJ, Rae, L, Sloan, A et al (show 7 more authors) (2026) Double-stranded sperm DNA fragmentation assessed using comet assay is associated with recurrent pregnancy loss Reproductive Biomedicine Online, 52 (1). 105184-. ISSN 1472-6483, 1472-6491

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Abstract

Research question: Do men attending a recurrent miscarriage clinic have high double-stranded sperm DNA damage compared with a sperm donor population? Design: This prospective cohort study included 100 men attending a recurrent miscarriage clinic, and 81 sperm donors from a European sperm bank who had proven fertility. All semen samples were evaluated using the Examen Lab alkaline (Exact) comet assay, which identifies the global (single and double strand) DNA damage, and the neutral (Extend) comet assay, measuring only double-stranded sperm DNA fragmentation (dsSDF). Results: Semen analysis showed that 66 male partners of women with a history of recurrent miscarriage were classified as being within normal parameters. Of these, however, 66 men (61%) had raised global SDF, and 52% had raised dsSDF. When evaluating each test separately, the Exact comet (global SDF) assay presented an area under the curve (AUC) of 0.690 (95% CI 0.623–0.756), with the neutral Extend comet (dsSDF only) assay having an AUC of 0.876 (95% CI 0.834–0.914), and the incidence of damage showed an improved AUC of 0.909 (95% CI 0.874–0.940). Conclusions: This study of male factor SDF in a large cohort of men attending a recurrent miscarriage clinic, where they are rarely the focus of clinical investigation, shows a strong association with dsSDF and male factor-driven miscarriage contribution, highlighting the importance of male investigation in couples experiencing recurrent pregnancy loss.

Item Type: Article
Uncontrolled Keywords: Spermatozoa, Humans, Abortion, Habitual, Comet Assay, Prospective Studies, DNA Fragmentation, Pregnancy, Adult, Female, Male, Semen Analysis
Divisions: Faculty of Health & Life Sciences
Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 27 Aug 2025 09:41
Last Modified: 28 Feb 2026 01:35
DOI: 10.1016/j.rbmo.2025.105184
Open Access URL: https://doi.org/10.1016/j.rbmo.2025.105184
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3194178
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