Sperm DNA fragmentation is a novel biomarker for early pregnancy loss

Sperm DNA fragmentation is a novel biomarker for early pregnancy loss

Lesley Haddock, Stephen Gordon, Sheena E.M. Lewis, Peter Larsen, Amjad Shehata, Hassan Shehata

Examenlab Ltd, Unit 18A, Block K, Weavers Court Business Park, Linfield Road, Belfast BT12 5GH, UK; Urology at Epsom and St Helier University Hospitals NHS Trust, Dorking Rd, Epsom KT18 7EG, UK; Cryos International, Vesterbro Torv I, Aarhus 8000, Denmark; Centre for Reproductive Immunology and Pregnancy, Bramshott House, 137/139 High Street, Epsom KT19 8EH, UK; Maternal Medicine at Epsom and St Helier University Hospitals NHS Trust, Dorking Road, Epsom KT18 7EG, UK

Abstract:

Research question: Spontaneous pregnancy loss affects 10–15% of couples, with 1–2% suffering recurrent pregnancy loss and 50% of miscarriages remaining unexplained. Male genomic integrity is essential for healthy offspring, meaning sperm DNA quality may be important in maintaining a pregnancy. Does sperm DNA fragmentation measured by alkaline Comet assay act as a biomarker for early pregnancy loss?

Design: Sperm DNA fragmentation was measured by alkaline Comet test in 76 fertile donors and 217 men whose partners had recently experienced miscarriage. Couples were divided into five groups for analysis: one miscarriage after spontaneous conception; two or more miscarriages after spontaneous conception; one miscarriage after fertility treatment; two or more miscarriages after fertility treatment and biochemical pregnancy.

Results: Receiver operator characteristic curve analysis was used to determine ability of the average Comet score (ACS), low Comet score (LCS) and high Comet score (HCS) to diagnose miscarriage and develop clinical thresholds comparing men whose partners have miscarried with men with recently proven fertility. Male partners of women who had miscarried had higher sperm DNA damage (ACS 33.32 ± 0.57%) than fertile men (ACS 14.87 ± 0.66%; P < 0.001). Average Comet score, HCS and LCS all have promise as being highly predictive of sporadic and recurrent miscarriage using clinical thresholds from comparisons with fertile men’s spermatozoa: receiver operating characteristic curve AUC for ACS ≥26%, 0.965; LCS ≤70%, 0.969; HCS ≥2%, 0.883; P <0.0001.

Conclusions: Sperm DNA damage measured by the alkaline Comet has promise as a robust biomarker for sporadic and recurrent miscarriage after spontaneous or assisted conception, and may provide novel diagnoses and guidance for future fertility pathways.

Reproductive Biomedicine Online (RBMO) – DOI: https://doi.org/10.1016/j.rbmo.2020.09.016
Published: September 21, 2020