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Sperm DNA fragmentation is a novel biomarker for early pregnancy loss

Published:September 21, 2020DOI:https://doi.org/10.1016/j.rbmo.2020.09.016

      Highlights

      • Men with miscarriages have twice the sperm DNA damage than fertile donors
      • Alkaline Comet assay shows links between miscarriage and poor sperm DNA quality
      • Average, Low and High Comet Scores are all robust biomarkers for miscarriage
      • Sperm DNA testing may provide diagnosis and novel options for miscarriage couples

      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.

      KEYWORDS

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      Biography

      Lesley Haddock is the research and development manager at Examen Lab Ltd, a diagnostic company focusing on male infertility. Her research activities focus on the measurement of sperm DNA fragmentation.
      Key message
      Average Comet score, low Comet score and high Comet score measures of sperm DNA damage by the alkaline Comet may all be robust biomarkers for sporadic and recurrent miscarriage after either spontaneous or assisted conception and may provide pioneering diagnosis and guidance for future routes to fertility, if confirmed by other studies.