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.
Article info
Publication history
Published online: September 21, 2020
Accepted:
September 13,
2020
Received in revised form:
August 27,
2020
Received:
May 22,
2020
Declaration: Sheena Lewis and Lesley Haddock both work for Examenlab Ltd, a diagnostic company looking at sperm DNA fragmentation.Identification
Copyright
© 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
