P-033 A third of men with normospermia attending for initial fertility assessment could have DNA damage
Authors: Aggrwal A , Lunt R , Lesley H , Hockenhull S , Nithin L , Shukla A , Gregoire R , Lewis S , Drakeley A 
Published: June 2022

Abstract

Study question
What is the incidence of sperm DNA damage in men with normal semen analyses attending for initial fertility investigation?

Summary answer
Half of men (54%) attending for infertilty investigation had a normal semen analysis of which a third (32%) of these had abnormal sperm DNA.

What is known already
Conventional semen analysis assesses sperm concentration, motility, and morphology but with a high degree of biological variability. Around 25% of men are given a diagnosis of unexplained infertility by normal semen analysis. The World Health Organisation (WHO) stated in 2021 that ‘clinically there is a growing awareness that chromosomal anomalies and gene mutations underlie a diverse spectrum of male infertility,’ so now recommends that sperm DNA is determined as an extended analysis. Sperm DNA damage occurs more often in infertile men and DNA damage is associated with recurrent pregnancy loss and decreased live birth rates following fertility treatment.

Study design, size, duration
A prospective cohort study of men attending a secondary fertility clinic were offered a standard semen analysis plus sperm DNA fragmentation using SpermComet technology. UK IRAS ethical approval was obtained. Men attending were given a patient information leaflet at their first appointment. The study duration was 6 months. In total, 142 men were recruited out of a possible maximum of 409 attendees.

Participants/materials, setting, methods
Participants included men who had been referred as a couple to a secondary level infertility clinic for an initial assessment. Information leaflets were either posted to them prior to their first appointment or given to them at the initial nurse-led consultation. Those who subsequently contacted our research team re-attended for a sperm analysis and an aliquot was cryopreserved and sent in weekly batches to Examen (Northern Ireland) for SpermComet DNA fragmentation assessment.

Main results and the role of chance
Between May and November 2021, there were 409 attendees of whom 142 consented to the study.
Sperm DNA quality for the participants was assessed and reported as average, low and high DNA damage as a percentage compared with clinical thresholds used by Examen from their sperm bank of 63 fertile sperm donors who had recently achieved clinical pregnancies.
Of the 142 recruited, 77 men (54%) attending for initial investigations had normospermia assessed against the WHO criteria, so were initially classified as unexplained. Of these, 25 (32%) had abnormal sperm DNA values. The average comet score was 39.7% +/-1.3, low comet score was 37.8% +/- 4.4 and high comet score was 17.0% +/-2.0. These values were all significantly outside ( p &lt; 0.001) of the fertile parameters from 63 fertile donors used by Examen (fertile range: average &lt;26%%, low &gt;74% and high &lt;4%).
Our results suggest that up to a third of men reported to have normospermia will have DNA damaged sperm. This is important to consider before labelling a couple as 'unexplained'. Knowing the male's sperm DNA fragmentation assessment would allow for further discussion and exploration of lifestyle and dietary advice.

Limitations, reasons for caution
During the study period, not all attendees agreed to participate as it required an additional hospital visit. In this single site study, men have not yet been followed up for future fertility outcome such as natural conception and need or success of assisted conception.

Wider implications of the findings
Sperm DNA damage was found in a third of men who would previously have been classified as fertile and offered no further investigations or treatment to improve their sperm quality. Thus, this tool could be a useful adjunct to semen analysis to guide these couples’ future treatment pathways.

Trial registration number
not applicable