Endocrine Abstracts (2017) 50 OC5.4 | DOI: 10.1530/endoabs.50.OC5.4

Reactive oxygen species as a novel metabolic pathway for sperm DNA damage and Recurrent Pregnancy Loss

Utsav K Radia1, Channa N Jayasena1,2,3, Monica Figueiredo1,2, Larissa Franklin Revill3, Anastasia Dimakopoulou2, Maria Osagie3, Wayne Vessey2, Lesley Regan3, Rajendra Rai3 & Waljit S Dhillo1

1Section of Investigative Medicine, Imperial College London, London, UK; 2Department of Andrology, Hammersmith Hospital, London, UK; 3Department of Obstetrics and Gynaecology, St. Mary’s Hospital, London, UK.

Background: Recurrent pregnancy loss (RPL) affects 1–2% couples, and is defined as ≧3 consecutive pregnancy losses before 20-weeks’ gestation. RPL is caused by foetal chromosomal abnormalities, or maternal factors such as thrombophilia. It was recently reported that men with RPL have high levels of sperm DNA fragmentation (a marker of infertility); however, the cause of this damage is currently not known. Seminal plasma has high levels of granulocyte-derived oxidative stress to prevent bacterial infection; however, sperm are also susceptible to oxidative stress. Oxidative stress may therefore play a role in male factor RPL.

Aims: Measure seminal reactive oxidative stress (ROS) and sperm DNA fragmentation in men with RPL vs. age- and BMI-matched controls.

Methods: Following ethical approval, seminal ROS was measured using a previously described in-house luminol chemiluminescence assay in men with RPL (n=47) and men unaffected by RPL (n=63). Sperm DNA fragmentation was measured using Halosperm assay.

Results: Men with RPL had similar mean age, weight and BMI compared with controls. Men with RPL had 50% higher ROS levels compared with controls (median ROS (IQR) (RLU/sec/106sperm): 0.8 (1.3), controls; 1.3 (3.8), RPL; P<0.01). Men with RPL had a four-fold higher risk of ROS elevation compared with controls (5/63, controls; 16/47, RPL, P=0.001). Sperm DNA fragmentation was 80% higher in men with RPL compared with controls (median DNA fragmentation (IQR) (%): 6.0 (8.0), controls; 11.0 (7.5); P<0.05). Men with RPL were significantly more likely to have abnormal sperm morphology compared with controls.

Conclusions: Our data show for the first time that men with RPL have increased seminal oxidative stress, which is known to cause DNA damage and reduced function in sperm. Seminal ROS presents a novel diagnostic tool and potential novel metabolic pathway for treating couples with RPL. These data therefore have important potential clinical implications for couples affected by RPL.