The impact of coenzyme Q10 on seminal oxidative stress markers, sperm DNA fragmentation, and predictors of pregnancy in men with idiopathic infertility

Oxidative stress (OS) and sperm DNA fragmentation (SDF) have been linked to idiopathic male infertility (IMI) but the underlying mechanisms remain unknown. Oral antioxidants including coenzyme Q10 (CoQ10) have been tried to treat IMI with inconsistent outcomes and lack of agreement on a standardized treatment regimen. In addition, data on the impact of CoQ10 on oxidative stress markers, SDF, and pregnancy outcomes are limited. Therefore, in this research portfolio, I led several clinical studies to explore the impact of CoQ10 therapy (200 mg/day for 36 months) on seminal antioxidant markers, SDF, pregnancy outcome, time to pregnancy (TTP), and their predictors. The submitted work represents the outcome of my research experience from working for sixteen years as a lecturer, researcher, and specialist doctor at the College of Medicine, University of Babylon, Iraq. I have published 10 papers in specialized international journals with impact factor. I have used different clinical study designs, established and validated research methodologies including systematic reviews, meta-analysis, narrative reviews, prospective randomized and controlled clinical studies. These papers represent a coherent work that is focused on the seminal antioxidant status, SDF, and determinants of pregnancy and TTP outcomes in men with IMI before and after CoQ10 therapy. To explore this theme, different parameters including reactive oxygen species (ROS), total antioxidant capacity, catalase, superoxide dismutase, glutathione peroxidase, SDF, seminal CoQ10 level, and sex hormones were assessed in men with IMI and fertile controls in follow-up studies. I have also compared different doses of CoQ10, CoQ10 with selenium, and CoQ10 with Centrum multivitamin. In addition, the main paper (P10) included the largest number of participants (178 patients and 84 controls) who received CoQ10 for an extended period of 6 months and a total follow-up of 24 months. This paper further explored the pregnancy rate, TTP, and their clinical and biochemical predictors in patients with idiopathic oligoasthenospermia (OA) using binomial logistic regression and Cox regression (survival analysis). Overall, the studies demonstrated that 3-6 months of CoQ10 therapy (200 mg/day) significantly increased seminal CoQ10 levels, semen parameters, antioxidant capacity, and reduced SDF and ROS with a pregnancy rate of 24.2% in men with idiopathic OA after 24 months. In addition, the concluding study has identified several independent clinical and biochemical reproductive predictors. CoQ10 level, sperm concentration, motility, and ROS could be independent predictors of pregnancy outcome. CoQ10 level, male age, sperm concentration, motility, ROS, and glutathione peroxidase could be independent predictors of TTP in men with idiopathic OA. The studies have been cited in journals with impact factor and represent a significant contribution to the understanding of the underlying mechanisms and oxidative stress and SDF contribution for IMI. Further, the identified predictors could be used as a diagnostic and therapeutic target in men with IMI, and CoQ10 therapy (200 mg/day) for 6 months could be a potential therapy for the challenging group of men with IMI. Therefore, the studies provide a set of potential clinical and biochemical markers and an optimized targeted therapy that may facilitate the management of men with IMI in the clinical setting and may enhance their fertility potential. Thus, our findings may improve the diagnosis and treatment of IMI, OS, and SDF testing, indication, pregnancy outcome, provide prognostic data, and may reduce the psychological, and financial burden on infertile couples with improved quality of health care. The observed reduction of SDF may also be associated with enhanced wellbeing of the offspring. In addition, the current work will also enhance my career as a lecturer, researcher, and specialist doctor at the University of Babylon through incorporating the current knowledge into the clinical practice and management of infertile men with IMI. Further, the findings of the studies will motivate me to conduct further large-scale studies to consolidate the evidence on the impact of CoQ10 and other antioxidants on fertility biomarkers and determinants of pregnancy and ART outcomes in IMI. Finally, the current programme will also help me to supervise the research projects of postgraduate students at the University of Babylon.