Antioxidant pretreatment for male partner before ART for male factor subfertility: a randomized controlled trial.

study questionDoes oral antioxidant pretreatment for the male partner improve clinical pregnancy rate in couples undergoing ART for male factor subfertility? SUMMARY ANSWER: There was no significant difference in clinical pregnancy rate following oral antioxidant pretreatment for male partner in couples undergoing ART for male factor subfertility compared to no pretreatment. WHAT IS KNOWN ALREADY: Damage to sperm mediated by reactive oxygen species (ROS) contributes significantly to male factor infertility. The ROS-related injury reduces fertilization potential and adversely affects the sperm DNA integrity. Antioxidants act as free radical scavengers to protect spermatozoa against ROS induced damage. During ART, use of sperms which have been exposed to ROS-mediated damage may affect the treatment outcome. Pretreatment with antioxidants may reduce the ROS-mediated sperm DNA damage. Currently, antioxidants are commonly prescribed to men who require ART for male factor subfertility but there is ambiguity regarding their role. STUDY DESIGN SIZE DURATION: This was an open label, randomized controlled trial conducted at a tertiary level infertility clinic between February 2013 and October 2019. The trial included 200 subfertile couples who were undergoing ART treatment for male factor subfertility. PARTICIPANTS/MATERIALS SETTING

methodsCouples were randomized into treatment arm (n = 100) and control arm (n = 100). In the treatment arm, the male partner received oral antioxidants (Vitamin C, Vitamin E and Zinc) for 3 months just prior to the ART cycle. In the control arm, no antioxidant was given to the male partner. The primary outcome was clinical pregnancy rate, while live birth rate (LBR), miscarriage rate and changes in semen parameters were the secondary outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: Out of 200 women randomized, 135 underwent embryo transfer as per protocol. Following intention to treat analysis, no significant difference was noted in clinical pregnancy (36/100, 36% vs 26/100, 26%; odds ratio (OR) 1.60, 95% CI 0.87 to 2.93) and LBR (25/100, 25% vs 22/100, 22%; OR 1.18, 95% CI 0.61 to 2.27) between antioxidant and no pretreatment arms. The clinical pregnancy rate per embryo transfer was significantly higher following antioxidant pretreatment (35/64, 54.7% vs 26/71, 36.6%; OR 2.09, 95% CI 1.05 to 4.16) compared to no pretreatment. There was no significant difference in LBR per embryo transfer (25/64, 39.1%, vs 22/71, 31.0%; OR 1.43, 95% CI 0.70 to 2.91) after antioxidant pretreatment versus no pretreatment. The semen parameters of sperm concentration (median, interquartile range, IQR) (18.2, 8.6 to 37.5 vs 20.5, 8.0 to 52.5, million/ml; LIMITATIONS REASONS FOR CAUTION: The objective assessment of sperm DNA damage was not carried out before and after the antioxidant pretreatment. Since the clinicians were aware of the group allotment, performance bias cannot be ruled out. WIDER IMPLICATIONS OF THE

findingsThe current study did not show any significant difference in clinical pregnancy and LBR following antioxidant pretreatment for the male partner in couples undergoing ART for male subfertility. The findings need further validation in a larger placebo-controlled randomized trial. STUDY FUNDING/COMPETING INTERESTS: This trial has been funded by Fluid Research grant of Christian Medical College, Vellore (internal funding). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: CTRI/2013/02/003431. TRIAL REGISTRATION DATE: 26 February 2013. DATE OF FIRST PATIENT’S ENROLMENT: 11 February 2013.