Micronutrients in Support to The Carbon Cycle Activate Antioxidant Defences and Reduce Sperm DNA Damage in Infertile Men Attending Assisted Reproductive Technology Programs: Clinical Trial Study

Micronutrients in support of the carbon cycle have been shown to reduce sperm DNA damage both in animal models and in infertile men. Besides supporting DNA methylation, their positive effect may be sustained by an improved performance of the endogenous antioxidant system but this has not yet been proven in the clinical setting. The present study aimed at testing a micronutrient supplementation in infertile men partners to ART resistant couples and to investigate the nature of their effects.

Infertile men partners to couples resistant to at least one ART cycle and with a sperm fragmentation rate > 20% (TUNEL) underwent a 4-month oral supplementation with micronutrients in support to the carbon cycle including folates, B vitamins, zinc and cysteines. Semen analysis, sperm DNA fragmentation (TUNEL), nuclear maturation (CMA3 and blue aniline staining) and lipid peroxidation (BODIPY) were assessed before and after treatment. The couples were followed-up to record clinical outcomes.

Forty-three patients completed the program but full data pre and post treatment were available only for 25 patients. The treatment did not modify sperm concentration and motility but improved morphology. Nuclear maturation, DNA fragmentation and lipid peroxidation significantly improved after treatment. Overall 10 clinical pregnancies (23.3%) and 4 live births (9.3%) were recorded during the follow-up following expectant management (25 couples) or a new ICSI cycle (18 couples).

The micronutrients appeared to induce both DNA methylation, resulting in improved sperm nuclear maturation, and antioxidant defenses, resulting in less of DNA fragmentation and lipid peroxidation. The clinical outcomes were aligned with a possible positive effect on reproductive function. Micronutrients qualify as an alternative to antioxidants in correcting oxidative damage in infertile men and warrant further clinical investigation.