Oral Antioxidant Treatment of Men Significantly Improves the Reproductive Outcome of IVF Cycles

Abstract

Some 30% to 80% of male sub-fertility may be associated with oxidative stress that damages spermatozoa and can decrease success of in vitro fertilization (IVF) techniques. This multicenter, longitudinal, prospective study aimed to investigate whether oral antioxidant supplementation improved the reproductive competence of men who had had low fertilization rates in their previous intracytoplasmic sperm injection (ICSI) cycles without azoospermia or severe oligozoospermia or any identifiable andrological disease. Seventy-seven men from couples who had an ICSI attempt with unexplained <60% fertilization rate took an antioxidant mix of myo-inositol, alpha-lipoic acid, folic acid, coenzyme Q10, zinc, selenium, and vitamins B2, B6, and B12. Semen parameters were analyzed before (T0) and after 90 days (T90) of treatment, and outcomes of the paired T0 and T90 cycles were compared. After the treatment there was an increase in sperm concentration (p = 0.027), total motile sperm count (p = 0.003), progressive motility (p < 0.0001), and a decreasing trend of DNA-fragmented spermatozoa. Embryological outcomes (fertilization, embryo quality, blastocyst development) were significantly higher in T90 than T0 cycles. No T0 cycle resulted in an evolutive pregnancy. Conversely, in T90 cycles 29 singleton clinical pregnancies were obtained. No negative neonatal outcomes were recorded in newborns after antioxidant treatment. Diet supplementation of men who have had low fertilization rates in their previous ICSI cycles with a combination of myo-inositol, alpha-lipoic acid, folic acid, coenzyme Q10, zinc, selenium, betaine, and vitamins may improve semen reproductive potential and ICSI clinical outcome.

Reactive Oxygen Species and Their Consequences on the Structure and Function of Mammalian Spermatozoa

“…Matorras et al (110) studied the impact of vitamin E therapy in a double-blind, placebo-controlled, randomized study of 101 patients but did find a significant increase in life birth rate per transfer as a result of antioxidant therapy, although no impact on clinical pregnancy rate or semen quality was discernable (148). In contrast, Scaruffi et al (146) conducted a multicenter, longitudinal, uncontrolled prospective study of antioxidant (myo-inositol, alpha-lipoic acid, folic acid, coenzyme Q10, zinc, selenium, and vitamins B2, B6, and B12) therapy in men who had exhibited low fertilization rates in a previous ICSI cycle.…”

“…The IDO triggers the kynurenic pathway, whose metabolites have various properties, including anti-inflammatory, anti-apoptotic, and antioxidant (83). Interestingly, when inactivated in a transgenic mouse model, the absence of IDO expression in the epididymis leads to increased local epididymal inflammation and various alterations in sperm structures and functions, providing a link between innate immunity/ peripheral tolerance issues and post-testicular sperm quality control (84,146).…”

Effects of reactive oxygen species, lipids peroxidation, and total antioxidant capacity on sperm morphological functional characteristics and quality embryological development ICSI outcomes

“…Under pathological conditions, ROS induce lipids peroxidation that alters sperm plasma membrane permeability and fluidity, elevates protein modifications, increases sperm DNA fragmentation, and develop male infertility characteristic features Gualtieri et al, 2021). Under oxidative stress response, the high levels of ROS reduce antioxidant defense mechanisms of sperm cells and/or seminal plasma, sperm normal morphology, capacitation, sperm-oocyte interaction, oocytes fertilization, quality embryos development grade, and pregnancy rates Scaruffi et al, 2021).…”

“…In human body, oxidative stress response is considered as an imbalance between endogenous unstable free radicals generation and antioxidant capacity (Nishihara et al, 2018;Ritchie & Ko, 2021). Actually, 30-80% of infertile men have high concentrations of seminal reactive oxygen species (ROS) and low antioxidant capacity (Gualtieri et al, 2021;Scaruffi et al, 2021).…”

Micronutrientes en el tratamiento de la infertilidad masculina idiopática

“…En un ensayo prospectivo al azar, doble ciego que incluyó a 60 parejas con infertilidad masculina grave, una tableta oral diaria durante 3 meses antes del ciclo de fertilización in vitro mejoró la tasa de embarazo viable (38,5% de los embriones transferidos) en comparación con un grupo de placebo (16% de los embriones transferidos). 56 La infertilidad masculina es un proceso multifactorial con posibles causas contribuyentes. Considerando que la mayoría de los casos masculinos se deben a producción deficiente de espermatozoides de origen desconocido, se deben evaluar factores ambientales y nutricionales, incluidos exposición al calor, productos químicos y metales pesados.…”