NAC: A Powerful Antioxidant and Anti-inflammatory in Reproductive Health

Abstract

Oxidative stress and inflammation are known to be involved in the development of different female reproductive disorders, including polycystic ovary syndrome, endometriosis, subfertility/infertility, and pregnancy wastage. Excess ROS, mitochondrial dysfunction, and inflammation signaling can affect follicular development, quality of oocytes, receptivity of endometrium, implantation, and embryonic development. N-acetyl cysteine (NAC), a derivative of cysteine and a GSH precursor, has attracted interest because of its antioxidant, anti-inflammatory, and cytoprotective effects. The main aim is to assess the pharmacological actions of NAC and evidence of potential therapeutic benefit for female reproductive health, including PCOS, endometriosis, and assisted reproductive technologies (IVF/ICSI). All accessible experimental clinical RCT, SR, and meta-analytic data on NAC and female reproductive diseases were considered. The focus was on the effects of NAC on glutathione, ROS scavenging, the Nrf2 pathway, NF-B inflammation mitochondria, and reproductive term effects. Results: (1) PCOS: for ovulation and pregnancy, research suggested improvements, while a recent meta-analysis showed a trend towards benefit for progesterone and endometrial thickness. (2) Endometriosis: preliminary clinical evidence suggested notable impact on pelvic pain, analgesic requirements, and reductions in endometriosis size, but high study variability prevented aggregation in a meta-analysis. (3) IVF/ICSI, in which clinical pregnancy and live-birth datasets showed mixed effects. At last concluding that N-Acetyl cysteine appears to be a promising adjunctive antioxidant and anti-inflammatory treatment for female reproductive health. Though, it should not be regarded as a treatment for infertile women suffering from PCOS, endometriosis, or infertility per se. Well-powered, standardized randomized controlled trials are needed to determine the optimal dose and duration of treatment, patient selection, long-term safety, and effect on pregnancy outcome, particularly live birth.