N-Acetyl cysteine: could it be an effective adjuvant therapy in ICSI cycles? A preliminary study

Abstract

This randomized controlled trial tested the hypothesis that addition of N-acetyl cysteine (NAC) can increase the probability of pregnancy in intracytoplasmic sperm injection (ICSI) cycles using the long agonist protocol. Women undergoing ICSI cycles due to male factor were randomly assigned to receive either long protocol (group A, 38 women) or long protocol plus NAC (group B, 38 women). Clinical pregnancy was the primary outcome. Granulosa cell apoptosis, fertilization rate, number of grade-one embryos and ongoing pregnancy were the secondary outcomes. Clinical pregnancy rate was insignificantly higher in NAC group (52.6%) than control (47.4%). Early and late apoptosis were also insignificantly lower in group B than in group A. Irrespective of the used protocol, there was significant negative correlation between both early and late apoptosis and fertilization rate (both P<0.001) and the number of good-quality embryos (P=0.007 and P<0.001, respectively). Pregnant patients had significantly lower early and late apoptosis than those who didn't achieve pregnancy (P<0.001). In conclusion, NAC supplementation did not significantly increase the probability of pregnancy in ICSI cycles using long agonist protocol. It appears that granulosa cell apoptosis may be an important prognosticator for ICSI cycle outcome.

N-Acetylcysteine improves oocyte and embryo quality in polycystic ovary syndrome patients undergoing intracytoplasmic sperm injection: an alternative to metformin

“…The results of the present study confirm those of previous studies (Badawy and Abdelgawad 2007;Oner and Muderris 2011;Liu et al 2012). Conversely, similar to the results obtained by Elgindy et al (2010), NAC did not significantly increase the number of oocytes retrieved or the rate of fertilisation and pregnancy compared with the placebo group. Modifications in the dose and/or duration of treatment, sampling size and ovulation induction protocols may improve the results.…”

“…However, Elgindy et al (2010) reported that 1200 mg NAC supplementation in ICSI cycles, using the long agonist protocol, did not significantly increase the number of Grade I embryos or the rate of fertilisation and pregnancy. Elgindy et al (2010) suggested that larger-scale studies, possibly with higher doses and/or longer duration of NAC administration, should be performed to identify any significant effects of NAC. In this regard, Liu et al (2012) recently reported that the mice treated for 2 months with NAC exhibited an increased number and quality of oocytes and improved embryo development.…”

“…Although MET is believed to be useful for the treatment of many women with PCOS, NAC, with antioxidant, anti-apoptotic and lipid peroxidation-lowering properties, may be considered as an alternative supplement (Fulghesu et al 2002;Rizk et al 2005;Elgindy et al 2010). Considering the fact that NAC improves oocyte maturation and embryo quality, and decreases the rate of immature oocytes in women with PCOS while being a safe and well-tolerated agent, we also suggest the administration of NAC as an alternative to other insulin-sensitising agents like MET.…”

“…Because no randomized control trials have so far been performed to investigate the use of MET plus NAC during IVF treatment, the power calculation in the present study was based on data from retrospective studies on MET or NAC (Yaralı et al 2002;Tang et al 2006;Elnashar et al 2007;Elgindy et al 2010;Kjøtrød et al 2011). Common findings for patients with PCOS undergoing IVF are low fertilisation rates and impaired oocyte quality.…”

Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health

“…Nonenzymatic antioxidants include N-acetylcysteine (an acetylated form of the amino acid, L-cysteine), ascorbate (vitamin C) and tocopherol (vitamin E), selenium, zinc, glutathione, and beta-carotene (92,95). Working together against oxidative stress, for example, GSH reductase (in the presence of NADPH) maintains glutathione in its reduced form to suppress antral follicle atresia and inhibit granulosa cell apoptosis in conjunction with FSH (94); seleniumdependent glutathione peroxidase activity promotes oocyte fertilization (96).…”