Effect of N-Acetyl cysteine on Expression of MTHFR Gene during Implantation Window in Women with RecurrentImplantation Failure: A Double-Blinded Randomized Placebo-Controlled Trial, Phase II

Background: Despite significant developments in assisted reproductivetechnology (ART) that have overcome many underlyingcauses of infertility, pregnancy success rates remain relativelylow, mainly due to implantation failure. Embryo qualityand endometrial receptivity are two significant factors that believedto be the key points in implantation. The endometriumis receptive to blastocyst implantation during a spatially andtemporally restricted window, called ‘the implantation window.Folate metabolism is reported to be an essential regulator ofearly development and pregnancy. Methylenetetrahydrofolatereductase (MTHFR) plays a critical role in folate metabolismand in the homeostasis of homocysteine. Homocysteine is associatedwith oxidative stress through the production of reactiveoxygen species (ROS) and nitric oxide regulation. N-acetylcysteine (NAC) stimulates glutathione biosynthesis, promotesdetoxification, and act directly as a scavenger of free radicals,therefore, it has been greatly applied as an antioxidant recently.The aim of this study is the assessment of NAC in implantationby monitoring the mRNA expression level of MTHFR gene.Materials and Methods: A single center, double-blinded, placebo-controlled, randomized trial was performed over one yearwith ۴۰ women (age: ۲۲-۴۰ years) with at least two RIF (Recurrentimplantation failure) history who were undergoing in vitrofertilization (IVF) cycle. Forty infertile women with a diagnosisof RIF referred to Royan Institute were included in this studyand randomly divided into intervention and control groups. AtFirst, they received ۱۲۰۰ mg of effervescent tablets of NACor the placebo for ۶ weeks. The endometrial biopsy was takenfrom patients by catheter biopsy (Pipelle) on ۱۹-۲۱th day inthe cycle prior to IVF transfer procedure. Total RNA-extractionand cDNA synthesis were performed on samples. Real-TimePCR was conducted to evaluate expression of MTHFR gene.Results: The mean ± SE of the fold change of MTHFR expressionwas ۲.۷ ± ۰.۴ in the drug group and was ۲.۴ ± ۰.۴۴ in theplacebo group. No statistically significant difference were detectedbetween two analyzed groups.Conclusion: Related to our result, it seems N-acetyl cysteineeffects on other mechanisms in implantation that needs morestudies with larger population.

کلیدواژه ها:

Implantation ، Recurrent Implantation Failure ، Nacetyl Cysteine ، MTHFR Gene