NAC Effect on Hox Genes Expressions in RIF

Effect of N-Acetyl Cysteine on Expression of HOXA Cluster Genes in Endometrium of Women With Recurrent Implantation Failure (RIF) During Implantation Window: a Double-blinded Randomized Research

Comparison of the group treated with NAC-supplementation and placebo- administered groups showed elevations in HOXA cluster genes (all members) expression level in endometrium of women with RIF.

Study Overview

• Status: Completed
• Conditions: Female Infertility
• Intervention / Treatment: Drug: Placebos; Drug: N-acetyl cysteine

Detailed Description

Despite significant developments in assistant reproductive technology (ART) that have overcome many underlying causes of infertility, pregnancy success rates remain relatively low, mainly due to implantation failure. Embryo quality and endometrial receptivity are two significant factors that believed to be the key points in implantation. Since recent studies that showed high expression of some HOXA genes affects on successful implantation rate, thus we examined the expression of HOXA genes in NAC supplementation during window of implantation (WOI) in women with (RIF). Also the effect of NAC on the improvement of implantation in RIF patients was investigated. Forty unfertile women with a diagnosis of RIF, referred to Royan Institute were included in the study. The study was of the type a single center, double blinded, placebo controlled, randomized trial. Expression of HOXA genes were assessed on the day of WOI (using Real Time PCR) biopsies from endometrium. Subjects randomly assigned to receive either NAC (A) or placebo (B) with both effervescent tablets having similar color, size and appearance. The patients were randomly categorized in two groups (A/B) to receive NAC 1200 mg/day or placebo, for at-least 6 weeks before starting ovarian stimulation. Pipelled-based biopsy from endometrium was done on specific day (19-21) of their cycle. Then patients were undergone ovarian stimulation (using NAC) ended to IVF treatment. RNA extraction and cDNA synthesis were performed from endometrium samples and then we evaluated expressions levels by Real-time PCR. Then we analyzed our data by independent Sample T-test and Mann-whitney U Test.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Age between 20 and 40 years old
2. At least two IVF failure
3. BMI in the normal range

Exclusion Criteria:

1. Irregular menstrual cycle
2. Taking hormonal drugs except thyroid medication
3. Abnormal karyotype or chromosomal disorders
4. Coagulation problems.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N-acetyl cysteine; Twenty two infertile women with the onset of endometrial preparation for evaluating genes expression, received 1200 mg of oral N-acetyl cysteine for at-least six weeks before starting ovarian stimulation	Drug: N-acetyl cysteine; Other Names: NAC
Placebo Comparator: Placebos; Eighteen infertile women with the onset of endometrial preparation for evaluating genes expression, received placebo effervescent tablet for at-least six weeks before starting ovarian stimulation	Drug: Placebos; Other Names: Placebo effervescent tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression of HOXA in endometrium	mRNA expression by quantitative PCR for homeo box A	approximately 20 days after the first day of menstruation (each day is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive pregnancy test	Measurement of quantitative serum β-hCG	16 days after embryo transfer
Endometrium thickness	Endometrium thickness	approximately 20 day after the first day of menstruation (each day is 28 days)

Collaborators and Investigators

• Sponsor: Royan Institute
• Investigators: Study Director: Parvaneh Afsharian, PhD, Royan Institute; Study Chair: Ashraf Moini, MD, Royan Institute; Study Chair: Seyed Mehdi Kalantar, PhD, Shahid Sadoughi University of Medical Sciences; Study Director: Maryam Shahhoseini, PhD, Royan Institute; Principal Investigator: Vida Mokhtari, MSc, Royan Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: December 23, 2018
• First Submitted That Met QC Criteria: March 2, 2019
• First Posted (Actual): March 5, 2019

Study Record Updates

• Last Update Posted (Actual): March 5, 2019
• Last Update Submitted That Met QC Criteria: March 2, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: N-acetyl cysteine; Implantation; Recurrent implantation failure; HOXA cluster genes; Window of implantation
• Additional Relevant MeSH Terms: Infertility; Infertility, Female; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: Royan-Genetics

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No