NAC Effect on Hox Genes Expressions in RIF

Phase 3

Completed

• Conditions: Female Infertility
• Interventions: Drug: N-acetyl cysteine; Drug: Placebos

• Registration Number: NCT03862586
• Lead Sponsor: Royan Institute

Brief Summary

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.

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 Timeline

• Study Start: 2015-02-01
• Primary Completion: 2017-05-01
• Study Completion: 2017-07-01
• Study First Submitted: 2018-12-23
• Status Verified: 2019-03
• Study First Submitted QC: 2019-03-02
• Last Update Submitted: 2019-03-02
• Study First Posted: 2019-03-05
• Last Update Posted: 2019-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
N-acetyl cysteine	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
Placebos	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

Primary Outcome Measures

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

Secondary Outcome Measures

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