Clinical trial NCT03862586: NAC Effect on Hox Genes Expressions in RIF
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Female Infertility
Keywords: Implantation
Recurrent implantation failure
N-acetyl cysteine
HOXA cluster genes
Window of implantation
Lead sponsor: Royan Institute
Sponsor class: OTHER_GOV
First posted: 2019-03-05
Enrollment: 40
Sex: FEMALE
Minimum age (years): 22
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Expression of HOXA in endometrium
timeFrame: approximately 20 days after the first day of menstruation (each day is 28 days)
Secondary outcomes:
measure: Positive pregnancy test
timeFrame: 16 days after embryo transfer
measure: Endometrium thickness
timeFrame: approximately 20 day after the first day of menstruation (each day is 28 days)
Other outcomes:
Locations:
Study officials:
affiliation: Royan Institute
name: Parvaneh Afsharian, PhD
role: STUDY_DIRECTOR
affiliation: Royan Institute
name: Ashraf Moini, MD
role: STUDY_CHAIR
affiliation: Shahid Sadoughi University of Medical Sciences
name: Seyed Mehdi Kalantar, PhD
role: STUDY_CHAIR
affiliation: Royan Institute
name: Maryam Shahhoseini, PhD
role: STUDY_DIRECTOR
affiliation: Royan Institute
name: Vida Mokhtari, MSc
role: PRINCIPAL_INVESTIGATOR
References: