NAC Effect on Hox Genes Expressions in RIF

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Female Infertility

Intervention / Treatment
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* Drug: N-acetyl cysteine
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 20 and 40 years old At least two IVF failure BMI in the normal range Exclusion Criteria: Irregular menstrual cycle Taking hormonal drugs except thyroid medication Abnormal karyotype or chromosomal disorders Coagulation problems.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-acetyl cysteine<br>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<br> <br> * Other names: NAC;|
| Placebo Comparator: Placebos<br>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<br> <br> * Other names: Placebo effervescent tablet;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Implantation, Recurrent implantation failure, N-acetyl cysteine, HOXA cluster genes, Window of implantation