NAC Effect on Infertile Women With Endometrioma

Effect of N-acetyl Cysteine on Oxidative Stress Biochemical Factors and IVF/ICSI Outcomes in Women With Endometrioma: A Randomized, Double-blinded, Phase III Clinical Trial

Oxidative stress has been investigated as a key factor in the pathogenesis and progression of endometrioma. High follicular fluid ROS levels and serum can be related to negative IVF/ICSI outcomes in infertile women with endometrioma. Therefore, the use of antioxidants such as N-acetyl cysteine (NAC) may be reduced complications of endometrioma. To study this hypothesis, we designed a double-blind, randomized clinical trial study that aimed to determine the effect of N-acetyl cysteine (NAC) on stress oxidative factors and pregnancy outcomes in IVF/ICSI cycles in endometrioma patients.

Study Overview

• Status: Recruiting
• Conditions: Endometrioma; Female Infertility; Stress Oxidative
• Intervention / Treatment: Drug: placebo; Drug: N-acetyl cysteine

Detailed Description

This study will be conducted at Royan institute on 140 women with endometrioma who are eligible for the study after receiving written consent. After randomization, the participants will be divided into two intervention and control groups. Then, they will be received 1200 (2×600) mg of effervescent tablets of NAC or the placebo daily during 6 weeks simultaneous to start standard long agonist or antagonist protocols for induction.

Plasma blood will be collect before intervention and at the time of egg retrieval, in addition to, follicular fluid (FF) will be obtained from the mature follicles of each ovary and will be separated by centrifuging and will be frozen until analysis. Then, we will measure the levels of two markers of oxidative stress (TAC: Total antioxidant capacity and SOD: Superoxide dismutase) in plasma and FF of all samples by enzyme-linked immunosorbent assay (ELISA) method. In addition, the pregnancy outcomes will be investigated in treated and untreated groups. Also, we will study the effect of pain severity of by visual analogue scale (VAS) technique.

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Parvaneh Afsharian, PhD; Phone Number: +9821- 23562000; Email: p.afsharian@royan-rc.ac.ir

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 16635-148
    • Recruiting
    • Royan Institute
    • Contact: Parvaneh Afsharian, PhD; Phone Number: +9821- 23562000; Email: p.afsharian@royan-rc.ac.ir

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age between 20 and 42 years
• Ultrasound or laparoscopic diagnosis of moderate to sever endometrioma (endometriosis stage III and IV)
• Serum AMH levels between 0.7 and 4.5 ng/ml
• Standard long GnRH and antagonist ovulation stimulation cycle
• Body mass index (BMI) <30 kg/m2

Exclusion Criteria:

• Non-inclusion criteria: Congenital uterine malformations
• Severe male infertility (TESE, PESA)
• Past medical history of asthma

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N-acetyl cystein; Seventy participants who randomly assigned in the intervention group, during 6 weeks simultaneous to start standard long agonist protocol or antagonist induction, will be received 1200 (2×600) mg of effervescent tablets of NAC daily. Plasma blood will collect before the intervention and at the time of oocyte retrieval (end of 6 week), in addition to, follicular fluid will be obtained from the mature follicles. Also, we will measure severity of dysmenorea by visual analogue scale (VAS) technique.	Drug: N-acetyl cysteine; One hundred and forty participants randomize in the intervention and placebo groups, during 6 weeks simultaneous to start standard long agonist protocol or antagonist induction. They will be received 1200 (2×600) mg of effervescent tablets of NAC or placebo daily. Plasma blood will collect before the intervention and at the time of oocyte retrieval (end of 6 week), in addition to, follicular fluid will be obtained from the mature follicles.
Placebo Comparator: effervescent placebo; Seventy participants who randomly assigned to the control group, during 6 weeks simultaneous to start the standard long agonist protocol, or antagonist induction, will be received 1200 (2×600) mg of effervescent placebo tablets daily. Plasma blood will collect before the intervention and at the time of oocyte retrieval, in addition to, follicular fluid will be obtained from the mature follicles. Also, we measure severity of dysmenorrhea by visual analogue scale (VAS) technique.	Drug: placebo; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MII oocyte number and quality	Observation of oocytes that were mature at the time of oocyte collection	Immediately after oocyte puncture

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of TAC oxidative stress marker in blood plasma	Plasma will be obtained for studying TAC and measure by ELISA	Before intervention and 6 weeks after intervention
Measurement of SOD oxidative stress marker in blood plasma	Plasma will be obtained for studying SOD and measure by ELISA	Baseline and 6 weeks after intervention
Measurement of TAC oxidative stress marker in folicular fluid	Folicular fluid will be obtained for studying TAC and measure by ELISA	Immediately After oocyte puncture
Measurement of SOD oxidative stress marker in folicular fluid	Folicular fluid will be obtained for studying SOD and measure by ELISA	Immediately After oocyte puncture
Cleaved embryo numbers	2-3 days embryo from fertilization	2-3 days after oocyte puncture
Blastocyst numbers	The stage the embryo reaches after 5 days in culture from the egg retrieval	5 days after oocyte puncture and sperm insemination
Clinical pregnancy rate	The observation of gestational sac on ultrasound examination two-three weeks after positive serum βhCG	4-6 weeks after embryo transfer
Fertilization rate	Percentage of transformation of micro injected oocytes into two pronuclei embryo	2-5 days after sperm insemination

Collaborators and Investigators

• Sponsor: Royan Institute
• Investigators: Principal Investigator: Parvaneh Afsharian, PhD, Royan Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2021
• Primary Completion (Anticipated): September 23, 2023
• Study Completion (Anticipated): November 30, 2023

Study Registration Dates

• First Submitted: July 12, 2022
• First Submitted That Met QC Criteria: July 14, 2022
• First Posted (Actual): July 15, 2022

Study Record Updates

• Last Update Posted (Actual): July 15, 2022
• Last Update Submitted That Met QC Criteria: July 14, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: en
• Additional Relevant MeSH Terms: Infertility; Endometriosis; 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-NAC-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