NAC Effect on Infertile Women With Endometrioma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Female Infertility, Endometrioma, Stress Oxidative

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 42 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-acetyl cystein<br>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<br>* 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.<br>|
| Placebo Comparator: effervescent placebo<br>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<br>* placebo<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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en