Males, Antioxidants, and Infertility Trial

Study Overview
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Brief Summary
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The objective of the Males, Antioxidants, and Infertility (MOXI) Trial is to examine whether treatment of infertile males with an antioxidant formulation improves male fertility. The central hypothesis is that treatment of infertile males with antioxidants will improve sperm structure and function, resulting in higher fertilization rates and improved embryo development, leading to higher pregnancy and live birth rates. Findings from this research will be significant in that they will likely lead to an effective, non-hormonal treatment modality for male infertility. An effective treatment for men would also reduce the treatment burden on the female partner, lower costs, and provide effective alternatives to couples with religious or ethical contraindications to ART (Assisted Reproductive Technology). If antioxidants do not improve pregnancy rates, but do improve sperm motility and DNA integrity, they could allow for couples with male factor infertility to use less intensive therapies such as intrauterine insemination. Male fertility specialists currently prescribe antioxidants based on the limited data supporting their use. A negative finding, lack of any benefit, would also alter current treatment of infertile males.

Official Title
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Males, Antioxidants, and Infertility (MOXI) Trial

Conditions
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Male Infertility

Intervention / Treatment
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* Drug: Antioxidant Supplement
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:Couple 12 or more months of infertility (primary or secondary) Heterosexual Cohabitating and able to have regular intercourse Male: ≥ 18 years of age At least one abnormal semen parameter on a semen analysis within the past 6 months: Sperm concentration ≤15 Million/ml Total motility ≤40% Normal morphology (Kruger) ≤4% DNA fragmentation (SCSA, DNA fragmentation index) >25% Female: ≥18 years of age and ≤40 years of age For women ≥ 35 years of age, evidence of normal ovarian reserve as assessed by menstrual cycle day 3 (+/-2 days) FSH ≤10 IU/L with estradiol ≤ 70 pg/mL, AMH ≥ 1.0 ng/mL, OR antral follicle count >10 within one year prior to study initiation. Evidence of at least one patent fallopian tube as determined by an hysterosalpingogram or laparoscopy showing at least one patent fallopian tube or a saline infusion sonogram showing spillage of contrast material Regular cycles defined as ≥25 days and ≤35 days in duration Evidence of ovulation including biphasic basal body temperatures, positive ovulation predictor kits, or progesterone level ≥3 ng/ml. Exclusion Criteria: Couple: Previous sterilization procedures (vasectomy, tubal ligation). The prior procedure may affect study outcomes. Planning in vitro fertilization in the next 6 months Male: Sperm concentration < 5 million/mL on screening semen analysis Current use of a medication or drug that would affect reproductive function or metabolism (see Appendix C for list) Current multivitamin or herb use (requires 1 month wash-out) Current serious medical illnesses, such as cancer, heart disease, or cirrhosis Current use of anticoagulants Untreated hypothyroidism Uncontrolled diabetes mellitus Female: History of surgically or medically confirmed moderate or severe endometriosis Body mass index >35 kg/m2 Currently pregnant History of polycystic ovarian syndrome Current serious medical illnesses, such as cancer, heart disease, or cirrhosis History of systemic chemotherapy or pelvic radiation Current use of a medication or drug that would affect reproductive function or metabolism

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Antioxidant Supplement<br>Tablet: Vitamin C, 500 mg; Vitamin D3, 1000 IU; Vitamin E, 400 IU; Folic Acid 1000 mcg; Zinc, 20 mg; Selenium 200 mcg; Lycopene, 10 mg; Capsule: Vitamin D3, 1000 IU, L-Carnitine, 1000 mg | Drug: Antioxidant Supplement<br>* An antioxidant combination including Vitamin C, Vitamin E, folic acid, selenium, zinc, and L-carnitine<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live Birth Rate |  | up to 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy Rate |  | up to 7 months | 
| Miscarriage Rate | miscarriages per total number of pregnancies | up to 9 months | 
| Time to Pregnancy | Time to pregnancy will be the chronologic time from randomization to pregnancy detection in days, in which the pregnancy is defined as a human Chorionic Gonadotropin (hCG) value over 5 on 2 separate occasions. | up to 7 months | 
| Change in Total Motile Sperm Count | Samples will be assessed using a standard semen analysis | baseline and 3 months | 
| Change in Deoxyribonucleic Acid (DNA) Fragmentation Index (DFI) | DFI is the ratio of damaged sperm to total sperm. It is measured using Sperm Chromatin Structure Analysis (SCSA) which was performed on 5000 sperm per sample. | Baseline and 3 months | 
| Change in Semen Total Motility | Samples assessed using a standard semen analysis | baseline and 3 months | 
| Change in Sperm Concentration | Samples assessed using a standard semen analysis | baseline and 3 months | 
| Change in Normal Morphology of Semen, Using World Health Organization (WHO) 5 Criteria | Samples assessed using a standard semen analysis | baseline and 3 months | 
| Change in Total Sperm Count | Samples assessed using a standard semen analysis | baseline and 3 months |