Males, Antioxidants, and Infertility Trial
Condition: Male Infertility
MeSH terms: Infertility; Infertility, Male
Intervention: Antioxidant Supplement; Placebo
Intervention description: An antioxidant combination including Vitamin C, Vitamin E, folic acid, selenium, zinc, and L-carnitine; Placebo
Intervention MeSH terms: Antioxidants
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 171.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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