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.

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

IPD will be shared with other researchers through the NICHD DASH system. It will be available 6 months after publication of the primary results.

Following publication of the primary publication and when the de-identified data have been put into a format that is acceptable for DASH submission.

Adverse Event data was collected from start of study drug through 30 days after the last dose of study medication, on average 7 months. Subjects completed a monthly diary where they reported any adverse events. They were also queried by study staff at each study visit about any adverse events since the last visit.