Males, Antioxidants, and Infertility Trial

Phase 2

Completed

Brief 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.

Recruitment & Eligibility

Inclusion Criteria

Couple

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Antioxidant Supplement	Antioxidant Supplement	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

Primary Outcome Measures

Name	Time	Method
Live Birth Rate	up to 15 months

Secondary Outcome Measures

Name	Time	Method
Pregnancy Rate	up to 7 months
Miscarriage Rate	up to 9 months	miscarriages per total number of pregnancies
Time to Pregnancy	up to 7 months	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.
Change in Total Motile Sperm Count	baseline and 3 months	Samples will be assessed using a standard semen analysis
Change in Deoxyribonucleic Acid (DNA) Fragmentation Index (DFI)	Baseline and 3 months	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.
Change in Semen Total Motility	baseline and 3 months	Samples assessed using a standard semen analysis
Change in Sperm Concentration	baseline and 3 months	Samples assessed using a standard semen analysis
Change in Normal Morphology of Semen, Using World Health Organization (WHO) 5 Criteria	baseline and 3 months	Samples assessed using a standard semen analysis
Change in Total Sperm Count	baseline and 3 months	Samples assessed using a standard semen analysis

Locations (10): University of Oklahoma
🇺🇸
Oklahoma City, Oklahoma, United States
Augusta University
🇺🇸
Augusta, Georgia, United States
University of North Carolina
🇺🇸
Chapel Hill, North Carolina, United States
University of California San Francisco
🇺🇸
San Francisco, California, United States
Keck School of Medicine of University of Southern California
🇺🇸
Los Angeles, California, United States
Stanford University
🇺🇸
Sunnyvale, California, United States
Pennsylvania State University
🇺🇸
Hershey, Pennsylvania, United States
Wayne State University
🇺🇸
Southfield, Michigan, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Carolinas Medical Center - Women's Institute
🇺🇸
Charlotte, North Carolina, United States