Clinical trial NCT02421887: Males, Antioxidants, and Infertility Trial
Official title: Males, Antioxidants, and Infertility (MOXI) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Male Infertility
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: University of North Carolina
name: Augusta University
name: Penn State University
name: University of California, San Francisco
name: University of Oklahoma
name: University of Pennsylvania
First posted: 2015-04-21
Enrollment: 171
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Live Birth Rate
timeFrame: up to 15 months
Secondary outcomes:
measure: Pregnancy Rate
timeFrame: up to 7 months
measure: Miscarriage Rate
timeFrame: up to 9 months
measure: Time to Pregnancy
timeFrame: up to 7 months
measure: Change in Total Motile Sperm Count
timeFrame: baseline and 3 months
measure: Change in Deoxyribonucleic Acid (DNA) Fragmentation Index (DFI)
timeFrame: Baseline and 3 months
measure: Change in Semen Total Motility
timeFrame: baseline and 3 months
measure: Change in Sperm Concentration
timeFrame: baseline and 3 months
measure: Change in Normal Morphology of Semen, Using World Health Organization (WHO) 5 Criteria
timeFrame: baseline and 3 months
measure: Change in Total Sperm Count
timeFrame: baseline and 3 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Keck School of Medicine of University of Southern California
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Sunnyvale
country: United States
facility: Stanford University
state: California
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Southfield
country: United States
facility: Wayne State University
state: Michigan
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center - Women's Institute
state: North Carolina
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Hershey
country: United States
facility: Pennsylvania State University
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Eunice Kennedy Shriver National Institue of Child Health and Human Development
name: Esther Eisenberg, MD
role: STUDY_DIRECTOR
affiliation: University of Colorado, Denver
name: Nanette Santoro, MD
role: STUDY_CHAIR
affiliation: University of North Carolina
name: Anne Z Steiner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Augusta University
name: Michael P Diamond, MD
role: STUDY_DIRECTOR
affiliation: Penn State University
name: Richard S Legro, MD
role: STUDY_DIRECTOR
affiliation: University of California, San Francisco
name: Marcelle Cedars, MD
role: STUDY_DIRECTOR
affiliation: University of Oklahoma
name: Karl R Hansen, MD
role: STUDY_DIRECTOR
affiliation: University of Pennsylvania
name: Christos Coutifaris, MD
role: STUDY_DIRECTOR
affiliation: Yale University
name: Heping Zhang, PhD
role: STUDY_DIRECTOR
References:
citation: Spitzer TL, Trussell JC, Coward RM, Hansen KR, Barnhart KT, Cedars MI, Diamond MP, Krawetz SA, Sun F, Zhang H, Santoro N, Steiner AZ. Biomarkers of Stress and Male Fertility. Reprod Sci. 2022 Apr;29(4):1262-1270. doi: 10.1007/s43032-022-00853-x. Epub 2022 Feb 1.
citation: Steiner AZ, Hansen KR, Barnhart KT, Cedars MI, Legro RS, Diamond MP, Krawetz SA, Usadi R, Baker VL, Coward RM, Huang H, Wild R, Masson P, Smith JF, Santoro N, Eisenberg E, Zhang H; Reproductive Medicine Network. The effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial. Fertil Steril. 2020 Mar;113(3):552-560.e3. doi: 10.1016/j.fertnstert.2019.11.008. Epub 2020 Feb 25.