The DOI matches its Crossref record; 26 of the 28 references it cites were found in a registry or an index; 10 of the 12 sources its claims cite were checked for support.
The effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial
Open accessAbstract
Objective To determine whether antioxidants improve male fertility, as measured by semen parameters and DNA fragmentation at 3 months and pregnancy resulting in live birth after up to 6 months of treatment, among couples with male factor infertility. Design Multicenter, double-blind, randomized, placebo-controlled trial with an internal pilot study. Setting Nine fertility centers in the United States from December 2015 to December 2018. Patient(s) Men (N = 174) with sperm concentration ≤15 million/mL, motility ≤40%, normal morphology ≤4%, or DNA fragmentation >25%, and female partners who were ovulatory, ≤40 years old, and had documented tubal patency. Intervention(s) Males randomly assigned to receive an antioxidant formulation (n = 85) containing 500 mg of vitamin C, 400 mg of vitamin E, 0.20 mg of selenium, 1,000 mg of l-carnitine, 20 mg of zinc, 1,000 μg of folic acid, 10 mg of lycopene daily, or placebo (n = 86). Treatment lasted for a minimum of 3 months and maximum of 6 months, and couples attempted to conceive naturally during the first 3 months and with clomiphene citrate with intrauterine insemination of the female partner in months 4 through 6. Main outcome measure(s) Primary outcome was live birth; secondary outcomes included pregnancy within 6 months of treatment. For the internal pilot, the primary outcomes were semen parameters and sperm DNA fragmentation index after 3 months of treatment. Result(s) In the Males, Antioxidants, and Infertility (MOXI) study, after 3 months of treatment, the change in sperm concentration differed between the antioxidant group (median -4.0 [interquartile range-12.0, 5.7] million/mL) and placebo group (+2.4 [-9.0, 15.5] million/mL). However, there were no statistically significant differences between the two groups for changes in sperm morphology, motility, or DNA fragmentation. Among the 66 oligospermic men at randomization, sperm concentration did not differ at 3 months between the antioxidant and control groups: 8.5 (4.8, 15.0) million/mL versus 15.0 (6.0, 24.0) million/mL. Of the 75 asthenospermic men, motility did not differ at 3 months: 34% ± 16.3% versus 36.4% ± 15.8%. Among the 44 men with high DNA fragmentation, DNA fragmentation did not differ at 3 months: 29.5% (21.6%, 36.5%) versus 28.0% (20.6%, 36.4%). In the entire cohort, cumulative live birth did not differ at 6 months between the antioxidant and placebo groups: 15% versus 24%. Conclusion(s) Antioxidants do not improve semen parameters or DNA integrity among men with male factor infertility. Although limited by sample size, this study suggests that antioxidant treatment of the male partner does not improve in vivo pregnancy or live-birth rates. Clinical trial registration number NCT02421887.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In the MOXI randomized trial, a daily combination antioxidant formulation did not improve semen parameters or sperm DNA fragmentation in men with male factor infertility, and it did not increase pregnancy or live birth rates. The trial was stopped early after the internal pilot failed to show benefit.
Key findings
- After 3 months, change in sperm concentration differed between antioxidant and placebo groups [−4.0 (−12.0, 5.7) M/ml vs +2.4 (−9.0, 15.5) M/ml; p=0.03], but there were no significant differences in change in sperm morphology, motility, or DNA fragmentation.
- In subgroups, no significant differences were seen at 3 months: oligospermic men (n=66) sperm concentration 8.5 (4.8, 15.0) vs 15.0 (6.0, 24.0) M/ml, p=0.08; asthenospermic men (n=75) motility 34±16.3% vs 36.4±15.8%, p=0.53; men with high DNA fragmentation (n=44) 29.5 (21.6, 36.5)% vs 28.0 (20.6, 36.4)%, p=0.58.
- Cumulative live birth at 6 months did not differ: 15% (13/85) with antioxidants vs 24% (21/86) with placebo, p=0.14. Pregnancy rates did not differ in phase 1 (9% vs 9%, p=0.98) or phase 2 (12% vs 21%, p=0.11).
- Adherence was 88% in the antioxidant group and 82% in placebo (p=0.26); adverse events occurred in 41% vs 40% (p=0.83). Enrollment was stopped after the internal pilot failed to reject the null hypothesis for motility and DNA fragmentation.
Methods
- Multicenter, double-blind, randomized, placebo-controlled trial with a pre-specified internal pilot, conducted at 9 U.S. fertility centers from December 2015 to December 2018.
- Eligible couples had male factor infertility: men ≥18 years with at least one abnormal semen parameter (sperm concentration ≤15 M/ml, motility ≤40%, normal morphology ≤4%, or DNA fragmentation ≥25%); female partners were 18–40 years, ovulatory, and had documented tubal patency.
- Men were randomized 1:1 to a daily antioxidant formulation (500 mg vitamin C, 400 mg vitamin E, 0.20 mg selenium, 1000 mg L-carnitine, 20 mg zinc, 1000 mcg folic acid, 10 mg lycopene, and 2000 IU vitamin D) or placebo for 3–6 months. Couples attempted natural conception in months 1–3 and received clomiphene citrate with intrauterine insemination in months 4–6 if not pregnant. Primary outcome was live birth; pilot outcomes were semen parameters and SCSA-measured DNA fragmentation at 3 months. Intention-to-treat analyses used chi-square/Fisher exact, Wilcoxon rank-sum, and t-tests, with p<0.05.
Limitations
- Stated: the trial was limited by sample size for pregnancy/live birth outcomes and was not powered to determine group differences in live birth; larger trials are needed.
- Stated: the design could not differentiate effects of individual nutrients and assumed no interactions among antioxidants in the combination formulation.
- Stated: patients may have been selected who were unlikely to benefit, such as men without elevated reactive oxygen species; future studies could target subpopulations such as men with low vitamin levels or high seminal ROS.
- Evident from the text: baseline imbalances existed (placebo-group men were more likely to have fathered a pregnancy previously; antioxidant-group men had a lower percentage of morphologically normal sperm), and dropout was numerically higher in the antioxidant group (21% vs 11%, p=0.055).
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
Statistics
Verification
Claims the paper makes
10 of 12 cited sources checked · 6 supported · 1 flagged · accuracy not yet measured
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Similar to the MOXI trial, the high quality trials included in the Cochrane review did not find a benefit to antioxidants on live birth. (25, 26)”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > DISCUSSION
What the sources say
- Could not verifycites [25] Blomberg Jensen, 2018, Effects of vitamin D supplementation on semen quality, reproductive hormones, and live birth rate: a randomized clinical trial, J Clin Endocrinol Metab sourceExperimental — accuracy not yet measured
The Secondary end points and Discussion sections (pages unavailable) report no overall live-birth benefit from vitamin D plus calcium in this trial. Our copy does not address whether high-quality trials in a Cochrane review found no live-birth benefit from antioxidants; searches for the Cochrane review, antioxidants, and the MOXI trial found no supporting passage. (LLM, conf=0.76)
- Not checked — no full text of the sourcecites [26] Henkel, 2019, The excessive use of antioxidant therapy: a possible cause of male infertility?, Andrologia source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, the Cochrane meta-analysis did find a 12% absolute increase in motility in men treated with combination antioxidants for 3 months compared to controls. (7)”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > DISCUSSION
What the sources say
- Supportedcites [7] Smits, 2019, Antioxidants for male subfertility, Cochrane Database Syst Rev source
Figure 9, analysis 1.11.14, reports a mean difference of 12.43 in total sperm motility for combined antioxidants versus placebo or no treatment. Figure 9 identifies the outcome as motility at three months or less, consistent with the cited sentence’s rounded 12% increase. (LLM, conf=0.90)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Our negative findings contradict the overall conclusions from the Cochrane Review and meta-analysis.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > DISCUSSION
What the sources say
- Supportedcites [7] Smits, 2019, Antioxidants for male subfertility, Cochrane Database Syst Rev source
The Authors’ Conclusions (page unavailable) say antioxidant supplementation may improve live birth rates and may increase clinical pregnancy rates, although the evidence is low quality and overall inconclusive. The review’s live-birth meta-analysis reports an association with increased live birth, so negative findings would contrast with its reported direction of effect. (LLM, conf=0.86)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“or in phase 2 (12% versus 21%, p=0.11), when women received ovarian stimulation with clomiphene citrate and timed intrauterine insemination.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > RESULTS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Change in morphology, motility, and DNA fragmentation did not differ between the two groups.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > RESULTS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Change in morphology, motility, and DNA fragmentation did not differ between the two groups.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > RESULTS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The percentage of males who had at least one adverse event did not differ between groups (41% in antioxidant group, 40% in placebo group, p=0.83)”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > RESULTS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the 75 asthenospermic men, motility did not differ at 3 months (34±16.3% versus 36.4±15.8%; p=0.53).”
- Also stated in: § RESULTS · plain
“Among the 75 men with asthenospermia, there were no significant differences in change in sperm motility between the two treatment groups.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > Abstract > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After 3 months of treatment, change in sperm concentration differed between the antioxidant group [−4.0 (−12.0, 5.7) M/ml] and placebo group [+2.4 (−9.0, 15.5) M/ml] (p=0.03).”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > Abstract > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similar results were observed when the male participants were stratified based on baseline sperm morphology or prior pregnancy history (Supplemental Table 3).”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > RESULTS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- It may state two separate claims as one. 16
- Probably not a substantial claim. 16
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Taken together with previous findings, our results indicate that while antioxidants may reduce ROS, this does not appear to translate into reduced sperm DNA fragmentation.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > DISCUSSION
What the sources say
- Disputedcites [7] Smits, 2019, Antioxidants for male subfertility, Cochrane Database Syst Rev sourceExperimental — accuracy not yet measured
The review’s Sperm DNA fragmentation section says antioxidant use showed lower fragmentation than placebo, contrary to the claim that reduced fragmentation does not appear to follow. Its pooled estimate favoured antioxidants, although the 95% confidence interval included no effect, so the evidence for a reduction is uncertain. (LLM, conf=0.82)
Checked by a reasoning model — may be wrong.
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Disputed
Every source the paper cites for this claim was checked and supports it.
In the paper
“DNA fragmentation assessment using the Sperm Chromatin Structure Analysis (SCSA) test”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > METHODS > Study Treatment
What the sources say
- Supportedcites [14] Evenson, 2002, Sperm chromatin structure assay: its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with other techniques, J Androl source
The Sperm Chromatin Structure Assay section identifies SCSA as an assay of sperm DNA susceptibility to denaturation. The Data Analysis–New Terminology section states that SCSA measurements are used to calculate the level of DNA fragmentation (DFI). Page numbers are not provided in the passages. (LLM, conf=0.94)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The recent Cochrane Review found that antioxidant use increased the odds of pregnancy by 2.97 fold and the odd of live birth by 1.8 fold. (7)”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > DISCUSSION
What the sources say
- Supportedcites [7] Smits, 2019, Antioxidants for male subfertility, Cochrane Database Syst Rev source
The review’s meta-analysis reports a live-birth Peto odds ratio of 1.79 for antioxidants versus placebo or no treatment in subfertile men, matching the cited 1.8-fold figure. The evidence was rated low quality. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The recent Cochrane Review found that antioxidant use increased the odds of pregnancy by 2.97 fold and the odd of live birth by 1.8 fold. (7)”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > DISCUSSION
What the sources say
- Supportedcites [7] Smits, 2019, Antioxidants for male subfertility, Cochrane Database Syst Rev source
The Clinical pregnancy section reports a Peto odds ratio of 2.97 for antioxidants versus placebo or no treatment in subfertile men. This supports the attributed pregnancy figure; the review specifies that the outcome was clinical pregnancy and rates the evidence as low quality. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A recent meta-analysis concluded that antioxidant supplementation taken by subfertile males may increase the chance of live birth; however, large randomized, well-designed, placebo-controlled trials were needed. (7)”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > INTRODUCTION
What the sources say
- Supportedcites [7] Smits, 2019, Antioxidants for male subfertility, Cochrane Database Syst Rev source
The Authors’ Conclusions (Implications for practice) say that low-quality evidence from seven small randomized trials suggests antioxidant supplementation in subfertile males may improve couples’ live birth rates. The same section calls for further large, well-designed, randomized placebo-controlled trials, matching the citing sentence’s qualification. (LLM, conf=0.94)
Tests✗ Asserted: fails✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. The authors may not put it forward as true.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The recent Cochrane meta-analysis, which included 5 trials with a variety of antioxidants with a total of 254 subjects, found that men treated with antioxidants had on average 5% lower DNA fragmentation, but the confidence interval was broad and crossed 0. (7)”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > DISCUSSION
What the sources say
- Partly supportedcites [7] Smits, 2019, Antioxidants for male subfertility, Cochrane Database Syst Rev sourceExperimental — accuracy not yet measured
The Cochrane review reports a mean difference of −5.00 in DNA fragmentation for antioxidants versus placebo or no treatment, with a 95% confidence interval of −12.61 to 2.61, which crosses zero. It reports 254 men in four RCTs (six intervention arms), not five trials. The supplied passage gives no page number. (LLM, conf=0.92)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Approval for the study was obtained from the University of Pennsylvania, which served as the single IRB for each site with additional local site review.(12)”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > METHODS > Study design
What the sources say
- Partly supportedcites [12] Diamond, 2019, The efficiency of single institutional review board review in National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network-initiated clinical trials, Clin Trials sourceExperimental — accuracy not yet measured
The Methods say that the University of Pennsylvania was the single IRB of record for MOXI and FIT-PLESE at all participating primary sites, which also had to meet local institutional requirements. The Results report local protocol review at each site. The source does not establish that the citing document’s unspecified study received this approval; it says ACTorNOT was instead reviewed by IRBs at each institution. (LLM, conf=0.78)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Change in sperm concentration, total sperm count, and total motile sperm count differed significantly between the two groups, with an increase in the placebo group and a decline in the antioxidant group.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Selenium, vitamin E-α tocopherol, and Zinc levels increased after 3 months of treatment in the antioxidant group but did not change in the placebo group.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > RESULTS
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Selenium, vitamin E-α tocopherol, and Zinc levels increased after 3 months of treatment in the antioxidant group but did not change in the placebo group.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > RESULTS
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pregnancy and live birth rates also did not differ between groups in a per protocol analysis (Supplemental Table 5).”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > RESULTS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Change in sperm concentration, total sperm count, and total motile sperm count differed significantly between the two groups, with an increase in the placebo group and a decline in the antioxidant group.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Selenium, vitamin E-α tocopherol, and Zinc levels increased after 3 months of treatment in the antioxidant group but did not change in the placebo group.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > RESULTS
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Vitamin E-γ tocopherol levels did not change in either group”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > RESULTS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Semen smears were prepared from each sample and shipped to the University of Utah School of Medicine Andrology and IVF Laboratory for centralized assessment of sperm morphology using WHO 5.0 criteria.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > METHODS > Study Treatment
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Baseline characteristics were no different between the two groups, except males in the placebo group were more likely to have fathered a pregnancy in the past.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > RESULTS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasma vitamin levels confirm that men in the antioxidant group complied with the regimen, and men randomized to placebo did not crossover.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > DISCUSSION
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Intention to treat analyses were performed to compare the two groups.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > METHODS > Statistical analysis
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A pre-specified, internal pilot was created to examine the effect of the antioxidant formulation on male semen parameters and DNA fragmentation at 3 months of treatment compared to controls.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > METHODS > Outcomes
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Baseline semen characteristics (Table 2) were similar in the two groups, except males in the antioxidant group had a lower percentage of morphologically normal sperm.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > RESULTS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Written informed consent was obtained from all male and female participants.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > METHODS > Study design
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Antioxidants do not improve semen parameters or DNA integrity among men with male factor infertility.”
- Also stated in: § CONCLUSIONS · plain
“Antioxidant treatment does not improve semen parameters or DNA integrity in infertile males.”
- Also stated in: § DISCUSSION · plain
“In this randomized controlled trial of couples with male factor infertility, the use of an antioxidant combination in the male partner did not result in a significant improvement in semen parameters after 3 months of therapy, compared to placebo.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > Abstract > Conclusions
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § CONCLUSIONS · plain
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The randomization scheme was generated using a computer generated random number sequence in randomly varying blocks of 4 and 6 stratified by site and female age (<35 years and ≥35 years of age) with allocation 1:1 by the data coordinating center through a web-based, secured randomization service.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > METHODS > Study Treatment
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Multi-center, double blind, randomized, placebo-controlled trial with an internal pilot study [Males, Antioxidants, and Infertility (MOXI)]”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > Abstract > Design
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The protocol was designed such that if the pilot failed to reject the null hypothesis that motility and DNA fragmentation did not differ between the two treatment groups (antioxidant and placebo) after 3 months of treatment, the MOXI trial would stop enrollment.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > METHODS > Outcomes
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Study medications were assigned in a double-blind fashion.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > METHODS > Study Treatment
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“Prior trials have been small and of low or very low quality. (13)”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [13] Showell, 2014, Antioxidants for male subfertility, Cochrane Database Syst Rev source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Although a theoretical concern, the antioxidant formulation used in this study did not include excessive amounts of any given antioxidant. Doses aligned with those in prior trials.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Our inclusion criteria were similar if not more selective compared to prior trials.”
§ The Effect of Antioxidants on Male Factor Infertility: The MOXI Randomized Clinical Trial > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The authors state this as an assumption.
There are no interacting effects between the different antioxidants in the formulation.
“inherently assumes namely that there are no interacting effects between the different antioxidants in the formulation.”
The authors state this as an assumption.
The effect of the intervention on live births is at least partially mediated through improvements in sperm motility and a reduction in sperm DNA fragmentation.
“The trial stopping rule had the strong underlying hypothesis that the effect of the intervention on live births is (at least partially) mediated through improvements in sperm motility and a reduction in sperm DNA fragmentation.”
The paper relies on this without support.
Conventional semen quality parameters and even sperm DNA fragmentation are, at best, modest predictors of a couple’s fertility when trying with or without medical assistance.
“However, conventional semen quality parameters and even sperm DNA fragmentation are, at best, modest predictors of a couple’s fertility when trying with or without medical assistance.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In brief, the MOXI trial was a multicenter, randomized, double-blind, placebo-controlled trial analyzing the effect of antioxidants on semen parameters among couples with mild male factor infertility.”
From Poor reproducibility of percentage of normally shaped sperm using the World Health Organization Fifth Edition strict grading criteria (2022) · cites this paper as [22]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Completion claim conflicts with reported dropouts
MinorThe paper says all enrolled couples completed the study protocol, but earlier reports that only 144 of 171 randomized couples completed the study.
“all enrolled couples completed the study protocol.”
“171 were eligible and were randomly assigned to a treatment group (see Supplemental Figure 1); 144 of those couples completed the study.”
Citations
Cites
Generation of Reactive Oxygen Species, Lipid Peroxidation, and Human Sperm Function
Aitken, R. J., Clarkson, J. S., & Fishel, S. B. (1989) · Biology of Reproduction · doi:10.1095/biolreprod41.1.183 · Cited by 1,227 · cited 1×
“Oxidative stress can cause lipid peroxidation, thereby producing structural modifications to the sperm plasma membrane, which have been shown to interfere with sperm motility, acrosome reactions, and sperm– oocyte fusion (4).”
BackgroundEVENSON, D. P., LARSON, K. L., & JOST, L. K. (2002) · Journal of Andrology · doi:10.1002/j.1939-4640.2002.tb02599.x · Cited by 1,072 · cited 1×
“In addition, 1 mL of semen was stored at 80 C and subsequently shipped frozen to the Utah Andrology Laboratory for DNA fragmentation assessment using the sperm chromatin structure analysis (SCSA) test (14), when 10 million sperm were present.”
MethodLipid Peroxidation and Human Sperm Motility: Protective Role of Vitamin E
SULEIMAN, S. A., Ali, M., Zaki, Z. M. S., Elmalik, E. M. A., & NASR, M. A. (1996) · Journal of Andrology · doi:10.1002/j.1939-4640.1996.tb01830.x · Cited by 662 · cited 1×
“Follow-up evaluation in the natural conception trials was not systematic (22, 23).”
BackgroundAntioxidants for male subfertility
Showell, M. G., Brown, J., Yazdani, A., Stankiewicz, M. T., & Hart, R. J. (2011) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007411.pub2 · Cited by 587
Gharagozloo, P., & Aitken, R. J. (2011) · Human Reproduction · doi:10.1093/humrep/der132 · Cited by 523 · cited 1×
“Oxidative stress may also damage the nuclear and mitochondrial genome by causing single and double DNA breaks, chemical modifications of bases, DNA crosslinks, and DNA protein crosslinks (5).”
BackgroundReduction of the Incidence of Sperm DNA Fragmentation by Oral Antioxidant Treatment
Greco, E., Iacobelli, M., Rienzi, L. F., Ubaldi, F. M., Ferrero, S., & Tesařík, J. (2005) · Journal of Andrology · doi:10.2164/jandrol.04146 · Cited by 511 · cited 2×
“(11) enrolled 64 men with DNA fragmentation levelsR15%, as measured using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.”
BackgroundMethodSaleh, R. A., Agarwal, A. K., Sharma, R. K., Nelson, D. R., & Thomas, A. J., Jr. (2002) · Fertility and Sterility · doi:10.1016/s0015-0282(02)03294-6 · Cited by 394
Kessopoulou, E., Powers, H. J., Sharma, K. K., Pearson, M. J., Russell, J., Cooke, I. D., & Barratt, C. L. R. (1995) · Fertility and Sterility · doi:10.1016/s0015-0282(16)57861-3 · Cited by 336 · cited 3×
“A number of the included trials used antioxidants in combination with in vitro fertilization (IVF); it is certainly possible that the response to antioxidants would differ with IVF.”
BackgroundInfluentialAntioxidants for male subfertility
Showell, M. G., Mackenzie-Proctor, R., Brown, J., Yazdani, A., Stankiewicz, M. T., & Hart, R. J. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007411.pub3 · Cited by 285 · cited 6×
“In semen, antioxidants decrease oxidative stress (6), potentially improving sperm motility and reducing DNA fragmentation (7).”
BackgroundMethodInfluentialAntioxidants for male subfertility
Smits, R. M., Mackenzie-Proctor, R., Yazdani, A., Stankiewicz, M. T., Jordan, V., & Showell, M. G. (2019) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007411.pub4 · Cited by 277
Flagged first, then by citations
2 of the 28 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Peivandi, 2010, Effects of l-carnitine on infertile men’s spermogram; a randomised clinical trial, J Reprod Infertil, 10, 245
Cited by
Sorted by citations
Items 201–213 of 213
Achermann, A. P. P., Pereira, T. A., & Esteves, S. C. (2026) · Andrology · doi:10.1111/andr.70369
Antioxidants and Male Infertility: State of Current Evidence
Ziouziou, I., Bahar, F., & Mostafa, T. (2026) · Advances in Andrology · doi:10.1007/978-3-032-29112-7_7
Peramo, B., Upadhyay, D., Bouhafs, L., & AlSafar, H. S. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1870154
“The supplement may have been neutral at best in adequately defended men, and potentially deleterious by inducing reductive stress in those with high baseline antioxidant capacity, a distinction that no pre-treatment assessment was designed to detect (57).”
Jinka, C., Zakaria, N. H., Majid, F. A. A., et al. (2026) · Journal of Holistic Integrative Pharmacy · doi:10.1016/j.jhip.2026.09.004
Parks, S., Miller, R. H., Millar, L., Barnett, B., Jenkins, T. G., Brogaard, K., & Turek, P. J. (2026) · Systems Biology in Reproductive Medicine · doi:10.1080/19396368.2026.2722986
Lifestyle Intervention in Men With Abnormal Semen Analysis who Desire Fertility: A Feasibility Study
Mohan, H., Niranjan, V. P., Gowri, M. S., Sridhar, R., Chinta, P., Kunjummen, A. T., & Kamath, M. S. (2026) · Andrologia · doi:10.1155/and/1689554
Gao, Y., Lv, X., & Sun, Z. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1943471
Interventions Using Various Natural Antioxidant Therapies to Manage Male Fertility: A Review
Nicy, V., Kharwar, R. K., Gurusubramanian, G., et al. (2026) · International Journal of Pharmacology · doi:10.31083/ijp50143
Gharibi, A., Niazvand, F., Teimouri, M., et al. (2026) · Plant Biotechnology Persa · doi:10.66224/pbp.8.2.16
Antioxidants in male infertility: from empirical supplementation to phenotype directed therapy
Zafar, M. I., & Qu, M. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1971018
Persisting challenges for antioxidants use in treatment of male infertility
Eldamnhoury, E. M., & El‐Sakka, A. I. (2026) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2026.2749640
Autoimmunity and Inflammaging in Male Infertility
Monticciolo, I., Simone, N. D., Lomuscio, V., Selmi, C., & Motta, F. (2026) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-026-09208-9
Pharmacotherapy: Adjuvant Pharmacotherapy in Fertility Care for Men and Women
Ulker, A., & Craig, L. B. (2026) · Springer eBooks · doi:10.1007/978-3-032-24372-0_7
Metadata
- Authors
- Steiner, A. Z., Hansen, K. R., Barnhart, K. T., Cedars, M. I., Legro, R. S., Diamond, M. P., Krawetz, S. A., Usadi, R., Baker, V. L., Coward, R. M., Huang, H., Wild, R., Masson, P., Smith, J. F., Santoro, N., Eisenberg, E., & Zhang, H.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of Oklahoma Health Sciences Center (US)
- University of Pennsylvania (US)
- University of California, San Francisco (US)
- Pennsylvania State University (US)
- Augusta University (US)
- Wayne State University (US)
- Stanford University (US)
- Yale University (US)
- University of Colorado Denver (US)
- National Institutes of Health (US)
- Corresponding author
- Steiner, Anne Z.
- ORCID
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 113
- Issue
- 3
- Pages
- 552-560.e3
- ISSN
- 0015-0282 (ISSN-L)
- PMC
- PMC7219515
- OpenAlex
- W3006771562
- Cited by
- 213
- References
- 28
- Citations by year
- 2026: 33 · 2025: 29 · 2024: 25 · 2023: 31 · 2022: 42 · 2021: 32 · 2020: 21
- FWCI
- 22.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Health and Technologies
- Health Sciences › Medicine › Urology › Male Reproductive Health Studies
- Keywords
- male factor infertility, antioxidants, male fertility, sperm DNA fragmentation, semen parameters, sperm concentration, live birth, vitamin C, vitamin E, selenium, L-carnitine, zinc, folic acid, lycopene, intrauterine insemination, clomiphene citrate, oligozoospermia, internal pilot study
- MeSH terms
- Adult, Antioxidants, Double-Blind Method, Female, Humans, Infant, Newborn, Infertility, Male, Insemination, Artificial, Homologous, Male, Ovulation Induction, Pilot Projects, Pregnancy, United States, Pregnancy Rate
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-26, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-26 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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