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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. [ABSTRACT FROM AUTHOR]

Context: Promoting patient value-concordant end-of-life care is a priority in health care systems but has rarely been examined in randomized clinical trials.Objectives: To examine the effectiveness of an advance care planning intervention in facilitating concordance between cancer patients' preferred and received life-sustaining treatment (LST) states and to explore modifiable factors facilitating or impeding such concordance.Methods: Terminal cancer patients (N = 460) were randomly assigned 1:1 to the experimental and control arms of a randomized clinical trial, with 430 deceased participants comprising the final sample. States of preferred LSTs (cardiopulmonary resuscitation, intensive care unit care, chest compression, intubation with mechanical ventilation, intravenous nutrition, and nasogastric tube feeding) and LSTs received in the last month were examined by hidden Markov modeling. Concordance and its modifiable predictors were evaluated by kappa and multivariate logistic regression, respectively.Results: We identified three LST-preference states (uniformly preferring LSTs, rejecting LSTs except intravenous nutrition support, and mixed LST preferences) and three received LST states (uniformly receiving LSTs, received intravenous nutrition only, and selectively receiving LSTs). Concordance was not significantly higher in the experimental than the control arm (kappa [95% CI]: 0.126 [0.032, 0.221] vs. 0.050 [-0.028, 0.128]; arm difference: odds ratio [95% CI]: 1.008 [0.675, 1.5001]). Preferred-received LST-state concordance was facilitated by accurate prognostic awareness, better quality of life, and more depressive symptoms, whereas concordance was impeded by more anxiety symptoms.Conclusions: Our advance care planning intervention did not facilitate concordance between terminally ill cancer patients' preferred and received LST states, but patient value-concordant end-of-life care may be facilitated by interventions to cultivate accurate prognostic awareness, improve quality of life, support depressive patients, and clarify anxious patients' overexpectations of LST efficacy. [ABSTRACT FROM AUTHOR]