Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, North Carolina.
Department of Obstetrics and Gynecology, Health Sciences Center, University of Oklahoma, Oklahoma City, Oklahoma.
Fertil Steril. 2020 Mar;113(3):552-560.e3. doi: 10.1016/j.fertnstert.2019.11.008. Epub 2020 Feb 25.
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.
Multicenter, double-blind, randomized, placebo-controlled trial with an internal pilot study.
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.
NCT02421887.
在患有男性因素不育症的夫妇中，评估抗氧化剂是否能在 3 个月时通过精液参数和 DNA 碎片化，以及在治疗后最长 6 个月时通过活产妊娠来改善男性生育能力。
多中心、双盲、随机、安慰剂对照试验，内部先导研究。
美国 9 个生育中心，时间为 2015 年 12 月至 2018 年 12 月。
精子浓度≤1500 万/ml、活力≤40%、正常形态≤4%或 DNA 碎片化>25%的男性（n=174），以及排卵正常、年龄≤40 岁且有记录的输卵管通畅的女性伴侣。
男性随机分配接受含有 500mg 维生素 C、400mg 维生素 E、0.20mg 硒、1000mg 左旋肉碱、20mg 锌、1000μg 叶酸、10mg 番茄红素的抗氧化剂配方（n=85）或安慰剂（n=86）。治疗持续至少 3 个月，最长 6 个月，前 3 个月夫妇尝试自然受孕，第 4 个月至第 6 个月使用克罗米芬并进行宫腔内人工授精。
主要结局是活产；次要结局包括治疗 6 个月内的妊娠。对于内部先导研究，主要结局是治疗 3 个月后的精液参数和精子 DNA 碎片化指数。
在男性、抗氧化剂和不育症（MOXI）研究中，治疗 3 个月后，抗氧化剂组（中位数-400 万/ml，四分位距[-1200 万/ml，570 万/ml]）和安慰剂组（+240 万/ml，四分位距[-900 万/ml，1550 万/ml]）的精子浓度变化不同。然而，两组间精子形态、活力或 DNA 碎片化的变化无统计学差异。在随机分组的 66 名少精子症男性中，3 个月时抗氧化剂组和对照组的精子浓度无差异：850 万/ml（四分位距 480 万/ml，1500 万/ml）和 1500 万/ml（四分位距 600 万/ml，2400 万/ml）。在 75 名弱精子症男性中，3 个月时运动率无差异：34%±16.3%与 36.4%±15.8%。在 44 名 DNA 碎片化程度高的男性中，3 个月时 DNA 碎片化程度无差异：29.5%（21.6%，36.5%）与 28.0%（20.6%，36.4%）。在整个队列中，治疗 6 个月时抗氧化剂组和安慰剂组的累积活产率无差异：15%与 24%。
抗氧化剂不能改善男性因素不育症患者的精液参数或 DNA 完整性。尽管受到样本量的限制，本研究表明，男性伴侣的抗氧化剂治疗不能提高体内妊娠或活产率。
NCT02421887。
