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. 2019 Mar 14;2019(3):CD007411. doi: 10.1002/14651858.CD007411.pub4

Comparison 1. Antioxidant(s) versus placebo or no treatment.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
1 Live birth; type of antioxidant 7 750 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.79 [1.20, 2.67]
1.1 Carnitines 1 60 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.0 [0.24, 4.25]
1.2 Coenzyme Q10 1 60 Peto Odds Ratio (Peto, Fixed, 95% CI) 2.16 [0.53, 8.82]
1.3 Vitamin D + Calcium 1 330 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.03 [0.59, 1.80]
1.4 Vitamin E 2 140 Peto Odds Ratio (Peto, Fixed, 95% CI) 8.51 [2.36, 30.70]
1.5 Zinc 1 100 Peto Odds Ratio (Peto, Fixed, 95% CI) 3.74 [1.02, 13.74]
1.6 Combined antioxidants 1 60 Peto Odds Ratio (Peto, Fixed, 95% CI) 3.42 [1.15, 10.13]
2 Live birth; placebo or no treatment 7 750 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.79 [1.20, 2.67]
2.1 Placebo 6 650 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.65 [1.08, 2.52]
2.2 No treatment 1 100 Peto Odds Ratio (Peto, Fixed, 95% CI) 3.74 [1.02, 13.74]
3 Live birth; IVF/ICSI 2 90 Peto Odds Ratio (Peto, Fixed, 95% CI) 3.61 [1.27, 10.29]
4 Live birth; as‐treated analysis 7 649 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.71 [1.13, 2.58]
4.1 Carnitines 1 59 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.04 [0.25, 4.41]
4.2 Coenzyme Q10 1 55 Peto Odds Ratio (Peto, Fixed, 95% CI) 2.10 [0.51, 8.64]
4.3 Vitamin D + Calcium 1 269 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.01 [0.57, 1.81]
4.4 Vitamin E 2 117 Peto Odds Ratio (Peto, Fixed, 95% CI) 6.44 [1.72, 24.04]
4.5 Zinc 1 97 Peto Odds Ratio (Peto, Fixed, 95% CI) 3.67 [1.00, 13.51]
4.6 Combined antioxidants 1 52 Peto Odds Ratio (Peto, Fixed, 95% CI) 3.34 [1.04, 10.76]
5 Clinical pregnancy; type of antioxidant 11 786 Peto Odds Ratio (Peto, Fixed, 95% CI) 2.97 [1.91, 4.63]
5.1 Carnitines 1 60 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.0 [0.24, 4.25]
5.2 Coenzyme Q10 1 60 Peto Odds Ratio (Peto, Fixed, 95% CI) 2.16 [0.53, 8.82]
5.3 Folic acid 1 53 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.0 [0.0, 0.0]
5.4 Magnesium 1 26 Peto Odds Ratio (Peto, Fixed, 95% CI) 8.73 [0.17, 445.08]
5.5 N‐acetylcysteine (NAC) 2 100 Peto Odds Ratio (Peto, Fixed, 95% CI) 2.00 [0.71, 5.63]
5.6 Vitamin E 2 117 Peto Odds Ratio (Peto, Fixed, 95% CI) 6.71 [1.98, 22.69]
5.7 Zinc 2 153 Peto Odds Ratio (Peto, Fixed, 95% CI) 4.43 [1.39, 14.14]
5.8 Zinc + Folic acid 1 53 Peto Odds Ratio (Peto, Fixed, 95% CI) 3.86 [0.15, 99.84]
5.9 Combined antioxidants 2 164 Peto Odds Ratio (Peto, Fixed, 95% CI) 3.19 [1.44, 7.08]
6 Clinical pregnancy; placebo or no treatment 11 786 Peto Odds Ratio (Peto, Fixed, 95% CI) 2.97 [1.91, 4.63]
6.1 Placebo 9 626 Peto Odds Ratio (Peto, Fixed, 95% CI) 3.01 [1.81, 5.03]
6.2 No treatment 2 160 Peto Odds Ratio (Peto, Fixed, 95% CI) 2.84 [1.16, 6.96]
7 Clinical pregnancy; IVF/ICSI 2 90 Peto Odds Ratio (Peto, Fixed, 95% CI) 2.64 [0.94, 7.41]
8 Adverse events 13   Peto Odds Ratio (Peto, Fixed, 95% CI) Subtotals only
8.1 Miscarriage 3 247 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.74 [0.40, 7.60]
8.2 Gastrointestinal 11 948 Peto Odds Ratio (Peto, Fixed, 95% CI) 2.51 [1.25, 5.03]
8.3 Euphoria 1 86 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.21 [0.16, 9.01]
8.4 Ectopic pregnancy 1 60 Peto Odds Ratio (Peto, Fixed, 95% CI) 4.48 [0.07, 286.49]
9 Sperm DNA fragmentation; type of antioxidant 4 254 Mean Difference (IV, Random, 95% CI) ‐3.00 [‐12.61, 2.61]
9.1 Docosahexaenoic acid (DHA) 1 36 Mean Difference (IV, Random, 95% CI) ‐14.10 [‐23.22, ‐4.98]
9.2 Folic acid 1 38 Mean Difference (IV, Random, 95% CI) ‐5.80 [‐13.40, 1.80]
9.3 Folic acid + Zinc 1 39 Mean Difference (IV, Random, 95% CI) ‐1.20 [‐9.36, 6.96]
9.4 N‐acetylcysteine (NAC) 1 35 Mean Difference (IV, Random, 95% CI) 3.90 [‐0.42, 8.22]
9.5 Vitamin C + Vitamin E 1 64 Mean Difference (IV, Random, 95% CI) ‐13.80 [‐17.50, ‐10.10]
9.6 Zinc 1 42 Mean Difference (IV, Random, 95% CI) 1.30 [‐8.62, 11.22]
10 Sperm DNA fragmentation (data not suitable for meta‐analysis)     Other data No numeric data
10.1 Folic acid     Other data No numeric data
10.2 Combined antioxidants     Other data No numeric data
11 Total sperm motility at 3 months or less; type of antioxidant 18   Mean Difference (IV, Random, 95% CI) Subtotals only
11.1 Carnitines 5 244 Mean Difference (IV, Random, 95% CI) 11.91 [‐0.85, 24.66]
11.2 Coenzyme Q10 1 47 Mean Difference (IV, Random, 95% CI) 3.61 [‐6.13, 13.35]
11.3 Folic acid 1 51 Mean Difference (IV, Random, 95% CI) 8.40 [‐5.81, 22.61]
11.4 Magnesium 1 20 Mean Difference (IV, Random, 95% CI) 14.5 [‐6.01, 35.01]
11.5 N‐acetylcysteine (NAC) 1 35 Mean Difference (IV, Random, 95% CI) 14.60 [0.32, 28.88]
11.6 PUFAs 2 64 Mean Difference (IV, Random, 95% CI) ‐8.35 [‐17.40, 0.69]
11.7 Selenium 1 34 Mean Difference (IV, Random, 95% CI) 14.9 [1.14, 28.66]
11.8 Vitamin C + Vitamin E 1 64 Mean Difference (IV, Random, 95% CI) 2.90 [‐7.76, 13.56]
11.9 Vitamin E 1 45 Mean Difference (IV, Random, 95% CI) 18.9 [4.90, 32.90]
11.10 Zinc 2 76 Mean Difference (IV, Random, 95% CI) 15.37 [‐5.14, 35.88]
11.11 Zinc + Folic acid 1 54 Mean Difference (IV, Random, 95% CI) 6.80 [‐7.57, 21.17]
11.12 Zinc + Vitamin E 1 20 Mean Difference (IV, Random, 95% CI) 26.0 [12.85, 39.15]
11.13 Zinc + Vitamin E + Vitamin C 1 22 Mean Difference (IV, Random, 95% CI) 26.0 [12.62, 39.38]
11.14 Combined antioxidants 4 383 Mean Difference (IV, Random, 95% CI) 12.43 [8.39, 16.46]
12 Total sperm motility at 3 months or less (data not suitable for meta analysis)     Other data No numeric data
12.1 Carnitines     Other data No numeric data
12.3 Folic acid     Other data No numeric data
12.4 Folic acid + Zinc     Other data No numeric data
12.5 Vitamin E     Other data No numeric data
12.6 Zinc     Other data No numeric data
12.7 Combined antioxidants     Other data No numeric data
13 Total sperm motility at 6 months; type of antioxidant 13   Mean Difference (IV, Random, 95% CI) Subtotals only
13.1 Carnitines 3 136 Mean Difference (IV, Random, 95% CI) 11.73 [1.87, 21.60]
13.2 Coenzyme Q10 3 479 Mean Difference (IV, Random, 95% CI) 6.59 [1.80, 11.37]
13.3 Folic acid 1 51 Mean Difference (IV, Random, 95% CI) 1.70 [‐8.49, 11.89]
13.4 N‐acetylcysteine (NAC) 1 211 Mean Difference (IV, Random, 95% CI) 1.90 [1.20, 2.60]
13.5 Selenium 1 211 Mean Difference (IV, Random, 95% CI) 3.20 [2.50, 3.90]
13.6 Selenium + N‐acetylcysteine (NAC) 1 210 Mean Difference (IV, Random, 95% CI) 6.30 [5.60, 7.00]
13.7 Vitamin D + Calcium 1 260 Mean Difference (IV, Random, 95% CI) ‐4.0 [‐9.57, 1.57]
13.8 Vitamin E 2 132 Mean Difference (IV, Random, 95% CI) 11.20 [4.70, 17.70]
13.9 Zinc 1 57 Mean Difference (IV, Random, 95% CI) 0.0 [‐10.19, 10.19]
13.10 Zinc + Folic acid 1 54 Mean Difference (IV, Random, 95% CI) 2.60 [‐8.82, 14.02]
13.11 Combined antioxidants 2 229 Mean Difference (IV, Random, 95% CI) 9.35 [3.19, 15.51]
14 Total sperm motility at 6 months(data not suitable for meta analysis)     Other data No numeric data
14.1 Carnitines     Other data No numeric data
14.2 Folic acid     Other data No numeric data
14.3 Zinc     Other data No numeric data
14.4 Zinc + Folic acid     Other data No numeric data
14.5 Combined antioxidants     Other data No numeric data
15 Total sperm motility at 9 months or more; type of antioxidant 5   Mean Difference (IV, Random, 95% CI) Subtotals only
15.1 Carnitines 1 59 Mean Difference (IV, Random, 95% CI) 8.54 [3.01, 14.07]
15.2 Coenzyme Q10 3 479 Mean Difference (IV, Random, 95% CI) 1.90 [‐1.56, 5.36]
15.3 Vitamin E 1 45 Mean Difference (IV, Random, 95% CI) 2.20 [‐8.48, 12.88]
16 Total sperm motility over time 26   Mean Difference (IV, Random, 95% CI) Subtotals only
16.1 Total sperm motility at 3 months or less 18 1105 Mean Difference (IV, Random, 95% CI) 10.19 [4.35, 16.04]
16.2 Total sperm motility at 6 months 13 1768 Mean Difference (IV, Random, 95% CI) 6.00 [3.92, 8.09]
16.3 Total sperm motility at 9 months or more 5 583 Mean Difference (IV, Random, 95% CI) 3.29 [0.36, 6.23]
17 Progressive sperm motility at 3 months or less; type of antioxidant 14   Mean Difference (IV, Random, 95% CI) Subtotals only
17.1 Carnitines 3 199 Mean Difference (IV, Random, 95% CI) 20.63 [19.40, 21.87]
17.2 Coenzyme Q10 1 47 Mean Difference (IV, Random, 95% CI) 4.60 [‐3.54, 12.74]
17.3 Docosahexaenoic acid (DHA) 1 36 Mean Difference (IV, Random, 95% CI) ‐6.60 [‐8.57, ‐4.63]
17.4 Folic acid 2 81 Mean Difference (IV, Random, 95% CI) 5.68 [‐5.02, 16.38]
17.5 N‐acetylcysteine (NAC) 1 60 Mean Difference (IV, Random, 95% CI) 3.80 [‐1.03, 8.63]
17.6 PUFAs 1 44 Mean Difference (IV, Random, 95% CI) 6.40 [4.83, 7.97]
17.7 Vitamin C 2 145 Mean Difference (IV, Random, 95% CI) 16.03 [‐3.90, 35.95]
17.8 Vitamin C + Vitamin E 1 31 Mean Difference (IV, Random, 95% CI) 0.20 [‐9.77, 10.17]
17.9 Zinc 2 157 Mean Difference (IV, Random, 95% CI) 1.14 [‐3.37, 5.64]
17.10 Zinc + Folic acid 1 54 Mean Difference (IV, Random, 95% CI) 3.80 [‐13.66, 21.26]
17.11 Combined antioxidants 1 180 Mean Difference (IV, Random, 95% CI) 15.20 [13.62, 16.78]
18 Progressive sperm motility at 3 months (data not usable for meta‐analysis)     Other data No numeric data
18.1 Combined antioxidants     Other data No numeric data
19 Progressive sperm motility at 6 months; type of antioxidant 5   Mean Difference (IV, Random, 95% CI) Subtotals only
19.1 Carnitines 1 59 Mean Difference (IV, Random, 95% CI) 15.94 [11.01, 20.87]
19.2 Coenzyme Q10 1 60 Mean Difference (IV, Random, 95% CI) 5.0 [2.13, 7.87]
19.3 Folic acid 2 81 Mean Difference (IV, Random, 95% CI) ‐1.77 [‐10.21, 6.67]
19.4 Vitamin D + Calcium 1 260 Mean Difference (IV, Random, 95% CI) ‐4.0 [‐9.59, 1.59]
19.5 Zinc 1 57 Mean Difference (IV, Random, 95% CI) 2.0 [‐13.56, 17.56]
19.6 Zinc + Folic acid 1 54 Mean Difference (IV, Random, 95% CI) 2.70 [‐14.58, 19.98]
20 Progessive sperm motility at 6 months (data not usable for meta‐analysis)     Other data No numeric data
20.1 Combined antioxidants     Other data No numeric data
21 Progressive sperm motility at 9 months or more; type of antioxidant 2   Mean Difference (IV, Random, 95% CI) Subtotals only
21.1 Carnitines 1 59 Mean Difference (IV, Random, 95% CI) 7.77 [2.68, 12.87]
21.2 Coenzyme Q10 1 60 Mean Difference (IV, Random, 95% CI) ‐0.90 [‐2.68, 0.88]
22 Progressive sperm motility over time 15   Mean Difference (IV, Random, 95% CI) Subtotals only
22.1 Progressive sperm motility at 3 months or less 13 884 Mean Difference (IV, Random, 95% CI) 9.75 [5.26, 14.24]
22.2 Progressive sperm motility at 6 months 5 521 Mean Difference (IV, Random, 95% CI) 6.11 [0.57, 11.66]
22.3 Progressive sperm motility at 9 months or more 2 119 Mean Difference (IV, Random, 95% CI) 4.64 [‐1.67, 10.95]
23 Sperm concentration at 3 months or less; type of antioxidant 21   Mean Difference (IV, Random, 95% CI) Subtotals only
23.1 Carnitines 4 247 Mean Difference (IV, Random, 95% CI) 10.43 [0.99, 19.87]
23.2 Coenzyme Q10 1 47 Mean Difference (IV, Random, 95% CI) ‐0.10 [‐12.37, 12.17]
23.3 Folic acid 2 81 Mean Difference (IV, Random, 95% CI) 8.54 [‐22.31, 39.39]
23.4 Magnesium 1 20 Mean Difference (IV, Random, 95% CI) 5.20 [‐2.61, 13.01]
23.5 N‐acetylcysteine (NAC) 2 95 Mean Difference (IV, Random, 95% CI) 4.59 [‐0.27, 9.46]
23.6 PUFAs 3 108 Mean Difference (IV, Random, 95% CI) 3.44 [1.70, 5.17]
23.7 Selenium 1 25 Mean Difference (IV, Random, 95% CI) 21.20 [‐11.43, 53.83]
23.8 Vitamin C 1 115 Mean Difference (IV, Random, 95% CI) 9.70 [0.09, 19.31]
23.9 Vitamin C + Vitamin E 2 95 Mean Difference (IV, Random, 95% CI) 1.36 [‐10.01, 12.72]
23.10 Vitamin E 1 45 Mean Difference (IV, Random, 95% CI) 18.9 [3.92, 33.88]
23.11 Zinc 2 157 Mean Difference (IV, Random, 95% CI) 8.75 [2.25, 15.24]
23.12 Zinc + Folic acid 1 54 Mean Difference (IV, Random, 95% CI) 18.0 [1.11, 34.89]
23.13 Combined antioxidants 3 344 Mean Difference (IV, Random, 95% CI) 6.71 [‐1.91, 15.33]
24 Sperm concentration at 3 months or less (data not suitable for meta analysis)     Other data No numeric data
24.1 Carnitines     Other data No numeric data
24.2 Vitamin E     Other data No numeric data
24.3 Folic acid     Other data No numeric data
24.4 Zinc     Other data No numeric data
24.5 Folic acid + Zinc     Other data No numeric data
24.6 Combined antioxidants     Other data No numeric data
25 Sperm concentration at 6 months; type of antioxidant 11   Mean Difference (IV, Random, 95% CI) Subtotals only
25.1 Carnitines 2 115 Mean Difference (IV, Random, 95% CI) 2.60 [‐3.13, 8.33]
25.2 Coenzyme Q10 3 479 Mean Difference (IV, Random, 95% CI) 6.87 [1.18, 12.55]
25.3 Folic acid 2 81 Mean Difference (IV, Random, 95% CI) 2.44 [‐37.87, 42.75]
25.4 N‐acetylcysteine (NAC) 1 211 Mean Difference (IV, Random, 95% CI) 3.30 [1.80, 4.80]
25.5 Selenium 1 211 Mean Difference (IV, Random, 95% CI) 4.10 [2.45, 5.75]
25.6 Selenium + N‐acetylcysteine (NAC) 1 210 Mean Difference (IV, Random, 95% CI) 8.60 [6.89, 10.31]
25.7 Vitamin E 1 45 Mean Difference (IV, Random, 95% CI) 5.90 [‐10.83, 22.63]
25.8 Zinc 1 57 Mean Difference (IV, Random, 95% CI) 9.70 [‐7.00, 26.40]
25.9 Zinc + Folic acid 1 54 Mean Difference (IV, Random, 95% CI) 17.70 [‐1.88, 37.28]
25.10 Combined antioxidants 2 229 Mean Difference (IV, Random, 95% CI) 13.68 [8.06, 19.31]
26 Sperm concentration at 6 months(data not suitable for meta analysis)     Other data No numeric data
26.1 Carnitines     Other data No numeric data
26.2 Folic acid     Other data No numeric data
26.3 Zinc     Other data No numeric data
26.4 Zinc + Folic acid     Other data No numeric data
26.5 Vitamin D + Calcium     Other data No numeric data
27 Sperm concentration at 9 months; type of antioxidant 5   Mean Difference (IV, Random, 95% CI) Subtotals only
27.1 Carnitines 1 59 Mean Difference (IV, Random, 95% CI) 4.17 [‐1.71, 10.06]
27.2 Coenzyme Q10 3 479 Mean Difference (IV, Random, 95% CI) 2.74 [‐1.57, 7.05]
27.3 Vitamin E 1 45 Mean Difference (IV, Random, 95% CI) 11.40 [‐2.56, 25.36]
28 Sperm concentration over time 26   Mean Difference (IV, Random, 95% CI) Subtotals only
28.1 Sperm concentration at 3 months or less 20 1244 Mean Difference (IV, Random, 95% CI) 7.51 [4.23, 10.79]
28.2 Sperm concentration 6 months 11 1430 Mean Difference (IV, Random, 95% CI) 7.49 [4.76, 10.23]
28.3 Sperm concentration at 9 months or more 5 583 Mean Difference (IV, Random, 95% CI) 3.61 [0.17, 7.06]