Antioxidants for female subfertility

Marian G Showell; Rebecca Mackenzie-Proctor; Vanessa Jordan; Roger J Hart

doi:10.1002/14651858.CD007807.pub4

Scolaris Content Display Scolaris Content Display

Topics

Figure 1

Study flow diagram.

Navigate to figure in ReviewOpen in new tab

Figure 2

Methodological risk of bias summary: review authors' judgements about each methodological bias item for each included study.

Navigate to figure in ReviewOpen in new tab

Figure 3

Methodological risk of bias graph: review authors' judgements about each methodological bias item presented as percentages across all included trials.

Navigate to figure in ReviewOpen in new tab

Figure 4

Funnel plot of comparison: 1 Antioxidant(s) versus placebo or no treatment/standard treatment, outcome: 1.5 Clinical pregnancy; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments).

Navigate to figure in ReviewOpen in new tab

Figure 5

Forest plot of comparison: 1 Antioxidant(s) versus placebo or no treatment/standard treatment, outcome: 1.1 Live birth; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments).

Navigate to figure in ReviewOpen in new tab

Figure 6

Forest plot of comparison: 1 Antioxidant(s) versus placebo or no treatment/standard treatment, outcome: 1.5 Clinical pregnancy; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments).

Navigate to figure in ReviewOpen in new tab

Figure 7

Forest plot of comparison: 1 Antioxidant(s) versus placebo or no treatment/standard treatment, outcome: 1.9 Adverse events.

Navigate to figure in ReviewOpen in new tab

Figure 8

Forest plot of comparison: 2 Head‐to‐head antioxidants, outcome: 2.1 Live birth; type of antioxidant (natural conceptions and undergoing fertility treatments).

Navigate to figure in ReviewOpen in new tab

Figure 9

Forest plot of comparison: 2 Head‐to‐head antioxidants, outcome: 2.4 Clinical pregnancy; type of antioxidant (natural conceptions and undergoing fertility treatments).

Navigate to figure in ReviewOpen in new tab

Figure 10

Forest plot of comparison: 2 Head‐to‐head antioxidants, outcome: 2.7 Adverse events.

Navigate to figure in ReviewOpen in new tab

Analysis 1.1

Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 1: Live birth; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments)

Navigate to figure in ReviewOpen in new tab

Analysis 1.2

Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 2: Live birth; type of antioxidant

Navigate to figure in ReviewOpen in new tab

Analysis 1.3

Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 3: Live birth; indications for subfertility

Navigate to figure in ReviewOpen in new tab

Analysis 1.4

Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 4: Live birth; IVF/ICSI

Navigate to figure in ReviewOpen in new tab

Analysis 1.5

Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 5: Clinical pregnancy; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments)

Navigate to figure in ReviewOpen in new tab

Analysis 1.6

Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 6: Clinical pregnancy; type of antioxidant

Navigate to figure in ReviewOpen in new tab

Analysis 1.7

Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 7: Clinical pregnancy; indications for subfertility

Navigate to figure in ReviewOpen in new tab

Analysis 1.8

Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 8: Clinical pregnancy; IVF/ICSI

Navigate to figure in ReviewOpen in new tab

Analysis 1.9

Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 9: Adverse events

Navigate to figure in ReviewOpen in new tab

Analysis 2.1

Comparison 2: Head‐to‐head antioxidants, Outcome 1: Live birth; type of antioxidant (natural conceptions and undergoing fertility treatments)

Navigate to figure in ReviewOpen in new tab

Analysis 2.2

Comparison 2: Head‐to‐head antioxidants, Outcome 2: Live Birth; indications for subfertility

Navigate to figure in ReviewOpen in new tab

Analysis 2.3

Comparison 2: Head‐to‐head antioxidants, Outcome 3: Live Birth; IVF/ICSI

Navigate to figure in ReviewOpen in new tab

Analysis 2.4

Comparison 2: Head‐to‐head antioxidants, Outcome 4: Clinical pregnancy; type of antioxidant (natural conceptions and undergoing fertility treatments)

Navigate to figure in ReviewOpen in new tab

Analysis 2.5

Comparison 2: Head‐to‐head antioxidants, Outcome 5: Clinical pregnancy; indications for subfertility

Navigate to figure in ReviewOpen in new tab

Analysis 2.6

Comparison 2: Head‐to‐head antioxidants, Outcome 6: Clinical pregnancy; IVF/ICSI

Navigate to figure in ReviewOpen in new tab

Analysis 2.7

Comparison 2: Head‐to‐head antioxidants, Outcome 7: Adverse events

Navigate to figure in ReviewOpen in new tab

Summary of findings 1. Antioxidant(s) compared to placebo or no treatment/standard treatment for female subfertility

Outcomes	Relative effect (95% CI)	*Anticipated absolute effects^ (95% CI)**			Quality of the evidence (GRADE)	What happens
Antioxidant(s) compared to placebo or no treatment/standard treatment for female subfertility
Patient or population: women with subfertility Setting: Infertility clinics Intervention: Antioxidant(s) Comparison: placebo or no treatment/standard treatment
Outcomes	Relative effect (95% CI)	Without antioxidant(s)	With antioxidant(s)	Difference	Quality of the evidence (GRADE)	What happens
Live birth; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments) № of participants: 1227 (13 RCTs)	OR 1.81 (1.36 to 2.43)	19.0%	29.8% (24.2 to 36.3)	10.8% more (5.2 more to 17.3 more)	⊕⊝⊝⊝ VERY LOW^a,b,c	We are uncertain whether antioxidants improve live birth rate compared with placebo or no treatment/standard treatment.
Clinical pregnancy; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments) № of participants: 5165 (35 RCTs)	OR 1.65 (1.43 to 1.89)	18.8%	27.6% (24.8 to 30.4)	8.8% more (6.1 more to 11.6 more)	⊕⊕⊝⊝ LOW^a,d	Antioxidant(s) may improve clinical pregnancy rate, compared with placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments).
Adverse events ‐ Miscarriage № of participants: 3229 (24 RCTs)	OR 1.13 (0.82 to 1.55)	4.8%	5.4% (4 to 7.3)	0.6% more (0.8 fewer to 2.5 more)	⊕⊕⊝⊝ LOW^a,c	Antioxidant(s) may result in little to no difference in adverse events ‐ Miscarriage
Adverse events ‐ Multiple pregnancy № of participants: 1886 (9 RCTs)	OR 1.00 (0.63 to 1.56)	4.3%	4.3% (2.7 to 6.5)	0.0% fewer (1.6 fewer to 2.2 more)	⊕⊕⊝⊝ LOW^a,c	Antioxidant(s) may result in little to no difference in adverse events ‐ Multiple pregnancy
Adverse events ‐ Gastrointestinal disturbances № of participants: 343 (3 RCTs)	OR 1.55 (0.47 to 5.10)	2.4%	3.7% (1.2 to 11.2)	1.3% more (1.2 fewer to 8.8 more)	⊕⊕⊝⊝ LOW^a,c	Antioxidant(s) may result in little to no difference in adverse events ‐ Gastrointestinal disturbances
Adverse events ‐ Ectopic pregnancy № of participants: 404 (4 RCTs)	OR 1.40 (0.27 to 7.20)	0.6%	0.9% (0.2 to 4.3)	0.3% more (0.4 fewer to 3.7 more)	⊕⊕⊝⊝ LOW^a,c	Antioxidant(s) may result in little to no difference in adverse events ‐ Ectopic pregnancy
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
^aDowngraded one level due to serious risk of bias. The no‐treatment group increases risk due to the lack of blinding. ^bDowngraded one level; overall the heterogeneity is low (0%), but in the placebo subgroup the heterogeneity statistic is 60% and some trials are showing potential benefit of the intervention while others are showing benefit of the placebo. ^cDowngraded one level as the event rate is low (< 400). ^dDowngraded one level as the heterogeneity statistic (63%) is considered to represent moderate to substantive heterogeneity.

Summary of findings 1. Antioxidant(s) compared to placebo or no treatment/standard treatment for female subfertility

Navigate to table in Review

Summary of findings 2. Head‐to‐head antioxidants for female subfertility

Outcomes	Relative effect (95% CI)	*Anticipated absolute effects^ (95% CI)**			Quality of the evidence (GRADE)	What happens
Head‐to‐head antioxidants for female subfertility
Patient or population: women with subfertility Setting: Infertility clinics Intervention: Head‐to‐head antioxidants Comparison: Other antioxidant
Outcomes	Relative effect (95% CI)	With one antioxidant	With another antioxidant	Difference	Quality of the evidence (GRADE)	What happens
Live birth; type of antioxidant (natural conceptions and undergoing fertility treatments) ‐ Melatonin lower dose versus melatonin higher dose № of participants: 140 (2 RCTs)	OR 0.94 (0.41 to 2.15)	24.0%	22.9% (11.5 to 40.4)	1.1% fewer (12.5 fewer to 16.4 more)	⊕⊕⊝⊝ LOW^a,b	There was no clear evidence of a difference between the lower and higher doses of melatonin
Clinical pregnancy; type of antioxidant (natural conceptions and undergoing fertility treatments) ‐ N‐acetylcysteine versus L‐carnitine № of participants: 164 (1 RCT)	OR 0.81 (0.33 to 2.00)	14.6%	12.2% (5.4 to 25.5)	2.4% fewer (9.2 fewer to 10.9 more)	⊕⊝⊝⊝ VERY LOW^c,d	There was no clear evidence of a difference between N‐acetylcysteine versus L‐carnitine
Clinical pregnancy; type of antioxidant (natural conceptions and undergoing fertility treatments) ‐ Melatonin lower dose versus melatonin higher dose № of participants: 140 (2 RCTs)	OR 0.94 (0.41 to 2.15)	24.0%	22.9% (11.5 to 40.4)	1.1% fewer (12.5 fewer to 16.4 more)	⊕⊕⊝⊝ LOW^a,b	There was no clear evidence of a difference between the lower and higher doses of melatonin
Adverse events ‐ Miscarriage № of participants: 304 (3 RCTs)	OR 1.54 (0.42 to 5.67)	3.0%	4.6% (1.3 to 15.1)	1.6 more (1.7 fewer to 12.1 more)	⊕⊕⊝⊝ LOW^a,b	There were no miscarriages in either melatonin study (140 women) There was no clear evidence of a difference between N‐acetylcysteine versus L‐carnitine (164 women)
Adverse events ‐ Multiple pregnancy	There were no trials reporting multiple pregnancy
Adverse events ‐ Gastrointestinal disturbances	There were no trials reporting gastrointestinal disturbances
Adverse events ‐ Ectopic pregnancy Melatonin lower dose versus melatonin higher dose № of participants: 120 (1 RCT)	Not estimable, there were no ectopic pregnancies in either group				⊕⊝⊝⊝ VERY LOW ^{3 4}	There was no clear evidence of a difference between the lower and higher doses of melatonin
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
^aDowngraded one level as there are only two trials in this analysis and one is small. ^bDowngraded one level as event rate is low (< 400). ^cDowngraded two levels as one study can not represent possible subfertile populations. ^dDowngraded two levels as only one study, event rate low and small number of participants

Summary of findings 2. Head‐to‐head antioxidants for female subfertility

Navigate to table in Review

Table 1. Gerli 2007‐ data not included in meta‐analysis

Outcome	Data	Notes
Clinical pregnancy rate; myo‐inositol + folic acid	4/23	Only 42 of the 92 women enrolled in this trial declared a desire to become pregnant
Clinical pregnancy rate; folic acid + placebo	1/19	‐
Miscarriage rate; myo‐inositol + folic acid	Miscarriage reported, but unknown whether from treatment or control	1 miscarriage occurred in the first trimester, but it is unknown from which group
Miscarriage rate; folic acid + placebo	Unknown	‐

Table 1. Gerli 2007‐ data not included in meta‐analysis

Navigate to table in Review

Table 2. 'Biochemical' and 'pregnancy' data for those trials that did not specifically report 'clinical pregnancy'

Trial	Pregnancy in antioxidant group	Pregnancy in control group
Mier‐Cabrera 2008	0/16 (vitamins C + E), at follow‐up over 9 months 3/16	0/18 (placebo), at follow‐up over 9 months 2/18
Mohammadbeigi 2012	9/22 (vitamin D)	7/22 (placebo)
Razavi 2015	6/32 (selenium)	1/32 (placebo)
Al‐Alousi 2018	20/60 (omega)	15/58 (placebo)
Ghomian 2019	7/33 (NAC + CC)	5/33 (CC)
Heidar 2019	6/20 (selenium)	5/20 (placebo)
Siavashani 2018	5/20 (chromium)	4/20 (placebo)
Schillaci 2012	0/6 (myo‐inositol + 200 µg folic acid twice a day)	0/6 (400 µg folic acid once a day)
CC: clomiphene citrate; NAC: N‐acetylcysteine

Table 2. 'Biochemical' and 'pregnancy' data for those trials that did not specifically report 'clinical pregnancy'

Navigate to table in Review

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

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Live birth; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments) Show forest plot	13	1227	Odds Ratio (M‐H, Fixed, 95% CI)	1.81 [1.36, 2.43]

1.1.1 Placebo	7	628	Odds Ratio (M‐H, Fixed, 95% CI)	1.89 [1.18, 3.03]
1.1.2 No treatment	6	599	Odds Ratio (M‐H, Fixed, 95% CI)	1.77 [1.22, 2.56]
1.2 Live birth; type of antioxidant Show forest plot	13	1227	Odds Ratio (M‐H, Fixed, 95% CI)	1.81 [1.36, 2.43]

1.2.1 N‐acetyl‐cysteine	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	3.00 [1.05, 8.60]
1.2.2 L‐arginine	1	37	Odds Ratio (M‐H, Fixed, 95% CI)	0.43 [0.09, 2.09]
1.2.3 CoQ10	2	225	Odds Ratio (M‐H, Fixed, 95% CI)	1.50 [0.78, 2.88]
1.2.4 Vitamin D	1	52	Odds Ratio (M‐H, Fixed, 95% CI)	0.79 [0.21, 3.02]
1.2.5 Vitamin B complex	1	102	Odds Ratio (M‐H, Fixed, 95% CI)	2.07 [0.93, 4.57]
1.2.6 Combined antioxidants	3	378	Odds Ratio (M‐H, Fixed, 95% CI)	2.59 [1.52, 4.40]
1.2.7 Vitamin E	1	103	Odds Ratio (M‐H, Fixed, 95% CI)	1.43 [0.50, 4.10]
1.2.8 Melatonin	3	270	Odds Ratio (M‐H, Fixed, 95% CI)	1.60 [0.68, 3.76]
1.3 Live birth; indications for subfertility Show forest plot	11		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.3.1 Polycystic ovary syndrome	3	362	Odds Ratio (M‐H, Fixed, 95% CI)	3.34 [1.90, 5.86]
1.3.2 Tubal subfertility	1	37	Odds Ratio (M‐H, Fixed, 95% CI)	0.43 [0.09, 2.09]
1.3.3 Varying indications	3	338	Odds Ratio (M‐H, Fixed, 95% CI)	1.70 [1.02, 2.83]
1.3.4 Unexplained subfertility	2	133	Odds Ratio (M‐H, Fixed, 95% CI)	1.50 [0.60, 3.72]
1.3.5 Poor ovarian reserve	2	266	Odds Ratio (M‐H, Fixed, 95% CI)	1.75 [0.83, 3.67]
1.4 Live birth; IVF/ICSI Show forest plot	9	806	Odds Ratio (M‐H, Fixed, 95% CI)	1.36 [0.96, 1.93]

1.5 Clinical pregnancy; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments) Show forest plot	35	5165	Odds Ratio (M‐H, Fixed, 95% CI)	1.65 [1.43, 1.89]

1.5.1 Placebo	17	3292	Odds Ratio (M‐H, Fixed, 95% CI)	1.70 [1.42, 2.05]
1.5.2 No treatment/standard treatment	19	1873	Odds Ratio (M‐H, Fixed, 95% CI)	1.57 [1.28, 1.94]
1.6 Clinical pregnancy; type of antioxidant Show forest plot	35	5165	Odds Ratio (M‐H, Fixed, 95% CI)	1.65 [1.43, 1.89]

1.6.1 N‐acetylcysteine	8	1590	Odds Ratio (M‐H, Fixed, 95% CI)	1.36 [1.05, 1.77]
1.6.2 Combined antioxidants	5	689	Odds Ratio (M‐H, Fixed, 95% CI)	1.90 [1.33, 2.70]
1.6.3 Melatonin	7	678	Odds Ratio (M‐H, Fixed, 95% CI)	1.66 [1.12, 2.47]
1.6.4 Vitamin E	1	103	Odds Ratio (M‐H, Fixed, 95% CI)	1.43 [0.50, 4.10]
1.6.5 Ascorbic acid	2	899	Odds Ratio (M‐H, Fixed, 95% CI)	0.91 [0.66, 1.25]
1.6.6 L‐arginine	2	71	Odds Ratio (M‐H, Fixed, 95% CI)	1.05 [0.32, 3.46]
1.6.7 Myo‐inositol plus folic acid	1	94	Odds Ratio (M‐H, Fixed, 95% CI)	1.24 [0.50, 3.06]
1.6.8 CoQ10	4	397	Odds Ratio (M‐H, Fixed, 95% CI)	2.49 [1.50, 4.13]
1.6.9 L‐carnitine	2	450	Odds Ratio (M‐H, Fixed, 95% CI)	11.14 [5.70, 21.81]
1.6.10 Vitamin D	2	92	Odds Ratio (M‐H, Fixed, 95% CI)	0.83 [0.25, 2.76]
1.6.11 Vitamin B complex	1	102	Odds Ratio (M‐H, Fixed, 95% CI)	1.94 [0.82, 4.58]
1.7 Clinical pregnancy; indications for subfertility Show forest plot	31		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.7.1 Polycystic ovary syndrome	15	1908	Odds Ratio (M‐H, Fixed, 95% CI)	4.24 [3.23, 5.56]
1.7.2 Unexplained	4	997	Odds Ratio (M‐H, Fixed, 95% CI)	0.84 [0.61, 1.16]
1.7.3 Tubal subfertility	2	71	Odds Ratio (M‐H, Fixed, 95% CI)	1.05 [0.32, 3.46]
1.7.4 Varying indications	6	1135	Odds Ratio (M‐H, Fixed, 95% CI)	1.14 [0.85, 1.52]
1.7.5 Poor responders	1	65	Odds Ratio (M‐H, Fixed, 95% CI)	1.88 [0.64, 5.47]
1.7.6 Poor ovarian reserve	2	266	Odds Ratio (M‐H, Fixed, 95% CI)	1.70 [0.86, 3.37]
1.7.7 Endometriosis	1	280	Odds Ratio (M‐H, Fixed, 95% CI)	1.19 [0.71, 1.98]
1.8 Clinical pregnancy; IVF/ICSI Show forest plot	18	2341	Odds Ratio (M‐H, Fixed, 95% CI)	1.15 [0.95, 1.40]

1.9 Adverse events Show forest plot	27		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.9.1 Miscarriage	24	3229	Odds Ratio (M‐H, Fixed, 95% CI)	1.13 [0.82, 1.55]
1.9.2 Multiple pregnancy	9	1886	Odds Ratio (M‐H, Fixed, 95% CI)	1.00 [0.63, 1.56]
1.9.3 Gastrointestinal disturbances	3	343	Odds Ratio (M‐H, Fixed, 95% CI)	1.55 [0.47, 5.10]
1.9.4 Ectopic pregnancy	4	404	Odds Ratio (M‐H, Fixed, 95% CI)	1.40 [0.27, 7.20]
1.9.5 Headache	2	330	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.45, 1.75]
1.9.6 Congenital (missing kidney)	1	160	Odds Ratio (M‐H, Fixed, 95% CI)	1.02 [0.04, 25.46]
1.9.7 Low birth weight < 2.500 g	1	160	Odds Ratio (M‐H, Fixed, 95% CI)	0.11 [0.00, 2.74]
1.9.8 Preterm birth	2	220	Odds Ratio (M‐H, Fixed, 95% CI)	1.31 [0.17, 9.93]
1.9.9 Placenta praevia	1	160	Odds Ratio (M‐H, Fixed, 95% CI)	1.02 [0.04, 25.46]
1.9.10 Pre‐eclampsia	1	160	Odds Ratio (M‐H, Fixed, 95% CI)	1.71 [0.08, 36.35]
1.9.11 Fatigue	1	160	Odds Ratio (M‐H, Fixed, 95% CI)	1.86 [0.75, 4.62]
1.9.12 Ovarian hyperstimulation syndrome (OHSS)	1	150	Odds Ratio (M‐H, Fixed, 95% CI)	Not estimable

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

Navigate to table in Review

Comparison 2. Head‐to‐head antioxidants

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Live birth; type of antioxidant (natural conceptions and undergoing fertility treatments) Show forest plot	2	140	Odds Ratio (M‐H, Fixed, 95% CI)	0.94 [0.41, 2.15]

2.1.1 Melatonin lower dose versus melatonin higher dose	2	140	Odds Ratio (M‐H, Fixed, 95% CI)	0.94 [0.41, 2.15]
2.2 Live Birth; indications for subfertility Show forest plot	2		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.2.1 Unexplained subfertility	1	20	Odds Ratio (M‐H, Fixed, 95% CI)	1.00 [0.15, 6.77]
2.2.2 Varying Indications	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	0.93 [0.37, 2.32]
2.3 Live Birth; IVF/ICSI Show forest plot	2	140	Odds Ratio (M‐H, Fixed, 95% CI)	0.94 [0.41, 2.15]

2.4 Clinical pregnancy; type of antioxidant (natural conceptions and undergoing fertility treatments) Show forest plot	3		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.4.1 N‐acetylcysteine versus L‐carnitine	1	164	Odds Ratio (M‐H, Fixed, 95% CI)	0.81 [0.33, 2.00]
2.4.2 Melatonin lower dose versus melatonin higher dose	2	140	Odds Ratio (M‐H, Fixed, 95% CI)	0.94 [0.41, 2.15]
2.5 Clinical pregnancy; indications for subfertility Show forest plot	3		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.5.1 Polycystic ovary syndrome	1	164	Odds Ratio (M‐H, Fixed, 95% CI)	0.81 [0.33, 2.00]
2.5.2 Unexplained subfertility	1	20	Odds Ratio (M‐H, Fixed, 95% CI)	1.00 [0.15, 6.77]
2.5.3 Varying indications	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	0.93 [0.37, 2.32]
2.6 Clinical pregnancy; IVF/ICSI Show forest plot	2	140	Odds Ratio (M‐H, Fixed, 95% CI)	0.94 [0.41, 2.15]

2.7 Adverse events Show forest plot	3		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.7.1 Miscarriage	3	304	Odds Ratio (M‐H, Fixed, 95% CI)	1.54 [0.42, 5.67]
2.7.2 Ectopic pregnancy	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	Not estimable
2.7.3 Congenital (missing kidney)	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	1.53 [0.06, 38.36]
2.7.4 Low birth weight < 2.500 g	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	Not estimable
2.7.5 Birth between 34 and 37 weeks	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	0.49 [0.03, 8.10]
2.7.6 Placenta praevia	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	1.53 [0.06, 38.36]
2.7.7 Pre‐eclampsia	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	0.49 [0.03, 8.10]

Comparison 2. Head‐to‐head antioxidants

Navigate to table in Review

The Cochrane Library

Scolaris Language Selector Scolaris Language Selector

Cochrane Review language

Website language

Scolaris Content Language Banner Portlet Scolaris Content Language Banner Portlet

Scolaris Content Display Scolaris Content Display

Topics

Scolaris Language Selector Scolaris Language Selector

Scolaris Content Display Scolaris Content Display

Previously accessed institutions

Scolaris Content Display Scolaris Content Display

Institutional users

Previously accessed institutions

Other access options

	Cochrane Review language Select your preferred language for Cochrane Reviews and other content. Sections without translation will be in English.

	Website language Select your preferred language for the Cochrane Library website.

Cochrane Review language

Website language

Related content

Related reviews and protocols

Related Podcast

Cochrane Clinical Answers

Topics

Copy or download citation

Cochrane Review language

Website language

Previously accessed institutions

Institutional users

Previously accessed institutions

Other access options