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Study flow diagram search August 2016.
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Figure 1

Study flow diagram search August 2016.

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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
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Figure 3

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

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Forest plot of comparison 1: Dopamine agonist (without co‐intervention) versus placebo/no intervention, outcome: 1.1 moderate or severe ovarian hyperstimulation syndrome.
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Figure 4

Forest plot of comparison 1: Dopamine agonist (without co‐intervention) versus placebo/no intervention, outcome: 1.1 moderate or severe ovarian hyperstimulation syndrome.

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Forest plot of comparison: 2 Dopamine agonist plus co‐intervention versus co‐intervention, outcome: 2.1 Moderate or severe ovarian hyperstimulation syndrome.
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Figure 5

Forest plot of comparison: 2 Dopamine agonist plus co‐intervention versus co‐intervention, outcome: 2.1 Moderate or severe ovarian hyperstimulation syndrome.

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Forest plot of comparison 3: Cabergoline versus active interventions, outcome: 3.1 moderate or severe ovarian hyperstimulation syndrome.
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Figure 6

Forest plot of comparison 3: Cabergoline versus active interventions, outcome: 3.1 moderate or severe ovarian hyperstimulation syndrome.

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Comparison 1 Dopamine agonist versus placebo/no intervention, Outcome 1 Moderate or severe ovarian hyperstimulation syndrome (OHSS).
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Analysis 1.1

Comparison 1 Dopamine agonist versus placebo/no intervention, Outcome 1 Moderate or severe ovarian hyperstimulation syndrome (OHSS).

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Comparison 1 Dopamine agonist versus placebo/no intervention, Outcome 2 Subgroup analysis by severity of OHSS.
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Analysis 1.2

Comparison 1 Dopamine agonist versus placebo/no intervention, Outcome 2 Subgroup analysis by severity of OHSS.

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Comparison 1 Dopamine agonist versus placebo/no intervention, Outcome 3 Live birth.
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Analysis 1.3

Comparison 1 Dopamine agonist versus placebo/no intervention, Outcome 3 Live birth.

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Comparison 1 Dopamine agonist versus placebo/no intervention, Outcome 4 Clinical pregnancy rate.
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Analysis 1.4

Comparison 1 Dopamine agonist versus placebo/no intervention, Outcome 4 Clinical pregnancy rate.

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Comparison 1 Dopamine agonist versus placebo/no intervention, Outcome 5 Multiple pregnancy.
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Analysis 1.5

Comparison 1 Dopamine agonist versus placebo/no intervention, Outcome 5 Multiple pregnancy.

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Comparison 1 Dopamine agonist versus placebo/no intervention, Outcome 6 Miscarriage.
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Analysis 1.6

Comparison 1 Dopamine agonist versus placebo/no intervention, Outcome 6 Miscarriage.

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Comparison 1 Dopamine agonist versus placebo/no intervention, Outcome 7 Adverse events.
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Analysis 1.7

Comparison 1 Dopamine agonist versus placebo/no intervention, Outcome 7 Adverse events.

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Comparison 2 Dopamine agonist plus co‐intervention versus co‐intervention, Outcome 1 Moderate or severe ovarian hyperstimulation syndrome (OHSS).
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Analysis 2.1

Comparison 2 Dopamine agonist plus co‐intervention versus co‐intervention, Outcome 1 Moderate or severe ovarian hyperstimulation syndrome (OHSS).

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Comparison 2 Dopamine agonist plus co‐intervention versus co‐intervention, Outcome 2 Live birth.
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Analysis 2.2

Comparison 2 Dopamine agonist plus co‐intervention versus co‐intervention, Outcome 2 Live birth.

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Comparison 2 Dopamine agonist plus co‐intervention versus co‐intervention, Outcome 3 Clinical pregnancy rate.
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Analysis 2.3

Comparison 2 Dopamine agonist plus co‐intervention versus co‐intervention, Outcome 3 Clinical pregnancy rate.

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Comparison 2 Dopamine agonist plus co‐intervention versus co‐intervention, Outcome 4 Multiple pregnancy.
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Analysis 2.4

Comparison 2 Dopamine agonist plus co‐intervention versus co‐intervention, Outcome 4 Multiple pregnancy.

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Comparison 2 Dopamine agonist plus co‐intervention versus co‐intervention, Outcome 5 Miscarriage.
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Analysis 2.5

Comparison 2 Dopamine agonist plus co‐intervention versus co‐intervention, Outcome 5 Miscarriage.

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Comparison 2 Dopamine agonist plus co‐intervention versus co‐intervention, Outcome 6 Adverse events.
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Analysis 2.6

Comparison 2 Dopamine agonist plus co‐intervention versus co‐intervention, Outcome 6 Adverse events.

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Comparison 3 Dopamine agonist versus active interventions, Outcome 1 Moderate or severe ovarian hyperstimulation syndrome (OHSS).
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Analysis 3.1

Comparison 3 Dopamine agonist versus active interventions, Outcome 1 Moderate or severe ovarian hyperstimulation syndrome (OHSS).

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Comparison 3 Dopamine agonist versus active interventions, Outcome 2 Clinical pregnancy rate.
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Analysis 3.2

Comparison 3 Dopamine agonist versus active interventions, Outcome 2 Clinical pregnancy rate.

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Comparison 3 Dopamine agonist versus active interventions, Outcome 3 Multiple pregnancy.
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Analysis 3.3

Comparison 3 Dopamine agonist versus active interventions, Outcome 3 Multiple pregnancy.

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Comparison 3 Dopamine agonist versus active interventions, Outcome 4 Miscarriage.
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Analysis 3.4

Comparison 3 Dopamine agonist versus active interventions, Outcome 4 Miscarriage.

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Summary of findings for the main comparison. Dopamine agonist versus placebo/no intervention

Dopamine agonist vs placebo/no intervention

Patient or population: women of reproductive age undergoing any ART therapy

Settings: ART unit

Intervention: dopamine agonist

Comparison: placebo/no intervention

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with placebo/no intervention

Risk with dopamine agonist

Incidence of moderate or severe OHSS

286 per 1000

97 per 1000

(71 to 135)

OR 0.27

(0.19 to 0.39)

1022

(8 studies)

⊕⊕⊕⊝
Moderate 1

‐

Live birth rate

509 per 1000

512 per 1000

(355 to 665)

OR 1.01

(0.53 to 1.91)

182
(1 studies)

⊕⊕⊝⊝
Low 1,2

Clinical pregnancy rate

401 per 1000

352 per 1000

(266 to 450)

OR 0.81

(0.54 to 1.22)

432

(4 studies)

⊕⊕⊕⊝
Moderate 1

Multiple pregnancy

50 per 1000

17 per 1000

(1 to 303)

OR 0.32

(0.01 to 8.26)

40
(1 study)

⊕⊝⊝⊝
Very low 1,3

Miscarriage pregnancy rate

72 per 1000

49 per 1000

(15 to 151)

OR 0.66

(0.19 to 2.28)

168

(2 studies)

⊕⊕⊝⊝
Low 1,4

Adverse events

43 per 1000

168 per 1000

(62 to 381)

OR 4.54

(1.49 to 13.84)

264
(2 studies)

⊕⊝⊝⊝
Very low 1,5

*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).

ART: assisted reproductive technology; CI: confidence interval; OHSS: ovarian hyperstimulation syndrome; OR: odds ratio.

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: 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 quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Downgraded one level for serious risk of bias associated with poor reporting of study methods.

2 Downgraded one level for serious risk of imprecision: confidence interval compatible with benefit in either arm or with no difference between the groups.

3 Downgraded two levels for very serious risk of imprecision: only one event.

4 Downgraded one level for serious risk of imprecision: only 10 events.

5 Downgraded one level for serious risk of imprecision: only 29 events.

Figuras y tablas -
Summary of findings for the main comparison. Dopamine agonist versus placebo/no intervention
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Comparison 1. Dopamine agonist versus placebo/no intervention

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Moderate or severe ovarian hyperstimulation syndrome (OHSS) Show forest plot

8

1022

Odds Ratio (M‐H, Fixed, 95% CI)

0.27 [0.19, 0.39]

1.1 Cabergoline vs placebo/no treatment

5

521

Odds Ratio (M‐H, Fixed, 95% CI)

0.26 [0.16, 0.42]

1.2 Quinagolide vs placebo

2

454

Odds Ratio (M‐H, Fixed, 95% CI)

0.28 [0.15, 0.51]

1.3 Bromocriptine vs placebo (folic acid)

1

47

Odds Ratio (M‐H, Fixed, 95% CI)

0.29 [0.08, 1.14]

2 Subgroup analysis by severity of OHSS Show forest plot

7

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Severe OHSS

7

750

Odds Ratio (M‐H, Fixed, 95% CI)

0.28 [0.14, 0.56]

2.2 Moderate OHSS

7

750

Odds Ratio (M‐H, Fixed, 95% CI)

0.37 [0.24, 0.57]

3 Live birth Show forest plot

1

182

Odds Ratio (M‐H, Fixed, 95% CI)

1.01 [0.53, 1.91]

3.1 Quinagolide vs placebo

1

182

Odds Ratio (M‐H, Fixed, 95% CI)

1.01 [0.53, 1.91]

4 Clinical pregnancy rate Show forest plot

4

432

Odds Ratio (M‐H, Fixed, 95% CI)

0.81 [0.54, 1.22]

4.1 Cabergoline vs no intervention

3

250

Odds Ratio (M‐H, Fixed, 95% CI)

0.81 [0.48, 1.38]

4.2 Quinagolide vs placebo

1

182

Odds Ratio (M‐H, Fixed, 95% CI)

0.81 [0.43, 1.54]

5 Multiple pregnancy Show forest plot

1

40

Odds Ratio (M‐H, Fixed, 95% CI)

0.32 [0.01, 8.26]

5.1 Cabergoline vs placebo/no treatment

1

40

Odds Ratio (M‐H, Fixed, 95% CI)

0.32 [0.01, 8.26]

6 Miscarriage Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 Cabergoline vs placebo/no treatment

2

168

Odds Ratio (M‐H, Fixed, 95% CI)

0.66 [0.19, 2.28]

7 Adverse events Show forest plot

2

264

Odds Ratio (M‐H, Fixed, 95% CI)

4.54 [1.49, 13.84]

7.1 Cabergoline vs placebo/no treatment

1

82

Odds Ratio (M‐H, Fixed, 95% CI)

2.24 [0.62, 8.14]

7.2 Quinagolide vs placebo

1

182

Odds Ratio (M‐H, Fixed, 95% CI)

16.64 [0.98, 282.02]
Figuras y tablas -
Comparison 1. Dopamine agonist versus placebo/no intervention
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Comparison 2. Dopamine agonist plus co‐intervention versus co‐intervention

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Moderate or severe ovarian hyperstimulation syndrome (OHSS) Show forest plot

3

548

Odds Ratio (M‐H, Fixed, 95% CI)

0.57 [0.31, 1.03]

1.1 Cabergoline + albumin vs albumin

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

0.55 [0.23, 1.34]

1.2 Cabergoline + hydroxyethyl starch (HES) vs HES

2

382

Odds Ratio (M‐H, Fixed, 95% CI)

0.58 [0.26, 1.30]

2 Live birth Show forest plot

1

200

Odds Ratio (M‐H, Fixed, 95% CI)

1.04 [0.59, 1.86]

2.1 Cabergoline + HES vs HES

1

200

Odds Ratio (M‐H, Fixed, 95% CI)

1.04 [0.59, 1.86]

3 Clinical pregnancy rate Show forest plot

3

548

Odds Ratio (M‐H, Fixed, 95% CI)

1.0 [0.71, 1.40]

3.1 Cabergoline + albumin vs albumin

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

1.05 [0.56, 1.96]

3.2 Cabergoline + HES vs HES

2

382

Odds Ratio (M‐H, Fixed, 95% CI)

0.98 [0.65, 1.47]

4 Multiple pregnancy Show forest plot

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

2.02 [0.18, 22.77]

4.1 Cabergoline + albumin vs albumin

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

2.02 [0.18, 22.77]

5 Miscarriage Show forest plot

3

548

Odds Ratio (M‐H, Fixed, 95% CI)

0.65 [0.30, 1.42]

5.1 Cabergoline + albumin vs albumin

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

0.33 [0.03, 3.19]

5.2 Cabergoline + HES vs HES

2

382

Odds Ratio (M‐H, Fixed, 95% CI)

0.73 [0.31, 1.68]

6 Adverse events Show forest plot

2

366

Odds Ratio (M‐H, Fixed, 95% CI)

3.03 [0.12, 75.28]

6.1 Cabergoline + albumin vs albumin

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6.2 Cabergoline + HES vs HES

1

200

Odds Ratio (M‐H, Fixed, 95% CI)

3.03 [0.12, 75.28]
Figuras y tablas -
Comparison 2. Dopamine agonist plus co‐intervention versus co‐intervention
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Comparison 3. Dopamine agonist versus active interventions

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Moderate or severe ovarian hyperstimulation syndrome (OHSS) Show forest plot

6

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 Cabergoline vs human albumin

3

296

Odds Ratio (M‐H, Fixed, 95% CI)

0.21 [0.12, 0.38]

1.2 Cabergoline vs prednisolone

1

150

Odds Ratio (M‐H, Fixed, 95% CI)

0.27 [0.05, 1.33]

1.3 Cabergoline vs hydroxyethyl starch (HES)

1

61

Odds Ratio (M‐H, Fixed, 95% CI)

2.69 [0.48, 15.10]

1.4 Cabergoline vs coasting

2

120

Odds Ratio (M‐H, Fixed, 95% CI)

0.50 [0.18, 1.45]

2 Clinical pregnancy rate Show forest plot

3

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Cabergoline vs human albumin

1

140

Odds Ratio (M‐H, Fixed, 95% CI)

0.68 [0.33, 1.38]

2.2 Cabergoline vs coasting

2

120

Odds Ratio (M‐H, Fixed, 95% CI)

2.65 [1.13, 6.21]

3 Multiple pregnancy Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Cabergoline vs human albumin

1

140

Odds Ratio (M‐H, Fixed, 95% CI)

0.58 [0.13, 2.54]

3.2 Cabergoline vs coasting

1

60

Odds Ratio (M‐H, Fixed, 95% CI)

5.35 [0.25, 116.31]

4 Miscarriage Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Cabergoline vs human albumin

1

140

Odds Ratio (M‐H, Fixed, 95% CI)

0.32 [0.03, 3.19]

4.2 Cabergoline vs coasting

1

60

Odds Ratio (M‐H, Fixed, 95% CI)

0.19 [0.01, 4.06]
Figuras y tablas -
Comparison 3. Dopamine agonist versus active interventions
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