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Study flow diagram.
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Figure 1

Study flow diagram.

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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 GnRH antagonist versus long course GnRH agonist, outcome: 1.1 Live birth rate per woman randomised.
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Figure 4

Forest plot of comparison: 1 GnRH antagonist versus long course GnRH agonist, outcome: 1.1 Live birth rate per woman randomised.

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Funnel plot of comparison: 1 GnRH antagonist versus long course GnRH agonist, outcome: 1.1 Live birth rate per woman randomised.
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Figure 5

Funnel plot of comparison: 1 GnRH antagonist versus long course GnRH agonist, outcome: 1.1 Live birth rate per woman randomised.

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Forest plot of comparison: 1 GnRH antagonist versus long course GnRH agonist, outcome: 1.2 Live birth rate per woman randomised ‐ minimal stimulation.
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Figure 6

Forest plot of comparison: 1 GnRH antagonist versus long course GnRH agonist, outcome: 1.2 Live birth rate per woman randomised ‐ minimal stimulation.

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Forest plot of comparison: 1 GnRH antagonist versus long‐course GnRH agonist, outcome: 1.3 Live birth rate per woman randomised ‐ grouped by trigger.
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Figure 7

Forest plot of comparison: 1 GnRH antagonist versus long‐course GnRH agonist, outcome: 1.3 Live birth rate per woman randomised ‐ grouped by trigger.

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Forest plot of comparison: 1 GnRH antagonist versus long course GnRH agonist, outcome: 1.4 Ovarian hyperstimulation per woman randomised ‐ all women.
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Figure 8

Forest plot of comparison: 1 GnRH antagonist versus long course GnRH agonist, outcome: 1.4 Ovarian hyperstimulation per woman randomised ‐ all women.

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Forest plot of comparison: 1 GnRH antagonist versus long course GnRH agonist, outcome: 1.5 Ovarian hyperstimulation per woman randomised ‐ moderate or severe.
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Figure 9

Forest plot of comparison: 1 GnRH antagonist versus long course GnRH agonist, outcome: 1.5 Ovarian hyperstimulation per woman randomised ‐ moderate or severe.

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Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 1 Live birth rate per woman randomised.
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Analysis 1.1

Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 1 Live birth rate per woman randomised.

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Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 2 Live birth rate per woman randomised ‐ minimal stimulation.
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Analysis 1.2

Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 2 Live birth rate per woman randomised ‐ minimal stimulation.

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Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 3 Live birth rate per woman randomised ‐ grouped by trigger.
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Analysis 1.3

Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 3 Live birth rate per woman randomised ‐ grouped by trigger.

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Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 4 Ovarian hyperstimulation per woman randomised ‐ all women.
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Analysis 1.4

Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 4 Ovarian hyperstimulation per woman randomised ‐ all women.

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Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 5 Ovarian hyperstimulation per woman randomised ‐ moderate or severe.
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Analysis 1.5

Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 5 Ovarian hyperstimulation per woman randomised ‐ moderate or severe.

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Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 6 Ongoing pregnancy rate per woman randomised ‐ all women.
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Analysis 1.6

Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 6 Ongoing pregnancy rate per woman randomised ‐ all women.

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Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 7 Ongoing pregnancy rate per woman randomised ‐ minimal stimulation.
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Analysis 1.7

Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 7 Ongoing pregnancy rate per woman randomised ‐ minimal stimulation.

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Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 8 Ongoing pregnancy rate per women randomised ‐ grouped by trigger.
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Analysis 1.8

Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 8 Ongoing pregnancy rate per women randomised ‐ grouped by trigger.

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Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 9 Clinical pregnancy rate per woman randomised ‐ all women.
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Analysis 1.9

Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 9 Clinical pregnancy rate per woman randomised ‐ all women.

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Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 10 Clinical pregnancy rate per woman randomised ‐ minimal stimulation.
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Analysis 1.10

Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 10 Clinical pregnancy rate per woman randomised ‐ minimal stimulation.

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Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 11 Miscarriage rate per woman randomised.
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Analysis 1.11

Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 11 Miscarriage rate per woman randomised.

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Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 12 Miscarriage rate per clinical pregnancy.
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Analysis 1.12

Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 12 Miscarriage rate per clinical pregnancy.

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Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 13 Cycle cancellation rate per woman randomised.
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Analysis 1.13

Comparison 1 GnRH antagonist versus long‐course GnRH agonist, Outcome 13 Cycle cancellation rate per woman randomised.

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Summary of findings for the main comparison. GnRH antagonist compared to long‐course GnRH agonist for assisted reproductive technology (ART)

GnRH antagonist compared to long‐course GnRH agonist for assisted reproductive technology (ART)

Population: women undergoing assisted reproductive technology (ART)
Settings: clinic for ART
Intervention: GnRH antagonist
Comparison: long‐course GnRH agonist

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Long course GnRH agonist

GnRH antagonist

Live birth rate per woman randomised

286 per 1000

290 per 1000
(254 to 330)

OR 1.02
(0.85 to 1.23)

2303
(12 studies)

⊕⊕⊕⊝
moderate1

OHSS per woman randomised (any grade)

114 per 1000

73 per 1000
(62 to 85)

OR 0.61
(0.51 to 0.72)

7944
(36 studies)

⊕⊕⊕⊝
moderate2

Ongoing pregnancy rate per woman randomised

293 per 1000

276 per 1000
(256 to 295)

OR 0.92
(0.83 to 1.01)

8311
(37 studies)

⊕⊕⊕⊝
moderate2

Clinical pregnancy rate per woman randomised

303 per 1000

283 per 1000
(267 to 303)

OR 0.91
(0.83 to 1)

9959
(54 studies)

⊕⊕⊕⊝
moderate2

Miscarriage rate per woman randomised

48 per 1000

49 per 1000
(40 to 61)

OR 1.03
(0.82 to 1.29)

7082
(34 studies)

⊕⊕⊕⊝
moderate2

Cycle cancellation due to poor ovarian response

64 per 1000

83 per 1000
(68 to 101)

OR 1.32
(1.06 to 1.65)

5230
(25 studies)

⊕⊝⊝⊝
moderate3,4

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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 quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Asymmetry of the funnel plot with small study effects in favour of GnRH antagonist
2 Most domains of the risk of bias were assessed as either 'unclear' or 'high'
3 Presence of significant heterogeneity among studies with inconsistency in the directions of effect estimates
4 Effect estimate with wide confidence interval

Figuras y tablas -
Summary of findings for the main comparison. GnRH antagonist compared to long‐course GnRH agonist for assisted reproductive technology (ART)
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Comparison 1. GnRH antagonist versus long‐course GnRH agonist

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth rate per woman randomised Show forest plot

12

2303

Odds Ratio (M‐H, Fixed, 95% CI)

1.02 [0.85, 1.23]

2 Live birth rate per woman randomised ‐ minimal stimulation Show forest plot

2

524

Odds Ratio (M‐H, Fixed, 95% CI)

0.89 [0.62, 1.26]

3 Live birth rate per woman randomised ‐ grouped by trigger Show forest plot

12

2303

Odds Ratio (M‐H, Fixed, 95% CI)

1.02 [0.85, 1.23]

3.1 hCG trigger

11

1899

Odds Ratio (M‐H, Fixed, 95% CI)

1.09 [0.89, 1.34]

3.2 Unknown trigger

1

404

Odds Ratio (M‐H, Fixed, 95% CI)

0.80 [0.54, 1.21]

4 Ovarian hyperstimulation per woman randomised ‐ all women Show forest plot

36

7944

Odds Ratio (M‐H, Fixed, 95% CI)

0.61 [0.51, 0.72]

5 Ovarian hyperstimulation per woman randomised ‐ moderate or severe Show forest plot

20

5141

Odds Ratio (M‐H, Fixed, 95% CI)

0.53 [0.40, 0.69]

6 Ongoing pregnancy rate per woman randomised ‐ all women Show forest plot

37

8311

Odds Ratio (M‐H, Fixed, 95% CI)

0.92 [0.83, 1.01]

7 Ongoing pregnancy rate per woman randomised ‐ minimal stimulation Show forest plot

7

1456

Odds Ratio (M‐H, Fixed, 95% CI)

0.94 [0.75, 1.18]

8 Ongoing pregnancy rate per women randomised ‐ grouped by trigger Show forest plot

37

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 hCG trigger

29

5170

Odds Ratio (M‐H, Fixed, 95% CI)

0.95 [0.84, 1.08]

8.2 Mixed trigger (hCG/GnRH agonist)

1

66

Odds Ratio (M‐H, Fixed, 95% CI)

0.61 [0.23, 1.61]

8.3 Unknown trigger

7

3075

Odds Ratio (M‐H, Fixed, 95% CI)

0.87 [0.74, 1.03]

9 Clinical pregnancy rate per woman randomised ‐ all women Show forest plot

54

9959

Odds Ratio (M‐H, Fixed, 95% CI)

0.91 [0.83, 1.00]

10 Clinical pregnancy rate per woman randomised ‐ minimal stimulation Show forest plot

6

1102

Odds Ratio (M‐H, Fixed, 95% CI)

1.50 [1.15, 1.96]

11 Miscarriage rate per woman randomised Show forest plot

34

7082

Odds Ratio (M‐H, Fixed, 95% CI)

1.03 [0.82, 1.29]

12 Miscarriage rate per clinical pregnancy Show forest plot

34

2308

Odds Ratio (M‐H, Fixed, 95% CI)

1.08 [0.84, 1.37]

13 Cycle cancellation rate per woman randomised Show forest plot

34

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.1 Cancellation due to high risk of OHSS

19

4256

Odds Ratio (M‐H, Fixed, 95% CI)

0.47 [0.32, 0.69]

13.2 Cancellation due to poor ovarian response

25

5230

Odds Ratio (M‐H, Fixed, 95% CI)

1.32 [1.06, 1.65]
Figuras y tablas -
Comparison 1. GnRH antagonist versus long‐course GnRH agonist
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