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Study flow diagram.
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Figure 1

Study flow diagram.

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'Risk of bias' summary: review authors' judgements about each 'Risk of bias' category for each included study.
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Figure 2

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

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Forest plot of comparison: 1. Intentional endometrial injury vs. either no intervention or a sham procedure, outcome: 1.1 Live birth or ongoing pregnancy: sensitivity analysis excluding studies at high or unclear risk of allocation concealment.
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Figure 3

Forest plot of comparison: 1. Intentional endometrial injury vs. either no intervention or a sham procedure, outcome: 1.1 Live birth or ongoing pregnancy: sensitivity analysis excluding studies at high or unclear risk of allocation concealment.

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Forest plot of comparison: 1. Intentional endometrial injury vs. either no intervention or a sham procedure, outcome: 1.2 Live birth or ongoing pregnancy: sensitivity analysis.
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Figure 4

Forest plot of comparison: 1. Intentional endometrial injury vs. either no intervention or a sham procedure, outcome: 1.2 Live birth or ongoing pregnancy: sensitivity analysis.

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Forest plot of comparison: 2 Higher vs. lower degree of intentional endometrial injury, outcome: 2.1 Live birth or ongoing pregnancy.
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Figure 5

Forest plot of comparison: 2 Higher vs. lower degree of intentional endometrial injury, outcome: 2.1 Live birth or ongoing pregnancy.

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Forest plot of comparison: 3 Timing of intentional endometrial injury, outcome: 3.1 Live birth or ongoing pregnancy.
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Figure 6

Forest plot of comparison: 3 Timing of intentional endometrial injury, outcome: 3.1 Live birth or ongoing pregnancy.

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Comparison 1 Intentional endometrial injury vs. either no intervention or a sham procedure, Outcome 1 Live birth or ongoing pregnancy.
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Analysis 1.1

Comparison 1 Intentional endometrial injury vs. either no intervention or a sham procedure, Outcome 1 Live birth or ongoing pregnancy.

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Comparison 1 Intentional endometrial injury vs. either no intervention or a sham procedure, Outcome 2 Live birth or ongoing pregnancy: sensitivity analysis.
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Analysis 1.2

Comparison 1 Intentional endometrial injury vs. either no intervention or a sham procedure, Outcome 2 Live birth or ongoing pregnancy: sensitivity analysis.

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Comparison 1 Intentional endometrial injury vs. either no intervention or a sham procedure, Outcome 3 Clinical pregnancy.
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Analysis 1.3

Comparison 1 Intentional endometrial injury vs. either no intervention or a sham procedure, Outcome 3 Clinical pregnancy.

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Comparison 1 Intentional endometrial injury vs. either no intervention or a sham procedure, Outcome 4 Miscarriage per clinical pregnancy.
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Analysis 1.4

Comparison 1 Intentional endometrial injury vs. either no intervention or a sham procedure, Outcome 4 Miscarriage per clinical pregnancy.

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Comparison 1 Intentional endometrial injury vs. either no intervention or a sham procedure, Outcome 5 Multiple pregnancy per clinical pregnancy.
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Analysis 1.5

Comparison 1 Intentional endometrial injury vs. either no intervention or a sham procedure, Outcome 5 Multiple pregnancy per clinical pregnancy.

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Comparison 1 Intentional endometrial injury vs. either no intervention or a sham procedure, Outcome 6 Ectopic pregnancy per clinical pregnancy.
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Analysis 1.6

Comparison 1 Intentional endometrial injury vs. either no intervention or a sham procedure, Outcome 6 Ectopic pregnancy per clinical pregnancy.

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Comparison 2 Higher vs. lower degree of intentional endometrial injury, Outcome 1 Live birth or ongoing pregnancy.
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Analysis 2.1

Comparison 2 Higher vs. lower degree of intentional endometrial injury, Outcome 1 Live birth or ongoing pregnancy.

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Comparison 2 Higher vs. lower degree of intentional endometrial injury, Outcome 2 Clinical pregnancy.
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Analysis 2.2

Comparison 2 Higher vs. lower degree of intentional endometrial injury, Outcome 2 Clinical pregnancy.

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Comparison 2 Higher vs. lower degree of intentional endometrial injury, Outcome 3 Miscarriage per clinical pregnancy.
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Analysis 2.3

Comparison 2 Higher vs. lower degree of intentional endometrial injury, Outcome 3 Miscarriage per clinical pregnancy.

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Comparison 2 Higher vs. lower degree of intentional endometrial injury, Outcome 4 Multiple pregnancy per clinical pregnancy.
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Analysis 2.4

Comparison 2 Higher vs. lower degree of intentional endometrial injury, Outcome 4 Multiple pregnancy per clinical pregnancy.

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Comparison 3 Timing of intentional endometrial injury, Outcome 1 Live birth or ongoing pregnancy.
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Analysis 3.1

Comparison 3 Timing of intentional endometrial injury, Outcome 1 Live birth or ongoing pregnancy.

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Comparison 3 Timing of intentional endometrial injury, Outcome 2 Clinical pregnancy.
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Analysis 3.2

Comparison 3 Timing of intentional endometrial injury, Outcome 2 Clinical pregnancy.

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Comparison 3 Timing of intentional endometrial injury, Outcome 3 Miscarriage per clinical pregnancy.
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Analysis 3.3

Comparison 3 Timing of intentional endometrial injury, Outcome 3 Miscarriage per clinical pregnancy.

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Comparison 3 Timing of intentional endometrial injury, Outcome 4 Multiple pregnancy per clinical pregnancy.
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Analysis 3.4

Comparison 3 Timing of intentional endometrial injury, Outcome 4 Multiple pregnancy per clinical pregnancy.

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Summary of findings for the main comparison. Intentional endometrial injury vs. either no intervention or a sham procedure

Patient or population: women trying to get pregnant from intercourse or intrauterine insemination (IUI)
Setting: hospital or clinic
Intervention: intentional endometrial injury
Comparison: no intervention or a sham procedure

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Risk with either: no intervention, or a sham procedure

Risk with Intentional endometrial injury

Live birth or ongoing pregnancy

87 per 1000

194 per 1000
(136 to 275)

RR 2.22
(1.56 to 3.15)

950
(6 RCTs)

⊕⊝⊝⊝
very low1,2

Live birth or ongoing pregnancy ‐ sensitivity

98 per 1000

259 per 1000
(101 to 669)

RR 2.64
(1.03 to 6.82)

105
(1 RCT)

⊕⊝⊝⊝
very low3,4

Pain during the procedure

Pain was not recorded in the control group

Pain was only recorded in the intervention group with an average of 6/10, standard deviation (SD) = 1.5

—

(1 RCT)

—

Clinical pregnancy

122 per 1000

241 per 1,000
(184 to 315)

RR 1.98
(1.51 to 2.58)

1180
(8 RCTs)

⊕⊕⊝⊝
low1

*The risk in the intervention group (and its 95% CI) is based on the mean risk in the comparison group and the relative effect of the intervention (and its 95% CI).
Abbreviations: CI: confidence interval; RR: risk ratio; OR: odds ratio; IUI: intrauterine insemination; RCT: randomised controlled trial; SD: standard deviation; GRADE: Grading of Recommendations Assessment, Development and Evaluation.

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.

1Downgraded by 2 levels for risk of bias as many of the included studies are associated with a high risk of bias.
2Downgraded by 1 level for imprecision as the total number of events was relatively low.
3Downgraded by 2 levels for imprecision as the total number of events was relatively low.
4Downgraded by 1 level for indirectness as there was only 1 study available and results not likely generalisable to other populations.

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Summary of findings for the main comparison. Intentional endometrial injury vs. either no intervention or a sham procedure
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Summary of findings 2. Higher vs. lower degree of intentional endometrial injury

Patient or population: women trying to get pregnant from intercourse or intrauterine insemination (IUI)
Setting: hospital or clinic
Intervention: higher
Comparison: lower degree of intentional endometrial injury

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Risk with lower degree of intentional endometrial injury

Risk with Higher

Live birth or ongoing pregnancy

102 per 1000

132 per 1000
(73 to 241)

RR 1.29
(0.71 to 2.35)

332
(1 RCT)

⊕⊕⊝⊝
low1,2

Pain during the procedure

—

—

—

(0 study)

—

Clinical pregnancy

120 per 1000

139 per 1000
(80 to 242)

RR 1.15
(0.66 to 2.01)

332
(1 RCT)

⊕⊕⊝⊝
low1,2

*The risk in the intervention group (and its 95% confidence interval) is based on the mean risk in the comparison group and the relative effect of the intervention (and its 95% CI).
Abbreviations: CI: Confidence interval; RR: Risk ratio; OR: Odds ratio; IUI: intrauterine insemination; RCT: randomised controlled trial; GRADE: Grading of Recommendations Assessment, Development and Evaluation.

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

1Downgraded by 1 level for indirectness as there was only 1 included study. Therefore the result was applicable only to cases of hysteroscopy plus injury vs hysteroscopy alone, and not other cases of higher vs. lower injury.
2Downgraded by 1 level for imprecision as the total number of events was low.

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Summary of findings 2. Higher vs. lower degree of intentional endometrial injury
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Summary of findings 3. Different timing of intentional endometrial injury

Patient or population: women trying to get pregnant from intercourse or intrauterine insemination (IUI)
Setting: hospital or clinic
Intervention: IUI cycle
Comparison: preceding cycle

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Risk with injury in preceding cycle

Risk with injury in IUI cycle

Live birth or ongoing pregnancy

267 per 1000

173 per 1000
(99 to 309)

RR 0.65
(0.37 to 1.16)

176
(1 RCT)

⊕⊝⊝⊝
very low1,2,3

Pain during the procedure

—

—

—

(0 RCTs)

—

Clinical pregnancy

329 per 1000

269 per 1000
(164 to 447)

RR 0.82
(0.50 to 1.36)

276
(2 RCTs)

⊕⊝⊝⊝
very low1,2,3

*The risk in the intervention group (and its 95% CI) is based on the mean risk in the comparison group and the relative effect of the intervention (and its 95% CI).
Abbreviations: CI: confidence interval; RR: risk ratio; OR: odds ratio; IUI: intrauterine insemination; RCT: randomised controlled trial; GRADE: Grading of Recommendations Assessment, Development and Evaluation.

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

1Downgraded by 1 level for risk of bias as both studies were at high risk of bias.
2Downgraded by 1 level for imprecision as the total number of events was relatively low.
3Downgraded by 1 level for indirectness as all participants were undergoing stimulation with gonadotrophins.

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Summary of findings 3. Different timing of intentional endometrial injury
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Comparison 1. Intentional endometrial injury vs. either no intervention or a sham procedure

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth or ongoing pregnancy Show forest plot

6

950

Risk Ratio (M‐H, Random, 95% CI)

2.22 [1.56, 3.15]

1.1 Live birth

2

320

Risk Ratio (M‐H, Random, 95% CI)

2.48 [1.12, 5.49]

1.2 Ongoing pregnancy

4

630

Risk Ratio (M‐H, Random, 95% CI)

2.16 [1.46, 3.19]

2 Live birth or ongoing pregnancy: sensitivity analysis Show forest plot

1

105

Risk Ratio (M‐H, Random, 95% CI)

2.64 [1.03, 6.82]

2.1 Ongoing pregnancy

1

105

Risk Ratio (M‐H, Random, 95% CI)

2.64 [1.03, 6.82]

3 Clinical pregnancy Show forest plot

8

1180

Risk Ratio (M‐H, Random, 95% CI)

1.98 [1.51, 2.58]

4 Miscarriage per clinical pregnancy Show forest plot

6

174

Risk Ratio (M‐H, Random, 95% CI)

0.73 [0.38, 1.39]

5 Multiple pregnancy per clinical pregnancy Show forest plot

6

261

Risk Ratio (M‐H, Random, 95% CI)

0.93 [0.31, 2.78]

6 Ectopic pregnancy per clinical pregnancy Show forest plot

2

57

Risk Ratio (M‐H, Random, 95% CI)

0.54 [0.09, 3.46]
Figuras y tablas -
Comparison 1. Intentional endometrial injury vs. either no intervention or a sham procedure
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Comparison 2. Higher vs. lower degree of intentional endometrial injury

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth or ongoing pregnancy Show forest plot

1

332

Risk Ratio (M‐H, Random, 95% CI)

1.29 [0.71, 2.35]

2 Clinical pregnancy Show forest plot

1

332

Risk Ratio (M‐H, Random, 95% CI)

1.15 [0.66, 2.01]

3 Miscarriage per clinical pregnancy Show forest plot

1

43

Risk Ratio (M‐H, Random, 95% CI)

0.29 [0.03, 2.57]

4 Multiple pregnancy per clinical pregnancy Show forest plot

1

43

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.20, 3.83]
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Comparison 2. Higher vs. lower degree of intentional endometrial injury
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Comparison 3. Timing of intentional endometrial injury

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth or ongoing pregnancy Show forest plot

1

176

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.37, 1.16]

2 Clinical pregnancy Show forest plot

2

276

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.50, 1.36]

3 Miscarriage per clinical pregnancy Show forest plot

1

45

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.17, 4.03]

4 Multiple pregnancy per clinical pregnancy Show forest plot

2

82

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.17, 4.04]
Figuras y tablas -
Comparison 3. Timing of intentional endometrial injury
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