Laparoscopic ovarian drilling for ovulation induction in women with anovulatory polycystic ovary syndrome

Esmée M Bordewijk; Ka Ying Bonnie Ng; Lidija Rakic; Ben Willem J Mol; Julie Brown; Tineke J Crawford; Madelon van Wely

doi:10.1002/14651858.CD001122.pub5

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Figure 1

Study flow diagram.

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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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Figure 3

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

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Figure 4

Forest plot of comparison: 1 LOD with and without medical ovulation versus medical ovulation alone, outcome: 1.1 Live birth.

MOI: Medical ovulation induction alone

LOD: laparoscopic ovarian drilling with or without medical ovulation induction

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Figure 5

Funnel plot of comparison: 1 LOD with and without medical ovulation versus medical ovulation alone, outcome: 1.1 Live birth.

LOD: laparoscopic ovarian drilling with or without medical ovulation induction

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Figure 6

Forest plot of comparison: 5 Sensitivity analysis low risk of bias: LOD with and without medical ovulation versus medical ovulation alone, outcome: 5.1 Live birth.

MOI: Medical ovulation induction alone

LOD: laparoscopic ovarian drilling with or without medical ovulation induction

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Figure 7

Forest plot of comparison: 1 LOD with and without medical ovulation versus medical ovulation alone, outcome: 1.4 Multiple pregnancy rate (per ongoing pregnancy).

MOI: Medical ovulation induction alone

LOD: laparoscopic ovarian drilling with or without medical ovulation induction

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Analysis 1.1

Comparison 1 LOD with and without medical ovulation versus medical ovulation alone, Outcome 1 Live birth.

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Analysis 1.2

Comparison 1 LOD with and without medical ovulation versus medical ovulation alone, Outcome 2 Multiple pregnancy.

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Analysis 1.3

Comparison 1 LOD with and without medical ovulation versus medical ovulation alone, Outcome 3 Clinical pregnancy.

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Analysis 1.4

Comparison 1 LOD with and without medical ovulation versus medical ovulation alone, Outcome 4 Miscarriage.

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Analysis 1.5

Comparison 1 LOD with and without medical ovulation versus medical ovulation alone, Outcome 5 OHSS.

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Analysis 1.6

Comparison 1 LOD with and without medical ovulation versus medical ovulation alone, Outcome 6 Ovulation.

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Analysis 1.7

Comparison 1 LOD with and without medical ovulation versus medical ovulation alone, Outcome 7 Costs.

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Analysis 1.8

Comparison 1 LOD with and without medical ovulation versus medical ovulation alone, Outcome 8 Quality of Life (Health related quality of life: SF‐36).

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Analysis 1.9

Comparison 1 LOD with and without medical ovulation versus medical ovulation alone, Outcome 9 Quality of life (Rotterdam Symptom Checklist at 24 weeks).

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Analysis 1.10

Comparison 1 LOD with and without medical ovulation versus medical ovulation alone, Outcome 10 Quality of life (Depression scales (CES‐D) at 24 weeks).

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Analysis 1.11

Comparison 1 LOD with and without medical ovulation versus medical ovulation alone, Outcome 11 Multiple pregnancy per pregnancy.

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Analysis 1.12

Comparison 1 LOD with and without medical ovulation versus medical ovulation alone, Outcome 12 Miscarriage per pregnancy.

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Analysis 2.1

Comparison 2 LOD + IVF versus IVF, Outcome 1 Live birth.

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Analysis 2.2

Comparison 2 LOD + IVF versus IVF, Outcome 2 Multiple pregnancy.

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Analysis 2.3

Comparison 2 LOD + IVF versus IVF, Outcome 3 Clinical pregnancy.

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Analysis 2.4

Comparison 2 LOD + IVF versus IVF, Outcome 4 Miscarriage.

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Analysis 2.5

Comparison 2 LOD + IVF versus IVF, Outcome 5 OHSS.

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Analysis 2.6

Comparison 2 LOD + IVF versus IVF, Outcome 6 Multiple pregnancy per pregnancy.

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Analysis 2.7

Comparison 2 LOD + IVF versus IVF, Outcome 7 Miscarriage per pregnancy.

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Analysis 3.1

Comparison 3 LOD + second‐look laparoscopy versus LOD + expectant management, Outcome 1 Clinical pregnancy.

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Analysis 3.2

Comparison 3 LOD + second‐look laparoscopy versus LOD + expectant management, Outcome 2 Miscarriage.

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Analysis 3.3

Comparison 3 LOD + second‐look laparoscopy versus LOD + expectant management, Outcome 3 Ovulation.

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Analysis 3.4

Comparison 3 LOD + second‐look laparoscopy versus LOD + expectant management, Outcome 4 Miscarriage per pregnancy.

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Analysis 4.1

Comparison 4 Unilateral versus bilateral, Outcome 1 Live birth.

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Analysis 4.2

Comparison 4 Unilateral versus bilateral, Outcome 2 Clinical pregnancy.

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Analysis 4.3

Comparison 4 Unilateral versus bilateral, Outcome 3 Miscarriage.

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Analysis 4.4

Comparison 4 Unilateral versus bilateral, Outcome 4 Ovulation.

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Analysis 4.5

Comparison 4 Unilateral versus bilateral, Outcome 5 Miscarriage per pregnancy.

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Analysis 5.1

Comparison 5 Monopolar versus bipolar, Outcome 1 Clinical pregnancy.

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Analysis 5.2

Comparison 5 Monopolar versus bipolar, Outcome 2 Ovulation.

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Analysis 6.1

Comparison 6 Adjusted thermal dose versus fixed thermal dose, Outcome 1 Clinical pregnancy.

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Analysis 6.2

Comparison 6 Adjusted thermal dose versus fixed thermal dose, Outcome 2 Miscarriage.

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Analysis 6.3

Comparison 6 Adjusted thermal dose versus fixed thermal dose, Outcome 3 Ovulation.

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Analysis 7.1

Comparison 7 Sensitivity analysis low risk of bias: LOD with and without medical ovulation versus medical ovulation alone, Outcome 1 Live birth.

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Analysis 7.2

Comparison 7 Sensitivity analysis low risk of bias: LOD with and without medical ovulation versus medical ovulation alone, Outcome 2 Multiple pregnancy.

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Summary of findings for the main comparison. LOD with and without medical ovulation compared to medical ovulation induction alone

Laparoscopic ovarian drilling with and without medical ovulation compared to medical ovulation induction alone
Patient or population: women with anovulatory PCOS and CC resistance Setting: fertility clinics Intervention: laparoscopic ovarian drilling with and without medical ovulation Comparison: medical ovulation induction alone
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Outcomes	Risk with medical ovulation induction alone	Risk with LOD ±medical ovulation	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Live birth	418 per 1000	338 per 1000 (279 to 398)	OR 0.71 (0.54 to 0.92)	1015 (9 RCTs)	⊕⊕⊝⊝ Low^a
Live birth (sensitivity analysis)	439 per 1000	413 per 1000 (316 to 516)	OR 0.90 (0.59 to 1.36)	415 (4 RCTs)	⊕⊕⊝⊝ Low^b,c
Multiple pregnancy	50 per 1000	18 per 1000 (9 to 34)	Peto OR 0.34 (0.18 to 0.66)	1161 (14 RCTs)	⊕⊕⊕⊝ Moderate^b
Clincial pregnancy	460 per 1000	423 per 1000 (380 to 467)	OR 0.86 (0.72 to 1.03)	2016 (21 RCTs)	⊕⊕⊝⊝ Low^a
Miscarriage	64 per 1000	71 per 1000 (51 to 99)	Peto OR 1.11 (0.78 to 1.59)	1909 (19 RCTs)	⊕⊕⊝⊝ Low^a
OHSS	23 per 1000	6 per 1000 (2 to 21)	Peto OR 0.25 (0.07 to 0.91)	722 (8 RCTs)	⊕⊕⊝⊝ Low^b,c
*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 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.
^aDowngraded by two levels for very serious risk of bias; inadequate randomisation or allocation concealment and no evidence of blinding. ^bDowngraded by one level for serious risk of bias; no evidence of blinding. ^cDowngraded by one level for serious imprecision.

Summary of findings for the main comparison. LOD with and without medical ovulation compared to medical ovulation induction alone

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Summary of findings 2. LOD of one ovary (unilateral) versus LOD of both ovaries (bilateral)

LOD of one ovary (unilateral) versus LOD of both ovaries (bilateral)
Patient or population: women with anovulatory PCOS and CC resistance Setting: fertility clinics Intervention: bilateral LOD Comparison: unilateal LOD
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Outcomes	Risk with Bilateral	Risk with Unilateral	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Live birth	409 per 1000	365 per 1000 (142 to 658)	OR 0.83 (0.24 to 2.78)	44 (1 RCT)	⊕⊝⊝⊝ Very low^a,b	‐
Multiple pregnancy	‐	‐	‐	‐	‐	No data were reported for this outcome.
Clinical pregnancy	464 per 1000	331 per 1000 (253 to 421)	OR 0.57 (0.39 to 0.84)	470 (7 RCTs)	⊕⊕⊝⊝ Low^a	‐
Miscarriage	91 per 1000	93 per 1000 (30 to 250)	Peto OR 1.02 (0.31 to 3.33)	131 (2 RCTs)	⊕⊝⊝⊝ Very low^a,b	‐
OHSS	‐	‐	‐	‐	‐	No data were reported for this outcome.
*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 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.
^aDowngraded by two levels for very serious risk of bias; inadequate randomisation or allocation concealment and no evidence of blinding. ^bDowngraded by one level for serious imprecision.

Summary of findings 2. LOD of one ovary (unilateral) versus LOD of both ovaries (bilateral)

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Table 1. Costs

Study

LOD ± CC

Other treatment

P value

Palomba 2004

EUR 1050

Metformin ± CC

EUR 50

< 0.05

Farquhar 2002

Total cost per patient NZD 2953

Chance of pregnancy 28%

Cost per pregnancy NZD 10,938

Chance of live birth 14%

Cost per live birth NZD 21,095

Gonadotrophin

Total cost per woman NZD 5461

Chance of pregnancy 33%

Cost per pregnancy NZD 16,549

Chance of live birth 19%

Cost per live birth NZD 28,744

Table 1. Costs

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Comparison 1. LOD with and without medical ovulation versus medical ovulation alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Live birth Show forest plot	9	1015	Odds Ratio (M‐H, Fixed, 95% CI)	0.71 [0.54, 0.92]

1.1 LOD versus CC + metformin	2	170	Odds Ratio (M‐H, Fixed, 95% CI)	0.59 [0.32, 1.09]
1.2 LOD versus CC + tamoxifen	1	150	Odds Ratio (M‐H, Fixed, 95% CI)	0.81 [0.42, 1.53]
1.3 LOD versus gonadotrophins	4	407	Odds Ratio (M‐H, Fixed, 95% CI)	0.87 [0.56, 1.36]
1.4 LOD versus letrozole	2	288	Odds Ratio (M‐H, Fixed, 95% CI)	0.55 [0.32, 0.92]
2 Multiple pregnancy Show forest plot	14	1161	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.34 [0.18, 0.66]

2.1 LOD versus clomiphene citrate	1	72	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 LOD versus CC + metformin	2	170	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.3 LOD versus CC + rosiglitazone	1	43	Peto Odds Ratio (Peto, Fixed, 95% CI)	2.12 [0.21, 21.52]
2.4 LOD versus gonadotrophins	7	532	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.22 [0.10, 0.46]
2.5 LOD versus gonadotrophins (rFSH) + metformin	1	36	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.6 LOD versus letrozole	1	147	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.7 LOD versus metformin	1	161	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.32 [0.25, 6.94]
3 Clinical pregnancy Show forest plot	21	2016	Odds Ratio (M‐H, Fixed, 95% CI)	0.86 [0.72, 1.03]

3.1 LOD versus clomiphene citrate	1	72	Odds Ratio (M‐H, Fixed, 95% CI)	0.52 [0.19, 1.44]
3.2 LOD versus CC + metformin	2	170	Odds Ratio (M‐H, Fixed, 95% CI)	0.71 [0.39, 1.31]
3.3 LOD versus CC + tamoxifen	1	150	Odds Ratio (M‐H, Fixed, 95% CI)	0.90 [0.47, 1.71]
3.4 LOD versus CC + rosiglitazone	1	43	Odds Ratio (M‐H, Fixed, 95% CI)	0.75 [0.23, 2.50]
3.5 LOD versus gonadotrophins	9	760	Odds Ratio (M‐H, Fixed, 95% CI)	1.01 [0.74, 1.36]
3.6 LOD versus gonadotrophins (rFSH) + metformin	1	36	Odds Ratio (M‐H, Fixed, 95% CI)	0.21 [0.04, 1.00]
3.7 LOD versus letrozole	3	368	Odds Ratio (M‐H, Fixed, 95% CI)	0.65 [0.42, 1.01]
3.8 LOD versus letrozole + metformin	1	146	Odds Ratio (M‐H, Fixed, 95% CI)	0.83 [0.42, 1.65]
3.9 LOD versus metformin	2	271	Odds Ratio (M‐H, Fixed, 95% CI)	1.25 [0.75, 2.08]
4 Miscarriage Show forest plot	19	1909	Odds Ratio (M‐H, Fixed, 95% CI)	1.11 [0.78, 1.59]

4.1 LOD versus CC + metformin	2	170	Odds Ratio (M‐H, Fixed, 95% CI)	1.95 [0.69, 5.54]
4.2 LOD versus CC + tamoxifen	1	150	Odds Ratio (M‐H, Fixed, 95% CI)	1.71 [0.39, 7.45]
4.3 LOD versus CC + rosiglitazone	1	43	Odds Ratio (M‐H, Fixed, 95% CI)	1.05 [0.06, 17.95]
4.4 LOD versus gonadotrophins	8	725	Odds Ratio (M‐H, Fixed, 95% CI)	0.80 [0.49, 1.33]
4.5 LOD versus gonadotrophins (rFSH) + metformin	1	36	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.6 LOD versus letrozole	3	368	Odds Ratio (M‐H, Fixed, 95% CI)	1.86 [0.61, 5.67]
4.7 LOD versus letrozole + metformin	1	146	Odds Ratio (M‐H, Fixed, 95% CI)	0.74 [0.16, 3.43]
4.8 LOD versus metformin	2	271	Odds Ratio (M‐H, Fixed, 95% CI)	1.60 [0.53, 4.82]
5 OHSS Show forest plot	8	722	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.25 [0.07, 0.91]

5.1 LOD versus clomiphene citrate	1	72	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.14 [0.00, 6.82]
5.2 LOD versus CC + metformin	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.3 LOD versus CC + rosiglitazone	1	43	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.4 LOD versus gonadotrophins	5	446	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.12 [0.02, 0.64]
5.5 LOD versus letrozole	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.6 LOD versus metformin	1	161	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.31 [0.13, 13.44]
6 Ovulation Show forest plot	10	951	Odds Ratio (M‐H, Fixed, 95% CI)	0.96 [0.73, 1.28]

6.1 LOD versus clomiphene citrate	1	72	Odds Ratio (M‐H, Fixed, 95% CI)	0.7 [0.27, 1.83]
6.2 LOD versus CC + metformin	1	50	Odds Ratio (M‐H, Fixed, 95% CI)	1.0 [0.32, 3.10]
6.3 LOD versus CC + tamoxifen	1	150	Odds Ratio (M‐H, Fixed, 95% CI)	1.34 [0.56, 3.17]
6.4 LOD versus CC + rosiglitazone	1	43	Odds Ratio (M‐H, Fixed, 95% CI)	0.67 [0.13, 3.44]
6.5 LOD versus gonadotrophins	2	139	Odds Ratio (M‐H, Fixed, 95% CI)	0.66 [0.32, 1.36]
6.6 LOD versus letrozole	1	80	Odds Ratio (M‐H, Fixed, 95% CI)	0.58 [0.23, 1.46]
6.7 LOD versus letrozole + metformin	1	146	Odds Ratio (M‐H, Fixed, 95% CI)	0.95 [0.49, 1.81]
6.8 LOD versus metformin	2	271	Odds Ratio (M‐H, Fixed, 95% CI)	1.52 [0.86, 2.68]
7 Costs Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

7.1 LOD versus CC + metformin	1	50	Mean Difference (IV, Fixed, 95% CI)	3711.3 [3585.17, 3837.43]
7.2 LOD versus gonadotrophins only (short‐term)	2	203	Mean Difference (IV, Fixed, 95% CI)	‐1115.75 [‐1309.72, ‐921.77]
7.3 LOD versus gonadotrophins only (long‐term)	1	168	Mean Difference (IV, Fixed, 95% CI)	‐2235.0 [‐4433.16, ‐36.84]
8 Quality of Life (Health related quality of life: SF‐36) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

8.1 Physical functioning at 24 weeks	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.2 Social functioning at 24 weeks	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.3 Role limitations (physical) at 24 weeks	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.4 Role limitations (emotional) at 24 weeks	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.5 Mental health at 24 weeks	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.6 Vitality at 24 weeks	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.7 Pain at 24 weeks	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.8 General health at 24 weeks	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Quality of life (Rotterdam Symptom Checklist at 24 weeks) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

9.1 Physical symptoms	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.2 Psychological distress	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.3 Activity level	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.4 Overall quality of life	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
10 Quality of life (Depression scales (CES‐D) at 24 weeks) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

10.1 Gonadotrophins	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
11 Multiple pregnancy per pregnancy Show forest plot	14	577	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.34 [0.17, 0.66]

11.1 LOD versus clomiphene citrate	1	23	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.2 LOD versus CC + metformin	2	99	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.3 LOD versus CC + rosiglitazone	1	20	Peto Odds Ratio (Peto, Fixed, 95% CI)	2.66 [0.24, 29.46]
11.4 LOD versus gonadotrophins	7	280	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.20 [0.09, 0.43]
11.5 LOD versus gonadotrophins (rFSH) + metformin	1	11	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.6 LOD versus letrozole	1	45	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.7 LOD versus metformin	1	99	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.42 [0.27, 7.53]
12 Miscarriage per pregnancy Show forest plot	19	900	Odds Ratio (M‐H, Fixed, 95% CI)	1.28 [0.88, 1.88]

12.1 LOD versus CC + metformin	2	120	Odds Ratio (M‐H, Fixed, 95% CI)	2.49 [0.86, 7.24]
12.2 LOD versus CC + tamoxifen	1	78	Odds Ratio (M‐H, Fixed, 95% CI)	1.87 [0.41, 8.43]
12.3 LOD versus CC + rosiglitazone	1	20	Odds Ratio (M‐H, Fixed, 95% CI)	1.25 [0.07, 23.26]
12.4 LOD versus gonadotrophins	8	373	Odds Ratio (M‐H, Fixed, 95% CI)	0.91 [0.53, 1.56]
12.5 LOD versus gonadotrophins (rFSH) + metformin	1	11	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
12.6 LOD versus letrozole	3	118	Odds Ratio (M‐H, Fixed, 95% CI)	2.75 [0.86, 8.79]
12.7 LOD versus letrozole + metformin	1	49	Odds Ratio (M‐H, Fixed, 95% CI)	0.83 [0.16, 4.15]
12.8 LOD versus metformin	2	131	Odds Ratio (M‐H, Fixed, 95% CI)	1.30 [0.41, 4.08]

Comparison 1. LOD with and without medical ovulation versus medical ovulation alone

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Comparison 2. LOD + IVF versus IVF

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Live birth Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Multiple pregnancy Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected

3 Clinical pregnancy Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Miscarriage Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 OHSS Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected

6 Multiple pregnancy per pregnancy Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected

7 Miscarriage per pregnancy Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 2. LOD + IVF versus IVF

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Comparison 3. LOD + second‐look laparoscopy versus LOD + expectant management

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical pregnancy Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Miscarriage Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Ovulation Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Miscarriage per pregnancy Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 3. LOD + second‐look laparoscopy versus LOD + expectant management

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Comparison 4. Unilateral versus bilateral

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Live birth Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Clinical pregnancy Show forest plot	7	470	Odds Ratio (M‐H, Fixed, 95% CI)	0.57 [0.39, 0.84]

3 Miscarriage Show forest plot	2	131	Odds Ratio (M‐H, Fixed, 95% CI)	1.02 [0.31, 3.33]

4 Ovulation Show forest plot	6	449	Odds Ratio (M‐H, Fixed, 95% CI)	0.60 [0.40, 0.90]

5 Miscarriage per pregnancy Show forest plot	2	71	Odds Ratio (M‐H, Fixed, 95% CI)	0.97 [0.28, 3.36]

Comparison 4. Unilateral versus bilateral

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Comparison 5. Monopolar versus bipolar

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical pregnancy Show forest plot	3	354	Odds Ratio (M‐H, Fixed, 95% CI)	0.94 [0.62, 1.44]

2 Ovulation Show forest plot	2	108	Odds Ratio (M‐H, Fixed, 95% CI)	0.33 [0.14, 0.76]

Comparison 5. Monopolar versus bipolar

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Comparison 6. Adjusted thermal dose versus fixed thermal dose

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical pregnancy Show forest plot	2	195	Odds Ratio (M‐H, Fixed, 95% CI)	1.84 [1.04, 3.26]

2 Miscarriage Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Ovulation Show forest plot	2	195	Odds Ratio (M‐H, Fixed, 95% CI)	1.83 [1.01, 3.33]

Comparison 6. Adjusted thermal dose versus fixed thermal dose

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Comparison 7. Sensitivity analysis low risk of bias: LOD with and without medical ovulation versus medical ovulation alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Live birth Show forest plot	4	415	Odds Ratio (M‐H, Fixed, 95% CI)	0.90 [0.59, 1.36]

1.1 LOD versus gonadotrophins	2	218	Odds Ratio (M‐H, Fixed, 95% CI)	1.04 [0.59, 1.85]
1.2 LOD versus CC + metformin	1	50	Odds Ratio (M‐H, Fixed, 95% CI)	1.17 [0.39, 3.56]
1.3 LOD versus letrozole	1	147	Odds Ratio (M‐H, Fixed, 95% CI)	0.62 [0.30, 1.31]
2 Multiple pregnancy Show forest plot	6	522	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.18 [0.06, 0.57]

2.1 LOD versus CC + metformin	1	50	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 LOD versus gonadotrophins	3	253	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.18 [0.06, 0.57]
2.3 LOD versus letrozole	1	147	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.4 LOD versus clomiphene citrate	1	72	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 7. Sensitivity analysis low risk of bias: LOD with and without medical ovulation versus medical ovulation alone

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