Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome

Cindy Farquhar; Julie Brown; Jane Marjoribanks

doi:10.1002/14651858.CD001122.pub4

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Figure 1

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Figure 2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Figure 3

Funnel plot of comparison: 1 LOD ± medical ovulation versus other treatment, outcome: 1.2 Pregnancy rate per woman randomised.

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Figure 4

Forest plot of comparison: 1 LOD ± medical ovulation versus other treatment, outcome: 1.1 Live birth rate.

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Figure 5

Forest plot of comparison: 1 LOD ± medical ovulation versus other treatment, outcome: 1.4 Multiple pregnancy rate (per ongoing pregnancy).

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Figure 6

Forest plot of comparison: 2 Unilateral versus bilateral ovarian drilling, outcome: 2.1 Live birth.

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Analysis 1.1

Comparison 1 LOD with and without medical ovulation versus other treatment, Outcome 1 Live birth rate.

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Analysis 1.2

Comparison 1 LOD with and without medical ovulation versus other treatment, Outcome 2 Multiple pregnancy rate (per ongoing pregnancy).

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Analysis 1.3

Comparison 1 LOD with and without medical ovulation versus other treatment, Outcome 3 Pregnancy rate per woman randomised.

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Analysis 1.4

Comparison 1 LOD with and without medical ovulation versus other treatment, Outcome 4 Miscarriage rate.

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Analysis 1.5

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

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Analysis 1.6

Comparison 1 LOD with and without medical ovulation versus other treatment, Outcome 6 Ovulation rate.

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Analysis 1.7

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

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Analysis 1.8

Comparison 1 LOD with and without medical ovulation versus other treatment, Outcome 8 Depression scales (CES‐D) at 24 weeks.

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Analysis 1.9

Comparison 1 LOD with and without medical ovulation versus other treatment, Outcome 9 Health related quality of life: SF‐36‐ gonadotrophin.

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Analysis 1.10

Comparison 1 LOD with and without medical ovulation versus other treatment, Outcome 10 Depression scales (CES‐D) at 24 weeks gonadotrophin.

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Analysis 1.11

Comparison 1 LOD with and without medical ovulation versus other treatment, Outcome 11 Rotterdam Symptom Checklist at 24 weeks‐ gonadotrophin.

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Analysis 2.1

Comparison 2 Unilateral versus bilateral ovarian drilling, Outcome 1 Live birth.

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Analysis 2.2

Comparison 2 Unilateral versus bilateral ovarian drilling, Outcome 2 Pregnancy rate (per patient).

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Analysis 2.3

Comparison 2 Unilateral versus bilateral ovarian drilling, Outcome 3 Ovulation rate (per patient).

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Analysis 2.4

Comparison 2 Unilateral versus bilateral ovarian drilling, Outcome 4 Miscarriage.

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Analysis 3.1

Comparison 3 Second‐look versus expectant management, Outcome 1 Pregnancy.

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Analysis 3.2

Comparison 3 Second‐look versus expectant management, Outcome 2 Ovulation.

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Analysis 3.3

Comparison 3 Second‐look versus expectant management, Outcome 3 Miscarriage.

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Analysis 4.1

Comparison 4 LOD + IVF versus IVF, Outcome 1 Live birth.

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Analysis 4.2

Comparison 4 LOD + IVF versus IVF, Outcome 2 Multiple pregnancy.

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Analysis 4.3

Comparison 4 LOD + IVF versus IVF, Outcome 3 Pregnancy rate per woman randomised.

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Analysis 4.4

Comparison 4 LOD + IVF versus IVF, Outcome 4 Miscarriage rate per woman randomised.

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Analysis 4.5

Comparison 4 LOD + IVF versus IVF, Outcome 5 OHSS.

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Summary of findings for the main comparison. LOD with and without medical ovulation compared to other treatment for anovulatory women with PCOS

LOD with and without medical ovulation compared to other treatment for anovulatory women with PCOS
Patient or population: patients with anovulatory women with PCOS Settings: Fertility clinics Intervention: LOD with and without medical ovulation Comparison: other treatment
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Other treatment	LOD ±medical ovulation
Live birth rate	402 per 1000	341 per 1000 (284 to 405)	OR 0.77 (0.59 to 1.01)	1034 (8studies)	⊕⊕⊕⊝ moderate¹
Pregnancy rate per woman randomised	411 per 1000	396per 1000 (352 to 443)	OR 0.94 (0.78 to 1.14)	1930 (18studies)	⊕⊕⊝⊝ low²
Miscarriage rate	67 per 1000	73 per 1000 (51 to 104)	OR 1.1 (0.74 to 1.61)	1592 (15 studies)	⊕⊕⊝⊝ low³
Multiple pregnancy rate (per ongoing pregnancy)	34 per 1000	7 per 1000 (3 to 20)	OR 0.21 (0.08 to 0.58)	1129 (12studies)	⊕⊕⊕⊝ moderate⁴
OHSS	11 per 1000	2 per 1000 (0 to 13)	OR 0.14 (0.02 to 1.19)	908 (7 studies)	⊕⊕⊝⊝ low^5,6
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 Four of the trials were open labelled and no evidence of blinding and one of the trials lacked adequate information regarding blinding ² There was inadequate explanation for randomisation (4 trials) and allocation concealment (9 trials) and lack of detail or no blinding in 14 trials. ³ There were inadequate explanations of randomisation (in 3 trials), allocation concealment (8 trials) and inadequate or no blinding reported in 8 trials ⁴ Six trials had an inadequate explanation of or no blinding ⁵ Five trials showed no evidence of blinding ⁶ The summary effect crossed the line of no effect and substantive benefit or harm

Summary of findings for the main comparison. LOD with and without medical ovulation compared to other treatment for anovulatory women with PCOS

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Summary of findings 2. Unilateral ovarian drilling compared to bilateral ovarian drilling for anovulatory women with PCOS

Unilateral ovarian drilling compared to bilateral ovarian drilling for anovulatory women with PCOS
Patient or population: patients with anovulatory women with PCOS Settings: Fertility clinics Intervention: Unilateral ovarian drilling Comparison: bilateral ovarian drilling
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Bilateral ovarian drilling	Unilateral ovarian drilling
Live birth	409 per 1000	365 per 1000 (142 to 658)	OR 0.83 (0.24 to 2.78)	44 (1 study)	⊕⊝⊝⊝ very low^1,2,3
Pregnancy rate (per patient)	505 per 1000	505 per 1000 (360 to 652)	OR 1 (0.55 to 1.83)	182 (5 studies)	⊕⊕⊝⊝ low⁴
Miscarriage	91 per 1000	93 per 1000 (30 to 250)	OR 1.02 (0.31 to 3.33)	131 (2 studies)	⊕⊕⊕⊝ moderate⁵
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 The trial lack an adequate explanation of randomisation and allocation concealment and there was no blinding ² The summary effect crossed the line of no effect and substantive benefit and harm ³ Evidence is based on a single trial ⁴ Only on trial provided an adequate explanation of randomisation, only one trial provided an adequate explanation of allocation concealment and blinded outcome assessors ⁵ Randomisation was not clearly reported by either trial, allocation concealment was only reported by one trial and blinding was only conducted by one trial

Summary of findings 2. Unilateral ovarian drilling compared to bilateral ovarian drilling for anovulatory women with PCOS

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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 $2953NZ

Chance of pregnancy 28%

Cost per pregnancy $10,938NZ

Chance of live birth 14%

Cost per live birth $21,095NZ

Gonadotrophin

Total cost per patient $5461NZ

Chance of pregnancy 33%

Cost per pregnancy $16,549NZ

Chance of live birth 19%

Cost per live birth $28,744NZ

Table 1. Costs

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Comparison 1. LOD with and without medical ovulation versus other treatment

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Live birth rate Show forest plot	8	1034	Odds Ratio (M‐H, Fixed, 95% CI)	0.77 [0.59, 1.01]

1.1 LOD versus Clomiphene citrate + metformin	2	159	Odds Ratio (M‐H, Fixed, 95% CI)	0.44 [0.24, 0.82]
1.2 LOD versus Clomiphene citrate + tamoxifen	1	150	Odds Ratio (M‐H, Fixed, 95% CI)	0.81 [0.42, 1.53]
1.3 LOD versus Gonadotrophin	3	318	Odds Ratio (M‐H, Fixed, 95% CI)	0.97 [0.59, 1.59]
1.4 LOD versus Aromatase inhibitor	2	407	Odds Ratio (M‐H, Fixed, 95% CI)	0.84 [0.54, 1.31]
2 Multiple pregnancy rate (per ongoing pregnancy) Show forest plot	12	1129	Odds Ratio (M‐H, Fixed, 95% CI)	0.21 [0.08, 0.58]

2.1 LOD versus Clomiphene citrate + metformin	3	441	Odds Ratio (M‐H, Fixed, 95% CI)	0.10 [0.01, 1.94]
2.2 LOD versus Gonadotrophin	5	166	Odds Ratio (M‐H, Fixed, 95% CI)	0.13 [0.03, 0.52]
2.3 LOD versus Aromatase inhibitor	2	407	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.4 LOD versus Clomiphene citrate	1	72	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.5 LOD versus Rosiglitazone + CC	1	43	Odds Ratio (M‐H, Fixed, 95% CI)	2.21 [0.19, 26.38]
3 Pregnancy rate per woman randomised Show forest plot	18	1930	Odds Ratio (M‐H, Fixed, 95% CI)	0.94 [0.78, 1.14]

3.1 LOD versus Clomiphene citrate + metformin	3	441	Odds Ratio (M‐H, Fixed, 95% CI)	0.79 [0.53, 1.18]
3.2 LOD versus Clomiphene citrate + tamoxifen	2	250	Odds Ratio (M‐H, Fixed, 95% CI)	0.97 [0.59, 1.59]
3.3 LOD versus Gonadotrophin	8	607	Odds Ratio (M‐H, Fixed, 95% CI)	1.01 [0.72, 1.42]
3.4 LOD versus Aromatase inhibitor	2	407	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.58, 1.37]
3.5 LOD versus Clomiphene citrate	1	72	Odds Ratio (M‐H, Fixed, 95% CI)	0.52 [0.19, 1.44]
3.6 LOD versus Metformin	1	110	Odds Ratio (M‐H, Fixed, 95% CI)	2.47 [1.05, 5.81]
3.7 LOD versus Rosiglitazone + CC	1	43	Odds Ratio (M‐H, Fixed, 95% CI)	0.75 [0.23, 2.50]
4 Miscarriage rate Show forest plot	15	1592	Odds Ratio (M‐H, Fixed, 95% CI)	1.10 [0.74, 1.61]

4.1 LOD versus Clomiphene citrate + metformin	3	441	Odds Ratio (M‐H, Fixed, 95% CI)	1.43 [0.70, 2.91]
4.2 LOD versus Clomiphene citrate + tamoxifen	1	150	Odds Ratio (M‐H, Fixed, 95% CI)	1.71 [0.39, 7.45]
4.3 LOD versus Gonadotrophin	7	441	Odds Ratio (M‐H, Fixed, 95% CI)	0.73 [0.40, 1.33]
4.4 LOD versus Aromatase inhibitor	2	407	Odds Ratio (M‐H, Fixed, 95% CI)	1.33 [0.45, 3.90]
4.5 LOD versus Metformin	1	110	Odds Ratio (M‐H, Fixed, 95% CI)	2.08 [0.36, 11.85]
4.6 LOD versus Rosiglitazone + CC	1	43	Odds Ratio (M‐H, Fixed, 95% CI)	1.05 [0.06, 17.95]
5 OHSS Show forest plot	7	908	Odds Ratio (M‐H, Fixed, 95% CI)	0.14 [0.02, 1.19]

5.1 LOD versus Clomiphene citrate + metformin	1	282	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 LOD versus Gonadotrophins	3	251	Odds Ratio (M‐H, Fixed, 95% CI)	0.08 [0.00, 1.61]
5.3 LOD versus Aromatase inhibitor	1	260	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.4 LOD versus Clomiphene citrate	1	72	Odds Ratio (M‐H, Fixed, 95% CI)	0.32 [0.01, 8.23]
5.5 LOD versus Rosiglitazone + CC	1	43	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Ovulation rate Show forest plot	7		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

6.1 LOD versus Clomiphene citrate + metformin	1	47	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.27, 2.93]
6.2 LOD versus Clomiphene citrate + tamoxifen	2	250	Odds Ratio (M‐H, Fixed, 95% CI)	1.34 [0.68, 2.63]
6.3 LOD versus Gonadotrophins	1	50	Odds Ratio (M‐H, Fixed, 95% CI)	0.66 [0.21, 2.07]
6.4 LOD versus Clomiphene citrate	1	72	Odds Ratio (M‐H, Fixed, 95% CI)	0.7 [0.27, 1.83]
6.5 LOD versus Metformin	1	110	Odds Ratio (M‐H, Fixed, 95% CI)	1.78 [0.80, 3.96]
6.6 LOD versus Rosiglitazone + CC	1	43	Odds Ratio (M‐H, Fixed, 95% CI)	0.67 [0.13, 3.44]
7 Costs Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

7.1 LOD versus Clomiphene citrate + 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 Depression scales (CES‐D) at 24 weeks Show forest plot	1	118	Mean Difference (IV, Fixed, 95% CI)	3.0 [‐0.61, 6.61]

8.1 Gonadotrophins	1	118	Mean Difference (IV, Fixed, 95% CI)	3.0 [‐0.61, 6.61]
9 Health related quality of life: SF‐36‐ gonadotrophin Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

9.1 Physical functioning at 24 weeks	1	118	Mean Difference (IV, Fixed, 95% CI)	‐7.0 [‐12.77, ‐1.23]
9.2 Social functioning at 24 weeks	1	118	Mean Difference (IV, Fixed, 95% CI)	‐3.0 [‐10.79, 4.79]
9.3 Role limitations (physical) at 24 weeks	1	118	Mean Difference (IV, Fixed, 95% CI)	‐7.0 [‐20.71, 6.71]
9.4 Role limitations (emotional) at 24 weeks	1	118	Mean Difference (IV, Fixed, 95% CI)	‐10.0 [‐24.44, 4.44]
9.5 Mental health at 24 weeks	1	118	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐6.71, 6.71]
9.6 Vitality at 24 weeks	1	118	Mean Difference (IV, Fixed, 95% CI)	‐3.0 [‐9.51, 3.51]
9.7 Pain at 24 weeks	1	118	Mean Difference (IV, Fixed, 95% CI)	1.0 [‐6.59, 8.59]
9.8 General health at 24 weeks	1	118	Mean Difference (IV, Fixed, 95% CI)	2.0 [‐5.04, 9.04]
10 Depression scales (CES‐D) at 24 weeks gonadotrophin Show forest plot	1	118	Mean Difference (IV, Fixed, 95% CI)	3.0 [‐0.61, 6.61]

11 Rotterdam Symptom Checklist at 24 weeks‐ gonadotrophin Show forest plot	1	472	Mean Difference (IV, Fixed, 95% CI)	3.18 [0.63, 5.74]

11.1 Physical symptoms	1	118	Mean Difference (IV, Fixed, 95% CI)	5.0 [‐0.96, 10.96]
11.2 Psychological distress	1	118	Mean Difference (IV, Fixed, 95% CI)	6.0 [‐1.05, 13.05]
11.3 Activity level	1	118	Mean Difference (IV, Fixed, 95% CI)	1.0 [‐2.44, 4.44]
11.4 Overall quality of life	1	118	Mean Difference (IV, Fixed, 95% CI)	7.00 [‐0.04, 14.04]

Comparison 1. LOD with and without medical ovulation versus other treatment

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Comparison 2. Unilateral versus bilateral ovarian drilling

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Live birth Show forest plot	1	44	Odds Ratio (M‐H, Fixed, 95% CI)	0.83 [0.24, 2.78]

2 Pregnancy rate (per patient) Show forest plot	5	182	Odds Ratio (M‐H, Fixed, 95% CI)	1.00 [0.55, 1.83]

3 Ovulation rate (per patient) Show forest plot	4	161	Odds Ratio (M‐H, Fixed, 95% CI)	1.21 [0.59, 2.48]

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

Comparison 2. Unilateral versus bilateral ovarian drilling

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Comparison 3. Second‐look versus expectant management

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pregnancy Show forest plot	1	40	Odds Ratio (M‐H, Fixed, 95% CI)	0.67 [0.19, 2.33]

2 Ovulation Show forest plot	1	40	Odds Ratio (M‐H, Fixed, 95% CI)	6.33 [0.67, 60.16]

3 Miscarriage Show forest plot	1	40	Odds Ratio (M‐H, Fixed, 95% CI)	1.0 [0.13, 7.89]

Comparison 3. Second‐look versus expectant management

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Comparison 4. 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	50	Odds Ratio (M‐H, Fixed, 95% CI)	1.26 [0.33, 4.84]

2 Multiple pregnancy Show forest plot	1	50	Odds Ratio (M‐H, Fixed, 95% CI)	1.0 [0.06, 16.93]

3 Pregnancy rate per woman randomised Show forest plot	1	50	Odds Ratio (M‐H, Fixed, 95% CI)	1.20 [0.37, 3.86]

4 Miscarriage rate per woman randomised Show forest plot	1	50	Odds Ratio (M‐H, Fixed, 95% CI)	1.0 [0.18, 5.51]

5 OHSS Show forest plot	1	50	Odds Ratio (M‐H, Fixed, 95% CI)	0.22 [0.02, 2.11]

Comparison 4. LOD + IVF versus IVF

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