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Methodological risk of bias graph: review authors' judgments about each methodological quality item presented as percentages across all included studies.
Figuras y tablas -
Figure 1

Methodological risk of bias graph: review authors' judgments about each methodological quality item presented as percentages across all included studies.

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Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Figuras y tablas -
Figure 2

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

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Funnel plot of comparison: 1 Metformin versus placebo or no treatment, outcome: 1.2 Clinical pregnancy rate.
Figuras y tablas -
Figure 3

Funnel plot of comparison: 1 Metformin versus placebo or no treatment, outcome: 1.2 Clinical pregnancy rate.

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Funnel plot of comparison: 1 Metformin versus placebo or no treatment, outcome: 1.3 Ovulation rate.
Figuras y tablas -
Figure 4

Funnel plot of comparison: 1 Metformin versus placebo or no treatment, outcome: 1.3 Ovulation rate.

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Funnel plot of comparison: 1 Metformin versus placebo or no treatment, outcome: 1.14 Fasting insulin (mIU/L).
Figuras y tablas -
Figure 5

Funnel plot of comparison: 1 Metformin versus placebo or no treatment, outcome: 1.14 Fasting insulin (mIU/L).

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Funnel plot of comparison: 1 Metformin versus placebo or no treatment, outcome: 1.15 Fasting glucose (mmol/L).
Figuras y tablas -
Figure 6

Funnel plot of comparison: 1 Metformin versus placebo or no treatment, outcome: 1.15 Fasting glucose (mmol/L).

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Funnel plot of comparison: 2 Metformin combined with ovulation induction agent versus ovulation induction agent alone, outcome: 2.2 Clinical pregnancy rate.
Figuras y tablas -
Figure 7

Funnel plot of comparison: 2 Metformin combined with ovulation induction agent versus ovulation induction agent alone, outcome: 2.2 Clinical pregnancy rate.

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Comparison 1 Metformin versus placebo or no treatment, Outcome 1 Live birth rate.
Figuras y tablas -
Analysis 1.1

Comparison 1 Metformin versus placebo or no treatment, Outcome 1 Live birth rate.

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Comparison 1 Metformin versus placebo or no treatment, Outcome 2 Clinical pregnancy rate.
Figuras y tablas -
Analysis 1.2

Comparison 1 Metformin versus placebo or no treatment, Outcome 2 Clinical pregnancy rate.

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Comparison 1 Metformin versus placebo or no treatment, Outcome 3 Ovulation rate.
Figuras y tablas -
Analysis 1.3

Comparison 1 Metformin versus placebo or no treatment, Outcome 3 Ovulation rate.

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Comparison 1 Metformin versus placebo or no treatment, Outcome 4 Improved menstrual pattern.
Figuras y tablas -
Analysis 1.4

Comparison 1 Metformin versus placebo or no treatment, Outcome 4 Improved menstrual pattern.

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Comparison 1 Metformin versus placebo or no treatment, Outcome 5 Miscarriage rate.
Figuras y tablas -
Analysis 1.5

Comparison 1 Metformin versus placebo or no treatment, Outcome 5 Miscarriage rate.

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Comparison 1 Metformin versus placebo or no treatment, Outcome 6 Body Mass Index (kg/m2).
Figuras y tablas -
Analysis 1.6

Comparison 1 Metformin versus placebo or no treatment, Outcome 6 Body Mass Index (kg/m2).

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Comparison 1 Metformin versus placebo or no treatment, Outcome 7 Waist circumference (cm).
Figuras y tablas -
Analysis 1.7

Comparison 1 Metformin versus placebo or no treatment, Outcome 7 Waist circumference (cm).

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Comparison 1 Metformin versus placebo or no treatment, Outcome 8 Waist‐hip ratio.
Figuras y tablas -
Analysis 1.8

Comparison 1 Metformin versus placebo or no treatment, Outcome 8 Waist‐hip ratio.

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Comparison 1 Metformin versus placebo or no treatment, Outcome 9 Blood pressure ‐ systolic (mm Hg).
Figuras y tablas -
Analysis 1.9

Comparison 1 Metformin versus placebo or no treatment, Outcome 9 Blood pressure ‐ systolic (mm Hg).

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Comparison 1 Metformin versus placebo or no treatment, Outcome 10 Blood pressure ‐ diastolic (mm Hg).
Figuras y tablas -
Analysis 1.10

Comparison 1 Metformin versus placebo or no treatment, Outcome 10 Blood pressure ‐ diastolic (mm Hg).

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Comparison 1 Metformin versus placebo or no treatment, Outcome 11 Serum testosterone (nmol/L).
Figuras y tablas -
Analysis 1.11

Comparison 1 Metformin versus placebo or no treatment, Outcome 11 Serum testosterone (nmol/L).

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Comparison 1 Metformin versus placebo or no treatment, Outcome 12 Serum sex hormone‐binding globulin (nmol/L).
Figuras y tablas -
Analysis 1.12

Comparison 1 Metformin versus placebo or no treatment, Outcome 12 Serum sex hormone‐binding globulin (nmol/L).

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Comparison 1 Metformin versus placebo or no treatment, Outcome 13 Fasting insulin (mIU/L).
Figuras y tablas -
Analysis 1.13

Comparison 1 Metformin versus placebo or no treatment, Outcome 13 Fasting insulin (mIU/L).

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Comparison 1 Metformin versus placebo or no treatment, Outcome 14 Fasting glucose (mmol/L).
Figuras y tablas -
Analysis 1.14

Comparison 1 Metformin versus placebo or no treatment, Outcome 14 Fasting glucose (mmol/L).

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Comparison 1 Metformin versus placebo or no treatment, Outcome 15 Total cholesterol (mmol/l).
Figuras y tablas -
Analysis 1.15

Comparison 1 Metformin versus placebo or no treatment, Outcome 15 Total cholesterol (mmol/l).

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Comparison 1 Metformin versus placebo or no treatment, Outcome 16 HDL Cholesterol (mmol/L).
Figuras y tablas -
Analysis 1.16

Comparison 1 Metformin versus placebo or no treatment, Outcome 16 HDL Cholesterol (mmol/L).

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Comparison 1 Metformin versus placebo or no treatment, Outcome 17 Triglyceride levels (mmol/L).
Figuras y tablas -
Analysis 1.17

Comparison 1 Metformin versus placebo or no treatment, Outcome 17 Triglyceride levels (mmol/L).

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Comparison 1 Metformin versus placebo or no treatment, Outcome 18 Adverse events (gastrointestinal side effects).
Figuras y tablas -
Analysis 1.18

Comparison 1 Metformin versus placebo or no treatment, Outcome 18 Adverse events (gastrointestinal side effects).

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Comparison 2 Metformin combined with ovulation induction agent versus ovulation induction agent alone, Outcome 1 Live birth rate.
Figuras y tablas -
Analysis 2.1

Comparison 2 Metformin combined with ovulation induction agent versus ovulation induction agent alone, Outcome 1 Live birth rate.

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Comparison 2 Metformin combined with ovulation induction agent versus ovulation induction agent alone, Outcome 2 Clinical pregnancy rate.
Figuras y tablas -
Analysis 2.2

Comparison 2 Metformin combined with ovulation induction agent versus ovulation induction agent alone, Outcome 2 Clinical pregnancy rate.

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Comparison 2 Metformin combined with ovulation induction agent versus ovulation induction agent alone, Outcome 3 Ovulation rate (grouped by sensitivity to clomiphene).
Figuras y tablas -
Analysis 2.3

Comparison 2 Metformin combined with ovulation induction agent versus ovulation induction agent alone, Outcome 3 Ovulation rate (grouped by sensitivity to clomiphene).

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Comparison 2 Metformin combined with ovulation induction agent versus ovulation induction agent alone, Outcome 4 Ovulation rate (grouped by BMI).
Figuras y tablas -
Analysis 2.4

Comparison 2 Metformin combined with ovulation induction agent versus ovulation induction agent alone, Outcome 4 Ovulation rate (grouped by BMI).

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Comparison 2 Metformin combined with ovulation induction agent versus ovulation induction agent alone, Outcome 5 Adverse events (miscarriage, multiple pregnancy, side effects).
Figuras y tablas -
Analysis 2.5

Comparison 2 Metformin combined with ovulation induction agent versus ovulation induction agent alone, Outcome 5 Adverse events (miscarriage, multiple pregnancy, side effects).

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Comparison 3 Metformin versus clomiphene citrate, Outcome 1 Live birth.
Figuras y tablas -
Analysis 3.1

Comparison 3 Metformin versus clomiphene citrate, Outcome 1 Live birth.

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Comparison 3 Metformin versus clomiphene citrate, Outcome 2 Clinical pregnancy rate.
Figuras y tablas -
Analysis 3.2

Comparison 3 Metformin versus clomiphene citrate, Outcome 2 Clinical pregnancy rate.

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Comparison 3 Metformin versus clomiphene citrate, Outcome 3 Ovulation rate.
Figuras y tablas -
Analysis 3.3

Comparison 3 Metformin versus clomiphene citrate, Outcome 3 Ovulation rate.

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Comparison 3 Metformin versus clomiphene citrate, Outcome 4 Miscarrage rate.
Figuras y tablas -
Analysis 3.4

Comparison 3 Metformin versus clomiphene citrate, Outcome 4 Miscarrage rate.

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Comparison 3 Metformin versus clomiphene citrate, Outcome 5 Multiple pregnancy.
Figuras y tablas -
Analysis 3.5

Comparison 3 Metformin versus clomiphene citrate, Outcome 5 Multiple pregnancy.

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Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 1 Ovulation.
Figuras y tablas -
Analysis 4.1

Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 1 Ovulation.

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Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 2 Body Mass Index (kg/m2).
Figuras y tablas -
Analysis 4.2

Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 2 Body Mass Index (kg/m2).

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Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 3 Waist‐hip ratio.
Figuras y tablas -
Analysis 4.3

Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 3 Waist‐hip ratio.

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Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 4 Blood pressure ‐ systolic (mm Hg).
Figuras y tablas -
Analysis 4.4

Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 4 Blood pressure ‐ systolic (mm Hg).

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Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 5 Blood pressure ‐ Diastolic (mm Hg).
Figuras y tablas -
Analysis 4.5

Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 5 Blood pressure ‐ Diastolic (mm Hg).

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Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 6 Serum testosterone (nmol/L).
Figuras y tablas -
Analysis 4.6

Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 6 Serum testosterone (nmol/L).

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Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 7 Serum sex hormone‐binding globulin (nmol/L).
Figuras y tablas -
Analysis 4.7

Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 7 Serum sex hormone‐binding globulin (nmol/L).

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Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 8 Fasting insulin (mIU/L).
Figuras y tablas -
Analysis 4.8

Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 8 Fasting insulin (mIU/L).

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Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 9 Fasting glucose (mmol/L).
Figuras y tablas -
Analysis 4.9

Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 9 Fasting glucose (mmol/L).

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Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 10 HDL Cholesterol (mmol/L).
Figuras y tablas -
Analysis 4.10

Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 10 HDL Cholesterol (mmol/L).

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Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 11 Cholesterol (mmol/L).
Figuras y tablas -
Analysis 4.11

Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 11 Cholesterol (mmol/L).

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Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 12 Triglyceride levels (mmol/L).
Figuras y tablas -
Analysis 4.12

Comparison 4 D‐chiro‐inositol versus placebo or no treatment, Outcome 12 Triglyceride levels (mmol/L).

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Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 1 Ovulation rate.
Figuras y tablas -
Analysis 5.1

Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 1 Ovulation rate.

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Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 2 Improved menstrual pattern.
Figuras y tablas -
Analysis 5.2

Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 2 Improved menstrual pattern.

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Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 3 Body Mass Index (kg/m2).
Figuras y tablas -
Analysis 5.3

Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 3 Body Mass Index (kg/m2).

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Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 4 Waist‐hip ratio.
Figuras y tablas -
Analysis 5.4

Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 4 Waist‐hip ratio.

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Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 5 Blood pressure‐systolic (mm Hg).
Figuras y tablas -
Analysis 5.5

Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 5 Blood pressure‐systolic (mm Hg).

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Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 6 Blood pressure‐diastolic (mm Hg).
Figuras y tablas -
Analysis 5.6

Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 6 Blood pressure‐diastolic (mm Hg).

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Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 7 serum sex hormone‐binding globulin (nmol/L).
Figuras y tablas -
Analysis 5.7

Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 7 serum sex hormone‐binding globulin (nmol/L).

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Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 8 Fasting insulin (mIU/L).
Figuras y tablas -
Analysis 5.8

Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 8 Fasting insulin (mIU/L).

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Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 9 Fasting glucose (mmol/L).
Figuras y tablas -
Analysis 5.9

Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 9 Fasting glucose (mmol/L).

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Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 10 Cholesterol.
Figuras y tablas -
Analysis 5.10

Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 10 Cholesterol.

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Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 11 HDL Cholesterol.
Figuras y tablas -
Analysis 5.11

Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 11 HDL Cholesterol.

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Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 12 Triglyceride levels.
Figuras y tablas -
Analysis 5.12

Comparison 5 Rosiglitazone versus placebo or no treatment, Outcome 12 Triglyceride levels.

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Comparison 6 Pioglitazone versus placebo or no treatment, Outcome 1 Improved menstrual pattern.
Figuras y tablas -
Analysis 6.1

Comparison 6 Pioglitazone versus placebo or no treatment, Outcome 1 Improved menstrual pattern.

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Comparison 6 Pioglitazone versus placebo or no treatment, Outcome 2 Body Mass Index (kg/m2).
Figuras y tablas -
Analysis 6.2

Comparison 6 Pioglitazone versus placebo or no treatment, Outcome 2 Body Mass Index (kg/m2).

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Comparison 6 Pioglitazone versus placebo or no treatment, Outcome 3 Waist circumference.
Figuras y tablas -
Analysis 6.3

Comparison 6 Pioglitazone versus placebo or no treatment, Outcome 3 Waist circumference.

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Comparison 6 Pioglitazone versus placebo or no treatment, Outcome 4 Waist‐hip ratio.
Figuras y tablas -
Analysis 6.4

Comparison 6 Pioglitazone versus placebo or no treatment, Outcome 4 Waist‐hip ratio.

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Comparison 6 Pioglitazone versus placebo or no treatment, Outcome 5 Serum testosterone (nmol/L).
Figuras y tablas -
Analysis 6.5

Comparison 6 Pioglitazone versus placebo or no treatment, Outcome 5 Serum testosterone (nmol/L).

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Comparison 6 Pioglitazone versus placebo or no treatment, Outcome 6 Serum sex hormone‐binding globulin (nmol/L).
Figuras y tablas -
Analysis 6.6

Comparison 6 Pioglitazone versus placebo or no treatment, Outcome 6 Serum sex hormone‐binding globulin (nmol/L).

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Comparison 6 Pioglitazone versus placebo or no treatment, Outcome 7 Fasting insulin (mIU/L).
Figuras y tablas -
Analysis 6.7

Comparison 6 Pioglitazone versus placebo or no treatment, Outcome 7 Fasting insulin (mIU/L).

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Table 1. Conversion Factors

Convert from

Convert to

Conversion factor

Cholesterol

mg/dl

mmol/L

0.026

Triglycerides

mg/dl

mmol/L

0.11

Insulin

pmol/L

mIU/L (=microIU/ml)

0.1667

Glucose

mg/dl

mmol/L

0.056

Progesterone

ng/ml

nmol/L

3.18

Testosterone

ng/dl

nmol/L

0.03467

Androstenedione

ng/dl

nmol/L

0.0349

Oestradiol

ng/dl

pmol/L

36.71

17‐beta oestradiol

ng/dl

pmol/L

36.71

Dehydroepiandrosterone sulphate

microg/dl

micromol/L

0.02714

Sex hormone binding globulin

microg/dl

nmol/L

34.7

Standard deviation

Standard error

Standard deviation

Sqrt n

Confidence Intervals

Confidence Intervals

Standard error

(upper limit ‐ lower limit) / 3.92
Figuras y tablas -
Table 1. Conversion Factors
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Comparison 1. Metformin versus placebo or no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth rate Show forest plot

2

50

Odds Ratio (M‐H, Fixed, 95% CI)

1.0 [0.16, 6.39]

2 Clinical pregnancy rate Show forest plot

6

479

Odds Ratio (M‐H, Fixed, 95% CI)

3.86 [2.18, 6.84]

2.1 Patients with BMI < 30kg/m2

3

250

Odds Ratio (M‐H, Fixed, 95% CI)

4.41 [2.24, 8.66]

2.2 Patients with BMI > 30kg/m2

3

229

Odds Ratio (M‐H, Fixed, 95% CI)

2.78 [0.95, 8.12]

3 Ovulation rate Show forest plot

13

875

Odds Ratio (M‐H, Fixed, 95% CI)

2.12 [1.50, 3.00]

3.1 Patients with BMI < 30kg/m2

4

417

Odds Ratio (M‐H, Fixed, 95% CI)

2.33 [1.43, 3.81]

3.2 Patients with BMI > 30kg/m2

9

458

Odds Ratio (M‐H, Fixed, 95% CI)

1.94 [1.20, 3.15]

4 Improved menstrual pattern Show forest plot

8

427

Odds Ratio (M‐H, Fixed, 95% CI)

1.72 [1.14, 2.61]

4.1 Patients with BMI <30 kg/m2

1

23

Odds Ratio (M‐H, Fixed, 95% CI)

21.15 [1.01, 445.00]

4.2 Patients with BMI > 30kg/m2

7

404

Odds Ratio (M‐H, Fixed, 95% CI)

1.57 [1.03, 2.41]

5 Miscarriage rate Show forest plot

1

51

Odds Ratio (M‐H, Fixed, 95% CI)

0.30 [0.06, 1.59]

6 Body Mass Index (kg/m2) Show forest plot

14

504

Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.29, 0.22]

6.1 Patients with BMI < 30kg/m2

5

143

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.30, 0.25]

6.2 Patients with BMI >30kg/m2

9

361

Mean Difference (IV, Fixed, 95% CI)

‐0.08 [‐0.82, 0.66]

7 Waist circumference (cm) Show forest plot

2

153

Mean Difference (IV, Fixed, 95% CI)

0.51 [‐3.62, 4.64]

8 Waist‐hip ratio Show forest plot

8

408

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.01, ‐0.00]

8.1 Patients with BMI < 30kg/m2

3

113

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.01, ‐0.00]

8.2 Patients with BMI >30kg/m2

5

295

Mean Difference (IV, Fixed, 95% CI)

‐0.00 [‐0.02, 0.02]

9 Blood pressure ‐ systolic (mm Hg) Show forest plot

8

379

Mean Difference (IV, Fixed, 95% CI)

‐3.59 [‐5.13, ‐2.04]

9.1 Patients with BMI <30kg/m2

3

96

Mean Difference (IV, Fixed, 95% CI)

‐3.52 [‐5.29, ‐1.76]

9.2 Patients with BMI >30kg/m2

5

283

Mean Difference (IV, Fixed, 95% CI)

‐3.80 [‐5.00, ‐0.60]

10 Blood pressure ‐ diastolic (mm Hg) Show forest plot

7

292

Mean Difference (IV, Fixed, 95% CI)

‐0.14 [‐1.35, 1.07]

10.1 Patients with BMI < 30kg/m2

3

96

Mean Difference (IV, Fixed, 95% CI)

‐0.21 [‐1.55, 1.13]

10.2 Patients with BMI > 30kg/m2

4

196

Mean Difference (IV, Fixed, 95% CI)

0.18 [‐2.65, 3.02]

11 Serum testosterone (nmol/L) Show forest plot

16

607

Mean Difference (IV, Fixed, 95% CI)

‐0.60 [‐0.73, ‐0.47]

11.1 Patients with BMI < 30kg/m2

5

143

Mean Difference (IV, Fixed, 95% CI)

‐1.79 [‐2.07, ‐1.51]

11.2 Patients with BMI > 30kg/m2

11

464

Mean Difference (IV, Fixed, 95% CI)

‐0.29 [‐0.43, ‐0.15]

12 Serum sex hormone‐binding globulin (nmol/L) Show forest plot

15

549

Mean Difference (IV, Fixed, 95% CI)

‐1.23 [‐3.89, 1.43]

12.1 Patients with BMI < 30kg/m2

4

111

Mean Difference (IV, Fixed, 95% CI)

‐5.72 [‐17.48, 6.04]

12.2 Patients with BMI > 30kg/m2

11

438

Mean Difference (IV, Fixed, 95% CI)

‐0.99 [‐3.72, 1.75]

13 Fasting insulin (mIU/L) Show forest plot

14

526

Mean Difference (IV, Random, 95% CI)

‐3.38 [‐6.81, 0.04]

13.1 Patients with BMI < 30kg/m2

4

85

Mean Difference (IV, Random, 95% CI)

‐5.65 [‐10.25, ‐1.06]

13.2 Patients with BMI > 30kg/m2

10

441

Mean Difference (IV, Random, 95% CI)

‐2.47 [‐6.88, 1.93]

14 Fasting glucose (mmol/L) Show forest plot

14

549

Mean Difference (IV, Fixed, 95% CI)

‐0.15 [‐0.25, ‐0.05]

14.1 Patients with BMI < 30kg/m2

4

111

Mean Difference (IV, Fixed, 95% CI)

‐0.13 [‐0.31, 0.05]

14.2 Patients with BMI > 30kg/m2

10

438

Mean Difference (IV, Fixed, 95% CI)

‐0.16 [‐0.27, ‐0.04]

15 Total cholesterol (mmol/l) Show forest plot

9

510

Mean Difference (IV, Fixed, 95% CI)

‐0.12 [‐0.30, 0.06]

15.1 Patients with BMI< 30kg/m2

4

253

Mean Difference (IV, Fixed, 95% CI)

‐0.06 [‐0.33, 0.20]

15.2 Patients with BMI ≥ 30kg/m2

5

257

Mean Difference (IV, Fixed, 95% CI)

‐0.17 [‐0.42, 0.08]

16 HDL Cholesterol (mmol/L) Show forest plot

9

472

Mean Difference (IV, Random, 95% CI)

‐0.10 [‐0.27, 0.06]

16.1 Patients with BMI < 30kg/m2

4

253

Mean Difference (IV, Random, 95% CI)

0.06 [‐0.16, 0.27]

16.2 Patients with BMI >30kg/m2

5

219

Mean Difference (IV, Random, 95% CI)

‐0.22 [‐0.44, 0.01]

17 Triglyceride levels (mmol/L) Show forest plot

9

329

Mean Difference (IV, Fixed, 95% CI)

0.13 [‐0.05, 0.31]

17.1 Patients with BMI < 30kg/m2

3

53

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐0.33, 0.34]

17.2 Patients with BMI > 30kg/m2

6

276

Mean Difference (IV, Fixed, 95% CI)

0.18 [‐0.03, 0.40]

18 Adverse events (gastrointestinal side effects) Show forest plot

5

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

18.1 Nausea and vomiting

3

73

Odds Ratio (M‐H, Fixed, 95% CI)

3.91 [0.98, 15.64]

18.2 Gastrointestinal disturbance (other than nausea and vomiting)

4

253

Odds Ratio (M‐H, Fixed, 95% CI)

9.23 [4.18, 20.37]
Figuras y tablas -
Comparison 1. Metformin versus placebo or no treatment
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Comparison 2. Metformin combined with ovulation induction agent versus ovulation induction agent alone

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth rate Show forest plot

4

752

Odds Ratio (M‐H, Fixed, 95% CI)

1.05 [0.75, 1.47]

1.1 Patients with BMI < 30kg/m2

1

225

Odds Ratio (M‐H, Fixed, 95% CI)

0.62 [0.33, 1.17]

1.2 Patients with BMI > 30kg/m2

3

527

Odds Ratio (M‐H, Fixed, 95% CI)

1.31 [0.87, 1.96]

2 Clinical pregnancy rate Show forest plot

8

976

Odds Ratio (M‐H, Fixed, 95% CI)

1.48 [1.12, 1.95]

2.1 Patients with BMI < 30kg/m2

3

333

Odds Ratio (M‐H, Fixed, 95% CI)

1.19 [0.74, 1.90]

2.2 Patients with BMI > 30kg/m2

5

643

Odds Ratio (M‐H, Fixed, 95% CI)

1.67 [1.18, 2.36]

3 Ovulation rate (grouped by sensitivity to clomiphene) Show forest plot

11

2668

Odds Ratio (M‐H, Fixed, 95% CI)

1.76 [1.51, 2.06]

3.1 PCOS and clomifene sensitive

1

56

Odds Ratio (M‐H, Fixed, 95% CI)

3.55 [0.65, 19.37]

3.2 PCOS and clomifene resistant

5

179

Odds Ratio (M‐H, Fixed, 95% CI)

4.86 [2.43, 9.74]

3.3 PCOS and clomifene sensitivity not defined

5

2433

Odds Ratio (M‐H, Fixed, 95% CI)

1.65 [1.40, 1.94]

4 Ovulation rate (grouped by BMI) Show forest plot

11

2668

Odds Ratio (M‐H, Fixed, 95% CI)

1.76 [1.51, 2.06]

4.1 BMI <30 kg/m2

5

525

Odds Ratio (M‐H, Fixed, 95% CI)

1.61 [1.13, 2.31]

4.2 BMI ≥30kg/m2

6

2143

Odds Ratio (M‐H, Fixed, 95% CI)

1.80 [1.51, 2.14]

5 Adverse events (miscarriage, multiple pregnancy, side effects) Show forest plot

5

1828

Odds Ratio (M‐H, Fixed, 95% CI)

2.07 [1.49, 2.87]

5.1 Multiple pregnancy rate

4

665

Odds Ratio (M‐H, Fixed, 95% CI)

0.50 [0.12, 2.02]

5.2 Miscarriage rate

5

745

Odds Ratio (M‐H, Fixed, 95% CI)

1.48 [0.90, 2.43]

5.3 Nausea and vomiting

1

418

Odds Ratio (M‐H, Fixed, 95% CI)

3.40 [2.08, 5.54]

5.4 Gastrointestinal disturbance (other than nausea and vomiting)

0

0

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Figuras y tablas -
Comparison 2. Metformin combined with ovulation induction agent versus ovulation induction agent alone
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Comparison 3. Metformin versus clomiphene citrate

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth Show forest plot

3

600

Odds Ratio (M‐H, Fixed, 95% CI)

0.67 [0.44, 1.02]

1.1 Patients with BMI < 30kg/m2

1

100

Odds Ratio (M‐H, Fixed, 95% CI)

4.94 [1.99, 12.26]

1.2 Patients with BMI > 30kg/m2

2

500

Odds Ratio (M‐H, Fixed, 95% CI)

0.30 [0.17, 0.52]

2 Clinical pregnancy rate Show forest plot

3

600

Odds Ratio (M‐H, Fixed, 95% CI)

0.63 [0.43, 0.92]

2.1 Patients with BMI < 30kg/m2

1

100

Odds Ratio (M‐H, Fixed, 95% CI)

3.47 [1.52, 7.90]

2.2 Patients with BMI > 30kg/m2

2

500

Odds Ratio (M‐H, Fixed, 95% CI)

0.34 [0.21, 0.55]

3 Ovulation rate Show forest plot

3

2470

Odds Ratio (M‐H, Fixed, 95% CI)

0.48 [0.41, 0.57]

3.1 Patients with BMI < 30kg/m2

1

426

Odds Ratio (M‐H, Fixed, 95% CI)

0.84 [0.56, 1.25]

3.2 Patients with BMI > 30kg/m2

2

2044

Odds Ratio (M‐H, Fixed, 95% CI)

0.43 [0.36, 0.51]

4 Miscarrage rate Show forest plot

3

145

Odds Ratio (M‐H, Fixed, 95% CI)

0.94 [0.42, 2.07]

5 Multiple pregnancy Show forest plot

3

145

Odds Ratio (M‐H, Fixed, 95% CI)

0.33 [0.02, 6.69]
Figuras y tablas -
Comparison 3. Metformin versus clomiphene citrate
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Comparison 4. D‐chiro‐inositol versus placebo or no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Ovulation Show forest plot

2

327

Odds Ratio (M‐H, Random, 95% CI)

5.38 [0.70, 41.31]

2 Body Mass Index (kg/m2) Show forest plot

1

44

Mean Difference (IV, Fixed, 95% CI)

0.5 [‐0.86, 1.86]

3 Waist‐hip ratio Show forest plot

1

44

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.05, 0.03]

4 Blood pressure ‐ systolic (mm Hg) Show forest plot

1

44

Mean Difference (IV, Fixed, 95% CI)

‐2.0 [‐5.85, 1.85]

5 Blood pressure ‐ Diastolic (mm Hg) Show forest plot

1

44

Mean Difference (IV, Fixed, 95% CI)

‐4.0 [‐7.26, ‐0.74]

6 Serum testosterone (nmol/L) Show forest plot

1

44

Mean Difference (IV, Fixed, 95% CI)

‐0.63 [‐1.37, 0.11]

7 Serum sex hormone‐binding globulin (nmol/L) Show forest plot

1

44

Mean Difference (IV, Fixed, 95% CI)

69.44 [34.97, 103.91]

8 Fasting insulin (mIU/L) Show forest plot

1

44

Mean Difference (IV, Fixed, 95% CI)

‐20.0 [‐43.43, 3.43]

9 Fasting glucose (mmol/L) Show forest plot

1

44

Mean Difference (IV, Fixed, 95% CI)

‐0.28 [‐0.99, 0.43]

10 HDL Cholesterol (mmol/L) Show forest plot

1

44

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.12, 0.12]

11 Cholesterol (mmol/L) Show forest plot

1

44

Mean Difference (IV, Fixed, 95% CI)

‐0.23 [‐0.99, 0.53]

12 Triglyceride levels (mmol/L) Show forest plot

1

44

Mean Difference (IV, Fixed, 95% CI)

‐2.20 [‐6.23, 1.83]
Figuras y tablas -
Comparison 4. D‐chiro‐inositol versus placebo or no treatment
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Comparison 5. Rosiglitazone versus placebo or no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Ovulation rate Show forest plot

1

64

Odds Ratio (M‐H, Fixed, 95% CI)

31.0 [3.76, 255.30]

2 Improved menstrual pattern Show forest plot

1

30

Odds Ratio (M‐H, Fixed, 95% CI)

13.0 [2.07, 81.48]

3 Body Mass Index (kg/m2) Show forest plot

2

78

Mean Difference (IV, Fixed, 95% CI)

0.70 [0.42, 0.97]

4 Waist‐hip ratio Show forest plot

2

78

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.02, ‐0.00]

5 Blood pressure‐systolic (mm Hg) Show forest plot

1

52

Mean Difference (IV, Fixed, 95% CI)

‐2.0 [‐3.95, ‐0.05]

6 Blood pressure‐diastolic (mm Hg) Show forest plot

1

52

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐1.72, 1.32]

7 serum sex hormone‐binding globulin (nmol/L) Show forest plot

2

78

Mean Difference (IV, Random, 95% CI)

‐29.23 [‐96.85, 38.39]

8 Fasting insulin (mIU/L) Show forest plot

1

26

Mean Difference (IV, Fixed, 95% CI)

‐6.06 [‐15.30, 3.18]

9 Fasting glucose (mmol/L) Show forest plot

2

78

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐0.42, 0.03]

10 Cholesterol Show forest plot

1

26

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐0.21, ‐0.19]

11 HDL Cholesterol Show forest plot

1

26

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐0.21, ‐0.19]

12 Triglyceride levels Show forest plot

1

26

Mean Difference (IV, Fixed, 95% CI)

1.0 [0.89, 1.11]
Figuras y tablas -
Comparison 5. Rosiglitazone versus placebo or no treatment
Ir a la tabla de la revisión
Comparison 6. Pioglitazone versus placebo or no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Improved menstrual pattern Show forest plot

1

30

Odds Ratio (M‐H, Fixed, 95% CI)

8.0 [1.52, 42.04]

2 Body Mass Index (kg/m2) Show forest plot

1

28

Mean Difference (IV, Fixed, 95% CI)

‐0.40 [‐4.22, 3.42]

3 Waist circumference Show forest plot

1

28

Mean Difference (IV, Fixed, 95% CI)

2.0 [‐6.18, 10.18]

4 Waist‐hip ratio Show forest plot

1

28

Mean Difference (IV, Fixed, 95% CI)

0.02 [‐0.02, 0.06]

5 Serum testosterone (nmol/L) Show forest plot

1

28

Mean Difference (IV, Fixed, 95% CI)

0.28 [‐0.36, 0.92]

6 Serum sex hormone‐binding globulin (nmol/L) Show forest plot

1

28

Mean Difference (IV, Fixed, 95% CI)

‐1.0 [‐14.09, 12.09]

7 Fasting insulin (mIU/L) Show forest plot

1

28

Mean Difference (IV, Fixed, 95% CI)

‐1.5 [‐5.52, 2.52]
Figuras y tablas -
Comparison 6. Pioglitazone versus placebo or no treatment
Ir a la tabla de la revisión
Table 2. Abbreviations Used

Abbreviation

Definition

BMI

Body mass index

CI

Confidence interval

CT

Computerised tomography scan

DHEAS

Dehydroepiandrosterone sulphate

FSH

Follicle stimulating hormone

GTT

Glucose tolerance test

HbA1C

Glycosylated haemoglobin

HDL

High density lipoprotein cholesterol

IGFBP‐1

Insulin growth factor binding protein 1

LDL

Low density lipoprotein cholesterol

LH

Luteinising hormone

NIDDM

Non insulin dependent diabetes mellitus

NNT

Number needed to treat

PAI‐1

Plasminogen activator inhibitor 1

PCOS

Polycystic ovary syndrome

RCT

Randomised controlled trial

rFSH

Recombinant follicle stimulating hormone

SD

Standard deviation

SE

Standard error of the mean

SHBG

Sex hormone binding globulin

VLDL

Very low density lipoprotein cholesterol

vs

Versus

MD

Weighted mean difference
Figuras y tablas -
Table 2. Abbreviations Used
Ir a la tabla de la revisión
Table 2. Abbreviations Used

Abbreviation

Definition

BMI

Body mass index

CI

Confidence interval

CT

Computerised tomography scan

DHEAS

Dehydroepiandrosterone sulphate

FSH

Follicle stimulating hormone

GTT

Glucose tolerance test

HbA1C

Glycosylated haemoglobin

HDL

High density lipoprotein cholesterol

IGFBP‐1

Insulin growth factor binding protein 1

LDL

Low density lipoprotein cholesterol

LH

Luteinising hormone

NIDDM

Non insulin dependent diabetes mellitus

NNT

Number needed to treat

PAI‐1

Plasminogen activator inhibitor 1

PCOS

Polycystic ovary syndrome

RCT

Randomised controlled trial

rFSH

Recombinant follicle stimulating hormone

SD

Standard deviation

SE

Standard error of the mean

SHBG

Sex hormone binding globulin

VLDL

Very low density lipoprotein cholesterol

vs

Versus

MD

Weighted mean difference
Figuras y tablas -
Table 2. Abbreviations Used
Ir a la tabla de la revisión