Summary of findings 1. Metformin compared to placebo or no treatment in women with polycystic ovary syndrome.
| Metformin compared to placebo or no treatment in women with polycystic ovary syndrome | ||||||
| Patient or population: women with polycystic ovary syndrome Setting: Human reproduction center Intervention: metformin Comparison: placebo or no treatment | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Risk with placebo or no treatment | Risk with metformin | |||||
| Live birth rate per woman ‐ long protocol GnRH‐agonist | Study population | RR 1.30 (0.94 to 1.79) | 651 (6 RCTs) | ⊕⊕⊝⊝ LOW 1 2 | The evidence for the effect of metformin on live birth rate per woman ‐ long protocol GnRH‐agonist is uncertain. | |
| 283 per 1000 | 368 per 1000 (266 to 507) | |||||
| Live birth rate per woman ‐ short protocol GnRH‐antagonist | Study population | RR 0.48 (0.29 to 0.79) | 153 (1 RCT) | ⊕⊕⊝⊝ LOW 3 | Metformin may reduce live birth rate per woman ‐ short protocol GnRH‐antagonist. | |
| 434 per 1000 | 208 per 1000 (126 to 343) | |||||
| Incidence of OHSS per woman | Study population | RR 0.46 (0.29 to 0.72) | 1091 (11 RCTs) | ⊕⊕⊝⊝ LOW 1 4 | Metformin may reduce incidence of OHSS per woman. | |
| 196 per 1000 | 90 per 1000 (57 to 141) | |||||
| Clinical pregnancy rate per woman ‐ long protocol GnRH‐agonist | Study population | RR 1.32 (1.08 to 1.63) | 915 (10 RCTs) | ⊕⊕⊝⊝ LOW 1 2 | Metformin may increase clinical pregnancy rate per woman ‐ long protocol GnRH‐agonist. | |
| 275 per 1000 | 363 per 1000 (297 to 449) | |||||
| Clinical pregnancy rate per woman ‐ short protocol GnRH‐antagonist | Study population | RR 1.38 (0.21 to 9.14) | 177 (2 RCTs) | ⊕⊝⊝⊝ VERY LOW 5 6 7 | The evidence for the effect of metformin on clinical pregnancy rate per woman ‐ short protocol GnRH‐antagonist is uncertain. | |
| 443 per 1000 | 612 per 1000 (93 to 1000) | |||||
| Miscarriage rate per woman | Study population | RR 0.86 (0.56 to 1.32) | 821 (8 RCTs) | ⊕⊕⊝⊝ LOW 1 8 | The evidence for the effect of metformin on miscarriage rate per woman is uncertain. | |
| 106 per 1000 | 91 per 1000 (59 to 141) | |||||
| Side effects per woman | Study population | RR 3.35 (2.34 to 4.79) | 748 (8 RCTs) | ⊕⊕⊝⊝ LOW 1 4 | Metformin may result in an increase in side effects per woman. | |
| 88 per 1000 | 296 per 1000 (207 to 424) | |||||
| *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; GnRH: gonadotrophin‐releasing hormone; OHSS: ovarian hyperstimulation syndrome; RCT: randomised controlled trial; RR: risk ratio | ||||||
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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. | ||||||
1Evidence downgraded by one level for serious risk of bias: the majority of the RCTs have unclear or high risk of bias. 2Evidence downgraded by one level for serious imprecision: low number of events (total number of events < 300) and 95% CI includes both appreciable effect and little or no effect. 3Evidence downgraded by two levels for very serious imprecision: low number of events (total number of events < 300) and data based on one small RCT. 4Evidence downgraded by one level for serious imprecision: low number of events (total number of events < 300). 5Evidence downgraded by one level for serious risk of bias: all studies considered as at unclear risk of bias for at least one domain. 6Evidence downgraded by two levels for serious inconsistency (I2 = 87%) as unexplained heterogeneity (i.e. heterogeneity not explained by subgrouping of data according to stimulation protocol). 7Evidence downgraded by two levels for very serious imprecision: low number of events (total number of events < 300) and data based on two RCTs, and 95% CI includes both appreciable benefit and harm. 8Evidence downgraded by one level for serious imprecision: low number of events (total number of events < 300), and 95% CI includes both appreciable benefit and harm.