A Cochrane review [Abstract] 1 included 42 studies with a total of 4 024 women on metformin. Metformin alone slightly improved live birth rate (see Table T1), but not significantly in combination with clomiphene (OR 1.21, 95% CI 0.92 to 1.59; 9 trials, n=1079). Clinical pregnancy rates were improved for metformin versus placebo (Table T1) and for metformin and clomiphene versus clomiphene alone (OR 1.59, 95% CI 1.27 to 1.99; 16 trials, n=1529).
| Outcome | Relative effect : OR (95% CI) | Assumed risk - control | Corresponding risk (95% CI) -metformin | Participants (studies) |
|---|---|---|---|---|
| Live birth rate | 1.59 (1.00 to 2.51) | 141 per 1000 | 208 per 1000 (141 to 292) | 435 (4) |
| Clinical pregnancy rate | 1.93 (1.42 to 2.64) | 110 per 1000 | 193 per 1000 (149 to 246) | 1027 (9) |
| Ovulation rate | 2.55(1.81 to 3.59) | 2 00 per 1000 | 389 per 1000 (312 to 473) | 701 (14) |
| Miscarriage rate | 1.08 (0.50 to 2.35) | 40 per 1000 | 43per 1000 (20 to 89) | 748 (4) |
| Adverse events (gastrointestinal) | 4.76(3.06 to 7.41) | 106 per 1000 | 362 per 1000(267 to 469) | 670(7) |
In the studies that compared metformin and clomiphene, there was evidence of an improved live birth rate (OR 0.3, 95% CI 0.17 to 0.52, 2 studies, n=500) and clinical pregnancy rate (OR 0.34, 95% 0.21 to 0.55, 2 studies, n=500) in the group of obese women who took clomiphene.
Metformin was associated with a significantly higher incidence of gastrointestinal disturbances than placebo T1.
Another Cochrane review [Abstract] 2 included 41 studies with a total of 4 552 women. Metformin improved live birth rates compared with placebo (OR 1.59, 95% CI 1.00 to 2.51; 4 studies, n=435 women). For a live birth rate of 19% following placebo, the live birth rate following metformin would be between 19% and 37%. There were higher rates of clinical pregnancy (OR 1.98, 95% CI 1.47 to 2.65; 11 studies, n=1213) and ovulation rates with metformin (OR 2.64, 95% CI 1.85 to 3.75; 13 studies,n= 684). Comparing metformin plus CC to CC alone, live birth rates did not improve significantly (OR 1.27, 95% CI 0.98 to 1.65; 10 studies, n=1219 women). The live birth rate with CC alone is 24%, which may change to between 23% to 34% with combined therapy.
Comment: The quality of evidence is downgraded by inconsistency (variability in results across studies) and by imprecise results (wide confidence intervals).
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