A Cochrane review «Insulin‐sensitising drugs (metformin, rosiglitazone, pioglitazone, D‐chiro‐inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility»1 «Morley LC, Tang T, Yasmin E et al. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Co»1 included 42 studies with a total of 4 024 women on metformin. Metformin alone slightly improved live birth rate (see Table «Metformin compared to placebo or no treatment for women with polycystic ovary syndrome»1), 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 «Metformin compared to placebo or no treatment for women with polycystic ovary syndrome»1) 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 «Metformin compared to placebo or no treatment for women with polycystic ovary syndrome»1.
Another Cochrane review «Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome»2 «Sharpe A, Morley LC, Tang T et al. Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2019;(12):CD013505. »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).
The following decision support rules contain links to this evidence summary: