Open AccessCombined metformin‐clomiphene in clomiphene‐resistant polycystic ovary syndrome: a systematic review and meta‐analysis of randomized controlled trials
Author(s) -
Abu Hashim Hatem,
Foda Osama,
Ghayaty Essam
Publication year - 2015
Publication title -
acta obstetricia et gynecologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.401
H-Index - 102
eISSN - 1600-0412
pISSN - 0001-6349
DOI - 10.1111/aogs.12673
Subject(s) - polycystic ovary , medicine , odds ratio , confidence interval , metformin , randomized controlled trial , gynecology , pregnancy , insulin resistance , insulin , biology , genetics
Objective Our objective was to compare the effectiveness of metformin plus clomiphene citrate vs. gonadotrophins, laparoscopic ovarian diathermy, aromatase inhibitors, N ‐acetyl‐cysteine and other insulin sensitizers+clomiphene for improving fertility outcomes in women with clomiphene‐resistant polycystic ovary syndrome. Design PubMed, SCOPUS and CENTRAL databases were searched until April 2014 with the key words: PCOS, polycystic ovary syndrome, metformin, clomiphene citrate, ovulation induction and pregnancy. The search was limited to articles conducted with humans and published in English. Sample The PRISMA statement was followed. Twelve randomized controlled trials ( n = 1411 women) were included. Main outcome measures Ovulation and clinical pregnancy rates per woman randomized. Results Compared with gonadotrophins, the metformin+clomiphene combination resulted in significantly fewer ovulations (odds ratio 0.25; 95% confidence interval 0.15–0.41; p < 0.00001, 3 trials, I 2 = 85%, n = 323) and pregnancies (odds ratio 0.45; 95% confidence interval 0.27–0.75; p = 0.002, 3 trials, I 2 = 0%, n = 323). No significant differences were found when metformin+clomiphene was compared with laparoscopic ovarian diathermy (odds ratio 0.88; 95% confidence interval 0.53–1.47; p = 0.62, 1 trial, n = 282; odds ratio 0.96; 95% confidence interval 0.60–1.54; p = 0.88, 2 trials, I 2 = 0%, n = 332, for ovulation and pregnancy rates, respectively). Likewise, no differences were observed in comparison with aromatase inhibitors (odds ratio 0.88; 95% confidence interval 0.58–1.34; p = 0.55, 3 trials, I 2 = 3%, n = 409; odds ratio 0.85; 95% confidence interval 0.53–1.36; p = 0.50, 2 trials, n = 309, for ovulation and pregnancy rates, respectively). Conclusions There is evidence for the superiority of gonadotrophins, but the metformin+clomiphene combination is mainly relevant for clomiphene‐resistant polycystic ovary syndrome patients and, if not effective, a next step could be gonadotrophins. More attempts with metformin+clomiphene are only relevant if there is limited access to gonadotrophins.