METFORMIN USAGE TO INDUCE OVULATION IN WOMEN WITH POLYCYSTIC OVARY SYNDROME: META-ANALYSIS (original) (raw)
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Reproductive Biology and Endocrinology, 2014
The current systematic review with meta-analysis of randomized controlled trials (RCTs) was aimed to evaluate the effects of metformin on reproductive outcomes in patients with polycystic ovary syndrome (PCOS) who receive gonadotropins for ovulation induction. After systematic review of electronic databases and websites for registration of RCTs, a total of 7 RCTs reporting data on 1023 cycles were included in the final analysis. Descriptive data showed an overall low studies' quality due to unclear sequence generation and allocation concealment, lack of blinding procedure, incomplete outcome data and several biases and/or confounders. Data synthesis showed that metformin improved live-birth (odds ratio [OR] = 1.94, 95% confidence interval [CI] 1.10 to 3.44; P = 0.020) and pregnancy (OR = 2.25, 95% CI 1.50 to 3.38; P < 0.0001) rates, without significant heterogeneity across the studies (P = 0.230, estimation of inconsistency = 30%; and P = 0.710, estimation of inconsistency = 0%, respectively, for live-birth and pregnancy rates). A significant reduction of cancellation rate was observed after metformin administration (OR = 0.41, 95% CI 0.24 to 0.72, P = 0.002) without significant heterogeneity across the studies (P = 0.500, estimation of inconsistency = 0%). Metformin administration influenced or did not influence other secondary endpoints assessed with a significant heterogeneity. In conclusion, metformin administration increases the live-birth and pregnancy rate in PCOS patients who receive gonadotropins for ovulation induction. Further well designed, blinded, placebo-controlled, and adequately powered RCTs are need to confirm that metanalytic results.
Fertility and Sterility, 2002
To assess pregnancy outcome in anovulatory infertility patients diagnosed with polycystic ovary syndrome (PCOS) who were treated with metformin. Case series. Outpatient. Anovulatory patients (n = 48) with a diagnosis of PCOS based on clinical, diagnostic, and laboratory evaluations were enrolled in the study over a 15-month period. Metformin was started at 500 mg b.i.d. for 6 weeks and then increased to 500 mg t.i.d. if no ovulation occurred. Clomiphene citrate (CC; 50 mg) was added if no ovulatory response occurred after 6 weeks. Resumption of menses, presumptive ovulation, and pregnancy. Nineteen of 48 (40%) patients resumed spontaneous menses following treatment and showed presumptive evidence of ovulation with metformin alone; 15/48 (31%) required CC (50 mg) in conjunction with metformin therapy, and 10 of these 15 (67%) had evidence of ovulation; 20/48 (42%) conceived with a median time to conception of 3 months, and 7 of these 20 (35%) had spontaneous abortions (SAB); 19/48 (40%) had gastrointestinal-related side effects, and 5 of 48 patients (10%) had to decrease the dosage of metformin. Only 1 patient discontinued therapy. Metformin alone in patients with PCOS results in a substantial number of pregnancies, with 69% (20/29) of those who ovulated conceiving in less than 6 months.
Fertility and Sterility, 2007
To determine which first-line medication is more effective in polycystic ovary syndrome (PCOS) patients for ovulation induction and pregnancy achievement and to verify whether any patient characteristic is associated with a better response to therapy. Design: Observational comparative study. Setting: Fertility clinic. Patient(s): One hundred fifty-four infertile women with oligomenorrhea and hyperandrogenism. Intervention(s): Group 1 (56 patients) received clomiphene citrate (CC) 50 mg from days 5-9 of the cycle. Group 2 (57 patients) received 500 mg of metformin 3 times a day. Group 3 (41 patients) received both medications. Main Outcome Measure(s): Ovulation and pregnancy. Result(s): Patients receiving metformin alone had an increased ovulation rate compared with those receiving CC alone (75.4% vs. 50%). Patients on metformin had similar ovulation rates compared with those in the combination group (75.4% vs. 63.4%). Pregnancy rates were equivalent in the 3 groups. Response to metformin was independent of body weight and dose. Finally, nonsmoking predicted better ovulatory response overall as well as lower fasting glucose for CC and lower androgens for metformin.
Archives of Gynecology and Obstetrics, 2010
Objective To compare the eYcacy of metformin and clomiphene citrate (CC) therapies for ovulation induction in anovulatory infertile women with polycystic ovary syndrome (PCOS). Methods A total of 69 consecutive infertile, anovulatory women with PCOS were enrolled in this prospective, nonrandomized trial. The women were prescribed either 1,700 mg/day metformin or CC with a starting dose of 50 mg/day up to 150 mg/day for a period of six consecutive cycles. Results Metformin and CC groups were followed for a total of 136 and 94 cycles, respectively. Metformin group had lower rates of ovulation when compared with CC group (32.3 vs. 60.6%, respectively; p = 0.004). There was no statistical diVerence in pregnancy rates per cycle between the treatment groups (8 vs. 11.7%, respectively; p = 0.33) leading to similar cumulative pregnancy rates (36.6 vs. 35.4%, respectively; p = 0.45). No diVerence was observed among the abortion rates (10 vs. 10%, respectively; p > 0.05) between the groups. Discussion Although metformin and CC are two eVective Wrst-line approaches for improving pregnancy rates in anovulatory PCOS women, CC is associated with higher rates of ovulation.
Human Reproduction, 2006
BACKGROUND: A systematic review of randomized controlled trials (RCTs) comparing whether metformin coadministration with gonadotrophins for ovulation induction (OI) with timed intercourse or IVF improves outcome in women with polycystic ovary syndrome (PCOS). METHODS: The quality of reporting of meta-analyses (QUOROM) guidelines were followed. A systematic computerized literature search of three bibliographic databases was performed. RESULTS: Eight RCTs were included in the overall review. Meta-analysis demonstrated that the co-administration of metformin to gonadotrophin OI does not significantly improve ovulation [odds ratio (OR) = 3.27; 95% confidence interval (95% CI) = 0.31-34.72] or pregnancy (OR = 3.46; 95% CI = 0.98-12.2) rates. Metformin co-administration to IVF treatment does not improve pregnancy (OR = 1.29; 95% CI = 0.84-1.98) or live birth (OR = 2.02, 95% CI = 0.98-4.14) rates but reduces the risk of ovarian hyperstimulation syndrome (OHSS) (OR = 0.21; 95% CI = 0.11-0.41, P < 0.00001). CONCLUSIONS: Current data on the use of metformin in the gonadotrophin OI or IVF treatment settings are inconclusive because of the review's failure to exclude an important clinical treatment effect. Further RCTs are necessary to definitively clarify whether metformin co-administration during gonadotrophin OI or IVF will improve the efficacy of these treatments in PCOS women.
The role of metformin in polycystic ovary syndrome: a systematic review
Human Reproduction Update, 2007
This meta-analysis evaluated the effectiveness of metformin in subfertile women with polycystic ovary syndrome (PCOS). Only randomized trials investigating the effectiveness of metformin and PCOS definition consistent with the Rotterdam consensus criteria, were eligible. Primary outcome was live birth rate. A literature search identified 27 trials. In therapy naïve women, we found no evidence of a difference in live birth rate when comparing metformin with clomifene citrate (CC) [relative risks (RR) 0.73; 95% confidence interval (CI) 0.51-1.1] or comparing metformin plus CC with CC (RR 1.0; 95% CI 0.82-1.3). In CC-resistant women, metformin plus CC led to higher live birth rates than CC alone (RR 6.4; 95% CI 1.2-35); metformin also led to higher live birth rates than laparoscopic ovarian drilling (LOD) (RR 1.6; 95% CI 1.1-2.5). We found no evidence for a positive effect of metformin on live birth when added to LOD (RR 1.3; 95% CI 0.39-4.0) or FSH (RR 1.6; 95% CI 0.95-2.9), or when co-administered in IVF (RR 1.5; 95% CI 0.92-2.5). In IVF, metformin led to fewer cases of ovarian hyperstimulation syndrome (OHSS) (RR 0.33; 95% CI 0.13-0.80). This meta-analysis demonstrates that CC is still first choice therapy for women with therapy naïve PCOS. In CC-resistant women, the combination of CC plus metformin is the preferred treatment option before starting with LOD or FSH. At present, there is no evidence of an improvement in live birth when adding metformin to LOD or FSH. In IVF, metformin leads to a reduced risk of OHSS.