Title : The clinical safety and effectiveness of sequential letrozole and gonadotropins therapy for ovulation induction in infertile women with polycystic ovarian syndrome: A systematic review and meta-analysis of randomized controlled trials
Abstract:
Background: Polycystic ovarian syndrome (PCOS), genetically heterogeneous endocrine disorder in reproductive-aged women, affecting 5% to 20% worldwide, is major cause of hyperandrogenism, anovulatory infertility, menstrual dysfunction, and hirsutism. It is commonly treated with ovulation induction therapies like Clomiphene citrate (CC) and ovarian drilling.
Objective: This meta-analysis evaluated the clinical safety and effectiveness of sequential letrozole plus gonadotropins (LE+G) therapy in ovulation induction in infertile women with PCOS.
Methods: We searched PubMed, Embase, Cochrane, Scopus and clinicaltrials.gov databases for articles relevant to the sequential LE+G therapy for PCOS. Pooled outcomes estimates were reported as odds ratio (OR) and 95% confidence interval (CI) for dichotomous data, and as mean difference (MD) and 95% CI for continuous data. Statistical heterogeneity among the studies was assessed using I¬¬–squared (I2) and chi-squared (Chi2) statistics. I2 values of >75% were indicative of significant heterogeneity. Sensitivity analysis was performed to deal heterogeneity.
Results: This review included 8 RCTs with 956 patients in both groups. We found significant increase in ovulation rates in control group (OR 1.74; 95% CI 1.02–2.99; I2=27%) in 5 studies, no significant increase in pregnancy rates in both groups (OR 1.11; 95% CI 0.66–187, I2=60%) in 8 studies, no significant mean difference (MD) in No. of dominant follicles in both groups (MD 0.36; 95% CI -0.18 to 0.91, I2=97%) in 7 studies, no significant increase in size of dominant follicles (mm) in both groups (MD -0.27; 95% CI -0.95 to 0.41; I2=88%) in 4 studies, significant increase in endometrial thickness (mm) in the control group (MD 0.78; 95% CI 0.19–1.38; I2=97%) in 7 studies and no significant mean difference of serum E2 levels (pg/ml) in the both groups (MD 17.54; 95% CI -143.76 to 178.84; I2=99%) in 5 studies.
Conclusion: The LE+G is clinically less effective in terms of pregnancy rates, No. and size of dominant follicles, endometrial thickness and serum E2 levels as compared to other standard interventions. Further, large-scale, high-quality RCTs need to be conducted to establish conclusive evidence.
