OBJECTIVE: To determine the effectiveness of the addition of estrogen during clomifene induced ovulation cycles among infertile women in improving endometrial thickness, endometrial echogenicity and pregnancy rates.
DESIGN: Meta-analysis.
SETTING: University-based tertiary center.
MATERIALS AND METHODS: All clinical trials of estrogen in whatever form and route of administration with clomifene citrate compared with clomifene alone or plus placebo in the treatment of infertile women were identified thru electronic search through Medline Cochrane and HERDIN databases, reference hand searching of obtained journals and request for information from relevant organizations and then reviewed for methodological quality. Meta-analysis of weighted mean differences (WMD) for the endometrial thickness, uterine artery pulsatility index, number and size of dominant follicles as well as pooled odds ratios (OR) using Mantel-Haenszel Statistic for pregnancy were performed using Review Manager version 4.1.
RESULTS: Randomized controlled trials were included involving 354 women aged 21-37 years with unexplained/ anovulatory infertility. The pooled WMD for endometrial thickness was 1.71 mm (95% confidence interval (0.71, 2.69) in favor of clomifene plus estrogen. Subgroup analysis revealed that the endometrium was thicker if ethinylestradiol administered at a dose range of 0.02-0.05 mg was given on the 7th-10th say of the cycle for 5 days. Two studies reported pregnancy rates as outcomes showing an almost 2 times higher chance of pregnancy among those treated with clomifene plus estrogen. (OR=1.74; 95% CI 0.93, 3.27). There was a small but significantly higher value for WMD of 16 pg/ml for serum estradiol levels (95% CI 4.56, 27.8). No evidence of any effect on uterine artery pulsatility index, dominant follicle size nor number was seen.
CONCLUSION: Meta-analysis demonstrates that estrogen supplementation in clomifene citrate ovulation induction increases endometrial thickness and serum estradiol levels with a trend towards increased chances of pregnancy among infertile women.

Human ; Clomiphene ; Infertility, Female ; Pregnancy Rate ; Ethinyl Estradiol ; Estradiol ; Uterine Artery ; Ovulation Induction ; Estrogens ; Ovarian Follicle ; Endometrium ; Ovulation ; Citrates