A pilot study to prevent a thin endometrium in patients undergoing clomiphene citrate treatment

BACKGROUND Clomiphene citrate (CC) is most commonly used as a first-line treatment of infertility. However, a disturbance of endometrial growth by the adverse effects of the CC has been recognized. Since a thin endometrium is recognized as a critical factor of implantation failure, preventing CC-induced thinning of the endometrium is important. This study was undertaken to investigate whether the modified CC treatments are useful to prevent a thin endometrium in patients undergoing CC treatments. METHODS This study is a prospective, randomized controlled study. The study was performed at the Saiseikai Shimonoseki General Hospital during a 4-month period (May 2012 to September 2012). Sixty-six infertile women who had a thin endometrium (< 8 mm) during the standard CC treatment (50 mg/day on days 5-9 of the menstrual cycle) were enrolled. The patients were randomly divided into three groups: 22 patients were given 25 mg/day CC on days 5-9 (half-dose group), 22 patients were given 50 mg/day CC on days 1-5 (early administration group) and 22 patients received a standard CC treatment again (control group). Endometrial thickness at the induction of ovulation was assessed by ultrasonography. The primary endpoint of this study was an endometrial thickness. RESULTS Half dose administration and early administration improved the endometrial thickness (≥ 8 mm) in 14 patients (70%) and in 19 patients (90%) respectively, while only 3 patients (15%) improved in endometrial thickness in the control group. The mean endometrial thickness was also significantly higher in the half dose group (8.6 ± 1.5 mm) and early administration group (9.4 ± 1.5 mm) compared to the control group (6.7 ± 1.8 mm). No side effect was observed in this study. CONCLUSIONS The modified treatment with a half-dose or early administration of CC significantly increased endometrial thickness in patients with a history of thin endometrium caused by the standard CC regimen. The modified CC treatments in this study can be beneficial for patients with a thin endometrium as a result of standard CC treatment. TRIAL REGISTRATION CLINICAL TRIAL REGISTRATION NUMBER UMIN000007959.