Sonographic Determination of a Possible Adverse Effect of Clomiphene Citrate on Endometrial Growth

We recently demonstrated, using transvaginal sonography, that conception cycles in in-vitro fertilization (IVF) are associated with a significantly thicker endometrium at midcycle than non-conception cycles, suggesting that endometrial growth may influence implantation. In the present study, to examine whether the type of stimulation protocol affects endometrial development, we compared the sonographic appearance of the endometrium in 22 patients randomized to receive clomiphene citrate and human menopausal gonadotrophin (CC/HMG) and in 19 who received HMG alone. A significantly thicker endometrium was observed in the HMG patients compared to the CC/HMG group (P less than 0.005) throughout the follicular phase of the cycle, although serum concentrations of oestradiol (E2) did not differ in the two groups. Twenty-three patients (13 in the HMG group and 10 in the CC/HMG group) had previous IVF cycles with CC/HMG stimulation in which endometrial thickness was measured. A thin endometrium recurred with subsequent CC/HMG cycles while increased growth occurred with HMG only compared to previous CC/HMG cycles. Therefore, ultrasound examination of the endometrium in this study demonstrated that CC results in a thinner endometrium than HMG alone. We believe these findings may be of importance in improving pregnancy rates in IVF and possibly in other infertility therapy which involves the use of clomiphene citrate.