Induction of luteal phase defect with clomiphene citrate

The effect of clomiphene citrate and progesterone on luteal function in infertile women was studied. Endometrial biopsies were performed in 103 women immediately prior to menstruation. Group 1 (n = 62) had secretory endometrium with a histologic lag time of ≥48 hours with respect to the subsequent menses, that is, luteal phase defect. Group 2 (n = 10) had normal histologic characteristics of the secretory phase. Group 3 (n = 31) had anovulatory endometrium. The last group was subdivided into those with polycystic ovary syndrome (n = 9) and those without the characteristic gonadotropin pattern of polycystic ovary syndrome (n = 22). Clomiphene citrate at doses of 50 to 250 mg daily for 5 days was administered for induction of ovulation, timing of ovulation, or treatment of luteal phase defect. An endometrial biopsy was obtained after three ovulatory treatment cycles. Only one fourth of the women with prior luteal phase defect had normalization of the biopsy specimen with clomiphene citrate, while one half of those treated with progesterone had normal specimens. Half of the normally ovulating women had induction of a luteal phase defect with clomiphene citrate. Only women with polycystic ovary syndrome had consistently well-timed endometrial histologic features with clomiphene citrate therapy. Despite successful induction of ovulation, 16 of the other 22 previously anovulatory women had endometrial histologic findings compatible with luteal phase defect. Increasing the clomiphene citrate dosage was unsuccessful in improving endometrial maturation. These results suggest that the use of clomiphene citrate may be associated with a high rate of luteal phase defect induction, except among women with polycystic ovary syndrome. Clomiphene citrate, even at high doses, appears to be ineffective therapy for luteal phase defect.