Effects of clomiphene citrate stimulation on endometrial structure in infertile women

Abstract

Investigations into the effect of clomiphene citrate stimulation on endometrial differentiation were retrospectively performed in the mid-luteal phase on 21 patients undergoing ovulation induction prior to artificial insemination. A high incidence of irregular endometrial development was seen using morphological and morphometric criteria; in addition, increasing stromal oedema after clomiphene citrate treatment was observed. Measurable differences in glandular development (i.e. numbers of glands and glandular epithelial height) were found in early luteal phase biopsies (LH+2/+6) from patients treated with clomiphene citrate and normal fertile controls. Impaired endometrial development in the early luteal phase, which is a sensitive interval in preparation for implantation, might lead to an effective asynchrony between embryonic and uterine development and unfavourably influence the outcome of implantation.

Defining the proliferative phase endometrial defect

“…Clomiphene has been shown to reduce the number of estrogen and progesterone receptors and glandular density in the endometrium, and increase the number of vacuolated cells (6,8). All of these features are consistent with a hypoestrogenic effect (5).…”

“…It is easily administered, has relatively few side effects, and the risk of multiple pregnancy is relatively low. The mechanism of action is as an anti-estrogen agent exerting effects on the hypothalamus, pituitary, and uterus (5)(6)(7)(8). Of clinical importance is the effect of CC on endometrial thickness and quality as detected sonographically.…”

Progesterone Resistance in PCOS Endometrium: A Microarray Analysis in Clomiphene Citrate-Treated and Artificial Menstrual Cycles

“…However, CC has been associated with lower pregnancy rates (15%) and a higher likelihood of miscarriage (18), suggesting that CC may adversely affect the endometrial receptivity (19). High-throughput DNA microarray techniques have demonstrated that human endometrium undergoes programmatic changes in gene expression throughout the menstrual cycle that can become dysfunctional in certain conditions such as endometriosis (11).…”

Role of an estrogen-upregulated 64.0-kDa uterine fluid glycoprotein in improving fertility in women

“…This differential protein response to estrogen can perhaps be explained in the light of antiestrogenic influence of CC at the target tissues (26,27). It is possible that CC exerted its antagonistic effect at the endometrial level (2) and attenuated the uterine production of 64.0-kDa protein.…”