Abstract
Obejective:Despite recent advances in assisted reproduction techniques, implantation and birth rates remain low. Although embryo quality is considered the main determinant of implantation success, maturity and endometrial receptivity are also important factors to consider. However, what precisely constitutes a receptive endometrium remains uncertain. The objective of this study is to investigate if clomiphene citrate alters the endometrial maturation in infertile patients.Methods: In a prospective self-matched cohort study, the ovulation of women was evaluated in spontaneous and stimulated cycles (with clomiphene citrate). Subjects were submitted to transvaginal ultrasounds to follow the cycle and to determine the day of ovulation. In both cycles, four blood samples (BS1 - at early proliferative phase, BS2 - at mid proliferative phase, BS3 - after ovulation and BS4 - at mid luteal phase) were taken to determine the serum concentrations of FSH, LH, estradiol and progesterone. An endometrial biopsy was performed five days after ovulation in both cycles and sent to Hospital de Clínicas de Porto Alegre pathology lab for analysis and classification according to Noyes criteria.Results:Twenty-two participants completed the study protocol. There were significant differences in FSH BS3 (p = 0.001), in LH BS3 and BS4 (p<0.001 and p=0.049, respectively), in estradiol BS2, BS3 and BS4 (p<0.001, p=0.024 and p<0.001, respectively) and in progesterone BS3 and BS4 (p = 0.028 and p<0.001, respectively). Considering Noyes criteria, there was a one-day delay when comparing the stimulated cycle with the spontaneous cycle (p=0.004), and a two-day delay when comparing the stimulated cycle with the biopsy day.Discussion: This study indicates that the ovarian stimulation with clomiphene citrate delays the endometrial maturity, and could possibly impair the implantation process. The antiestrogenic effects of clomiphene citrate in the endometrium may be responsible for this difference and, to avoid this effect, it is suggested to consider the freeze-all strategy when using clomiphene citrate for controlled ovarian stimulation, in order to minimize the endometrial asynchrony.
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