Received January 30, 2020
Accepted July 30, 2020

Introduction: Despite recent advances in assisted reproduction techniques, implantation and birth rates remain low, despite recent knowledge of embryo and endometrium quality. 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). The ovulation day was determined by ultrasound scanning. 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 retrieved five days after ovulation followed by blinded analysis and classification according to Noyes criteria, in both cycles. Results: Twenty-two participants completed the study. 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 due to asynchrony.