Effects of Clomiphene Citrate Plus Estradiol or Progesterone on Endometrial Ultrastructure: an RCT

Background: Pinopods concentrations in endometrial surface is a marker of implantation. Estradiol valerate (EV) was used to change the adverse effects of Clomiphene Citrate (CC) on the endometrium. Objective: The goal was to assess whether there is a significant difference in the endometrial pinopods concentrations and other parameters after adding EV and progesterone to higher doses of CC. Materials and Methods: In this prospective randomized clinical trial, a total of 30 women who did not respond to 100 mg of CC from February 2016 to June 2016 were evaluated. They were divided into three groups: group I) received 150 mg of CC alone, group II) CC with EV, and group III) CC plus progesterone. On day 21 of the menstrual cycle, endometrial biopsy, a blood sampling, and a scanning by electron microscopy were performed. Results: On day 21 of the menstrual cycle, there was no significant difference in the pinopods concentrations (p = 0.641) and serum estrogen levels (p = 0.276) between groups. However, the Serum progesterone levels in group I was higher than the other two groups (p = 0.007) in the same day. Conclusion: Since the addition of EV and progesterone to higher dosages of CC did not change the pinopods concentration and serum estrogen levels on day 21 of the menstrual cycle, and the serum progesterone levels was higher in CC alone group (i.e. group I) compared to other groups, it can be concluded that the anti-estrogenic effects of CC just appear on the endometrium and not on the plasma levels. Key words: Ovulation induction, Clomiphene, Estradiol, Progesterone, Electron microscopy, Endometrium