Traditional Clomiphene Citrate with Phytoestrogen Versus Traditional Clomiphene Citrate Versus Stair Step Protocol in Patients with Polycystic Ovaries: A Randomized Clinical Trial

Introduction: Polycystic ovary syndrome (PCOS) ranks among the most prevalent endocrine disease affecting women of reproductive age. Multiple therapeutic approaches have been suggested for the management of PCOS. Anovulation is responsible for approximately 40% of female infertility cases, and a significant portion of individuals dealing with infertility are also diagnosed with polycystic ovary syndrome.
Patients and methods: This was a prospective multi-center randomized clinical trial conducted from April 2022 till March 2023 involving one hundred fifty female patients with PCOS categorized into three categories, category I (traditional protocol) involved 50 subjects who received traditional clomiphene citrate (CC) 100 mg for 5 days, and category II stair-step protocol (SS) involved 50 subjects who received clomiphene citrate 50 mg for 5 days followed by 100 mg for another 5 days and phytoestrogen given for the whole 10 days. In addition, group III clomiphene + phytoestrogen (CCP) included 50 patients who received 100 mg of clomiphene citrate for 5 days and phytoestrogen for 10 days. Results: There was significantly thinner endometrium in the CC group as compared to the other two groups; the greatest endometrial thickness was in the SS protocol group, followed by the CCP group; a higher pregnancy rate and ovulation rate were in the SS protocol group, followed by the CCP group; and the lowest pregnancy rate and ovulation rate were in the CC group.
Conclusions: Clomiphene, when used as an SS regimen, improves pregnancy rates without any side effects compared to traditional regimens. Adding phytoestrogens to CC is associated with improving endometrial thickness and pregnancy rates.