Comparison of Vaginal Estradiol and Oral Guaifenesin Interventions in Patients Undergoing Ovulation Induction With Clomiphene Citrate: A Randomized Controlled Trial

Aim: To evaluate the effects of guaifenesin (G) and/or vaginal estradiol (E2) on cervical factors, endometrial thickness, and pregnancy outcomes among patients with anovulatory or unexplained infertility who received ovulation induction with clomiphene citrate (CC). Methods: This randomized controlled trial was conducted from January 2022 to July 2022 and included women diagnosed with primary or secondary infertility who were undergoing ovulation induction with CC. Three random groups were formed according to intervention: G only, vaginal E2 only, and G + vaginal E2. Endometrial wall thickness, Spinnbarkeit test, cervical mucus assessment score, treatment outcomes (canceled cycle, poor response, clinical pregnancy, and miscarriage), and factors associated with clinical pregnancy were examined. Results: Thirty women were included in each group. Age distributions were similar (p = 0.894). The E2 levels of the G + E2 group on the second day were significantly higher than the G group (p = 0.035). The endometrial thickness of the G group was significantly greater compared to the G + E2 and E2 groups on the hCG day (p < 0.001). Multivariable logistic regression showed that younger age (p = 0.002), shorter duration of unprotected sexual intercourse (p = 0.048), high Spinnbarkeit (p = 0.001), and the presence of convenient cervical mucus (p = 0.034) were independently associated with clinical pregnancy. Conclusion: The differing effects of G and vaginal E2 on cervical mucus changes, endometrial thickness, and pregnancy outcomes in CC cycles are unclear. However, efforts to improve cervical mucus characteristics in CC cycles may lead to better pregnancy outcomes. Trial Registration: ClinicalTrials.gov identifier: NCT07398924.