Comparison of Two Different Dosing Regimens of Vaginal Misoprostol for Cervical Priming Among Women Undergoing Vaginoscopic Hysteroscopy: A Non-inferiority Randomized Controlled Trial.

Abstract

Background: Hysteroscopy is considered the gold standard for diagnosing intrauterine pathology. Pain and discomfort experienced during the procedure may be reduced using vaginoscopic methods and cervical priming. Misoprostol is the agent of choice for cervical priming for transcervical procedures. However, the optimal dose, route and time of administration are debatable. Lower doses may reduce the side effects without reducing the effectiveness of facilitating cervical entry.

Objectives: To compare the efficacy of 100mcg with 200mcg of vaginal Misoprostol on ease of cervical entry among women undergoing vaginoscopic hysteroscopy.

Methods: This randomised controlled non-inferiority trial was conducted, enrolling 120 women who underwent hysteroscopy at a tertiary-level teaching hospital from November 2020 to June 2022. The intervention included two dosages of vaginal misoprostol - 200mcg (Group-A) and 100mcg (Group-B), administered three hours before the procedure. No analgesia or anaesthesia was used in either group. The primary outcomes measured included assessing the ease of cervical entry on a five-point Likert scale. The secondary outcomes included (i) Pain score assessed using a Visual Analogue Scale (VAS) at three-time points, (ii) time taken for cervical entry and completion of the procedure, and (iv) side effects (drug or procedure-related). A test for non-inferiority was conducted using a one-sided Wald test at a significance level of 0.05.

Results: Most cases (77.5%) had "easy or very easy" entry through the cervix, which was similar in both groups (Group A: 81.7%, (95% CI: 71.9-91.5) vs Group B: 73.3%, (95% CI: 62.1-84.5)). The difference between the groups was -8.3%, with one-sided 95% CI: -20.9% to 100%, p=0.063 using the intention to treat approach, marginally above the prespecified boundary of 20%, not confirming the noninferiority of the 100 mcg to 200 mcg dose of misoprostol. The median VAS score at three-time points, the mean entry time, and the total procedure duration were comparable between the two groups. Adverse effects were commonly noted among those receiving 200 mcg compared to 100 mcg misoprostol (13(21.7%) vs 6 (10%), p =0.079).

Conclusion: Regarding cervical priming during vaginoscopic hysteroscopy, using either 100 mcg of Misoprostol or 200 mcg of Misoprostol facilitated easy or very easy entry in most cases, though this study was not able to establish non-inferiority of the lower dose.