Ideal Time of Vaginal Misoprostol Administration in nulliparous women undergoing Office Hysteroscopy: a randomized double blind placebo controlled study

INTRODUCTION

Hysteroscopy had the process of viewing, operating in the endometrial from a transapproach. It had the gold standard procedure for uterine exploration¹.

Hysteroscopy allows direct visualization of the uterine, the endometrium, the canal. The examination might be practiced on an out-case basis, without anesthesia, using appropriate small-caliber instruments, irrigation with physiological saline².

Hysteroscopy had associated with minimal case discomfort, excellent visualization, very low complication, failure rates^3,4.

Taking into account that an efficient method to facilitate an easier uncomplicated entry during the hysteroscopic procedure could substantially minimize the risk of complications, several modalities for ripening prior had adopted⁵.

priming prior to diagnostic hysteroscopy softens the cervix, lessens the force needed for dilation, thereby potentially reducing the probability of procedural complication such as uterine perforation, laceration, failure to dilate, creation of a false track that could occur during entry⁶.

The synthetic analogue of prostaglandin E1, misoprostol, had the agent used most often for preparation prior ⁷.

It could be given orally, vaginally, sublingually, buccally, or rectally^8-10.

The route appears to be superior to the oral route¹¹.

Based on the available evidence on the use of misoprostol prior, the optimal time of misoprostol administration prior to the hysteroscopy. So we tried in our study to test for appropriate time by comparing between 3hours, 6hours, 12hours administration prior.

PATIENTS AND METHODS

Type of the study: Randomized double-blind placebo-controlled study.

Double blinded means that: neither participants nor operator know which intervention would be received.

Setting of the study: This study had conducted at El Sahel Teaching Hospital from October 2017 till October 2018.

Protocol approval by ethics committee: Before the beginning of the study, in accordance with the local regulation followed, the protocol, all corresponding documents had declared for Ethical, Research approval by the Council of Obstetrics, Gynecology Department, Al-Azhar University.

Sample size calculation: We had planning a study of a continuous response variable from 3equal study gatherings. We added 10% to each gathering to compensate for the dropped cases, so each gathering would be 66cases.

Case selection: One hundred ninety eight nulliparous cases had subjected with the following

Inclusion criteria: Age-childbearing period or postmenopause from 20-50years, Nulliparous cases, Indication for hysteroscopy; Infertile cases either primary or secondary infertility, Cases with history of recurrent miscarriage, Cases with history of abnormal uterine bleeding.

Exclusion criteria: Contraindications:Any uterine abnormality that would obviate passage of a catheter, marked stenosis, recent pelvic disease, uterine bleeding. Contraindications to prostaglandins.

After obtaining informed consent, all included cases had subjected to: thorough history taking, Full examination, Pelvic ultrasound, Laboratory investigations: Serum cases test: to exclude cases.

Interventions: The cases had divided into 3gatherings randomly, each gathering contained 66cases. Method of randomization: computerized randomization(covariate adaptive randomization) randomization.

First gathering (long interval misoprostol gathering): Two misoprostol (400micrograms) had given vaginally 12hours prior. Two placebo had given vaginally 6hours, 3hours prior.

Second gathering(intermediate interval misoprostol gathering):  Two placebo had given vaginally 12hours prior. Two misoprostol had given vaginally 6hours prior. Two placebo had given vaginally 3hours prior.

Third gathering(short interval misoprostol gathering):Two placebo had given vaginally 12hours, 6hours prior. Two misoprostol had given vaginally 3hours prior. The placebo had folic acid 500mcg. The hysteroscopy had scheduled in the proliferative menstrual phase from the 5^th day to the 14^th day of the cycle. Informed written consent had signed by all the cases.

Technique: Case preparation had one of the most important aspects for successful hysteroscopy, thus the procedure had described to every case prior to the examination, each step had explained during the procedure so the cases had an active participants, this helped them to understand the experience, relieved anxiety. The hysteroscope used in this study had that of Karl Storz,(Germany 1996). It had a rigid continuous flow panoramic hysteroscopy 25cm in length, 4mm in diameter with an outer sheath of 5.5mm, a 30degree fibro optic lens. The light source used in this study had a metal halide automatic light source from Circon Acmi G71A/Germany with 150watt lamp. A fibro optic cable had connected to the light source. The technique used to provide constant uterine distention had by 3L volume saline bags to dual infusion tubing which had suspended one meter above the case level. Each bag had then wrapped in a pressure infusion cuff similar to that used in BP to reach a pressure of 150-200mmHg. The tubing had connected to the hysteroscope. It had helpful, more comfortable for the operator to sit on a low chair, to elevate the foot of the examination table to perform the procedure. After the case had installed in the lithotomy position then the gynecologist used sterile gloves, checking the flow of the distention medium, the hysteroscope had introduced under direct vision into the cervix without the use of anesthesia or analgesia, using a specific technique. No dilatation had done.

Table 1: Technique of a traumatic diagnostic hysteroscopy:

The outcomes that had measured: The level of pelvic had rated according to a 10-point visual analogue scale(VAS). The VAS had applied immediately after the procedure ended. Ease of entry of the cervix recorded on a 5-point Likert scale(Likert 1932): very difficult=1, difficult=2, fair=3, easy=4, very easy=5. Baseline width at the beginning of the procedure had assessed by the largest number of Hegar dilator that could be inserted into the cervix without resistance. The bleeding during the procedures had assessed whether if there had no or moderate or severe bleeding. The time from introduction through the external os, the visualization of the uterine had recorded in minutes. Any complications or side critical to perform hysteroscopy.

Statistical analysis: Data had then transferred to the IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp.

RESULTS

Table 2: Comparison between gatherings as regard demographic data.

Table 3: Comparison between gatherings as regard outcome measures: Data had expressed as number±standard deviation, percent(%)

F- ANOVA test;

Table 4: Comparison between gatherings as regard side effect of misoprostol.

Data had expressed as number, percent(%)