Office hysteroscopy and pain control, a multicenter comparison by scope size and introducing a novel “hysteroscopic anesthesia” technique

Background: Office hysteroscopy is an affordable and popular approach in gynecology, offering high quality and inexpensive care. It has been made possible by miniaturization of instruments along with a range of technical variations and innovations which have made the procedure tolerable in outpatient care units. Pain is still a problem and has not to date been adequately managed. Objectives: Our main objective is to compare two centers where hysteroscopy is performed without general anesthesia or sedation in an office setting. In Lisbon a novel local anesthetic technique has been introduced when patients complained of pain. These centres have slightly different protocols namely in assessing pain and evaluating score results. Materials and methods: This was a prospective observation multicenter study, comparing pain in office hysteroscopy with three groups: mini-hysteroscopy (3 mm scope), conventional (5 mm) hysteroscopy without anesthesia and (5 mm) hysteroscopy with “hysteroscopic anesthesia”. Data collection and analysis: We analyzed data from two centers involving one hundred and eighty one participants who completed the intervention. Pain was evaluated using a 10 cm visual analogue scale and a numeric rating scale. Analysis included the Kruskal-Wallis and Mann-Whitney Tests for the three groups and the Wilcoxon Signed Ranks Test for comparing repeated measurements. Results were discussed at 5% significance level. Main results: Analysis revealed a significant reduction pain score (p value <0.001) in the group where “hysteroscopic anesthesia” was used. Conclusions: Pain scores in office hysteroscopy can be lowered with “hysteroscopic anesthesia”. Correspondence to: Office hysteroscopy and pain control, a multicenter comparison by scope size and introducing a novel “hysteroscopic anesthesia” technique had the following contribution to article; E-mail: antoniosantospaulo@sapo.pt


Introduction
Hysteroscopy allows direct visualization of unsuspected pathology, histological sampling, cancer staging and surgery. Office hysteroscopy (OH) is a high quality approach in gynecology.
Reduction in pain has led to performing examination and operations without anesthesia [1,2] and is associated to very low cost of gynecological care and justifies its generalized use [3]. Pain perception may vary among population subgroups [4,5].
The vaginoscopic no-touch approach [3,[6][7][8][9] improved tolerance as data in a 2010 systematic review by Cooper et al. [9] demonstrated. Use of mini-hysteroscopes avoid cervical dilation and previous ripening with misoprostol facilitates operations [1,10]. Both rigid and flexible mini-histeroscopes reduce pain and may be adequate for examination [11] but rigid scopes seem to have superior optical properties [12]. CO 2 and normal saline are adequate for diagnostic outpatient hysteroscopy [13] as Cooper's 2010 systematic review on effect on pain concluded, but saline is more convenient if surgery is to be done [14].
Various interventions [15,16], medications [17,18], para-cervical block cocktails and conscious sedation have been suggested to control pain with mixed results [10,[19][20][21][22][23]. Two systematic review in 2010, one by Ahmad et al. [24] and another by Cooper et al. [21] have however suggested a reduction of pain with local anesthetic, but "clinical significance of results is limited as the reduction in mean pain score is small" [24].

Objectives
Our main objectives are: to determine if difference in scope diameters and if the use of a novel technic of local anesthesia shows statistical difference in pain scores during office hysteroscopy.

Materials and methods
From February to September 2015 one hundred and eighteen patients scheduled for OH at Centro Hospitalar Tondela-Viseu, Portugal and eighty one from Hospital das Forças Armadas -Polo de Lisboa, Portugal were enrolled in this prospective observational study. Of theses one hundred and four from Viseu and eighty one from Lisbon accepted to participate. Four cases from Viseu had incomplete data and were excluded. A total of one hundred and eighty one cases were included and analyzed ( Figure 1). The study was approved by the Institutional Review Boards and conducted in compliance with the protocol, the Declaration of Helsinki, the Good Epidemiological Practice, and all applicable laws and regulations.
Hysteroscopy was performed using the vaginal no touch approach with a 3.5 mm outer sheet device (2.9 mm optics either from Fiegert Endotech ® Tuttlingen, Germany or Karl Storz Hopkins ® Tuttlingen, Germany) with a fore oblique 30º mini-hysteroscopy at Centro Hospitalar Tondela-Viseu and a 5 mm outer sheet device at Hospital das Forças Armadas Lisbon. An Ackermann ® xenon light source with a constant flow Richard Wolf ® hystero pump was used in Viseu and Endoflow ® by Socomed in Lisbon; saline at eighty to one hundred mm of mercury was standard in procedures.
Protocol was slightly different in each institution: no anesthesia was provided in Viseu and in Lisbon, when women complained, a new endoscopic local anesthetic technique by means of 35 cm Cystoscopy Injection Needle named by Vinagre et al. [25] "hysteroscopic anesthesia" was used.
While performing vaginoscopy the surgeon assessed patient's tolerance. If pain made the procedure uncomfortable, 1% lidocaine was injected directly through the endoscope in the endo-cervical region at the site where the women felt pain with the cystoscopic needle in small amounts (commonly near the internal os). Further along the hysteroscopy, if discomfort arose from distension of the uterus, the operator would retrieve the instrument into the vagina and the uterosacral ligaments were also injected with lidocaine. In case of see-and-treat septoplasty, polypectomy or myomectomy anesthetic was injected at the base of the mass to be excised, allowing for pain control during operation. Total amount of anesthetic used was about five centiliters and did not in any case exceed 10 cc for safety reasons.
Pain scoring was evaluated using a 10 cm Visual Analogue Scale (VAS) in Viseu and a ten points Numeric Rating Scale (NRS) in Lisbon.
Three groups were so compared: 3.5 mm mini-hysteroscopy, 5 mm hysteroscopy without anesthesia and 5 mm hysteroscopy with anesthesia. Patient's mean age tends to be higher in Lisbon's 5 mm series and even higher in the 5 mm group with anesthesia. Other variables don´t seem significantly different between groups (Table 1).
Statistical analysis was performed with SPSS 22.0 IBM for windows and in a statistical hypothesis test with a p value <0.05 the effect was considered significant so results are reported with 95% confidence level.

Results
We performed a Kruskal-Wallis test with the three groups and results showed there was at least one group of the three analyzed where pain score was significantly different. A plot comparing pain score in the groups can been seen in Figure 2. There seems to be a trend for higher pain score with menopausal state (Figure 3). As to other variables women's body mass index and weight was similar between the three groups ( Figure 4) but mean age is higher and statistically   Comparing groups two by two, the difference between pain score was demonstrated between 5 mm hysteroscopy and 5mm hysteroscopy with anesthesia groups. The Mann-Whitney test with Bonferroni correction ( Table 2) showed significant differences between the three groups (p value=0.012). Comparing repeated measurements using the Wilcoxon Signed Ranks Test (5 mm group before anesthesia and 5 mm group after anesthesia) showed a significant reduction in pain as seen in Table 4 (p valeu <0.001).

Discussion
Our data found a trend for lower pain reporting with 3.5 mm versus 5 mm scopes (Table 3) as would be expected in line with a recent meta-analysis and review [27].
The study also suggests hysteroscopy with 5 mm scopes and "hysteroscopic anesthesia" is less painful than hysteroscopy without anesthesia in an office setting. As seen, mean pain scores before anesthesia including all 5 mm hysteroscopies are higher in the group which was subsequently treated with anesthesia (NRS around six) as compared to patients where no anesthesia was used (NRS around four) ( Figure 5). The sub-group where anesthesia was used tends to be older (Figure 4) so, most likely the higher pain report is related to menopausal tissue atrophy. Significantly this group of women showed a dramatic decrease in discomfort after lidocaine ( Figure 6).
Introducing "hysteroscopic anesthesia" to women in outpatient OH units offers relief from distress, having a statistically significant effect on pain score. This result seems even more noteworthy as both 5 mm hysteroscopy groups came from the same institution, was seen by the same personnel and protocol pain assessment used the same tool, namely NRS.   This anesthesia technique is inexpensive (1% lidocaine without epinephrine), easy to learn and acts quickly, providing pain relief and comfort to gynecological outpatients. The 35 cm long Cystoscopy Injection Needle is marketed and easily acquirable; pricing in Portugal is around twenty euros per unit.

Main findings
"Hysteroscopic anesthesia" is very effective in lowering pain at hysteroscopy. It is also cheap, simple, very useful for improving tolerance in outpatient hysteroscopy examinations and surgery.

Strengths and limitations
Results showed pain in hysteroscopy can be controlled with this innovative local anesthesia technique. Authors believe that evidence is convincing, accurate, reproducible and can be extrapolated to general population.
Nevertheless authors suggest well-designed randomized controlled trials will most certainly give better evidence of efficacy of this novel technical improvement in hysteroscopy.

Interpretation (findings in light of other evidence)
Pain scores can be reduced by "hysteroscopic anesthesia" and make this procedure tolerable for outpatients.

Conclusions
From evidence gathered we must conclude that "hysteroscopic anesthesia" is very promising both for diagnostic and see and treat approach in outpatients'office hysteroscopy.
It may be especially important in older women who were more likely to complain of discomfort. Pain Score Statistics ab † a. type of procedure = 3.5 mm ‡ b.= 5 mm Table 3. Mean pain score and quartiles for 3.5 mm and 5 mm hysteroscopy.

Test Statistics a
Pain score post anesthesia -Pain Score  Table 4. Before and after hysteroscopic anesthesia.