A randomised trial comparing the H Pipelle with the standard Pipelle for endometrial sampling at no-touch (vaginoscopic) hysteroscopy

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1 DOI: /j x Gynaecological surgery A randomised trial comparing the H Pipelle with the standard Pipelle for endometrial sampling at no-touch (vaginoscopic) hysteroscopy S Madari, N Al-Shabibi, P Papalampros, A Papadimitriou, A Magos University Department of Obstetrics and Gynaecology, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK Correspondence: Dr A Magos, University Department of Obstetrics and Gynaecology, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK. a.magos@medsch.ucl.ac.uk Accepted 16 September Objectives To evaluate the effectiveness and tolerance of H Pipelle compared with the standard Pipelle as an endometrial biopsy device at outpatient no-touch hysteroscopy. Design A prospective randomised trial carried out in an outpatient diagnostic hysteroscopy clinic. Setting A large undergraduate teaching hospital. Population Sixty women investigated for abnormal menstruation in an outpatient diagnostic hysteroscopy clinic. Methods Prospective randomised trial comparing the H Pipelle with the standard Pipelle de Cornier. Main outcome measures Adequacy of the biopsy specimens and women s experience. Results Ninety-three percent (H Pipelle) and 87% (Pipelle) of the biopsy specimens were judged to be adequate for histological diagnosis (P > 0.05). However, obtaining endometrial sampling with the H Pipelle was significantly quicker (median times: 39 seconds [H Pipelle] and 102 seconds [Pipelle], P < ) and less painful (median visual analogue scale score: 1 [H Pipelle] and 5 [Pipelle], P = 0.011). Conclusions The H Pipelle not only makes it possible to perform hysteroscopy and endometrial biopsy with minimal instrumentation but is also associated with a shorter biopsy time and less discomfort than the standard Pipelle without any loss of biopsy adequacy. Keywords Endometrial biopsy, H Pipelle, no-touch hysteroscopy, Pipelle de Cornier, vaginoscopic hysteroscopy. Please cite this paper as: Madari S, Al-Shabibi N, Papalampros P, Papadimitriou A, Magos A. A randomised trial comparing the H Pipelle with the standard Pipelle for endometrial sampling at no-touch (vaginoscopic) hysteroscopy. BJOG 2009;116: Introduction Abnormal uterine bleeding is one of the most common presenting complaints encountered by gynaecologists. The majority of women with menorrhagia, intermenstrual bleeding, postcoital bleeding or postmenopausal bleeding ultimately undergo diagnostic hysteroscopy with endometrial sampling as part of their assessment, particularly if symptoms persist or pelvic imaging shows a uterine abnormality. 1 Hysteroscopy is generally acknowledged to be the gold standard technique for investigating the uterine cavity for endometrial abnormalities and focal lesions and is often performed as an office/outpatient procedure. 2 Traditionally, diagnostic hysteroscopy involves the use of a speculum and a tenaculum to visualise and hold the cervix while the hysteroscope is inserted into the uterine cavity. In recent years, a new approach to diagnostic hysteroscopy has been developed. This vaginoscopic or no-touch hysteroscopy is performed without instrumenting the vagina, the cervix being identified visually by hydrodistension of vagina. Several studies have shown that this approach is effective and reduces women s discomfort. 3 5 Until a few years ago, to obtain an endometrial sample at no-touch hysteroscopy, either an operating hysteroscope had to be used to allow the insertion of biopsy forceps or the diagnostic hysteroscope had to be removed and a speculum and a tenaculum inserted to obtain a biopsy with devices such as the Pipelle, Vabra aspirator or Vacurette. 6,7 The first approach would tend to make the hysteroscopy more uncomfortable because of the need to use a relatively wider instrument, while the second technique negated the benefits of the no-touch approach with the result that endometrial sampling often became the most uncomfortable part of the investigation ª 2008 The Authors Journal compilation ª RCOG 2008 BJOG An International Journal of Obstetrics and Gynaecology

2 H Pipelle compared with the standard Pipelle We developed a new device, the H Pipelle (Laboratoire C.C.D, Paris, France), with the specific aim of allowing an endometrial biopsy to be obtained at no-touch hysteroscopy using a narrow-bore, single-channel diagnostic hysteroscope without the need to insert additional instruments into the vagina. 9 The H Pipelle is based on the original Pipelle endometrial sampler (Laboratoire C.C.D) but has been lengthened from 23 to 50 cm so that it can be passed through the diagnostic sheath of a hysteroscope once the optic has been removed (Figure 1). It has the same diameter of 3.1 mm. In this prospective randomised study, we set out to compare the use of the H Pipelle and the original Pipelle at no-touch office diagnostic hysteroscopy in terms of biopsy quality and women experience. Materials and methods Women referred to our outpatient hysteroscopy clinic with abnormal uterine bleeding were invited to take part in the study. Women who were known found to have submucous fibroids, endometrial polyps or atrophic endometrium on previous ultrasound examination or were found with these abnormalities at hysteroscopy were excluded from the study as were those referred with intrauterine adhesions as endometrial biopsies are often inadequate in such cases. 6 After informed consent had been obtained, suitable women were randomised to have their endometrial biopsy taken using either the long H Pipelle or the standard short Pipelle using a speculum and a tenaculum to visualise and hold the cervix. A computer-generated list was used for randomisation. The study was approved by the locally organised Ethics Committee (no. 6056). All women underwent no-touch hysteroscopy with rigid 2.9-, 3- or 4.0-mm hysteroscopes depending on availability (Karl Storz, Tuttlingen, Germany) and normal saline as the distention medium as described previously. 10 Intracervical local anaesthetic ( ml Lignospan Special containing lignocaine hydrochloride 2% with adrenaline 1:80 000) was only given if cervical dilatation became necessary because of cervical stenosis or if the hysteroscopy proved too uncomfortable. All procedures were monitored on a high-resolution screen visible to the women. Following the hysteroscopy in the group randomised to biopsy with the H Pipelle, the optic was withdrawn from the diagnostic sheath while still in the uterine cavity, the H Pipelle was passed into the uterus through the sheath, the sheath was slid outside the vagina, and an endometrial biopsy was then taken in the usual fashion, a technique we call notouch biopsy at no-touch hysteroscopy (Figures 2 and 3). In case of the group randomised to endometrial biopsy with the standard Pipelle, the hysteroscope was removed completely and sampling was performed after visualising the cervix with a speculum and a tenaculum. All endometrial biopsies were sent for histopathological assessment, and to avoid any bias, the pathologist who examined the samples was blinded as to the sampler used. Apart from a histological diagnosis, the pathologist was asked to report the quality of the sample as adequate or inadequate for microscopic evaluation. The time taken to obtain an endometrial sample was noted in all cases, defined as the interval between completion of the diagnostic hysteroscopy and removal of the biopsy device from the uterine cavity. Prehysteroscopy participant anxiety (0 = no anxiety to 10 = worst possible anxiety) and discomfort (0 = no pain to 10 = worst possible pain) experienced during hysteroscopy and during biopsy in those women who did not require local anaesthesia were assessed using 10-cm visual analogue scales (VAS). Based on the published literature, we anticipated that we would obtain an adequate endometrial specimen for histological specimen with the standard Pipelle in 60% of women. 6 We predicted that this figure would increase to 90% with the longer H Pipelle and therefore planned to randomise 60 women to give the study a type I error of less than 5% and type II error of 20% at P < Figure 1. The H Pipelle and the standard Pipelle with a diagnostic hysteroscope. Figure 2. In vitro model showing H Pipelle introduced into the uterine cavity through diagnostic sheath of the hysteroscope once the optic has been removed. ª 2008 The Authors Journal compilation ª RCOG 2008 BJOG An International Journal of Obstetrics and Gynaecology 33

3 Madari et al. Figure 3. In vitro model showing H Pipelle in position for endometrial sampling after withdrawal of the diagnostic hysteroscope sheath from the uterine cavity. All data were entered on an Excel spreadsheet (Microsoft, 2003, USA), and statistical analysis was performed using GraphPad Prism version 4.00 for Windows (GraphPad Software, San Diego, CA, USA). We used nonparametric tests (Mann Whitney U test) to compare outcome in the two groups. Results Of 137 women seen in the hysteroscopy clinic during the period August 2006 to May 2007, 77 did not fulfil the study criteria and were therefore excluded, leaving 60 women who were suitable and agreed to participate; 30 were randomised to the H Pipelle arm and 30 to the standard Pipelle group once the hysteroscopy had been carried out (Figure 4). The characteristics of the study group are summarised in the Table 1. There were no significant differences between the two groups with regard to age, parity, menopausal status and indication for hysteroscopy. There were no statistically significant differences in the diameter of the optics used in the two groups (H Pipelle: median optic diameter 2.9; Pipelle: median optic diameter 3.0; P < 0.05). Two women in the H Pipelle group and five in the group randomised to Pipelle biopsy required cervical dilatation for hysteroscopy because of cervical stenosis, and 6 and 10 women were given cervical local anaesthesia (pain during endometrial sampling was not assessed in these women). All biopsies were, however, carried out by the intended method. Preprocedural anxiety scores were comparable between the two groups (H Pipelle: median VAS score 6, interquartile range ; Pipelle: median VAS score 5, interquartile range Assessed for eligibility (n = 137) Enrollment Excluded Not Meeting inclusion criteria (n = 77) Randomized (n = 60) Allocated to standard Pipelle Received allocated intervention Allocated to H Pipelle Received allocated intervention Analysed Analysed Figure 4. Consort flow chart. 34 ª 2008 The Authors Journal compilation ª RCOG 2008 BJOG An International Journal of Obstetrics and Gynaecology

4 H Pipelle compared with the standard Pipelle Table 1. Women s characteristics H Pipelle Standard Pipelle No. women Age (years), mean (SD) 45.1 (6) 46.1 (5.7) Parity Nulliparous 9 9 Parous Menopausal status Premenopausal Perimenopausal 9 10 Postmenopausal 1 1 Primary indication for investigation Heavy bleeding Irregular bleeding 3 4 Intermenstrual bleeding 4 2 Postmenopausal bleeding 1 1 Other indications ; P = 0.65), as were pain scores during no-touch hysteroscopy (H Pipelle group: median VAS score 3, interquartile range 2 5; Pipelle group: median VAS score 5, interquartile range ; P = 0.211). There was no statistical difference in the adequacy of the endometrial samples between the two groups (H Pipelle: 28 of 30 [93%] judged adequate; Pipelle: 26 of 30 [87%] judged adequate; P > 0.05). All the adequate samples were benign histologically (H Pipelle: 17 secretory endometrium, 8 proliferative, 2 menstrual and 1 endometritis; Pipelle: 13 secretory endometrium, 12 proliferative and 1 decidual). Conversely, the time taken to obtain an endometrial biopsy after completion of the hysteroscopy was significantly faster with H Pipelle (H Pipelle: median time 39 seconds, interquartile range 25 63; Pipelle: median time 102 seconds, interquartile range ; P < ) (Figure 5). Similarly, biopsy with the H Pipelle was significantly less painful (H Pipelle: median VAS score 1, interquartile range ; Pipelle: median VAS score 5, interquartile range ; P = 0.011) (Figure 6). These differences were not influenced by menopausal status or parity. Twelve women requested oral analgesia after their hysteroscopy and biopsy, five in the H Pipelle group and seven in the Pipelle group (P > 0.05). Figure 5. Time taken to biopsy endometrium after hysteroscopy. that significantly fewer samples would be inadequate with the H Pipelle, but despite this, the H Pipelle seems preferable to the Pipelle at no-touch hysteroscopy because of the other advantages found. One reason why we could not confirm any advantage of the H Pipelle in terms of biopsy adequacy was because of the unexpectedly high rate of adequate biopsies reported after the standard Pipelle in this study. We based our power calculation on one of the few studies looking at the use of the Pipelle Discussion Our study has shown that the H Pipelle is no better than the standard Pipelle in obtaining adequate endometrial tissue for histological diagnosis following diagnostic hysteroscopy, but the biopsy time is significantly shorter by an average of about 1 minute and the associated women s discomfort significantly less. We therefore failed to prove our hypothesis Figure 6. VAS pain scores for endometrial biopsy. ª 2008 The Authors Journal compilation ª RCOG 2008 BJOG An International Journal of Obstetrics and Gynaecology 35

5 Madari et al. device after hysteroscopy, which reported that 61% of samples were judged to be adequate for histological diagnosis. 6 However, in our study, the pathologist was able to make a diagnosis in a much higher proportion (87% of women), with the result that our study became underpowered; based on our results that 93% of biopsies are adequate with the H Pipelle compared with 87% with the Pipelle, we would have had to recruit 800 women to prove that the new device was indeed superior. The figure of 87% adequate biopsies with the Pipelle even exceeds what has been reported by some when endometrial sampling is performed as the primary procedure without previous hysteroscopy. For instance, a recently published comparative trial reported adequate biopsies in 73.3% of women investigated with the Pipelle. 11 Conversely, in an earlier comparative study between the Pipelle and the Vabra aspirator, 88% of the Pipelle samples were adequate for histological diagnosis. 12 Logically, a worse diagnostic rate would be expected after hysteroscopy when the uterine cavity has been distended with liquid as the biopsy device would be expected to withdraw liquid as well as endometrial tissue, and this indeed is consistent with the results reported by Agostini et al. 6 One of the theoretical advantages of the H Pipelle in this situation is that because of its longer length, there is more capacity for aspirating endometrial tissue together with any residual uterine irrigant. Indeed, it was our impression before this study that in many women following hysteroscopy, the aspiration with the standard Pipelle had to be repeated two to three times as little tissue was visible with the first biopsy. While our study could only demonstrate a relatively small advantage of the H Pipelle in terms of biopsy adequacy, we did clearly show that a no-touch endometrial biopsy with this device following a no-touch hysteroscopy is both quicker and less painful than when a conventional technique is used involving speculums, tenaculums and the standard Pipelle. A saving of 1 minute on average for taking the biopsy may not seem much but could represent a 10 20% time saving for the whole procedure in an office or an outpatient setting. With regard to pain, the Pipelle has already been found to be associated with less discomfort than other devices, and we can now say that the H Pipelle is even more patientfriendly, presumably because of the lack of need to instrument the vagina. We had strict criteria for inclusion into this study and did not recruit women in whom we expected high incidence of inadequate sampling (e.g. atrophic endometrium, intrauterine fibroids or polyps), as found by Agostini et al. 6 We did this to optimise tissue sampling and reduce the number of inadequate samples. This exclusion does not mean that the H Pipelle should not be used in these clinical situations as based on our results, it would seem likely that the biopsy would be less uncomfortable and quicker than with the standard Pipelle. We are currently evaluating this. It is also likely that there would be a slight advantage to the H Pipelle in terms of obtaining tissue for analysis. Conclusions Although hysteroscopy is generally promoted as an office or an outpatient investigation, a significant number of procedures are still performed under general anaesthesia because of a perception that the investigation is painful. By minimising vaginal instrumentation, a combination of hysteroscopy using a vaginoscopic approach and sampling with the H Pipelle simplifies the procedure, reduces the procedure time and lessens discomfort. This method of endometrial sampling with H Pipelle should make outpatient hysteroscopy acceptable to more women and their gynaecologists. 16 Funding The study received no external funding. Disclosure of interests We confirm that there are no conflicts of interests, including financial, for any of the authors. Contribution to authorship Author Acknowledgements The authors thank Sister Bola Sota and Staff Nurse Charlotte Miller for facilitating the study in the outpatient hysteroscopy clinic. j References S.M. N.A.-S. P.P. A.P. A.M. Concept and design of the study 1 Data collection Analysis and interpretation of data Drafting of manuscript 1 1 Approval of final manuscript Study supervision 1 1 Nagele F, O Connor H, Davies A, Badaway A, Mohammed H, Magos A Outpatient hysteroscopies. 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