DOI: 10.1111/j.1744-4667.2011.00091.x 2012;14:33–38 Review The Obstetrician & Gynaecologist http://onlinetog.org

The management of endometrial polyps in the 21st century

∗ John Jude Annan MRCOG,a Joseph Aquilina MD FRCOG,b Elizabeth Ball MD PhD MRCOGc, aSpecialist Registrar, Barts and The London NHS Trust, Whitechapel Road, London E1 1BB, UK bConsultant and Honorary Senior Lecturer, Barts and The London NHS Trust, London, UK cConsultant and Honorary Senior Lecturer, Barts and The London NHS Trust, London, UK ∗Correspondence: Elizabeth Ball. Email: [email protected]

r Key content To be able to compare the performance of diagnostic modalities. r r Hysteroscopic endometrial removal appears to be superior to To understand the role of outpatient vaginoscopy and the current practice of blind avulsion. . r Outpatient treatment is safe, cost effective and well tolerated, even in older or nulliparous women. Ethical issues r r New technologies facilitate office hysteroscopy. Given the cost effectiveness and acceptability of office ambulatory r Benign endometrial polyps can regress and rarely progress to diagnostic and interventional hysteroscopy, is it ethical not to offer malignancy. such a service?

Learning objectives r Keywords cost effectiveness / / malignancy / outpatient To learn how to diagnose and treat endometrial polyps in pre and hysteroscopy / ultrasonography postmenopausal women.

Please cite this paper as: Annan JJ, Aquilina J, Ball E. The management of endometrial polyps in the 21st century. The Obstetrician & Gynaecologist 2012;14:33–38.

Introduction Endometrial polyps are generally asymptomatic and may be an incidental finding during pelvic ultrasonography. However, Endometrial polyps are localised hyperplasic overgrowths they present in approximately one-quarter of symptomatic of endometrial glands and stroma which form projections pre and postmenopausal women.3 Half of the premenopausal from the surface of the . They can be single women may present with menorrhagia;3 other presentations or multiple and range from a few millimetres to several include postmenopausal bleeding, prolapse through the centimetres. cervical ostium, abnormal and breakthrough With the increased use of pelvic ultrasonography as a bleeding during hormonal therapy. basic investigation for gynaecological conditions, incidental endometrial polyps are diagnosed more frequently, which can pose a dilemma for women and for gynaecologists. The Epidemiology and risk factors presence of endometrial polyps in postmenopausal women Endometrial polyps are rare among women under the age can lead to anxiety about malignancy, even though the of 20 years. The incidence rises steadily with increasing malignant potential of endometrial polyps is low. The question age, peaks in the fifth decade of life and gradually declines is whether incidental and asymptomatic endometrial polyps after the . Depending on the population studied, should always be removed and how, and whether there is a 24–41% women with abnormal uterine bleeding and 10% subgroup of women at higher risk of malignancy. of asymptomatic women are diagnosed with endometrial polyps.4, 5 Ten percent of women are found to have endometrial 6 Aetiology and presentation polyps at autopsy. A number of studies report an increased incidence of The aetiology of endometrial polyps is unknown, but their endometrial polyps in women on hormone replacement close relationship with the background endometrium is therapy (HRT)7 and (8–36%), which acts as a demonstrated by the similar way in which they proliferate and selective receptor modulator and agonist on the express apoptosis-regulating proteins during the menstrual endometrium.8 The influence on endometrial polyps seems cycle.1 However, in both pre and postmenopausal women, to be through estrogen, on which endometrial polyps depend. endometrial polyps lose their apoptotic regulation2 and However, endometrial polyp formation appears to be related overexpress estrogen and progesterone receptors, thus avoiding to the type and dosage of the estrogen and progestogen in HRT; the usual control mechanisms. in particular, a progestogen with high anti-estrogenic activity

C 2012 Royal College of Obstetricians and Gynaecologists 33 The management of endometrial polyps in the 21st century may have an important role in preventing the development of Endometrial polyps and fertility endometrial polyps.9 Nappi et al.10 postulated that diabetes, and In the reproductive age group, large or multiple endometrial polyps can contribute to infertility and increase the risk of were independent risk factors for the development 20 of endometrial polyps, but statistical analysis of all the . Perez-Medina´ et al. randomised 215 infertile independent variables (odds ratio [OR] 1.05, 95% confidence women with ultrasonographically diagnosed endometrial interval [CI] 1.02–1.07, P <0.001) showed that only increasing polyps, prior to intrauterine insemination, to hysteroscopic patient age was a significant risk factor and that it acted as a polypectomy or polyp biopsy only. Women had a better chance confounder for all the postulated risk factors. of becoming pregnant after polypectomy (relative risk [RR] When looking for predictors of malignancy or 2.1, 95% CI 1.5–2.9) than after biopsy. In women in whom the 11 only reason for subfertility was endometrial polyps, Stamatellos premalignancy in endometrial polyps, Wang et al. observed 21 that a size of >10 mm (OR 2.93, 95% CI 1.19–7.20), et al. showed that hysteroscopic polypectomy improved the postmenopausal status (OR 4.85, 95% CI 2.09–11.27) and rate of spontaneous conception regardless of size or number of polyps, which may be due to the normalisation of endometrial abnormal uterine bleeding (OR 3.97, 95% CI 1.71–9.18) were 22 all independent risk factors (P<0.05). In addition, vaginal implantation factors. bleeding increased the malignant potential of endometrial polyps by a factor of 10 compared with asymptomatic Diagnostic modalities women, as shown in a study of 922 postmenopausal women.12 Wang et al. also reported that a polyp diameter Endometrial polyps can be diagnosed with ultrasound, saline of >18 mm in asymptomatic women increased the risk of infusion sonogram or hysteroscopy, which is the gold standard. malignancy (OR 6.9, CI 2.2–21.4), which was otherwise Saline infusion sonogram (SIS), which uses a sterile normal very low. Further studies are required to ascertain whether saline solution to distend the endometrial cavity and outline incidental endometrial polyps of <18 mm in asymptomatic polyps, is a highly sensitive, well-tolerated, safe, rapid and 23 postmenopausal women can be safely treated conservatively. minimally invasive diagnostic technique. It is superior to However, there is a higher incidence of concurrent endometrial transvaginal ultrasound scanning (TV USS) when diagnosing hyperplasia with endometrial polyps,13, 14 especially in women endometrial polyps: the likelihood ratios for a positive result on hormone replacement,15 which should also be taken into are 2.7 for TV USS and 15.5 for SIS. The likelihood ratios for 24 account in the management plan. a negative result are 0.46 for TV USS and 0.07 for SIS. Only hysteroscopy, however, allows for concurrent treatment. Malignant endometrial polyps Treatment of endometrial polyps A systematic review of endometrial polyp studies16 pooled data from 46 studies which included 9266 pre- and postmenopausal Although the risk of malignant transformation is low, symptomatic and asymptomatic women with endometrial endometrial polyps should be removed when detected, polyps. Most studies were retrospective and showed large as excision allows for both histological diagnosis and variation due to a heterogeneous case mix regarding patient effective treatment of abnormal uterine bleeding patterns and age and symptoms. The prevalence of atypia and malignancy excessive menstrual loss; in addition, endometrial polyps in was 0.8% and 3.1%, respectively. Hysteroscopic markers for postmenopausal women are more likely to be malignant when malignant endometrial polyps include surface irregularities symptomatic.12 such as necrosis, vascular irregularities and whitish thickened The question arises whether asymptomatic and incidental areas, which are indications for obtaining a histological endometrial polyps should be treated. DeWaay et al.5 observed diagnosis.17 Mittal et al.18 recommend once the natural regression of over half of endometrial polyps <1cm diagnosis of complex atypical hyperplasia or carcinoma in situ in asymptomatic premenopausal women who underwent in endometrial polyps is made, due to their findings that of 29 SIS with a 2.5 year follow-up, whereas larger endometrial women with complex atypical hyperplasia within a polyp, 19 polyps tended to become symptomatic. Similarly, Haimov- were found to have hyperplasia of the non-polyp endometrium Kochman et al.25 reported a small case series of asymptomatic and nine had uterine . Of the eight women women diagnosed with endometrial polyps of 5–8 mm on with adenocarcinoma in situ in the endometrial polyp, three hysteroscopy, which regressed after several months. had myoinvasive adenocarcinoma. In contrast, Scrimin et al.19 In the absence of a randomised trial, it is current report that after resectoscopic polypectomy of focal atypia in practice to remove all endometrial polyps in asymptomatic postmenopausal high-anaesthetic-risk women (n = 16), all the postmenopausal women. Retrospective reports are conflicting: women remained disease-free after 5 years. Larger prospective Domingues et al.26 found no cases of in a subgroup studies are needed to determine the optimal treatment. of postmenopausal women with asymptomatic endometrial

34 C 2012 Royal College of Obstetricians and Gynaecologists Annan et al.

Figure 1. Suggested treatment algorithm for women with endometrial polyps based on current evidence polyps (n = 89), but Lieng et al.27 reported that two out multicentre study funded by the Department of Health: the of 74 women with asymptomatic endometrial polyps had OPT(Outpatient PolypTreatment) Trial (see Websitessection). malignancy/atypical hyperplasia (CI 0.7–10.4). Unfortunately, The aim is to recruit 480 women and to compare the cost a much needed prospective study on conservative endometrial and acceptability of outpatient versus inpatient hysteroscopic polyp treatment in postmenopausal women was abandoned endometrial polyps removal. due to poor recruitment.28 At The Royal London Hospital endometrial polyps are Figure 1 shows a suggested treatment algorithm. routinely resected in the outpatient hysteroscopy unit. Patient discomfort is minimised by using suggestions from Clark et al.35 The procedure is carried out as follows: Hysteroscopic resection r Most endometrial polyps are blindly avulsed or removed by Non-steroidal anti-inflammatories or tramadol are given curettage and the cavity hysteroscopically inspected before orally 1 hour prior to the procedure, which can be carried and after, but not during, avulsion.29 Uterine bleeding often out at any time during the cycle unless the women is bleeding obscures the second look. However, there is good direct r heavily, without the need for routine antibiotic cover. and circumstantial evidence that hysteroscopic resection of With the woman in the lithotomy position and a staff endometrial polyps under vision is safe, simple and superior member providing one-to-one attention, vaginoscopy is to blind techniques: r carried out. A Gynecare VersascopeTM (ETHICONTM Women’s Health r Malignant cells at the base of the polyp can be missed with & Urology UK) hysteroscopy system (Figure 2), consisting 30 of an AlphascopeTM (1.9 mm) and a sheath with a 3.5 mm r blind avulsion. Hysteroscopic resection avoids excessive cervical dilatation, expandable operating channel is inserted into the posterior which is when uterine perforation and creation of a false r vaginal fornix under normal saline irrigation. 31 The is then ‘loaded’ onto the hysteroscope and during r passage usually occur. Not a single recurrence of endometrial polyps was reported gentle withdrawal of the hysteroscope the cervical canal when resection under vision was compared with removal moves into the field of vision. After allowing time for cervical with a grasping forceps (recurrence rate 15%).32 hydrodilatation the scope is gently navigated through the cervical canal with minimal lateral movement and tissue Resectionisfeasibleeveninanoutpatientsettingwithout r contact. general anaesthesia, which has become possible due to small- Once the endometrial polyp is visualised the hysteroscope diameter instruments, which obviate the need for cervical is adjusted by moving the sheath to allow good access to the dilatation. See-and-treat outpatient hysteroscopy is cheaper r endometrial polyp base from the operating channel. than inpatient hysteroscopy under general anaesthesia (£686 In The Royal London Hospital hysteroscopy outpatient and £779, respectively)33 but as acceptable to women and department, most endometrial polyps are resected with with faster recovery.34 Recruitment is under way for a cold scissors down to a thin stalk and then retrieved under

C 2012 Royal College of Obstetricians and Gynaecologists 35 The management of endometrial polyps in the 21st century

Figure 3. Hysteroscopy polyp snare. The loop is placed around the base of the polyp and closed. A current is applied and the endometrial polyp cut at the base. The loop is then used to grip the polyp, which is subsequently removed under vision, together with the hysteroscope. Image courtesy of Cook Medical Inc.

approach to hysteroscopy causes less pain than the traditional approach using a speculum and tenaculum40 but is similarly Figure 2. Gynecare Alphascope hysteroscopy system (reproduced 41 with permission from ETHICONTM Women’s Health & Urology UK), successful in achieving polypectomy. consisting of a 0-degree hysteroscope (bottom) and a single-use Failure of outpatient hysteroscopy is attributable to technical sheath (top), containing in and outflow tubing and an expandable difficulty due to anatomical factors, including cervical stenosis, operating channel inadequate visualisation and patient tolerance.38 It is important to stress that outpatient hysteroscopy is acceptable to most women42 and that, on average, it is considered less painful than vision with a hysteroscopic grasper. Bipolar electrosurgical menstruation.34 resection with bipolar twizzles (Figure 2)36 and polyp snares 37 r (Figure 3) also show good success and low pain scores. Polyps >2 cm require piecemeal removal, a longer operating Conclusion time and multiple instrument passes through the cervix. Endometrial polyps are a common finding in . In those cases we recommend removal under general Their generally low malignant potential increases with anaesthesia, but small-diameter hysteroscopic morcellators endometrial polyp size, symptoms and patient age. These are becoming available for this indication (see Figure 4 factors need to be taken into account when considering and Movie S1, a video of the TRUCLEARTM hysteroscopic treatment options (Figure 1). Incidental small endometrial morcellator in use). polyps in premenopausal women may be amenable to conservative treatment due to their low malignant potential There is good evidence that outpatient hysteroscopy is safe,38 and chances of regression. However, endometrial polyps that feasible and has similar outcomes when compared with lead to infertility, postmenopausal bleeding, menorrhagia and polypectomy under general anaesthesia.39 The vaginoscopic abnormal bleeding patterns and those in postmenopausal

Figure 4. The TRUCLEARTM 5 mm 0-degree hysteroscopic morcellator simultaneously resects and aspirates endometrial polyps and small fibroids. (Reproduced courtesy of Smith & Nephew)

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women warrant hysteroscopic removal under vision, which Palombino K, Castaldi MA, et al. Are diabetes, hypertension, is superior to blind avulsion. Adequate patient selection, and obesity independent risk factors for endometrial polyps? psychological support, a competent operator and a setting that J Minim Invasive Gynecol 2009;16:157–62 [http://dx.doi.org/ 10.1016/j.jmig.2008.11.004]. creates a private, caring and calm environment are prerequisites 11 Wang J, Zhao J, Lin J. Opportunities and risk factors for for carrying out this procedure in the outpatient setting. Future premalignant and malignant transformation of endometrial polyps: studies are required to determine the role of skin disinfection management strategies. J Minim Invasive Gynecol 2010;17:53–8 [http://dx.doi.org/10.1016/j.jmig.2009.10.012]. and the optimum distension pressure. 12 Ferrazzi E, Zupi E, Leone FP, Savelli L, Omodei U, Moscarini M, et al. 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