Abstract
Endometrial polyps are localised overgrowths of endometrial tissue that can occur anywhere in the uterine cavity. They contain variable amounts of glands, stroma and blood vessels that are covered by a layer of endometrium. Most commonly they are attached to the uterus by an elongated pedicle (pedunculated), but they may also have a large flat base (sessile). They range in size from a few millimetres to several centimetres (Figure 10.1).
10.1 Background
10.1.1 Definition of an Endometrial Polyp
Endometrial polyps are localised overgrowths of endometrial tissue that can occur anywhere in the uterine cavity. They contain variable amounts of glands, stroma and blood vessels that are covered by a layer of endometrium. Most commonly they are attached to the uterus by an elongated pedicle (pedunculated), but they may also have a large flat base (sessile). They range in size from a few millimetres to several centimetres (Figure 10.1).
10.1.2 Prevalence and Epidemiology of Uterine Polyps
Endometrial polyps are common. They are found in association with abnormal uterine bleeding (AUB) and reproductive problems, but can also be incidental. The prevalence of endometrial polyps in asymptomatic women has been derived from small case series, which indicate it to be around 10% [1], but approximations vary according to the population characteristics and the diagnostic modalities used. Higher estimates of 13% [2] and 16% [3] have been reported in asymptomatic post-menopausal women following investigation with ultrasound and hysteroscopy, respectively. In contrast, incidental polyps were found in 12% of pre-menopausal women [2] and in 6–11% of infertile women without AUB following transvaginal ultrasound (TVU) [4, 5].
The prevalence of endometrial polyps in a general adult female population with abnormal bleeding is higher, in the range of 20–30% [6–8]. The wide variation in estimates reflects differences in population, the criteria used to define a polyp and the diagnostic test used. In addition to AUB, risk factors for developing endometrial polyps include older age, obesity, hypertension and tamoxifen use [2, 9]. The role of hormone replacement therapy in the formation of polyps is uncertain, with some studies showing a positive association and others not [6, 10].
10.1.3 Aetiology of Endometrial Polyps
The aetiology of endometrial polyps remains unclear. There are similarities between polyp tissue and background endometrium in the proliferation and expression of apoptosis regulators in relation to the menstrual cycle [11]. However, compared to normal endometrium, polyps show a higher expression of hormone receptors and less apoptosis, leading to focal overgrowths of stromal and glandular tissue [12]. It is unclear whether this overgrowth of tissue is caused by the elevated concentrations of hormone receptors making the tissue more sensitive to oestrogenic stimulation, or greater longevity from inhibited apoptosis leading to increased cell mass [12, 13]. It is likely that polyp formation combines these factors.
10.1.4 Diagnosis of Uterine Polyps
Ultrasound
The least invasive method of identifying endometrial polyps is TVU. Endometrial polyps typically appear as hyperechoic areas with regular contours within the uterine lumen, surrounded by a thin hyperechoic halo (Figure 10.2). Cystic spaces may be seen within the polyp, and sometimes the polyp may appear as a thickening or a focal mass, but these findings are non-specific and can be found in other diseases. Colour-flow Doppler can identify a feeding vessel for the polyp, which can further increase the diagnostic capability of the TVU. The development of 3D-sonography has also shown potential to improve the sensitivity and specificity of TVU [14].
TVU is generally used as the first-line investigation for bleeding disorders because of its convenience and acceptability. However, compared with outpatient hysteroscopy, the lower accuracy of TVU for detecting focal intrauterine pathologies has brought into question hierarchical testing based upon TVU. The sensitivity and specificity for diagnosing space-occupying lesions using TVU can be increased by instilling fluid to expand the uterine lumen and delineate the walls of the uterine cavity (saline infusion sonography; SIS). SIS and hysteroscopy are considered the gold-standard investigations for identifying polyps. While SIS enhances the accuracy of standard TVU, the addition of 3D imaging does not appear to improve the accuracy of simple 2D SIS [15].
SIS is not commonly used by gynaecologists in the UK but is more popular in parts of Europe and North America, where there is more expertise in the field. It has the advantage of enabling the assessment of structures outside the uterine cavity, such as myometrial and adnexal abnormalities, and can even be used to assess tubal patency. The information gleaned following SIS can be used to triage and plan subsequent surgical management. However, unlike outpatient hysteroscopy, SIS does not allow simultaneous treatment of detected endometrial polyps.
Blind Endometrial Biopsy
Traditionally, dilatation of the cervix and curettage of the endometrium (‘D&C’) was the accepted practice. However, this approach requires general anaesthesia and although the specificity approaches 100%, it has a low sensitivity [16]. Likewise, aspiration biopsy for use in the outpatient setting and based upon the miniature Pipelle® biopsy prototype has limited diagnostic accuracy for focal pathologies such as polyps. This is because the procedure is performed blindly such that a significant proportion of the endometrial cavity is not sampled. Previous analyses of outpatient endometrial biopsy have overestimated its accuracy because D&C, the previous gold standard modality, was also performed blind [17]. Recent data from a population of women with post-menopausal bleeding (PMB) and endometrial thickness >4 mm on TVU show that polyps are missed in up to 50% of cases. More worryingly, 6% of such polyps harbor pre-malignancy or frank malignancy such that the diagnostic workup for women with PMB and thickened endometrium on TVU should include additional investigation of the uterine cavity [17].
Hysteroscopy
The hysteroscopic diagnosis of endometrial polyps has a high accuracy, especially in post-menopausal women because visual discrimination of a focal endometrial lesion is easier in the presence of an inactive background endometrium. Hysteroscopy alone allows a subjective assessment of an endometrial lesion. Attempts are being made to provide more objectivity by developing a classification system for estimating the nature of endometrial polyps based upon visual appearances (personal communication, Clark T. J., on behalf of the FIGO Committee for Menstrual Disorders). However, hysteroscopy is usually combined with directed biopsy that further increases its diagnostic accuracy [18], and the introduction of hysteroscopic tissue removal systems has facilitated directed tissue sampling that had previously relied upon small, fragile hysteroscopic sampling forceps. Hysteroscopy has the advantage of being the only diagnostic modality that allows simultaneous treatment of the endometrial polyp. The procedure can be performed under a general anaesthetic, or in the outpatient setting, depending on the expertise and resources of the local clinicians.
Other Investigations
Hysterosalpingography is limited by the use of ionising radiation and patient discomfort, but filling defects suggesting the presence of space-occupying lesions may be identified as part of an investigation for tubal patency. Computed tomography and magnetic resonance imaging can be used to identify polyps but the limited availability and high cost of these modalities prevent their widespread use.
10.2 Clinical Significance of Endometrial Polyps
After diagnosis of an endometrial polyp, most gynaecologists will aim to remove it. The basis for this intervention is a belief that polyps are unlikely to regress, to treat symptoms such as AUB and subfertility, and to rule out malignant or pre-malignant disease.
10.2.1 Oncogenesis
The vast majority of polyps are benign, but a few will develop into endometrial cancer. Observational studies report cancer prevalence in cases of endometrial polyps to be in the range of 0.5–3% [19–22], with the prevalence of pre-malignant disease, or hyperplasia, reported as 1–3% [20–23]. A systematic review of observational studies evaluating the prevalence of malignant and pre-malignant disease found that post-menopausal women with AUB were at the highest risk of malignant and pre-malignant disease [24]. These findings are supported by data from a recent randomised controlled trial (RCT) showing that 6% of polyps detected in women with PMB contain atypical hyperplasia or cancer [17]. Conversely, asymptomatic women have a 4- to 10-fold lower risk of malignancy than women with AUB [25, 26]. Risk factors for malignant change within endometrial polyps other than AUB include obesity, diabetes [20–22] and an increased polyp diameter [22, 23]. In addition, use of tamoxifen appears to be associated with an increased risk of polyp formation and an increased risk of atypical hyperplasia and malignancy within uterine polyps [27, 28]. Hysteroscopic features suggestive of malignancy need further elucidation, but an irregular surface, areas of necrosis and the presence of vascular abnormalities, such as an increased number and bizarre branching of vessels, are thought to be predictive [29].
10.2.2 Abnormal Uterine Bleeding
The increasing use of hysteroscopy and high-resolution ultrasound to investigate AUB has shown that this symptom is frequently associated with endometrial polyps. This has prompted the International Federation of Gynecology and Obstetrics (FIGO) to approve a new classification system for causes of abnormal uterine bleeding in the reproductive years, based on the acronym PALM-COEIN, in which ‘P’ stands for ‘polyp’ (i.e., describing AUB associated with the presence of uterine polyps) [30] (see Table 7.1). The mechanisms by which endometrial polyps cause different forms of AUB are unclear but may relate to altered sex steroid interactions with the endometrium, inflammatory changes and/or disturbed angiogenesis [12, 31, 32]. Attempts are being made to produce a practical and reproducible subcategorisation system of the FIGO AUB-P category within the PALM-COEIN nomenclature (personal communication, Clark T. J.). By developing such a system based upon features such as the number, size, shape, location, surface, composition and vascularity of polyps, it is hoped that questions pertaining to the significance of uterine polyps found in association with particular AUB presentations may be more readily answered.
10.2.3 Fertility
Most of the work on the impact of polyps on fertility has come from cohort or case–control studies [24]. One RCT has been reported, looking at 215 women with ultrasonographically diagnosed endometrial polyps undergoing intrauterine insemination (IUI), who were randomly allocated to either polypectomy or biopsy alone [33]. Women who had polypectomy were significantly more likely to get pregnant (relative risk 2.1; 95% confidence interval 1.5–2.9). In fact, 65% of pregnancies in the polypectomy group occurred before IUI. Two recently published RCTs showed no benefit of routine hysteroscopy in fertility workup prior to in vitro fertilisation if a preceding TVU was normal [34, 35]. However, only a small number of women allocated hysteroscopy had polyps, so future trials are needed to evaluate the effectiveness of polypectomy in the treatment of subfertility.
10.3 Treatment of Uterine Polyps
10.3.1 Expectant Management
As the majority of polyps are benign, and some may naturally regress, expectant management with no intervention might be suitable, thus avoiding unnecessary morbidity and use of healthcare resources. Two RCTs have tried to address whether polyps in women with AUB should be removed [36, 37]. The first had to be stopped because neither clinicians nor patients were willing to be randomised into a group that did not have the polyp removed [36]. This is consistent with previous work that has shown that post-menopausal women would prefer more thorough hysteroscopic investigation and treatment, even if it is more invasive [25]. The second trial randomised 150 patients, but only 60% of them had AUB. It showed no difference in abnormal uterine bleeding, but a significant reduction in intermenstrual bleeding in those that had undergone polypectomy [37]. However, the results of this study should be interpreted with caution because of its small size, and only pre-menopausal women with heterogeneous symptoms were studied.
The evidence on spontaneous regression of polyps suggests it is more likely to occur in pre-menopausal women and in polyps smaller than 10 mm [26, 38]. This was demonstrated by work in which polyps were identified incidentally in asymptomatic women before being followed up for 2.5 years [26]. The authors concluded that more than 50% of polyps smaller than 10 mm regressed, while those that were bigger were likely to become symptomatic. This was backed up by a case series of asymptomatic polyps of 5–8 mm that spontaneously regressed after a few months [38]. Therefore, an expectant management strategy could be considered for polyps smaller than 10 mm in pre-menopausal women with no symptoms.
10.3.2 Medical Management
Medical management is successfully used to treat a range of menstrual disorders, but there is limited evidence for its use with endometrial polyps, and it is not recommended [39]. The levonorgestrel-releasing intrauterine system (LNG-IUS) has successfully been used to reduce the incidence of polyp formation in women taking tamoxifen [40]. It may also have a role in decreasing polyp formation in other groups of women who are at increased risk of polyps, but its use should be restricted to research protocols. Gonadotrophin-releasing hormone analogues (GnRHa) have previously been used to suppress the endometrium and create a favourable surgical environment for resection in pre-menopausal women [41]. However, their cost and side effects are hard to justify for the removal of endometrial polyps.
10.3.3 Surgical Management
Surveys in the UK and Europe have confirmed that most gynaecologists favour surgical removal of endometrial polyps [42, 43]. Polypectomy is an effective tool both diagnostically and therapeutically. In the past, in the UK, the predominant methods for surgical removal were blind avulsion or curettage after hysteroscopic inspection of the cavity under general anaesthesia. However, such techniques are being superseded by direct removal under hysteroscopic vision, increasingly in an outpatient setting; this change has been driven by technological advances in instrumentation and the publication of evidence supporting this intervention.
Blind Polypectomy
Traditional techniques of blind endometrial polypectomy using curettage or polyp forceps are associated with incomplete removal of polyps. These techniques are still used today, although most gynaecologists perform hysteroscopy beforehand to locate the polyp and direct blind avulsion of the lesion before curettage. As wide dilatation of the cervix (‘D&C’) is necessary to accommodate the blind instruments, inpatient hospital admission and general anaesthesia are required, with an associated increase in healthcare costs. Blind techniques are also associated with uterine trauma, which may be unrecognised and lead to serious complications from intra-abdominal damage.
Hysteroscopic Polypectomy
A range of mechanical instruments including scissors, loops, biopsy cups and graspers are available for insertion into the 5 or 7 Fr operating channels of rigid operative hysteroscopes ≤5.5 mm in outer diameter (Figure 3.8). The safety and feasibility of such approaches have been evaluated [1]. However, these fine mechanical instruments can be flimsy, making it difficult to remove large or fibrous pathology and in some instances there can be problems with bleeding. Electrosurgical instruments provide more efficient cutting and large diameter resectoscopes have been used under general or regional anaesthesia to remove polyps. These large electrical resection loops can also be used to remove endometrium and resect submucous fibroids (Figure 3.11). However, they require general anaesthesia and a high level of skill because they have been associated with serious complications including fluid overload and electrosurgical damage.
In contrast to fibroids (which are vascular and dense tissue formations, partially embedded in the underlying myometrium), polyps are softer, more accessible and wholly intra-cavity endometrial structures. Large-diameter resecting loops are overpowered and unnecessarily traumatic for achieving simple polypectomy, so smaller, less traumatic electrosurgical equipment was developed specifically for polyp removal. The Versapoint® bipolar electrosurgical system (Gynecare, Ethicon, Somerville, NJ, USA) was the first miniature 5 Fr (1.8 mm) bipolar electrode for use in physiological saline that can be used down standard operating hysteroscopes ≤5.5 mm to cut away polyps (Figure 3.9). This equipment has been reported to be safe and feasible, including in an outpatient setting [44]. Miniature monopolar electrosurgical snares can also be used [45] (Figure 10.3 and Video 10.1).
More recently, mechanical tissue morcellation devices have been developed, which avoid the need for electricity and can simultaneously cut and aspirate tissue. This capability overcomes inherent problems associated with the use of miniature electrodes such as suboptimal visualisation, risk of non-target thermal injury and difficulties retrieving removed polyp tissue from the uterine cavity. The first such tissue removal system (TRS) to be developed was the TruClear™ 5.0 (Medtronic, Minneapolis, MN, USA) (Figure 3.10a), followed by the IBS® Integrated Bigatti Shaver (Karl Storz, Tuttlingen, Germany) (Figure 3.10c) and the MyoSure® (Hologic®, Marlborough, MA, USA) (Figure 3.10b).
Even more recently, manually operated systems have been introduced that avoid the need for an electrical generator, the blades being rotated by repeated squeezing and releasing of an integrated hand-held pump. In addition, a tissue removal system combined with bipolar radiofrequency energy is now available. These are described in Chapter 19.
One RCT compared the TruClear™ TRS to monopolar resection of fibroids and polyps while patients were asleep, and showed that the TRS was easier to learn and quicker to perform [46]. Another RCT comparing the same TRS to the Versapoint® bipolar electrosurgical system in the outpatient setting showed that the TRS was faster, more acceptable, less painful and more likely to completely remove polyps [47]. Nevertheless, choice of technique may be guided by local expertise, availability of equipment, size, multiplicity and location of pathology, and patient factors.
Related posts:
Chapter 2 – Anatomy and Physiology of the Uterus
Chapter 3 – Infrastructure and Instrumentation for Hysteroscopy
Chapter 9 – Complications of Hysteroscopic Surgery
Chapter 8 – Hysteroscopic Electrosurgery
Chapter 17 – Audit, Data Collection and Clinical Governance in Hysteroscopy
Chapter 18 – Training in Hysteroscopic Skills
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