European Journal of Obstetrics & Gynecology and Reproductive Biology 157 (2011) 206211

Contents lists available at ScienceDirect

European Journal of Obstetrics & Gynecology and Reproductive Biology

Adenomyosis and junctional zone changes in patients with endometriosis

Department of Gynaecology and Obstetrics, Aarhus University Hospital, Skejby, Denmark Department of Diagnostic Imaging, Aarhus University Hospital, Skejby, Denmark

A R T I C L E I N F O

A B S T R A C T

Article history: Received 1 September 2010 Received in revised form 21 December 2010 Accepted 6 March 2011 Keywords: Adenomyosis Endometriosis Magnetic resonance imaging

Objectives: To evaluate image ndings in the junctional zone (JZ) in patients with endometriosis and correlate with image ndings of adenomyosis. To attempt a correlation of the degree of adenomyotic inltration with the degree of inltration and stage of endometriosis. Study design: Magnetic resonance imaging (MRI) of the uterus was performed in 153 women with suspected deeply inltrating endometriosis and planned surgery, and in a reference group of 129 women without endometriosis, veried during hysterectomy. Changes in the JZ and endometriosis in the pelvis were described in detail. Diagnosis of adenomyosis at MRI was based on optimal criteria derived from the hysterectomy control group. The stage of endometriosis (AFS stage) was determined during surgery. Results: In the group of women with endometriosis 34.6% had adenomyosis compared with 19.4% in the reference group (p < 0.05). More women with endometriosis (39.9%) had an irregular JZ compared to 22.5% in the reference group (p < 0.01). Among women with severe endometriosis (AFS stage IV) 42.8% had adenomyosis compared to 29.4% in the women with other stages of endometriosis (AFS stages I + II + III) (p = 0.10). More women with severe endometriosis (AFS stage IV) had deeper wall invasion of adenomyosis (p > 0.05) but the presence of deep inltrative rectovaginal endometriosis and the size of inltration were not correlated to adenomyosis or depth of inltration of adenomyosis. Conclusions: In a group of young women with severe symptomatic endometriosis and planned surgery a systematic evaluation of the JZ revealed that one third had uterine adenomyosis, but the invasive potential of endometrial cells in the uterus and in the peritoneum corresponded only to a limited degree. 2011 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Adenomyosis and endometriosis are both characterised by ectopic growth of endometrium-like or endometrium-derived tissue [1,2] and might be causally related. Leyendecker suggested that abnormal function of the inner smooth muscle of the uterus, the archimetra, or the junctional zone (JZ), could represent a common pathogenetic factor [3]. Alterations in the JZ thickness and bre orientation may change the uterine contractions leading to disturbed peristalsis [46]. The hyperperistalsis induces uterine auto-traumatisation and desquamation of basal endometrium which is transported into the peritoneal cavity [7]. Basal endometrium has an increased potential for implantation and proliferation resulting in pelvic endometriosis [7]. In addition, traumatization of the basal endometrium and the JZ could allow endometrial glands to penetrate into the myometrium and develop

* Corresponding author at: Solveig Brixen Larsen, Sleipnersvej 12, 3300 Frederiksvaerk, Denmark. Tel.: +45 50588489. E-mail address: brixen@dadlnet.dk (S.B. Larsen). 0301-2115/$ see front matter 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2011.03.003

adenomyosis [7]. In particular, inltrating endometriosis might be related to adenomyosis due to the inltrating growth pattern. The JZ is easily visualized by MRI. Abnormal widening (diffuse or focal) of the inner myometrium or JZ is one of the MRI features associated with adenomyosis (Fig. 1). It is the consequence of uncoordinated inner myocyte proliferation called JZ hyperplasia [5]. The JZ hyperplasia and accompanying disruption could initiate endometrial mucosal penetration of endometrial glands into the myometrium [8]. MRI is highly accurate in the diagnosis of uterine adenomyosis [911]. At MRI the heterotopic endometrial tissue may be seen as small foci of increased signal intensity in the JZ. This sign has a high diagnostic specicity for adenomyosis but cannot stand as the only criterion, as it may only be seen in less than half the cases. In periand post-menopausal women, a JZ thickness of !12 mm was established as the optimal isolated criterion for adenomyosis [9]. The JZ thickness, however, is hormone dependent and increases in the premenopause [12], and therefore other criteri describing the invasion of the JZ related to unaffected JZ or total uterine wall thickness should be added [10,11]. With the use of these criteria in combination, MRI is highly accurate in the diagnosis of uterine adenomyosis [13].

S.B. Larsen et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 157 (2011) 206211

207

shaving of endometriotic tissue from the bowel wall, and discoid resection when needed. The operative ndings represented the denitive diagnosis of endometriosis. Deeply inltrating endometriosis was dened as more than 5 mm invasion (assessed during surgery) of endometriosis into underlying tissues. The AFS stage and extent of endometriosis were determined during surgery according to the revised classication of the American Society for Reproductive Medicine (1996) [17]. 2.1.2. Group 2: patients with cervical cancer (N = 29) These women participated in a study concerning urological complications following radical hysterectomy. The women underwent MRI before surgery (1 December 2001 until 1 April 2005), and the occurrence of endometriosis was noted peroperatively. 2.1.3. Group 3: patients undergoing hysterectomy for benign conditions (N = 100) This group consisted of all consecutive pre-menopausal women who had a hysterectomy due to a benign condition at Aarhus University Hospital, from September 1998 to February 2000. The study population included 178 patients. Three were not invited to participate because of language problems, 14 could not be reached by phone for an appointment, 53 declined the invitation, and 2 patients were excluded because the uterus was morcellated at hysterectomy. All patients underwent MRI followed by hysterectomy within 14 days. The prevalence of adenomyosis in the excluded patients was 22%, which was no different from the prevalence in the included patients. In six patients, endometriosis was diagnosed during surgery. These patients were excluded from the present study, leaving 100 patients without endometriosis for analysis. The main indications for surgery were: abnormal bleeding 51, symptomatic myomas 35, lower abdominal pain 11 (9 of these 11 patients had concomitant myomas or abnormal bleeding), dysplasia and borderline ovarian tumour 3. MRI diagnoses of adenomyosis based on different MRI criteria were compared with the ndings of the pathologic examinations. The experience of our team for evaluation of adenomyosis, with a high accuracy of MRI for diagnosis of adenomyosis, has been established in this previous study [10], and we used MRI criteria with the histologically conrmed highest diagnostic accuracy of 84% (sensitivity 65%, specicity 89%). 2.2. MRI The association between endometriosis and adenomyosis has been evaluated in only a few studies [1416] and in only one study with optimal criteria [14]. In the present study, the occurrence of adenomyosis and image changes in the JZ was assessed by MRI in patients with rectovaginal endometriosis, as compared to ndings in patients with other forms of endometriosis, and in patients without the disease. 2. Material and methods 2.1. Patients 2.1.1. Group 1: patients with suspected rectovaginal endometriosis (N = 153) From 1 January 2001 until 1 June 2005, 153 patients were referred for MRI and subsequent laparoscopy due to suspected deeply inltrating endometriosis. In this period all patients with suspicion of deeply inltrating endometriosis were routinely referred for preoperative MRI to map out and describe the relation of endometriotic nodules to the rectum and ureters. All patients were booked for diagnostic laparoscopy and laparoscopic resection of all visible endometriotic lesions. Patients with laparoscopically conrmed rectovaginal endometriosis were treated mainly with Before 2000, MRI was performed with 1.5 T scanners (Signa, General Electric Medical systems, Milwaukee, WI and Gyroscan ACS.NT, Philips). We acquired 4-mm slices with 1-mm spacing in the sagittal, coronal, and axial planes relative to the orientation of the uterine cavity, using T2-weighted fast (turbo) spin echo sequences (TR/TeEf, 35004000 ms/90 ms, echo train length 16) in all three planes using a matrix of 512 448. We used surface coils (phase array pelvic coils) for data collection and completed the examination in 3045 min. After 2000, MRI was performed with new 1.5 T scanners (Signa, Twin-Speed, General Electric Medical systems, and Achieva, Philips). We optimized our sequences in each system, which gave us different settings of the sequences in the two systems. The Philips system provided 4 mm slices with 0.5 mm spacing in the sagittal, coronal, and axial planes relative to the orientation of the uterine cavity, using T2-weighted fast (turbo) spin echo sequences (TR/TeEf, 35004000 ms/110 ms, echo train length 22) in all three planes. We used a surface coil (sense cardiac phase array) for data collection using a matrix of 512 448. The General Electric system provided 4 mm slices with 0.5-mm spacing in the sagittal, coronal, and axial planes relative to the orientation of the uterine cavity, using T2-weighted fast (turbo) spin echo sequences (TR/TeEf, 35004000 ms/90 ms, echo train length 12) in

Fig. 1. Magnetic resonance imaging. (a) Normal uterus, (b) Adenomyosis.

208

S.B. Larsen et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 157 (2011) 206211

all tree planes. We used a pelvic phased array surface coil for data collection using a matrix of 512 448. All examinations were completed in 3045 min. The thickness was measured at the thinnest (JZ-min) and thickest (JZ-max) parts of the anterior and posterior wall in the sagittal slices. The difference between JZ-max and JZ-min (JZ-dif) was calculated for the anterior and posterior border. The largest parameter, either anterior or posterior, was used in all calculations. For each patient all areas with poorly dened margins suspected of being adenomyosis were described. For these areas we registered their size, the JZ-max, and presence of high signal foci. In patients with endometriosis the maximal anterior (AW) and posterior (PW) uterine wall thickness was measured and invasion depth of the anterior and posterior wall was calculated as JZ-max/ maximum wall thickness. The largest invasion depth in either the anterior or posterior wall was used. In the reference group of women this parameter was inappropriate as several patients had myomas, which increased AW and PW. Adenomyosis was thought to be present: (a) in the presence of focal poorly demarcated low intensity areas in the myometrium with high intensity myometrial spots arising from the endometrial myometrial boarder, or (b) with >15 mm junztional thickness, or (c) when a JZ-dif of >5 mm was present. At MRI the presence and size of inltrating recto-vaginal endometriosis were measured in three perpendicular planes (d1, d2, d3) and the relation to rectum and ureters was described. Volume of inltrations was calculated according to ellipse volume p/6 d1 d2 d3. MRI scans were evaluated by the same MRI specialist (EL). 2.2.1. Data analysis and statistics The statistical analyses were performed using X2, Fishers exact test (F), and KruskalWallis test (KW) when non-parametric tests were appropriate. Median and 1090 percentiles (p10p90) were used for distributions where means and standard deviations (SD)

were unsuitable. MantelHaenszel test was used when two groups were compared and adjusted for control variables. The group of patients with endometriosis (group 1) were compared to the groups of controls (groups 2 + 3) in the analysis. 3. Results Most women with endometriosis had severe inltrating disease (Table 1). The women with endometriosis were younger, had fewer children and were more often on hormone therapy. The prevalence of adenomyosis in the group of women with endometriosis was 34.6%, and higher than the prevalence found in the control group (groups 2 + 3) (19.4%) (Table 2). Among women with endometriosis, more women had an irregular JZ compared to the control group. Moreover the irregularity was more pronounced, with higher values of JZ-dif in patients with endometriosis. The JZ was not so broad among endometriosis patients (lower median of JZ-max). Fifty percent of the women with endometriosis had a JZ-max of 7 mm or lower. Among women without adenomyosis, the group of endometriosis patients had a signicantly thinner JZ-max compared with group (2 + 3) (median, p10 p90: 6.0 mm, 3.010.4, vs 9.0 mm, 5.012.0) (p < 0.01 KW). In patients with endometriosis there were more cases with adenomyosis in the posterior wall compared to the anterior wall, but there was no difference in the invasion depth between the anterior and posterior walls (Table 2). In patients with adenomyosis there was no difference in the invasion depth measured as JZ-dif (means SD) between patients with endometriosis (11.1 6 mm) and the control group (2 + 3) (9.9 6 mm). Using the established single MRI criteria of endometrial thickness of !12 mm for adenomyosis [18], the prevalence of adenomyosis in the group of women with endometriosis was 42.9% and higher than the prevalence found in the control group (groups 2 + 3) (31.9%) (p = 0.07), but the additional cases of adenomyosis were not veried at histopathology in the hysterectomy group.

Table 1 Characteristics of the women in the three groups. Group1 Patients with endometriosis (N = 153) N (%) Age, years <30.0 30.034.9 35.039.9 40.044.9 !45.0 Mean SD Parity 0 1 2 !3 Missing Hormone therapy Yes AFS stage I II III IV Missing value Never laparoscopy Rectovaginal inltration Vaginal inltration Endometrioma Ureter compression 65 (42.5%) 52 (34.0%) 25 (16.3%) 9 (5.9%) 2 (1.3%) 31.5 5.5 98 29 20 5 1 (64.5%) (19.1%) (13.1%) (3.3%) Group 2 Patients with cervical cancer (N = 29) N (%) 2 (6.9%) 6 (20.7%) 4 (13.8%) 4 (13.8%) 13 (44.8%) 43.9 11.0 3 8 9 8 1 (10.7%) (28.6%) (32.1%) (28.6%) Group 3 Patients who had a hysterectomy (N = 100) N (%) 0 (0%) 2 (2.0%) 15 (15.0%) 22 (22.0%) 61 (61.0%) 45.7 5.1 23 12 31 31 3 (23.7%) (12.4%) (31.9%) (31.9%)

88 (58.3%) 15 37 33 56 5 7 116 52 42 7 (10.6%) (26.3%) (23.4%) (39.7%)

3 (10.7%)

20 (20.2%)

(75.8%) (33.9%) (27.5%) (4.6%)

S.B. Larsen et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 157 (2011) 206211 Table 2 Characteristics of the junctional zone (JZ) in the three groups of women. Group 1 Patients with endometriosis (N = 153) Adenomyosis Yes, N (%) 53 (34.6%) Location (N) 12 Anterior wall Posterior wall 28 Anterior and posterior wall 13 High signal foci N (%) 2 (1.3%) Irregular JZ (JZ-dif>2), N (%) 61(39.9%) JZ-dif 1 mm 92 (60.1%) 25 mm 12 (8.6%) !6 mm 49 (35%) JZ-max, median 7.0 (p10p90) (3.020.9) JZ-max 7 mm 70 (50.0%) 811 mm 24 (17.1%) 15 (9.8%) 1215 >15 31 (20.3%) Not evident at MRI 13 Dept. of invasion (jzmax/wall thickness) median ((p10p90)) Posterior 0.38 (0.110.85) Anterior 0.39 (0.120.87) 0.47 (0.140.90) Maximum invasion
**

209

Group 2 Patients with cervical cancer (N = 29) 6 (20.7%) 3 3 1 (3.4%) 6 (20.7%) 19 (65.5%) 5 (17.2%) 5 (17.2%) 9.0 (5.018.9) 9 9 5 3 3 (34.6%) (34.6%) (17.2%) (10.3%)

Group 3 Patients who had a hysterectomy (N = 100) 19 (19.0%) 1 1 17 10 (10.0%) 23(23.0%) 73 (73.0%) 10 (11.5%) 17 (19.5%) 10.0 (6.018.4) 20 41 13 13 13 (23.0%) (47.1%) (13.0%) (13.0%)

Signicance (p)**

<0.05 (Chi2)

<0.01 (F) <0.01 (KW)

<0.05 (Chi2) <0.01 (KW)

<0.01 (Chi2)

For the statistical analyses the two control groups (cervical cancer (group 2) and hysterectomy (group 3) were combined.

Among women with severe endometriosis (AFS stage IV) 42.8% had adenomyosis compared to 29.4% among women in the other 3 stages (AFS stages I + II + III) (p = 0.10) (Table 3). Deeper wall invasion and JZ-dif were seen in more women with AFS stage IV compared to stages IIII (Table 4). Adjustment for the presence of endometriomas did not change the estimates for AFS stage. MRI revealed deeply inltrating recto-vaginal endometriosis among 75.8% of the endometriotic patients, and 34.5% of these had adenomyosis compared to 35.1% in the group without rectovaginal endometriosis (p > 0.05). There were no more cases of adenomyosis in patients with large inltrations, and the depth of inltration of adenomyosis was no deeper in patients with large volumes of inltrations (Table 3). No more patients with both AFS

stage IV and rectovaginal inltrations had adenomyosis, and there was no deeper inltration of adenomyosis in these patients. 4. Comments One third of young women with clinically suspected deeply inltrating endometriosis had MRI ndings of uterine adenomyosis. Symptomatic and severe inltrating endometriosis seems to be correlated with adenomyosis and should motivate a diagnostic evaluation of adenomyosis among these patients. Persistence of dysmenorrhoea and non-menstrual pain after optimal surgical resection of peritoneal endometriosis are more likely in patients with increasing JZ thickness suggesting adenomyosis [1921]. Postoperative treatment of these patients may thus be needed. Moreover, adenomyosis may be an important cause of infertility [7,22], which seems to improve after proper treatment [23]. Classic adenomyosis is present in 2035% of patients undergoing hysterectomy [24], and is more commonly diagnosed in the forties or fties, whereas endometriosis is diagnosed in younger age groups [25]. Younger patients with endometriosis had a thin JZ, whereas the control group of older women had a broader

Table 3 Relationship between the stage of endometriosis and different variables. N AFS stage AFS stage AFS stage AFS stage Statistics I 15 II 37 III 33 IV 56 Adenomyosisyes N (%) 4 (26.7) 13 (35.1) 8 (24.2) 24 (42.8) p 0.10 (Chi2) JZ-max (mm), Median (p10p90) 13 (35.1) 13 (36.1) 9 (31.0) 11 (40.7) 7 (29.2) p > 0.75 (Chi2) 13 (25.0) 16 (38.1) 1(14.3) JZ-max (mm) Median (p10p90) 6.50 (2.5018.50) 6.00 (2.019.20) 6.00 (4.019.6) 8.00 (3.328.8) p 0.06 (MW) Dept. of invasion (jzmax/wall thickness) Means (SD) 0.51 (0.31) 0.55 (0.30) 0.58 (0.31) 0.46 (0.26) p > 0.5 (F-test)

Rectovaginal inltration Volume cm3 (N) No inltration (37) 11.9 (36) 2.0 4.9 (29) 5.0 9.9 (27) 10.0 30.0 (24)

Table 4 Adenomyosis and depth of invasions in women with endometriosis measured as largest JZ thicknessthinnest JZ thickness (JZ-dif) or largest JZ thickness/total wall thickness in relation to stage of disease. AFS IIII N (%) JZ dif <6 mm 63 (74.1) 68 mm 11 (12.9) >8 mm 11 (12.9) Dept. of invasion (jzmax/wall thickness) <0.4 38 (51.3) 0.40.7 23 (31.1) >0.7 13 (17.5) AFS IV N (%) 33 (58.9) 6 (10.7) 17 (30.4) 18 (37.5) 12 (25.4) 18 (37.5)

6.5 (2.519.50) 9.0 (3.028.0) 6.5 (2.719.3) 7.0 (3.129.5) p > 0.8 (MW)

p < 0.05

Vaginal inltration (52) Endometrioma (42) Ureter compression (7)

p < 0.05

210

S.B. Larsen et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 157 (2011) 206211

JZ. The JZ increase with age before the menopause [12,26] and a regular broader symmetric JZ may most likely just be a hormonedependent age-related change [27]. It may have clinical signicance but should be separated from, and seems not to be related to, adenomyosis [28]. Adenomyosis requires inltration of endometrial glands and stroma into the myometrium, and image reection of invasion as jzmax/wall thickness >40% [11] or JZ-diff >5 [10] should be used. The latter might not correlate to patients custom JZ and be more appropriate in the presence of myomas. It should be distinguished from uterine contractions, which are seen as transient regular swellings of the JZ. Even these measures, however, should be evaluated in a young age group with histopathology for verication. In younger patients with endometriosis, adenomyosis was seen as localized irregular burst in a thin JZ. It could indicate that adenomyosis is initiated by a primary break in the endomyometrial border followed by, but not preceded by, localised muscular JZ-hypertrophy. It may be caused by intrinsic auto-traumatic factors [7,29], or external traumatisation by, for example, pregnancy [30]. Nevertheless, although JZ thickness differed, the depth of invasion of adenomyosis was the same in patients with adenomyosis in the group with endometriosis compared to the control group. Thus image ndings in this young population of patients might most likely just be an earlier manifestation of adenomyosis found in the older population with adenomyosis, and JZ changes in endometriosis are not histologically veried and may constitute disease other than adenomyosis [28]. More studies are needed to clarify the cause of different image ndings. The association between endometriosis and adenomyosis has been evaluated in only a few studies. Our ndings were in line with the nding in another study [14] but differed from the results in a study of infertility patients [15], where the prevalence of adenomyosis was 79% and 28% in patients with and without endometriosis, respectively. This was unexpected since the majority of our patients had deeply inltrating disease, where more aggressive adenomyosis might have been expected. The diverging ndings might be due to different MRI criteria for the diagnosis of adenomyosis, which are still controversial. Kunz et al. used a JZ of 10 mm for diagnosis of adenomyosis [15] in contrast to others, where MRI ndings were correlated with histopathology [9,10,31]. Our use of a restrictive MRI diagnosis of adenomyosis compared to the criteria proposed by Reinhold et al. [32] resulted in a lower prevalence of adenomyosis in both groups without changing the difference between the groups. Adenomyotic changes were not evident in two thirds of the patients with endometriosis, and the presence and size of rectovaginal inltrating endometriosis was not correlated with adenomyosis or depth of inltration of adenomyosis. The theory of endometriosis as a primary disease of the archiometra [7] was not clearly reinforced in this study, as no correspondence in level of invasive potential in the myometrium and peritoneum was seen. This goes against a common intrinsic abnormality in eutopic and ectopic endometrium. There could, however, be different expressions of invasive potential dependent on local factors accounting for the different ndings. Nevertheless, in line with Kunz et al. [15], adenomyosis seemed to be more invasive in AFS stage 4. The AFS score does not address the clinically most important extent of disease which is deep inltrating endometriosis. The AFS score corresponds more with the inammatory and adhesive components of endometriosis and with endometriomas. Dysperistalsis and menorrhagia in adenomyosis could give rise to a larger load of peritoneal endometrial cells during menstruation, which could promote adhesion and inammation and account for this nding, but this inammation did not seem to give rise to more deep inltration.

The optimal control group would have been an age-matched group of patients with no clinical symptoms. It is very difcult and expensive, however, to establish such a group with a sufcient number of patients, and no histopathology verication can be established. The diagnostic criteria at MRI for diagnosis of adenomyosis are still controversial, and motivate our use of a control group with histopathology conrmation of the diagnostic criteria used [13]. Thus the prevalence of adenomyosis would be expected to be lower in a control group of younger asymptomatic patients compared to the used control group of older premenopausal women undergoing hysterectomy for benign conditions. Though no endometriosis was seen at histopathology and described during operation, exclusion of minor endometriosis would have required a uniform staging of a single experienced observer. In spite of the above-mentioned conditions the group of women with severe endometriosis demonstrated a higher prevalence of adenomyosis than the control groups and illustrates the need for an imaging technique for diagnosis of adenomyosis in patients with endometriosis. This should be by MRI or transvaginal ultrasound (TVS) by a clinician skilled in the sonographic ndings of adenomyosis. The diagnostic accuracy of TVS [33] is in line with MRI [13]. TVS is very observer-dependent in the evaluation of adenomyosis [34]. MRI has the advantage of being able to predict deep inltrating endometriosis at all locations even outside the pelvis and to dene the exact extent of both endometriosis and adenomyosis [35,36]. In summary, in this study a systematic description of JZ changes in endometriosis implied an association of severe symptomatic endometriosis with adenomyosis, but the invasive potential of endometrial cells in the uterus and peritoneum corresponded only to a limited extent. References
[1] Hudelist G, Keckstein J, Wright JT. The migrating adenomyoma: past views on the etiology of adenomyosis and endometriosis. Fertil Steril 2009;92:153643. [2] Benagiano G, Brosens I. History of adenomyosis. Best Pract Res Clin Obstet Gynaecol 2006;20:44963. [3] Leyendecker G, Kunz G, Noe M, Herbertz M, Mall G. Endometriosis: a dysfunction and disease of the archimetra. Hum Reprod Update 1998;4:75262. [4] Uduwela AS, Perera MA, Aiqing L, Fraser IS. Endometrial-myometrial interface: relationship to adenomyosis and changes in pregnancy. Obstet Gynecol Surv 2000;55:390400. [5] Brosens JJ, de SN, Barker FG. Uterine junctional zone: function and disease. Lancet 1995;346:55860. [6] Leyendecker G, Kunz G, Kissler S, Wildt L. Adenomyosis and reproduction. Best Pract Res Clin Obstet Gynaecol 2006;20:52346. [7] Leyendecker G, Kunz G, Herbertz M, et al. Uterine peristaltic activity and the development of endometriosis. Ann N Y Acad Sci 2004;1034:33855. [8] Brosens JJ, Barker FG, de SN. Myometrial zonal differentiation and uterine junctional zone hyperplasia in the non-pregnant uterus. Hum Reprod Update 1998;4:496502. [9] Reinhold C, McCarthy S, Bret PM, et al. Diffuse adenomyosis: comparison of endovaginal US and MR imaging with histopathologic correlation. Radiology 1996;199:1518. [10] Dueholm M, Lundorf E, Hansen ES, Ledertoug S, Srensen JS, Olesen F. Magnetic resonance imaging and transvaginal ultrasonography for diagnosis of adenomyosis. Fertil Steril 2001;76:58894. [11] Bazot M, Cortez A, Darai E, et al. Ultrasonography compared with magnetic resonance imaging for the diagnosis of adenomyosis: correlation with histopathology. Hum Reprod 2001;16:242733. [12] Hauth EA, Jaeger HJ, Libera H, Lange S, Forsting M. MR imaging of the uterus and cervix in healthy women: determination of normal values. Eur Radiol 2007;17:73442. [13] Dueholm M, Lundorf E. Transvaginal ultrasound or MRI for diagnosis of adenomyosis. Curr Opin Obstet Gynecol 2007;19:50512. [14] Bazot M, Fiori O, Darai E. Adenomyosis in endometriosisprevalence and impact on fertility. Evidence from magnetic resonance imaging. Hum Reprod 2006;21:11012. [15] Kunz G, Beil D, Huppert P, Noe M, Kissler S, Leyendecker G. Adenomyosis in endometriosisprevalence and impact on fertility. Evidence from magnetic resonance imaging. Hum Reprod 2005;20:230916. [16] Zacharia TT, ONeill MJ. Prevalence and distribution of adnexal ndings suggesting endometriosis in patients with MR diagnosis of adenomyosis. Br J Radiol 2006;79:3037.

S.B. Larsen et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 157 (2011) 206211 [17] Revised American Society for Reproductive Medicine classication of endometriosis: 1996. Fertil Steril 1997;67:81721. [18] Reinhold C, Tafazoli F, Mehio A, et al. Uterine adenomyosis: endovaginal US and MR imaging features with histopathologic correlation. Radiographics 1999;19 Spec No: S14760. [19] Landi S, Mereu L, Pontrelli G, et al. The inuence of adenomyosis in patients laparoscopically treated for deep endometriosis. J Minim Invasive Gynecol 2008;15:56670. [20] Parker JD, Leondires M, Sinaii N, Premkumar A, Nieman LK, Stratton P. Persistence of dysmenorrhea and nonmenstrual pain after optimal endometriosis surgery may indicate adenomyosis. Fertil Steril 2006;86:7115. [21] Ferrero S, Camerini G, Menada MV, Biscaldi E, Ragni N, Remorgida V. Uterine adenomyosis in persistence of dysmenorrhea after surgical excision of pelvic endometriosis and colorectal resection. J Reprod Med 2009;54:36672. [22] Kim MD, Kim S, Kim NK, et al. Long-term results of uterine artery embolization for symptomatic adenomyosis. AJR Am J Roentgenol 2007;188:17681. [23] Mijatovic V, Florijn E, Halim N, Schats R, Hompes P. Adenomyosis has no adverse effects on IVF/ICSI outcomes in women with endometriosis treated with long-term pituitary down-regulation before IVF/ICSI. Eur J Obstet Gynecol Reprod Biol 2010;19. [24] Vercellini P, Vigano P, Somigliana E, Daguati R, Abbiati A, Fedele L. Adenomyosis: epidemiological factors. Best Pract Res Clin Obstet Gynaecol 2006;20:46577. [25] Templeman C, Marshall SF, Ursin G, et al. Adenomyosis and endometriosis in the California Teachers Study. Fertil Steril 2008;90:41524. [26] Kunz G, Herbertz M, Beil D, Huppert P, Leyendecker G. Adenomyosis as a disorder of the early and late human reproductive period. Reprod Biomed Online 2007;15:6815.

211

[27] Tamai K, Togashi K, Ito T, Morisawa N, Fujiwara T, Koyama T. MR imaging ndings of adenomyosis: correlation with histopathologic features and diagnostic pitfalls. Radiographics 2005;25:2140. [28] Tocci A, Greco E, Ubaldi FM. Adenomyosis and endometrialsubendometrial myometrium unit disruption disease are two different entities. Reprod Biomed Online 2008;17:28191. [29] Giudice LC, Kao LC. Endometriosis. Lancet 2004;364:178999. [30] Vercellini P, Parazzini F, Oldani S, Panazza S, Bramante T, Crosignani PG. Adenomyosis at hysterectomy: a study on frequency distribution and patient characteristics. Hum Reprod 1995;10:11602. [31] Ascher SM, Arnold LL, Patt RH, et al. Adenomyosis: prospective comparison of MR imaging and transvaginal sonography. Radiology 1994;190:8036. [32] Reinhold C, Tafazoli F, Wang L. Imaging features of adenomyosis. Hum Reprod Update 1998;4:33749. [33] Meredith SM, Sanchez-Ramos L, Kaunitz AM. Diagnostic accuracy of transvaginal sonography for the diagnosis of adenomyosis: systematic review and metaanalysis. Am J Obstet Gynecol 2009;201:10716. [34] Dueholm M, Lundorf E, Sorensen JS, Ledertoug S, Olesen F, Laursen H. Reproducibility of evaluation of the uterus by transvaginal sonography, hysterosonographic examination, hysteroscopy and magnetic resonance imaging. Hum Reprod 2002;17:195200. [35] Bazot M, Bornier C, Dubernard G, Roseau G, Cortez A, Darai E. Accuracy of magnetic resonance imaging and rectal endoscopic sonography for the prediction of location of deep pelvic endometriosis. Hum Reprod 2007;22: 145763. [36] Bazot M, Detchev R, Cortez A, Amouyal P, Uzan S, Darai E. Transvaginal sonography and rectal endoscopic sonography for the assessment of pelvic endometriosis: a preliminary comparison. Hum Reprod 2003;18: 168692.