Differences clinical characteristics and factors in intrinsic and extrinsic adenomyosis

Differences clinical characteristics and factors in intrinsic and extrinsic adenomyosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Differences clinical characteristics and factors in intrinsic and extrinsic adenomyosis Yan Liang, Wei Shi, Feng Sun, Minjiao Zhu, Yuan Liu, Jian Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2752816/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Adenomyosis (AM) is a common gynecological condition that can be classified into different subtypes. This study aimed to evaluate the clinical characteristics, factors and treatment effect in women who diagnosed with intrinsic or extrinsic AM by MRI and underwent hysterectomies. A total of 181 women were enrolled in the study. Among these, 77 of which were identified to be in the intrinsic AM group (intrinsic group) and 54 in the extrinsic AM group (extrinsic group). Our results show that gravidity (P < 0.0001), parity (P < 0.0001), number of abortion (P < 0.0013) and endometrial curettage (P = 0.0167) were significantly higher in the intrinsic group, while the education level was lower in the intrinsic group (P = 0.0118). Women in the extrinsic group had earlier menarches (P = 0.0257) and were more coexist with ovarian endometrioma (OMA) (P < 0.0001) and deep infiltrating endometriosis (DIE) (P < 0.0001). In terms of clinical features, dysmenorrhea was more serious in the extrinsic group (P = 0.0091), whereas women in the intrinsic group had heavier menstrual volume (P < 0.0001). Surgery duration (P < 0.0001), surgical bleeding (P < 0.0013), hospitalization cost (P < 0.0001), and postoperative medical therapy (P < 0.001) were significantly higher in the extrinsic group than in the intrinsic group. In the multivariate analysis we performed, education level, gravidity and number of endometrial curettage were significantly associated with intrinsic AM. OMA and DIE were closely related to extrinsic AM. These results suggest that intrinsic and extrinsic AM have specific clinic characteristics, are associated with different factors, and may have different pathogenesis. Intrinsic adenomyosis extrinsic adenomyosis clinical characteristics factors Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Adenomyosis (AM) is a disorder of the uterus which has a substantial impact on both the physical and psychological health of women. AM consists in endometrial glands and stroma invading the myometrium, a phenomenon which is accompanied by hypertrophy and hyperplasia of the surrounding myometrial tissues [1], causing dysmenorrhea (15%-30%), menorrhagia (40%-60%) [2], and in some cases even infertility (7.5%-24.4%) [3]. It is estimated over the last 50 years prevalence of AM among performed hysterectomy women has ranged from 8.8–61.5% [4]. The exact pathogenesis and etiology of AM have not yet been fully understood. There are currently two main theories about the origin of AM: an invagination of the endometrial basalis into the myometrium or a de novo consequence of the metaplasia of embryonic Müllerian remnants [5]. With the advancements in transvaginal ultrasonography (TVUS) and magnetic resonance imaging (MRI), AM can now be diagnosed based on imaging parameters [6]. MRI has high sensitivity (70%-93%) and specificity (86%-93%) for the diagnosis of AM [7–9]. Yet the classification of AM is diverse [10,11]. Pistofidis et al. [12] have classified AM into diffuse, focal AM, and cystic adenomyoma, based on the different manifestations of the myometrium in MRI. According to assessment of the positional relationship between the AM lesions and other structural components by MRI, Kishi et al. [13] have proposed the most comprehensive and widely accepted classification of AM in four subtypes. Among these, intrinsic AM (subtype I: lesions occur in the inner myometrium) and extrinsic AM (subtype II: lesions occur in the outer myometrium) account respectively for 31.5% and 43.9% of the cases [6]. Previous studies have suggested hypothesis that intrinsic AM may be a product of direct endometrial invasion involving inner-mid myometrium, while extrinsic AM could be caused by pelvic endometriosis invading the uterine serous and the outer myometrium [13,14]. In addition, AM is a highly heterogeneous disease with several possible clinical manifestations, the relationship between AM subtypes and clinical characteristics is still not clear. The aim of our study is to compare baseline characteristics, clinic features, perioperative and postoperative conditions in women diagnosed with intrinsic or extrinsic AM by MRI, and who underwent hysterectomies as treatment. In-depth research on clinical data of women affected by different subtypes of AM is needed to perform prevention, get accurate diagnoses and treatments. Such research would also provide a clinical basis for further studies on the pathogenic mechanisms underlying the disease. Materials and Methods Study design and ethic We performed a retrospective observational study recruiting women who underwent hysterectomy as AM treatment at the International Peace Maternity and Child Health Hospital affiliated to the Shanghai Jiao Tong University between June 2019 and August 2022. The study was approved by the institutional ethics committee of the International Peace Maternity and Child Health Hospital (approval No. GKLW 2022-16). Data was fully anonymized. Population study and collected data The inclusion criteria were the following: 1) age > 18 and < 50 years, premenopausal; 2) did not received any hormone treatment for at least six months before the hysterectomy and condition histopathologically proven to be AM; 3) MRI examination on T1 and T2-weighted sequences prior to surgery and condition determined to be intrinsic or extrinsic AM. All MRI images were evaluated by two senior radiologists unaware of the clinical data of the patients. When the diagnosis of the two radiologists were different, a third senior radiologist was invited to give a further diagnosis. Exclusion criteria were the following: 1) previous excision of an AM lesion; 2) cancer or infectious disease; 3) incomplete information available. Women were then classified into two groups: the intrinsic AM group (intrinsic group) and the extrinsic AM group (extrinsic group). Data on baseline characteristics, clinical features, and perioperative data were obtained from the internal database of the hospital, while the postoperative of information was collected from outpatient interview data. The baseline characteristics collected included age, body mass index (BMI), education level, age of menarche, duration of menstruations, menstrual cycle, marital status, gravidity, parity, previous deliveries (cesarean or vaginal delivery), infertility, number of abortions, endometrial curettage, endometriosis surgery, drug therapy for AM (gonadotropin-releasing hormone-antagonist (GnRH-a), levonorgestrel intrauterine system (ING-IUS), progesterone, contraception, nonsteroidal anti-inflammatory drug, gestrinone), family history of AM, history of anemia, history of blood transfusion and presence of comorbidities. Clinical features collected were the intensity of dysmenorrhea, menstrual blood volume, presence of ovarian endometrioma (OMA), deep infiltrating endometriosis (DIE), endometrial hyperplasia, leiomyomas, stage of endometriosis, serum levels of carbohydrate antigen (Ca125), and Anti-Mullerian hormone (AMH). We also recorded uterine volume and position, if the lesions were focal or diffuse, and location of focal lesions based on MRI images. Surgery duration, bleeding, complications (intestinal, ureteral, bladder injury, large vessel injury, blood transfusion, conversion to laparotomy), postoperative morbidity, length of hospitalization, hospital cost, and drug therapy after the operation (GnRH-a, progesterone, contraceptives) were noted. The degree of satisfaction of treatment was also recorded. The collected data was independently checked by two researchers to ensure that there were no inconsistencies or errors. Criteria of evaluation AM cases were categorized into four subtypes depending on the characteristics of the lesions and on the MRI images based on Kishi’s criterion [13]: Subtype I (intrinsic): AM lesions occur in the uterine inner layer without affecting the outer structures. Subtype II (extrinsic): AM lesions occur in the uterine outer layer without affecting the inner structures, with healthy muscular structures between the lesions and the junction zone (JZ). Subtype III (intramural): AM lesions occur solitarily without relationship to structural components. Subtype IV: AM lesions do not satisfy any previously listed criteria. T2-weighted MRI images of intrinsic and extrinsic AM are shown in Figs. 1 and 2 . Diffuse and focal lesions were classified based on the following criteria: a diffuse lesion is characterized by foci of endometrial mucosa (glands and stroma) scattered throughout the uterine musculature, while a focal lesion is restricted in an area of hypertrophic and distorted endometrium and myometrium [14–16]. Dysmenorrhea intensity was evaluated with a Visual Analog Scale (VAS) system, using a 10 cm line where 0 represents “no pain” and 10 “maximum pain”. A VAS score ≥ 7 was considered to be severe pain [17,18]. Menstrual blood volume was assessed using the Mansfield–Voda–Jorgensen menstrual bleeding scale (MVJ), ranging from 1 (spotting) to 6 (gushing), and menorrhagia was defined as a MVJ score ≥ 5 [19]. 12 months or more of unprotected intercourse not resulting in pregnancy was considered as infertility [20]. The uterine volume was calculated by three-dimensional MRI examination using the following formula: volume = A × B × C × 0.52 where A, B and C represent respectively the length, width, and depth of the uterus [21]. The stage of endometriosis was evaluated according to the revised American Fertility Society classification (r-AFS): score 1–5 = stage I; score 6–15 = stage II; score 16–40 = stage Ⅲ; score > 40 = stage Ⅳ [22]. The normal serum levels of Ca125 and AMH were defined respectively as ≤ 35 U/ml and 2-6.8ng/ml, as usual practice in the clinical laboratory of our hospital. The surgical bleeding volume was assessed considering the difference in hemoglobin (Hb) between before surgery and the day after surgery. Patients were surveyed about their degree of satisfaction for the treatment at least three months after surgery through the outpatient interview and were given the following scale: very satisfied, satisfied, uncertain, dissatisfied or very dissatisfied [23]. Statistical analysis Statistical analysis was performed using SPSS version 24.0.0. (SPSS, Chicago, IL, USA) and Graphpad Prism 9.0.0 (Graphpad, San Diego, CA, USA). The normal distribution of continuous variables was tested with the Kolmogorov-Smirnov test. Descriptive statistics are reported as means ± standard deviation (SD) or percentages. Continuous variables were compared using the Student’s t-test. Categorical variables were analyzed by Chi square test and Fisher’s exact test between two groups, while non-parametric variables were compared using Wilcoxon signed-rank test or Kruskal–Wallis test. Logistic regression models were used for multivariate analysis, in which the variables included were those found to have P < 0.05 in the univariate analysis. The odds ratio (OR) and 95% confidence interval (CI) were calculated. Two-sided P < 0.05 was considered statistically significant. Results We enrolled in the study 181 women who underwent hysterectomy as treatment for AM after undergoing a pre-surgical MRI between June 2019 and August 2022. We excluded from analyses the women: >50 years (n = 5), with a history of AM lesion excision (n = 7), that were affected by subtype IV AM (n = 32), and patients for which incomplete information were recorded (n = 6). 131 women were considered for further analyses, among them 77 were in the intrinsic group and 54 in the extrinsic group (Fig. 3 ). All surgical procedures were performed by laparoscopy. The baseline characteristics of women between the two groups are shown in Table 1 . There are no differences between the two groups in terms of age, BMI, duration of menstruation and menstrual cycle. The intrinsic group had a lower education level (p = 0.0118), more gravidity (3.06 ± 1.39 vs 1.78 ± 1.19, P < 0.0001), parity (1.22 ± 0.64 vs 0.80 ± 0.45, P < 0.0001), more abortions (P = 0.0013), endometrial curettage (P = 0.0167) and anemia (P = 0.0015) compared to the extrinsic group. Earlier menarches (13.56 ± 1.08 vs 14.06 ± 1.50 years, P = 0.0257) were observed in extrinsic group, as well as higher likelihood of unmarried status (P = 0.0337), infertility (23.1% vs 6.6%, p = 0.0087), especially primary infertility (83.3% vs 60%, P = 0.006), and previous endometriosis surgery (P = 0.0225). Table 1 Comparison of baseline characteristics of intrinsic and extrinsic group Intrinsic group Extrinsic group P value Age (years) 44.73 ± 4.16 43.43 ± 4.21 0.0823 BMI (kg/m 2 ) 23.69 ± 3.05 23.29 ± 3.17 0.4701 Education level 0.0118* Primary school 7.79 (6/77) 1.85 (1/54) Junior high school 32.46 (25/77) 14.81 (8/54) High school and above 59.74 (46/77) 83.33 (45/54) Menarche age (years) 14.06 ± 1.50 13.56 ± 1.08 0.0257* Duration of menstruation (days) 6.04 ± 1.28 6.43 ± 1.55 0.1212 Menstrual cycle (days) 29.08 ± 8.71 28.81 ± 6.66 0.5464 Marital status 0.0337* Married 93.51 (72/77) 81.48 (44/54) Unmarried 6.49 (5/77) 18.52 (10/54) Gravidity < 0.0001* 0 2.59 (2/77) 14.81 (8/54) 1 11.68 (9/77) 22.22 (12/54) ≥ 2 85.71 (66/77) 62.96 (34/54) Parity < 0.0001* 0 7.79 (6/77) 22.22 (12/54) 1 66.23 (51/77) 75.92 (41/54) ≥ 2 25.97 (20/77) 1.85 (1/54) Cesarean delivery 0.7695 0 54.54 (42/77) 53.70 (29/54) 1 41.55 (32/77) 44.44 (24/54) ≥ 2 3.89 (3/77) 1.85 (1/54) Vaginal delivery 0.0024* 0 46.75 (36/77) 68.51 (37/54) 1 38.96 (30/77) 31.48 (17/54) ≥ 2 14.28 (11/77) 0 (0/54) Infertility 0.0087* No 92.20 (71/77) 76.92 (40/52) Yes 7.79 (6/77) 23.07 (12/52) Infertility types 0.0063* Primary 60.0 (3/5) 83.33 (10/12) Secondary 40.0 (2/5) 16.66 (2/12) Number of abortion 0.0013* 0 12.98 (10/77) 38.88 (21/54) 1 28.57 (22/77) 42.59 (23/54) ≥ 2 58.44 (45/77) 18.51 (10/54) Number of endometrial curettage 0.0167* 0 53.24 (41/77) 74.07 (40/54) 1 33.76 (26/77) 22.22 (12/54) ≥ 2 12.98 (10/77) 3.70 (2/54) Number of endometriosis surgery 0.0225* 0 90.90 (70/77) 68.51 (37/54) 1 7.79 (6/77) 24.07 (13/54) ≥ 2 1.29 (1/77) 7.40 (4/54) Family history of AM 0.7174 No 97.40 (75/77) 96.29 (52/54) Yes 2.59 (2/77) 3.70 (2/54) History of therapy to AM 0.6061 GnRH-a 18.18 (14/77) 27.77 (15/54) ING-IUS 19.48 (15/77) 20.37 (11/54) Progesterone 19.48 (15/77) 14.81 (8/54) Others † 12.98 (10/77) 7.40 (4/54) History of anemia 0.0015* No 19.48 (15/77) 40.74 (22/54) Yes 80.51 (62/77) 51.85 (28/54) History of blood transfusion 3.89 (3/77) 0 (0/54) 0.3826 Comorbidities ‡ 0.1939 No 81.81 (63/77) 72.22 (39/54) Yes 12.98 (14/77) 27.77 (15/54) BMI body mass index (calculated as weight in kilograms divided by the square of height in meters), AM adenomyosis, GnRH-a gonadotropin-releasing hormone-antagonist, LNG-IUS levonorgestrel intrauterine system Others † : including contraception, nonsteroidal anti-inflammatory drug, gestrinone Medicinal comorbidities ‡ : including hypertension, arrhythmia, diabetes mellitus, chronic nephritis, hyperthyroidism, rheumatoid arthritis Values are given as mean ± standard deviation or %(n/N) *Significant In terms of clinical feature, VAS scores (7.91 ± 1.9 vs 6.00 ± 3.50, P = 0.009), comorbidity with OMA (72.7% vs 3.9%, P = 0.0091), DIE (81.1% vs 1.3%, P < 0.0001) and stage IV endometriosis (64.2% vs 1.3%, P < 0.0001) were significantly higher in the extrinsic group. Conversely, higher MVJ scores (5.57 ± 1.90 vs 4.70 ± 1.30, P < 0.0001) and more endometrial hyperplasias (51.95% vs 27.8%, P = 0.0074) were significantly associated with the intrinsic group. This group also presented larger uterine volumes (348.82 ± 155.49 vs 260.30 ± 113.08 cm 3 , P = 0.0054). In terms of AM lesions, the intrinsic group had more diffuse lesions (76.6% vs 14.8%) while the extrinsic group had more focal lesions (85.2% vs 23.4%). The presence of focal lesions in the posterior wall was more frequent in the extrinsic group (95.7% vs 55.6%, P = 0.0023). (Table 2 ). Table 2 Comparison of clinical features of intrinsic and extrinsic group Intrinsic group Extrinsic group P value Dysmenorrhea 0.0354* No dysmenorrhea 10.38 (8/77) 3.70 (2/54) Primary 25.97 (20/77) 46.29 (25/54) Secondary 63.63 (49/77) 50.0 (27/54) VAS 6.00 ± 3.50 7.91 ± 1.91 0.0091* MVJ 5.57 ± 1.90 4.70 ± 1.30 < 0.0001* Leiomyoma 0.1823 No 36.36 (28/77) 50.0 (27/54) Yes 63.63 (49/77) 48.14 (26/54) Leiomyomas maximum diameter (cm) 19.61 ± 16.37 20.78 ± 14.12 0.5424 OMA < 0.0001* No 97.40 (75/77) 27.77 (15/54) Yes 2.59 (2/77) 72.22 (39/54) DIE < 0.0001* No 98.70 (76/77) 20.37 (11/54) Yes 1.30 (1/77) 79.62 (43/54) Stages of endometriosis 0.0015* I 7.79 (6/77) 9.25 (5/54) II 0 5.55 (3/54) III 0 9.25 (5/54) IV 1.29 (1/77) 62.96 (34/54) Endometrial hyperplasia 0.0074* No 48.05 (37/77) 72.22 (39/54) Yes 51.94 (40/77) 27.77 (15/54) Uterine volume (cm 3 ) 348.82 ± 155.49 260.30 ± 113.08 0.0054* Uterine position 0.0673 Anterior 79.22 (61/77) 61.11 (33/54) Median 5.19 (4/77) 12.96 (7/54) Posterior 15.58 (12/77) 25.92 (14/54) Lesion type 0.0016* Focal 23.37 (18/77) 85.18 (46/54) Diffuse 76.62 (59/77) 14.81 (8/54) Location of focal lesion 0.0023* Anterior 33.33 (6/18) 4.34 (2/46) Posterior 55.55 (10/18) 95.65 (44/46) Bottom of uterus 11.11 (2/18) 0 (0/46) Ca125 (U/ml) 133.97 ± 124.38 157.33 ± 128.31 0.3281 AMH (ng/ml) 0.94 ± 1.09 0.79 ± 0.84 0.6171 VAS visual analog scale, MVJ Mansfield–Voda–Jorgensen menstrual bleeding scale, OMA ovarian endometrioma, DIE deep infiltrating endometriosis, r-AFS the revised American Fertility Society (r-AFS) classification for endometriosis, Ca125 carbohydrate antigen 125, AMH anti-Müllerian hormone Values are given as mean ± standard deviation or %(n/N) *Significant The perioperative and postoperative situation were also studied. Women in the extrinsic group had longer surgery durations (185.69 ± 65.40 vs 100.26 ± 22.27 min, P < 0.0001), presented more surgical bleeding (12.15 ± 8.68 vs 6.81 ± 7.78 g/L, P = 0.0013), a higher proportion of excision of OMA or/and DIE (63.0% vs 2.6%, P < 0.0001), and had a higher hospitalization cost (23246.81 ± 3975.89 vs 19278.01 ± 2241.54 RMB, P < 0.0001) compared to intrinsic group. No surgical complications were observed in the intrinsic group, and only one case of complications occurred in the extrinsic group, which resolved well after intraoperative repair. There were no significant differences in the periods after surgery (intrinsic group: 13.4 months vs extrinsic group: 12.6 months), while the use of drug therapy after surgery was markedly higher in the extrinsic group (35.2% vs 2.6%, P = 0.0014). The degree of satisfaction reported by the patients was similar between the two groups (Table 3 ). Table 3 Comparison of perioperative and postoperative situation of intrinsic and extrinsic group Intrinsic group External group P value Surgery duration (min) 100.26 ± 22.27 185.69 ± 65.40 < 0.0001* Hb before operation (g/L) 115.17 ± 15.40 116.67 ± 15.78 0.5881 Surgical bleeding (g/L) 6.81 ± 7.78 12.15 ± 8.68 0.0013* Excision of OMA or/and DIE < 0.0001* No 97.40 (75/77) 37.03 (20/54) Yes 2.59 (2/77) 62.96 (34/54) Postoperative morbidity 0.0644 No 89.61 (69/77) 77.77 (42/54) Yes 10.38 (8/77) 22.22 (12/54) Length of hospitalization (days) 7.91 ± 1.58 8.15 ± 1.58 0.3963 Hospital cost (RMB) 19278.01 ± 2241.54 23246.81 ± 3975.89 < 0.0001* Postoperative drug therapy 0.0014* No 97.40 (75/77) 64.81 (35/54) Yes 2.59 (2/77) 35.18 (19/54) Treatment satisfaction 0.9710 Very satisfied 74.02 (57/77) 75.93 (41/54) Satisfied 23.37 (18/77) 22.22 (12/54) Uncertain 2.59 (2/77) 1.85 (1/54) Dissatisfied 0 (0/77) 0 (0/77) Very dissatisfied 0 (0/77) 0 (0/77) RMB RenMinBi, Yuan, Hb hemoglobin, DIE deeply infiltrating endometriosis Values are given as mean ± standard deviation or %(n/N) *Significant In order to screen potential related factors for intrinsic and extrinsic AM, we conducted a univariate analysis. Education level, age of menarche, gravidity, parity and number of endometrial curettage were included in the analysis of the intrinsic group. Number of endometriosis surgery, OMA, DIE, and endometriosis stage were included in the analysis of the extrinsic group. We then performed logistic regression analysis to adjust for confounding variables. We found that education level, gravidity and number of endometrial curettage remained significantly associated with intrinsic AM. OMA and DIE were independently associated with extrinsic AM (Fig. 4 A and 4 B). Discussion We found that the women affected by intrinsic AM had a higher menstrual volume, easy to cause anemia, and that AM was closely related to the education level of the patients, gravidity and endometrial curettage. Dysmenorrhea was instead more severe in women with extrinsic AM, which was significantly associated with pelvic OMA and DIE. In addition, we observed that the distribution of AM lesions in the two AM subtypes had different characteristics. Surgery duration, bleeding volume, hospital cost, and drug therapy after surgery were all significantly higher in the extrinsic group than in the intrinsic group. Yet the satisfaction levels of patients reported were no different between two subtypes of AM. A number of epidemiological studies have shown that both a history of uterine surgery and multiple births are risk factors for AM [24–26]. Another study has suggested macrophage infiltration in the endometrium may be significantly higher in intrinsic AM than in extrinsic AM [27]. Our study found that the education level of the patients, gravidity, and number of endometrial curettage are all factors closely related to intrinsic AM. This may be due to the trophoblast invasion of the inner myometrium during pregnancy and mechanical factors during surgeries that can damage the endometrial-myometrial interface (EMI), resulting in inflammation. Inflammation in turn could perpetuate oxytocin-mediated uterine activity, local estrogen production, and chronic peristaltic myometrial contractions that are exacerbated with repetitive cycles, leading to endometrial cell migration into the myometrium [28]. We also observed a close relationship between OMA, DIE and extrinsic AM. Comorbidities with DIE and OMA in extrinsic AM cases were respectively 81.1% and 72.7%. Focal lesions mostly occurred in the posterior wall of the uterus (95.7%, 44/46). Previous studies have evaluated the prevalence of DIE in women affected by extrinsic AM to be up to 47–97% [29,30] and observed that 50% of AM lesions of the bladder in cases of AM and DIE were in the anterior wall of the uterus [31]. Data from molecular studies has shown distinct expression patterns of fibrosis related proteins between intrinsic and extrinsic of AM [32]. The lesion’s pattern of gland and stromal cells was the same as in the endometrium in intrinsic AM, the pattern of Ber-EP4-stained glands and CD10-stained stromal cells of extrinsic AM was similar to that of coexistent DIE lesions [29]. Liu et al. have found that the use of tamoxifen and DPN both caused AM in newborn ICR mice, and the lesions caused resembled those found in extrinsic AM cases [33]. We therefore suggest that the origin and pathogenesis of intrinsic and extrinsic AM may differ. We also believe extrinsic AM and pelvic endometriosis, such as OMA or DIE, may share a common epigenetic pathogenesis. Whether pelvic endometriotic lesions invading the uterine serous and AM can cause pelvic endometriosis needs to be further investigated. Meanwhile, subtypes of AM could be possible to prevent by intervening on different factors, for instance, improving the level of education and contraceptive awareness, reducing abortions and curettage may decrease the incidence of intrinsic AM. Dysmenorrhea and menorrhagia are considered classic symptoms of AM [34]. Dysmenorrhea is associated with increased levels of oxytocin receptor (OTR), higher intensity and frequency of uterine contractions, neurological overgrowth within the lesion and the endometrium, and central sensitization [35–37]. Several studies have investigated how intrinsic and extrinsic AM result in pelvic pain and dysmenorrhea and have no difference in intensity [6,18]. Our study reveals that dysmenorrhea is significantly worse in extrinsic AM. Our results also show that the menstrual volume in intrinsic AM cases is significantly higher than in extrinsic AM ones. This is due to the fact that intrinsic AM lesions are close to each other and tend to grow diffusely around to the endometrium, and fibrosis of these lesions is more likely to involve the endometrium, impairing the endometrial repair function [38]. In addition, the foci damaged microvessels are contiguous with decidualized human endometrial stromal cells at the inner myometrium. Larger uterine volume, diffuse lesions, and a higher rate of comorbidity with other endometrial hyperplastic diseases in intrinsic AM can also be the plausible explanation of menorrhagia [39]. In addition, this study we demonstrated that extrinsic AM is associated with primary infertility, consistently with the results of Bourdon et al. [40]. Collecting baseline characteristic and clinical features of patients may contribute to the accurate diagnosis of intrinsic and extrinsic AM. Chen et al. have explored the relationship between the subtypes of AM and the effects of LNG-IUD and discovered that the 3-year efficacy rate was 88.52% for subtype I, 81.54% for subtype II and 57.69% for subtype IV, but subtype IV had a high incidence of recurrence [30,41]. Another study has shown that intrinsic AM is a predictor of serious bleeding risk in patients receiving dienogest (DNG) therapy [42]. Our study shows that extrinsic AM generally coexists with OMA, DIE, and stage IV endometriosis. As a result, longer operation duration and more bleeding can be observed in the extrinsic group during surgery. We recommend that an adequate preoperative evaluation is carried out, and that the surgery is performed by experienced surgeons in order to effectively identify and remove lesions of endometriosis, especially in extrinsic AM. We recognize our study has a few limitations: the participant set consisted of women undergoing hysterectomy, which does not represent the overall AM population, and excluded especially younger women. In addition, the sample size of study is relatively small and it is a single-center study. Future research needs to include a larger population-based prospective study to screen the general population across its lifespan by TVUS or MRI, and follow up on clinical features of different subtypes of AM. In conclusion, intrinsic AM and extrinsic AM have distinctly different clinical characteristics and are associated with different factors. Interestingly, the plasma layer of the uterus is always intact in intrinsic AM cases regardless of the size of the lesions and of the uterine volume, while the plasma layer of the uterus is always invaded in extrinsic AM. The pathogenesis of these two AM subtypes warrants further investigation. Declarations Funding This work was supported by Shanghai Municipal Commission of Science and Technology Program [grant 22Y11906400]. Ethics Approval The present study was approved by the institutional ethics committee of the International Peace Maternity and Child Health Hospital (approval No. GKLW 2022-16). Consent for Publication The authors contributed to the study and consented to its submission after the final review. Competing Interests The authors declare no competing interests. Author contributions: Conception and design by Yan Liang and Jian Zhang, administrative support by Wei Shi and Feng Sun, provision of study materials or patients by Yan Liang and Yuan Liu, collection and assembly of data by Yuan Liu and Minjiao Zhu, data analysis and interpretation by Yan Liang and Wei Shi; All authors discussed the results, contributed to the manuscript writing, and approved the version for publication. References Gan L, Li Y, Chen Y, et al. 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Clinicopathological features of different subtypes in adenomyosis: Focus on early lesions. PLoS One.2021; 16:e0254147. C. Bergeron, F. Amant, A. Ferenczy. Pathology and physiopathology of adenomyosis. Best Pract Res Clin Obstet Gynaecol.2006; 20:511-21. C.B. Gilks, P.B. Clement, W.R. Hart, et al.Uterine adenomyomas excluding atypical polypoid adenomyomas and adenomyomas of endocervical type: a clinicopathologic study of 30 cases of an underemphasized lesion that may cause diagnostic problems with brief consideration of adenomyomas of other female genital tract sites. Int J Gynecol Pathol.2000; 19:195-205. Huskisson EC. Measurement of pain. Lancet.1974; 304:1127-31. Exacoustos C, Morosetti G, Conway F, et al. New sonographic classification of adenomyosis: Do Type and Degree of Adenomyosis Correlate to Severity of Symptoms? J Minim Invasive Gynecol. 2020;27:1308-15. Mansfield PK, Voda A, Allison G. Validating a pencil-and-paper measure of perimenopausal menstrual blood loss. Women’s Health Issues.2004; 14:24-7. Marcoux S, Maheux R, Berube S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis. N Engl J Med.1997; 337:217-22. Lee KH, Kim JK, Lee MA, et al. Relationship between uterine volume and discontinuation of treatment with levonorgestrel-releasing intrauterine devices in patients with adenomyosis. Arch Gynecol Obstet.2016; 294:561-6. Gong J, Chen L, Zhang D. Efficiency of postoperative ovulation induction on infertile women with minimal-mild endometriosis. Sichuan Da Xue Xue Bao Yi Xue Ban.2013; 44:677-80. Sheng J, Zhang WY, Zhang JP, et al. The LNG-IUS study on adenomyosis: a 3-year follow-up study on the efficacy and side effects of the use of levonorgestrel intrauterine system for the treatment of dysmenorrhea associated with adenomyosis. Contraception.2009; 79:189-93. Taran FA, Weaver AL, Coddington CC, et al. Understanding adenomyosis: a case control study. Fertil Steril.2010; 94:1223-28. Levgur M, Abadi MA, Tucker A. Adenomyosis: symptoms, histology, and pregnancy terminations. Obstet Gynecol.2000; 95:688-91. Templeman C, Marshall SF, Ursin G, et al. Adenomyosis and endometriosis in the California teachers study. Fertil Steril.2008; 90:415-24. Khan KN, Fujishita A, Ogawa K, et al. Occurrence of chronic endometritis in different types of human adenomyosis. Reprod Med Biol.2021;21:e12421. Guo SW. The Pathogenesis of Adenomyosis vis-à-vis Endometriosis. J Clin Med. 2020;9:485. Khan KN, Fujishita A, Koshiba A, et al. A Biological differences between intrinsic and extrinsic adenomyosis with coexisting deep infiltrating endometriosis. Reprod Biomed Online.2019; 39:343-53. Donnez J, Dolmans MM, Fellah L. What if deep endometriotic nodules and uterine adenomyosis were actually two forms of the same disease? Fertil Steril.2019; 111:454-6. Marcellin L, Santulli P, Bortolato S, et al. Anterior focal adenomyosis and bladder deep infiltrating endometriosis: Is there a link? J Minim Invasive Gynecol.2018; 25:896–901. Kishi Y, Shimada K, Fujii T, et al. Phenotypic characterization of adenomyosis occurring at the inner and outer myometrium. PLoS One.2017; 12:e0189522. Cao Y, Wang X, Liu X, et al. Neonatal feeding of an estrogen receptor β (ERβ) agonist induces external adenomyosis-like lesions in ICR mouse. Reprod Dev Med.2022; 6:144-51. Israel SL, Woutersz TB. Adenomyosis; a neglected diagnosis. Obstet Gynecol. 1959; 14:168–73. Greaves E, Collins F, Esnal-Zufiaurre A, et al. Estrogen receptor (ER) agonists differentially regulate neuroangiogenesis in peritoneal endometriosis via the repellent factor SLIT3. Endocrinology.2014;155: 4015-26. Guo SW, Mao XY, Ma QL, et al. Dysmenorrhea and its severity are associated with increased uterine contractility and overexpression of oxytocin receptor (OTR) in women with symptomatic adenomyosis. Fertil Steril.2013; 99:231-40. He WW, Liu XS, Zhang YQ, et al. Generalized hyperalgesia in women with endometriosis and its resolution following a successful surgery. Reprod Sci.2010; 17:1099-111. Huang QQ, Liu XS, Critchley H, et al. How does the extent of fibrosis in adenomyosis lesions contribute to heavy menstrual bleeding? Reprod Med Biol.2022; 21:e12442. Bourdon M, Santulli P, Oliveira J, et al. Focal adenomyosis is associated with primary infertility.Fertil Steril.2020; 114:1271-7. Gordts S, Grimbizis G, Campo R. Symptoms and classification of uterine adenomyosis, including the place of hysteroscopy in diagnosis. Fertil Steril.2018; 109:380-8.e1. Chen S, Wang J, Sun W, et al. Efficacy of the levonorgestrel-releasing intrauterine device is associated with different subtypes of adenomyosis: a retrospective study. Ann Transl Med.2020;8:1356. Matsubara S, Kawaguchi R, Akinishi M, et al. Subtype I (intrinsic) adenomyosis is an independent risk factor for dienogest-related serious unpredictable bleeding in patients with symptomatic adenomyosis.Sci Rep. 2019;27:17654. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2752816","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":195797356,"identity":"e5f8ef6f-8b44-426c-8b39-5d593b0543a3","order_by":0,"name":"Yan Liang","email":"","orcid":"","institution":"International Peace Maternity and Child Health Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Liang","suffix":""},{"id":195797357,"identity":"3f45aed9-802e-42ac-96f1-83ca51ff44f8","order_by":1,"name":"Wei Shi","email":"","orcid":"","institution":"International Peace Maternity and Child Health Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Shi","suffix":""},{"id":195797358,"identity":"4868ba59-efe1-49aa-a041-76b8ffe20e56","order_by":2,"name":"Feng Sun","email":"","orcid":"","institution":"International Peace Maternity and Child Health Hospital","correspondingAuthor":false,"prefix":"","firstName":"Feng","middleName":"","lastName":"Sun","suffix":""},{"id":195797359,"identity":"a893168f-8241-408f-811b-6ad56384544c","order_by":3,"name":"Minjiao Zhu","email":"","orcid":"","institution":"International Peace Maternity and Child Health Hospital","correspondingAuthor":false,"prefix":"","firstName":"Minjiao","middleName":"","lastName":"Zhu","suffix":""},{"id":195797360,"identity":"e52f656f-e142-4b00-b33d-4d2374283630","order_by":4,"name":"Yuan Liu","email":"","orcid":"","institution":"International Peace Maternity and Child Health Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Liu","suffix":""},{"id":195797361,"identity":"c2474175-c790-4bf6-ad2d-157b86b5fc68","order_by":5,"name":"Jian Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIiWNgGAWjYDACCRDBAyYZDBgYbHj42RtI0XKAIU1GsucAMVpg4ADDYRuDGw74dcjPbn728IuMhbw5A/uD4o9t53kYbjAwfviYg1sL45xj5sYyPBKGOxt4DAwOtt3mYZzdwCw5cxtuLcwSCWbSEjwSjBsO8DCAtTDLHGBj5sWjhU0i/RtIi/2GA+wPgFrO8bBJJODXwiORYyb5gUciccMBBpDDDvDwENIiIZFTJg3UmAx0mIHBmXPJPBI8B5vx+kV+Rvo2yZ89dbZAhz0zqCizs7c/3nzww0c8WsBBwNsD0vyAzQDCZ2zArx6k5McPiNYHBJWOglEwCkbBiAQAuVVMNsN19HcAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-6119-4388","institution":"International Peace Maternity and Child Health Hospital","correspondingAuthor":true,"prefix":"","firstName":"Jian","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2023-03-29 15:57:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2752816/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2752816/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":36544941,"identity":"5948bafc-84ac-422a-bbeb-920d2f0bcce5","added_by":"auto","created_at":"2023-05-02 20:53:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":555304,"visible":true,"origin":"","legend":"\u003cp\u003eT2-weighted MRI photograph of intrinsic AM. A and B: the AM lesions in the posterior wall of uterine; C and D: the AM lesion in the anterior wall of the uterus. (white arrow)\u003c/p\u003e","description":"","filename":"fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-2752816/v1/ab695e509a1220ce3f95ba01.png"},{"id":36544940,"identity":"76014324-deb6-4890-8d50-02925475f065","added_by":"auto","created_at":"2023-05-02 20:53:49","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":617747,"visible":true,"origin":"","legend":"\u003cp\u003eT2-weighted MRI photograph of extrinsic AM. A and B: focal AM lesions (white arrow) in the posterior wall of uterine combined with DIE (yellow star) and OMA (red triangle); C and D: the AM lesion in the posterior wall of the uterus (white arrow) and adhered to the rectum (yellow arrow)\u003c/p\u003e","description":"","filename":"fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-2752816/v1/4f821ae664995631d2cfc7a6.png"},{"id":36545657,"identity":"f948a7ab-7815-471a-a68d-f1d4064c0ac8","added_by":"auto","created_at":"2023-05-02 21:01:49","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":600961,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAM\u003c/em\u003e adenomyosis, \u003cem\u003eMRI\u003c/em\u003e magnetic resonance imaging\u003c/p\u003e","description":"","filename":"fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-2752816/v1/b1732beaad8eed023e678976.png"},{"id":36544943,"identity":"3c4aea6a-3fdb-4a5d-8e9e-ab2a1857c617","added_by":"auto","created_at":"2023-05-02 20:53:49","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":489098,"visible":true,"origin":"","legend":"\u003cp\u003eMultivariate analysis of related factors in different types of adenomyosis. A: in intrinsic adenomyosis; B: \u0026nbsp;in extrinsic adenomyosis\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOMA \u003c/em\u003eovarian endometrioma, \u003cem\u003eDIE\u003c/em\u003e deep infiltrating endometriosis, \u003cem\u003eOR\u003c/em\u003e odds ratio, \u003cem\u003eCI\u003c/em\u003e confidence interval, a multiple logistic regression analysis\u003c/p\u003e","description":"","filename":"fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-2752816/v1/115ab2e79572ae20be721e59.png"},{"id":40159739,"identity":"6d5ae1ab-9737-4297-9890-ceab9e81837b","added_by":"auto","created_at":"2023-07-18 00:55:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2276889,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2752816/v1/31011629-efac-4468-9d38-ebf8d158401b.pdf"}],"financialInterests":"","formattedTitle":"Differences clinical characteristics and factors in intrinsic and extrinsic adenomyosis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAdenomyosis (AM) is a disorder of the uterus which has a substantial impact on both the physical and psychological health of women. AM consists in endometrial glands and stroma invading the myometrium, a phenomenon which is accompanied by hypertrophy and hyperplasia of the surrounding myometrial tissues [1], causing dysmenorrhea (15%-30%), menorrhagia (40%-60%) [2], and in some cases even infertility (7.5%-24.4%) [3]. It is estimated over the last 50 years prevalence of AM among performed hysterectomy women has ranged from 8.8\u0026ndash;61.5% [4]. The exact pathogenesis and etiology of AM have not yet been fully understood. There are currently two main theories about the origin of AM: an invagination of the endometrial basalis into the myometrium or a de novo consequence of the metaplasia of embryonic M\u0026uuml;llerian remnants [5].\u003c/p\u003e \u003cp\u003eWith the advancements in transvaginal ultrasonography (TVUS) and magnetic resonance imaging (MRI), AM can now be diagnosed based on imaging parameters [6]. MRI has high sensitivity (70%-93%) and specificity (86%-93%) for the diagnosis of AM [7\u0026ndash;9]. Yet the classification of AM is diverse [10,11]. Pistofidis \u003cem\u003eet al.\u003c/em\u003e [12] have classified AM into diffuse, focal AM, and cystic adenomyoma, based on the different manifestations of the myometrium in MRI. According to assessment of the positional relationship between the AM lesions and other structural components by MRI, Kishi \u003cem\u003eet al.\u003c/em\u003e [13] have proposed the most comprehensive and widely accepted classification of AM in four subtypes. Among these, intrinsic AM (subtype I: lesions occur in the inner myometrium) and extrinsic AM (subtype II: lesions occur in the outer myometrium) account respectively for 31.5% and 43.9% of the cases [6].\u003c/p\u003e \u003cp\u003ePrevious studies have suggested hypothesis that intrinsic AM may be a product of direct endometrial invasion involving inner-mid myometrium, while extrinsic AM could be caused by pelvic endometriosis invading the uterine serous and the outer myometrium [13,14]. In addition, AM is a highly heterogeneous disease with several possible clinical manifestations, the relationship between AM subtypes and clinical characteristics is still not clear. The aim of our study is to compare baseline characteristics, clinic features, perioperative and postoperative conditions in women diagnosed with intrinsic or extrinsic AM by MRI, and who underwent hysterectomies as treatment. In-depth research on clinical data of women affected by different subtypes of AM is needed to perform prevention, get accurate diagnoses and treatments. Such research would also provide a clinical basis for further studies on the pathogenic mechanisms underlying the disease.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and ethic\u003c/h2\u003e \u003cp\u003eWe performed a retrospective observational study recruiting women who underwent hysterectomy as AM treatment at the International Peace Maternity and Child Health Hospital affiliated to the Shanghai Jiao Tong University between June 2019 and August 2022. The study was approved by the institutional ethics committee of the International Peace Maternity and Child Health Hospital (approval No. GKLW 2022-16). Data was fully anonymized.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePopulation study and collected data\u003c/h2\u003e \u003cp\u003eThe inclusion criteria were the following: 1) age\u0026thinsp;\u0026gt;\u0026thinsp;18 and \u0026lt;\u0026thinsp;50 years, premenopausal; 2) did not received any hormone treatment for at least six months before the hysterectomy and condition histopathologically proven to be AM; 3) MRI examination on T1 and T2-weighted sequences prior to surgery and condition determined to be intrinsic or extrinsic AM. All MRI images were evaluated by two senior radiologists unaware of the clinical data of the patients. When the diagnosis of the two radiologists were different, a third senior radiologist was invited to give a further diagnosis. Exclusion criteria were the following: 1) previous excision of an AM lesion; 2) cancer or infectious disease; 3) incomplete information available. Women were then classified into two groups: the intrinsic AM group (intrinsic group) and the extrinsic AM group (extrinsic group).\u003c/p\u003e \u003cp\u003eData on baseline characteristics, clinical features, and perioperative data were obtained from the internal database of the hospital, while the postoperative of information was collected from outpatient interview data.\u003c/p\u003e \u003cp\u003eThe baseline characteristics collected included age, body mass index (BMI), education level, age of menarche, duration of menstruations, menstrual cycle, marital status, gravidity, parity, previous deliveries (cesarean or vaginal delivery), infertility, number of abortions, endometrial curettage, endometriosis surgery, drug therapy for AM (gonadotropin-releasing hormone-antagonist (GnRH-a), levonorgestrel intrauterine system (ING-IUS), progesterone, contraception, nonsteroidal anti-inflammatory drug, gestrinone), family history of AM, history of anemia, history of blood transfusion and presence of comorbidities. Clinical features collected were the intensity of dysmenorrhea, menstrual blood volume, presence of ovarian endometrioma (OMA), deep infiltrating endometriosis (DIE), endometrial hyperplasia, leiomyomas, stage of endometriosis, serum levels of carbohydrate antigen (Ca125), and Anti-Mullerian hormone (AMH). We also recorded uterine volume and position, if the lesions were focal or diffuse, and location of focal lesions based on MRI images. Surgery duration, bleeding, complications (intestinal, ureteral, bladder injury, large vessel injury, blood transfusion, conversion to laparotomy), postoperative morbidity, length of hospitalization, hospital cost, and drug therapy after the operation (GnRH-a, progesterone, contraceptives) were noted. The degree of satisfaction of treatment was also recorded. The collected data was independently checked by two researchers to ensure that there were no inconsistencies or errors.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eCriteria of evaluation\u003c/h2\u003e \u003cp\u003eAM cases were categorized into four subtypes depending on the characteristics of the lesions and on the MRI images based on Kishi\u0026rsquo;s criterion [13]:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eSubtype I (intrinsic): AM lesions occur in the uterine inner layer without affecting the outer structures.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSubtype II (extrinsic): AM lesions occur in the uterine outer layer without affecting the inner structures, with healthy muscular structures between the lesions and the junction zone (JZ).\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSubtype III (intramural): AM lesions occur solitarily without relationship to structural components.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSubtype IV: AM lesions do not satisfy any previously listed criteria.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eT2-weighted MRI images of intrinsic and extrinsic AM are shown in Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eDiffuse and focal lesions were classified based on the following criteria: a diffuse lesion is characterized by foci of endometrial mucosa (glands and stroma) scattered throughout the uterine musculature, while a focal lesion is restricted in an area of hypertrophic and distorted endometrium and myometrium [14\u0026ndash;16].\u003c/p\u003e \u003cp\u003eDysmenorrhea intensity was evaluated with a Visual Analog Scale (VAS) system, using a 10 cm line where 0 represents \u0026ldquo;no pain\u0026rdquo; and 10 \u0026ldquo;maximum pain\u0026rdquo;. A VAS score\u0026thinsp;\u0026ge;\u0026thinsp;7 was considered to be severe pain [17,18]. Menstrual blood volume was assessed using the Mansfield\u0026ndash;Voda\u0026ndash;Jorgensen menstrual bleeding scale (MVJ), ranging from 1 (spotting) to 6 (gushing), and menorrhagia was defined as a MVJ score\u0026thinsp;\u0026ge;\u0026thinsp;5 [19]. 12 months or more of unprotected intercourse not resulting in pregnancy was considered as infertility [20]. The uterine volume was calculated by three-dimensional MRI examination using the following formula:\u003c/p\u003e \u003cp\u003evolume\u0026thinsp;=\u0026thinsp;A \u0026times; B \u0026times; C \u0026times; 0.52\u003c/p\u003e \u003cp\u003ewhere A, B and C represent respectively the length, width, and depth of the uterus [21]. The stage of endometriosis was evaluated according to the revised American Fertility Society classification (r-AFS): score 1\u0026ndash;5\u0026thinsp;=\u0026thinsp;stage I; score 6\u0026ndash;15\u0026thinsp;=\u0026thinsp;stage II; score 16\u0026ndash;40\u0026thinsp;=\u0026thinsp;stage Ⅲ; score\u0026thinsp;\u0026gt;\u0026thinsp;40\u0026thinsp;=\u0026thinsp;stage Ⅳ [22]. The normal serum levels of Ca125 and AMH were defined respectively as \u0026le;\u0026thinsp;35 U/ml and 2-6.8ng/ml, as usual practice in the clinical laboratory of our hospital. The surgical bleeding volume was assessed considering the difference in hemoglobin (Hb) between before surgery and the day after surgery. Patients were surveyed about their degree of satisfaction for the treatment at least three months after surgery through the outpatient interview and were given the following scale: very satisfied, satisfied, uncertain, dissatisfied or very dissatisfied [23].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS version 24.0.0. (SPSS, Chicago, IL, USA) and Graphpad Prism 9.0.0 (Graphpad, San Diego, CA, USA). The normal distribution of continuous variables was tested with the Kolmogorov-Smirnov test. Descriptive statistics are reported as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or percentages. Continuous variables were compared using the Student\u0026rsquo;s t-test. Categorical variables were analyzed by Chi square test and Fisher\u0026rsquo;s exact test between two groups, while non-parametric variables were compared using Wilcoxon signed-rank test or Kruskal\u0026ndash;Wallis test. Logistic regression models were used for multivariate analysis, in which the variables included were those found to have P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 in the univariate analysis. The odds ratio (OR) and 95% confidence interval (CI) were calculated. Two-sided P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eWe enrolled in the study 181 women who underwent hysterectomy as treatment for AM after undergoing a pre-surgical MRI between June 2019 and August 2022. We excluded from analyses the women: \u0026gt;50 years (n\u0026thinsp;=\u0026thinsp;5), with a history of AM lesion excision (n\u0026thinsp;=\u0026thinsp;7), that were affected by subtype IV AM (n\u0026thinsp;=\u0026thinsp;32), and patients for which incomplete information were recorded (n\u0026thinsp;=\u0026thinsp;6). 131 women were considered for further analyses, among them 77 were in the intrinsic group and 54 in the extrinsic group (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). All surgical procedures were performed by laparoscopy.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe baseline characteristics of women between the two groups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There are no differences between the two groups in terms of age, BMI, duration of menstruation and menstrual cycle. The intrinsic group had a lower education level (p\u0026thinsp;=\u0026thinsp;0.0118), more gravidity (3.06\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39 vs 1.78\u0026thinsp;\u0026plusmn;\u0026thinsp;1.19, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), parity (1.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64 vs 0.80\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), more abortions (P\u0026thinsp;=\u0026thinsp;0.0013), endometrial curettage (P\u0026thinsp;=\u0026thinsp;0.0167) and anemia (P\u0026thinsp;=\u0026thinsp;0.0015) compared to the extrinsic group. Earlier menarches (13.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08 vs 14.06\u0026thinsp;\u0026plusmn;\u0026thinsp;1.50 years, P\u0026thinsp;=\u0026thinsp;0.0257) were observed in extrinsic group, as well as higher likelihood of unmarried status (P\u0026thinsp;=\u0026thinsp;0.0337), infertility (23.1% vs 6.6%, p\u0026thinsp;=\u0026thinsp;0.0087), especially primary infertility (83.3% vs 60%, P\u0026thinsp;=\u0026thinsp;0.006), and previous endometriosis surgery (P\u0026thinsp;=\u0026thinsp;0.0225).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of baseline characteristics of intrinsic and extrinsic group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntrinsic group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eExtrinsic group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.73\u0026thinsp;\u0026plusmn;\u0026thinsp;4.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.43\u0026thinsp;\u0026plusmn;\u0026thinsp;4.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0823\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI (kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.69\u0026thinsp;\u0026plusmn;\u0026thinsp;3.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.29\u0026thinsp;\u0026plusmn;\u0026thinsp;3.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.4701\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEducation level\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0118*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.79 (6/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.85 (1/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJunior high school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.46 (25/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.81 (8/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school and above\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.74 (46/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.33 (45/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMenarche age (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.06\u0026thinsp;\u0026plusmn;\u0026thinsp;1.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0257*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration of menstruation (days)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.43\u0026thinsp;\u0026plusmn;\u0026thinsp;1.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1212\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMenstrual cycle (days)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.08\u0026thinsp;\u0026plusmn;\u0026thinsp;8.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.81\u0026thinsp;\u0026plusmn;\u0026thinsp;6.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5464\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMarital status\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0337*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarried\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93.51 (72/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81.48 (44/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnmarried\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.49 (5/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.52 (10/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGravidity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.59 (2/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.81 (8/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.68 (9/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.22 (12/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85.71 (66/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.96 (34/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eParity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.79 (6/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.22 (12/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.23 (51/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.92 (41/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.97 (20/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.85 (1/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCesarean delivery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7695\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.54 (42/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.70 (29/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.55 (32/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.44 (24/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.89 (3/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.85 (1/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVaginal delivery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0024*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46.75 (36/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.51 (37/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.96 (30/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.48 (17/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.28 (11/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInfertility\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0087*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92.20 (71/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.92 (40/52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.79 (6/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.07 (12/52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInfertility types\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0063*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.0 (3/5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.33 (10/12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.0 (2/5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.66 (2/12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of abortion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0013*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.98 (10/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.88 (21/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.57 (22/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.59 (23/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58.44 (45/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.51 (10/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eendometrial curettage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0167*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53.24 (41/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74.07 (40/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.76 (26/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.22 (12/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.98 (10/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.70 (2/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eendometriosis surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0225*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90.90 (70/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.51 (37/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.79 (6/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.07 (13/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.29 (1/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.40 (4/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFamily history of AM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7174\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97.40 (75/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96.29 (52/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.59 (2/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.70 (2/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of therapy to AM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6061\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGnRH-a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.18 (14/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.77 (15/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eING-IUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.48 (15/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.37 (11/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgesterone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.48 (15/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.81 (8/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.98 (10/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.40 (4/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of anemia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0015*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.48 (15/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.74 (22/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80.51 (62/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.85 (28/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of blood transfusion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.89 (3/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3826\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComorbidities\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026Dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1939\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81.81 (63/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.22 (39/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.98 (14/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.77 (15/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eBMI\u003c/em\u003e body mass index (calculated as weight in kilograms divided by the square of height in meters), \u003cem\u003eAM\u003c/em\u003e adenomyosis, \u003cem\u003eGnRH-a\u003c/em\u003e gonadotropin-releasing hormone-antagonist, \u003cem\u003eLNG-IUS\u003c/em\u003e levonorgestrel intrauterine system\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eOthers\u003csup\u003e\u0026dagger;\u003c/sup\u003e: including contraception, nonsteroidal anti-inflammatory drug, gestrinone\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eMedicinal comorbidities\u003csup\u003e\u0026Dagger;\u003c/sup\u003e: including hypertension, arrhythmia, diabetes mellitus, chronic nephritis, hyperthyroidism, rheumatoid arthritis\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eValues are given as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or %(n/N)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*Significant\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn terms of clinical feature, VAS scores (7.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9 vs 6.00\u0026thinsp;\u0026plusmn;\u0026thinsp;3.50, P\u0026thinsp;=\u0026thinsp;0.009), comorbidity with OMA (72.7% vs 3.9%, P\u0026thinsp;=\u0026thinsp;0.0091), DIE (81.1% vs 1.3%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and stage IV endometriosis (64.2% vs 1.3%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) were significantly higher in the extrinsic group. Conversely, higher MVJ scores (5.57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.90 vs 4.70\u0026thinsp;\u0026plusmn;\u0026thinsp;1.30, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and more endometrial hyperplasias (51.95% vs 27.8%, P\u0026thinsp;=\u0026thinsp;0.0074) were significantly associated with the intrinsic group. This group also presented larger uterine volumes (348.82\u0026thinsp;\u0026plusmn;\u0026thinsp;155.49 vs 260.30\u0026thinsp;\u0026plusmn;\u0026thinsp;113.08 cm\u003csup\u003e3\u003c/sup\u003e, P\u0026thinsp;=\u0026thinsp;0.0054). In terms of AM lesions, the intrinsic group had more diffuse lesions (76.6% vs 14.8%) while the extrinsic group had more focal lesions (85.2% vs 23.4%). The presence of focal lesions in the posterior wall was more frequent in the extrinsic group (95.7% vs 55.6%, P\u0026thinsp;=\u0026thinsp;0.0023). (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of clinical features of intrinsic and extrinsic group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntrinsic group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eExtrinsic group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDysmenorrhea\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0354*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo dysmenorrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.38 (8/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.70 (2/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.97 (20/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.29 (25/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63.63 (49/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.0 (27/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVAS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.00\u0026thinsp;\u0026plusmn;\u0026thinsp;3.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0091*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMVJ\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.70\u0026thinsp;\u0026plusmn;\u0026thinsp;1.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLeiomyoma\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1823\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.36 (28/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.0 (27/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63.63 (49/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48.14 (26/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLeiomyomas maximum diameter (cm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.61\u0026thinsp;\u0026plusmn;\u0026thinsp;16.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.78\u0026thinsp;\u0026plusmn;\u0026thinsp;14.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5424\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOMA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97.40 (75/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.77 (15/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.59 (2/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.22 (39/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDIE\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98.70 (76/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.37 (11/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.30 (1/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79.62 (43/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStages of endometriosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0015*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.79 (6/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.25 (5/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.55 (3/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.25 (5/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.29 (1/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.96 (34/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEndometrial hyperplasia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0074*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.05 (37/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.22 (39/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51.94 (40/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.77 (15/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUterine volume (cm\u003c/b\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e348.82\u0026thinsp;\u0026plusmn;\u0026thinsp;155.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e260.30\u0026thinsp;\u0026plusmn;\u0026thinsp;113.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0054*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUterine position\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0673\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79.22 (61/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.11 (33/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.19 (4/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.96 (7/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePosterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.58 (12/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.92 (14/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLesion type\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0016*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.37 (18/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85.18 (46/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiffuse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76.62 (59/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.81 (8/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLocation of focal lesion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0023*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.33 (6/18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.34 (2/46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePosterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.55 (10/18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95.65 (44/46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBottom of uterus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.11 (2/18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0/46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCa125 (U/ml)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e133.97\u0026thinsp;\u0026plusmn;\u0026thinsp;124.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e157.33\u0026thinsp;\u0026plusmn;\u0026thinsp;128.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3281\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAMH (ng/ml)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;1.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6171\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eVAS\u003c/em\u003e visual analog scale, \u003cem\u003eMVJ\u003c/em\u003e Mansfield\u0026ndash;Voda\u0026ndash;Jorgensen menstrual bleeding scale, \u003cem\u003eOMA\u003c/em\u003e ovarian endometrioma, \u003cem\u003eDIE\u003c/em\u003e deep infiltrating endometriosis, \u003cem\u003er-AFS\u003c/em\u003e the revised American Fertility Society (r-AFS) classification for endometriosis, \u003cem\u003eCa125\u003c/em\u003e carbohydrate antigen 125, \u003cem\u003eAMH\u003c/em\u003e anti-M\u0026uuml;llerian hormone\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eValues are given as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or %(n/N)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*Significant\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe perioperative and postoperative situation were also studied. Women in the extrinsic group had longer surgery durations (185.69\u0026thinsp;\u0026plusmn;\u0026thinsp;65.40 vs 100.26\u0026thinsp;\u0026plusmn;\u0026thinsp;22.27 min, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), presented more surgical bleeding (12.15\u0026thinsp;\u0026plusmn;\u0026thinsp;8.68 vs 6.81\u0026thinsp;\u0026plusmn;\u0026thinsp;7.78 g/L, P\u0026thinsp;=\u0026thinsp;0.0013), a higher proportion of excision of OMA or/and DIE (63.0% vs 2.6%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), and had a higher hospitalization cost (23246.81\u0026thinsp;\u0026plusmn;\u0026thinsp;3975.89 vs 19278.01\u0026thinsp;\u0026plusmn;\u0026thinsp;2241.54 RMB, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) compared to intrinsic group. No surgical complications were observed in the intrinsic group, and only one case of complications occurred in the extrinsic group, which resolved well after intraoperative repair. There were no significant differences in the periods after surgery (intrinsic group: 13.4 months vs extrinsic group: 12.6 months), while the use of drug therapy after surgery was markedly higher in the extrinsic group (35.2% vs 2.6%, P\u0026thinsp;=\u0026thinsp;0.0014). The degree of satisfaction reported by the patients was similar between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of perioperative and postoperative situation of intrinsic and extrinsic group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntrinsic group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eExternal group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgery duration (min)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100.26\u0026thinsp;\u0026plusmn;\u0026thinsp;22.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e185.69\u0026thinsp;\u0026plusmn;\u0026thinsp;65.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHb before operation (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115.17\u0026thinsp;\u0026plusmn;\u0026thinsp;15.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116.67\u0026thinsp;\u0026plusmn;\u0026thinsp;15.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5881\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgical bleeding (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.81\u0026thinsp;\u0026plusmn;\u0026thinsp;7.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.15\u0026thinsp;\u0026plusmn;\u0026thinsp;8.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0013*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExcision of OMA or/and DIE\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97.40 (75/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.03 (20/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.59 (2/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.96 (34/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostoperative morbidity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0644\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89.61 (69/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77.77 (42/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.38 (8/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.22 (12/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLength of hospitalization (days)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.15\u0026thinsp;\u0026plusmn;\u0026thinsp;1.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3963\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHospital cost (RMB)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19278.01\u0026thinsp;\u0026plusmn;\u0026thinsp;2241.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23246.81\u0026thinsp;\u0026plusmn;\u0026thinsp;3975.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostoperative drug\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003etherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0014*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97.40 (75/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.81 (35/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.59 (2/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.18 (19/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment satisfaction\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9710\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVery satisfied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74.02 (57/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.93 (41/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSatisfied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.37 (18/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.22 (12/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUncertain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.59 (2/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.85 (1/54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDissatisfied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVery dissatisfied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0/77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eRMB\u003c/em\u003e RenMinBi, Yuan, \u003cem\u003eHb\u003c/em\u003e hemoglobin, \u003cem\u003eDIE\u003c/em\u003e deeply infiltrating endometriosis\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eValues are given as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or %(n/N)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*Significant\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn order to screen potential related factors for intrinsic and extrinsic AM, we conducted a univariate analysis. Education level, age of menarche, gravidity, parity and number of endometrial curettage were included in the analysis of the intrinsic group. Number of endometriosis surgery, OMA, DIE, and endometriosis stage were included in the analysis of the extrinsic group. We then performed logistic regression analysis to adjust for confounding variables. We found that education level, gravidity and number of endometrial curettage remained significantly associated with intrinsic AM. OMA and DIE were independently associated with extrinsic AM (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe found that the women affected by intrinsic AM had a higher menstrual volume, easy to cause anemia, and that AM was closely related to the education level of the patients, gravidity and endometrial curettage. Dysmenorrhea was instead more severe in women with extrinsic AM, which was significantly associated with pelvic OMA and DIE. In addition, we observed that the distribution of AM lesions in the two AM subtypes had different characteristics. Surgery duration, bleeding volume, hospital cost, and drug therapy after surgery were all significantly higher in the extrinsic group than in the intrinsic group. Yet the satisfaction levels of patients reported were no different between two subtypes of AM.\u003c/p\u003e \u003cp\u003eA number of epidemiological studies have shown that both a history of uterine surgery and multiple births are risk factors for AM [24\u0026ndash;26]. Another study has suggested macrophage infiltration in the endometrium may be significantly higher in intrinsic AM than in extrinsic AM [27]. Our study found that the education level of the patients, gravidity, and number of endometrial curettage are all factors closely related to intrinsic AM. This may be due to the trophoblast invasion of the inner myometrium during pregnancy and mechanical factors during surgeries that can damage the endometrial-myometrial interface (EMI), resulting in inflammation. Inflammation in turn could perpetuate oxytocin-mediated uterine activity, local estrogen production, and chronic peristaltic myometrial contractions that are exacerbated with repetitive cycles, leading to endometrial cell migration into the myometrium [28]. We also observed a close relationship between OMA, DIE and extrinsic AM. Comorbidities with DIE and OMA in extrinsic AM cases were respectively 81.1% and 72.7%. Focal lesions mostly occurred in the posterior wall of the uterus (95.7%, 44/46). Previous studies have evaluated the prevalence of DIE in women affected by extrinsic AM to be up to 47\u0026ndash;97% [29,30] and observed that 50% of AM lesions of the bladder in cases of AM and DIE were in the anterior wall of the uterus [31]. Data from molecular studies has shown distinct expression patterns of fibrosis related proteins between intrinsic and extrinsic of AM [32]. The lesion\u0026rsquo;s pattern of gland and stromal cells was the same as in the endometrium in intrinsic AM, the pattern of Ber-EP4-stained glands and CD10-stained stromal cells of extrinsic AM was similar to that of coexistent DIE lesions [29]. Liu \u003cem\u003eet al.\u003c/em\u003e have found that the use of tamoxifen and DPN both caused AM in newborn ICR mice, and the lesions caused resembled those found in extrinsic AM cases [33]. We therefore suggest that the origin and pathogenesis of intrinsic and extrinsic AM may differ. We also believe extrinsic AM and pelvic endometriosis, such as OMA or DIE, may share a common epigenetic pathogenesis. Whether pelvic endometriotic lesions invading the uterine serous and AM can cause pelvic endometriosis needs to be further investigated. Meanwhile, subtypes of AM could be possible to prevent by intervening on different factors, for instance, improving the level of education and contraceptive awareness, reducing abortions and curettage may decrease the incidence of intrinsic AM.\u003c/p\u003e \u003cp\u003eDysmenorrhea and menorrhagia are considered classic symptoms of AM [34]. Dysmenorrhea is associated with increased levels of oxytocin receptor (OTR), higher intensity and frequency of uterine contractions, neurological overgrowth within the lesion and the endometrium, and central sensitization [35\u0026ndash;37]. Several studies have investigated how intrinsic and extrinsic AM result in pelvic pain and dysmenorrhea and have no difference in intensity [6,18]. Our study reveals that dysmenorrhea is significantly worse in extrinsic AM. Our results also show that the menstrual volume in intrinsic AM cases is significantly higher than in extrinsic AM ones. This is due to the fact that intrinsic AM lesions are close to each other and tend to grow diffusely around to the endometrium, and fibrosis of these lesions is more likely to involve the endometrium, impairing the endometrial repair function [38]. In addition, the foci damaged microvessels are contiguous with decidualized human endometrial stromal cells at the inner myometrium. Larger uterine volume, diffuse lesions, and a higher rate of comorbidity with other endometrial hyperplastic diseases in intrinsic AM can also be the plausible explanation of menorrhagia [39]. In addition, this study we demonstrated that extrinsic AM is associated with primary infertility, consistently with the results of Bourdon \u003cem\u003eet al.\u003c/em\u003e [40]. Collecting baseline characteristic and clinical features of patients may contribute to the accurate diagnosis of intrinsic and extrinsic AM.\u003c/p\u003e \u003cp\u003eChen \u003cem\u003eet al.\u003c/em\u003e have explored the relationship between the subtypes of AM and the effects of LNG-IUD and discovered that the 3-year efficacy rate was 88.52% for subtype I, 81.54% for subtype II and 57.69% for subtype IV, but subtype IV had a high incidence of recurrence [30,41]. Another study has shown that intrinsic AM is a predictor of serious bleeding risk in patients receiving dienogest (DNG) therapy [42]. Our study shows that extrinsic AM generally coexists with OMA, DIE, and stage IV endometriosis. As a result, longer operation duration and more bleeding can be observed in the extrinsic group during surgery. We recommend that an adequate preoperative evaluation is carried out, and that the surgery is performed by experienced surgeons in order to effectively identify and remove lesions of endometriosis, especially in extrinsic AM.\u003c/p\u003e \u003cp\u003eWe recognize our study has a few limitations: the participant set consisted of women undergoing hysterectomy, which does not represent the overall AM population, and excluded especially younger women. In addition, the sample size of study is relatively small and it is a single-center study. Future research needs to include a larger population-based prospective study to screen the general population across its lifespan by TVUS or MRI, and follow up on clinical features of different subtypes of AM.\u003c/p\u003e \u003cp\u003eIn conclusion, intrinsic AM and extrinsic AM have distinctly different clinical characteristics and are associated with different factors. Interestingly, the plasma layer of the uterus is always intact in intrinsic AM cases regardless of the size of the lesions and of the uterine volume, while the plasma layer of the uterus is always invaded in extrinsic AM. The pathogenesis of these two AM subtypes warrants further investigation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Shanghai Municipal Commission of Science and Technology Program [grant 22Y11906400].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval\u003c/strong\u003e The present study was approved by the institutional ethics committee of the International Peace Maternity and Child Health Hospital (approval No. GKLW 2022-16).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u0026nbsp;\u003c/strong\u003eThe authors contributed to the study and consented to its submission after the final review.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e Conception and design by Yan Liang and Jian Zhang, administrative support by Wei Shi and Feng Sun, provision of study materials or patients by Yan Liang and Yuan Liu, collection and assembly of data by Yuan Liu and Minjiao Zhu, data analysis and interpretation by Yan Liang and Wei Shi; All authors discussed the results, contributed to the manuscript writing, and approved the version for publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGan L, Li Y, Chen Y, et al. 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What if deep endometriotic nodules and uterine adenomyosis were actually two forms of the same disease? Fertil Steril.2019; 111:454-6.\u003c/li\u003e\n\u003cli\u003eMarcellin L, Santulli P, Bortolato S, et al. Anterior focal adenomyosis and bladder deep infiltrating endometriosis: Is there a link? J Minim Invasive Gynecol.2018; 25:896\u0026ndash;901.\u003c/li\u003e\n\u003cli\u003eKishi Y, Shimada K, Fujii T, et al. Phenotypic characterization of adenomyosis occurring at the inner and outer myometrium. PLoS One.2017; 12:e0189522.\u003c/li\u003e\n\u003cli\u003eCao Y, Wang X, Liu X, et al. Neonatal feeding of an estrogen receptor \u0026beta; (ER\u0026beta;) agonist induces external adenomyosis-like lesions in ICR mouse. Reprod Dev Med.2022; 6:144-51.\u003c/li\u003e\n\u003cli\u003eIsrael SL, Woutersz TB. Adenomyosis; a neglected diagnosis. Obstet Gynecol. 1959; 14:168\u0026ndash;73.\u003c/li\u003e\n\u003cli\u003eGreaves E, Collins F, Esnal-Zufiaurre A, et al. Estrogen receptor (ER) agonists differentially regulate neuroangiogenesis in peritoneal endometriosis via the repellent factor SLIT3. Endocrinology.2014;155: 4015-26.\u003c/li\u003e\n\u003cli\u003eGuo SW, Mao XY, Ma QL, et al. Dysmenorrhea and its severity are associated with increased uterine contractility and overexpression of oxytocin receptor (OTR) in women with symptomatic adenomyosis. Fertil Steril.2013; 99:231-40.\u003c/li\u003e\n\u003cli\u003eHe WW, Liu XS, Zhang YQ, et al. Generalized hyperalgesia in women with endometriosis and its resolution following a successful surgery. Reprod Sci.2010; 17:1099-111.\u003c/li\u003e\n\u003cli\u003eHuang QQ, Liu XS, Critchley H, et al. How does the extent of fibrosis in adenomyosis lesions contribute to heavy menstrual bleeding? Reprod Med Biol.2022; 21:e12442.\u003c/li\u003e\n\u003cli\u003eBourdon M, Santulli P, Oliveira J, et al. Focal adenomyosis is associated with primary infertility.Fertil Steril.2020; 114:1271-7.\u003c/li\u003e\n\u003cli\u003eGordts S, Grimbizis G, Campo R. Symptoms and classification of uterine adenomyosis, including the place of hysteroscopy in diagnosis. Fertil Steril.2018; 109:380-8.e1.\u003c/li\u003e\n\u003cli\u003eChen S, Wang J, Sun W, et al. Efficacy of the levonorgestrel-releasing intrauterine device is associated with different subtypes of adenomyosis: a retrospective study. Ann Transl Med.2020;8:1356.\u003c/li\u003e\n\u003cli\u003eMatsubara S, Kawaguchi R, Akinishi M, et al. Subtype I (intrinsic) adenomyosis is an independent risk factor for dienogest-related serious unpredictable bleeding in patients with symptomatic adenomyosis.Sci Rep. 2019;27:17654. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Intrinsic adenomyosis, extrinsic adenomyosis, clinical characteristics, factors","lastPublishedDoi":"10.21203/rs.3.rs-2752816/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2752816/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAdenomyosis (AM) is a common gynecological condition that can be classified into different subtypes. This study aimed to evaluate the clinical characteristics, factors and treatment effect in women who diagnosed with intrinsic or extrinsic AM by MRI and underwent hysterectomies. A total of 181 women were enrolled in the study. Among these, 77 of which were identified to be in the intrinsic AM group (intrinsic group) and 54 in the extrinsic AM group (extrinsic group). Our results show that gravidity (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), parity (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), number of abortion (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0013) and endometrial curettage (P\u0026thinsp;=\u0026thinsp;0.0167) were significantly higher in the intrinsic group, while the education level was lower in the intrinsic group (P\u0026thinsp;=\u0026thinsp;0.0118). Women in the extrinsic group had earlier menarches (P\u0026thinsp;=\u0026thinsp;0.0257) and were more coexist with ovarian endometrioma (OMA) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and deep infiltrating endometriosis (DIE) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). In terms of clinical features, dysmenorrhea was more serious in the extrinsic group (P\u0026thinsp;=\u0026thinsp;0.0091), whereas women in the intrinsic group had heavier menstrual volume (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Surgery duration (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), surgical bleeding (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0013), hospitalization cost (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), and postoperative medical therapy (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were significantly higher in the extrinsic group than in the intrinsic group. In the multivariate analysis we performed, education level, gravidity and number of endometrial curettage were significantly associated with intrinsic AM. OMA and DIE were closely related to extrinsic AM. These results suggest that intrinsic and extrinsic AM have specific clinic characteristics, are associated with different factors, and may have different pathogenesis.\u003c/p\u003e","manuscriptTitle":"Differences clinical characteristics and factors in intrinsic and extrinsic adenomyosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-05-02 20:53:45","doi":"10.21203/rs.3.rs-2752816/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2ad59aee-74a0-4d9e-b20a-45aa9340c3a7","owner":[],"postedDate":"May 2nd, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-08-20T14:29:23+00:00","versionOfRecord":[],"versionCreatedAt":"2023-05-02 20:53:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2752816","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2752816","identity":"rs-2752816","version":["v1"]},"buildId":"WvIrzKhiLBfengagbw6Ux","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}