Magnetic resonance imaging-based Classification criteria combined with Serum CA125 for dysmenorrhea before focused ultrasound ablation surgery in adenomyosis

doi:10.21203/rs.3.rs-5025850/v1

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Magnetic resonance imaging-based Classification criteria combined with Serum CA125 for dysmenorrhea before focused ultrasound ablation surgery in adenomyosis

https://doi.org/10.21203/rs.3.rs-5025850/v1

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Objectives

To inform dysmenorrhea for exploring the possible pathogenesis of adenomyosis based on MRI classification criteria and serum CA125.

Methods

Patients before focused ultrasound ablation surgery were categorized into MRI -based severity group (Group A) and MRI -based non-severity group (Group B). Binary logistic regression was employed to identify the factors associating dysmenorrhea and CA125 level in total cohort and subgroups via MRI-based classifications criteria. The receiver-operating characteristic (ROC) curve was applied to assess the utility of CA125 for dysmenorrhea the subgroups.

Results

Patients in dysmenorrhea subtype exhibited higher CA125 levels compared with those in non-dysmenorrhea subtype in total cohort and Group A(P<0.05). In terms of those with dysmenorrhea, CA125 levels of Group A were shown to be higher when compared with those of Group B(P<0.05). In Group A, multivariate logistic regression showed that age and CA125 were related to dysmenorrhea in adenomyosis(P<0.05). CA125 level of 44.8 U/ml was demonstrated as the optimal cut-off point for dysmenorrhea by ROC curves in Group A. In relative to patients whose CA125 ≤ 44.8 U/ml, those with CA125 levels > 44.8 U/ml were more probably to suffer from dysmenorrhea. Furthermore, the multiple regression analysis demonstrated that CA125 level exhibited a positive correlation with the lesion volume and negatively related to age(P<0.05).

Conclusion

Patients with CA125>44.8 U/ml were prone to suffer from dysmenorrhea secondary to adenomyosis in MRI -based severity group. Besides, age and the lesion volume were associated with CA125 levels.

Health sciences/Biomarkers

Health sciences/Diseases

Health sciences/Medical research

CA125

MRI

classification

adenomyosis

dysmenorrhea

severity

Adenomyosis is a commonly seen disorder of the uterus in women of child-bearing age, characterizing by the lesion invasion into uterus, present with dysmenorrhea, menorrhagia and larger uterus, affecting the quality of women^{1, 2}. The etiology and pathogenesis adenomyosis is not well known at present³, in which inflammation might be one main factor associated with dysmenorrhea secondary to adenomyosis.

Cancer antigen 125 (CA125), a high macromolecule glycoprotein, is increasingly secreting from the embryonic coelomic epithelium to serum by peritoneal irritation or peritoneal stretch in inflammatory microenviroment^4–6. It is mainly used as biomarker for investigating diagnosis and survival of ovarian cancer^{7, 8}. Our previous study has found that CA125 levels were closely correlated to dysmenorrhea in adenomyosis before focused ultrasound ablation surgery (FUAS), and CA125 levels in diffuse subtype was higher in relative to those in focal subtype, informing that CA125 might be one biomarker associated with disease severity for adenomyosis⁴.

Magnetic resonance imaging (MRI) is considered as a moderately accurate test to diagnose and predict the disease severity for patients before FUAS^9–11. Recently, researchers have explored the classifications of adenomyosis according to MRI^10–14. Our previous study has found that based on the affected area, pattern, size (volume), localization of adenomyotic lesions, and concomitant pathology, classification criterion 4 (C4) was considered to be the suitable classification criterion for dysmenorrhea secondary to adenomyosis¹². However, it is unclear which classification criterion is the suitable one for serum CA125 and whether classification criterion combined with CA125 could inform dysmenorrhea in adenomyosis.

Thus, we retrospectively explored the data from a cohort of patients before FUAS, aiming to investigate the combined value of classification criterion and serum CA125 for dysmenorrhea, and study the factors influencing dysmenorrhea and the elevated CA125 level for investigating the possible pathogenesis of adenomyosis.

Study design and patients

This retrospective study involved 502 patients, who were diagnosed as adenomyosis by MRI scan and treated by FUAS for dysmenorrhea or menorrhagia. Patients who had complete demographic and disease characteristics data were extracted from medical records in the Affiliated Nanchong Central Hospital of North Sichuan Medical College from June 2017 to March 2021. The study was conducted in accordance with the Declaration of Helsinki and performed in accordance with relevant guidelines/regulations. Approved by ethics committee of the Affiliated Nanchong Central Hospital of North Sichuan Medical College (permit number 2021/104), the study waived the need of obtaining informed consent due to the retrospective nature.

The inclusion criteria for patients were patients with dysmenorrhea or menorrhagia secondary to adenomyosis, diagnosed by MRI before FUAS, received CA125 test and MRI examination before FUAS, and performed by FUAS^{4, 5}.

The exclusion criteria for patients were those receiving no pre-FUAS CA125 test or MRI examination, with uterine fibroids or endometriosis or suspected malignant tumor in MRI imaging, which might lead to dysmenorrhea or menorrhagia, with inflammatory disease within a week, as well as a history of medicine for dysmenorrhea within 6 months, influencing the symptoms investigation before FUAS^{4, 5}.

Assessments

Adenomyosis was diagnosed by imaging physicians based on MRI examination, which was defined as the maximal junctional zone thickness (JZmax) max ≥ 12 mm)^{15, 16}, or the ratio of JZmax to the entire myometrium thickness > 40%¹¹, or the difference between the maximal and minimal JZ thickness > 5 mm ^{15, 17}. The lesion size of uterine wall was defined as the size of lesion invasive into uterine wall. The uterine volume and the adenomyotic lesion volume were calculated using the following formula: 4/3πABC, where A, B, and C represent the long diameter, wide diameter, and thickness diameter of the lesion, respectively¹.

As patient-reported pain during menstrual cycles, dysmenorrhea secondary to adenomyosis was acquired from medical records, and recorded in the clinical encounter before FUAS and follow-up^{1, 18}. Menorrhagia secondary to adenomyosis was set as the clinically recorded increasing patient-reported menstrual blood volume, and recorded in the clinical encounter before FUAS and follow-up^{1, 19}. Symptom recurrence was set as patient-reported dysmenorrhea and/or menorrhagia 12 months after a period when symptomatic relief lasted for at least 3 months after FUAS1.

Serum CA125 test before FUAS

CA125 test samples of collecting and measurement followed the standard procedure, which were transported to the laboratory center at room temperature, measured by two-step immunoassay for the quantitative determination with flexible assay protocols within 24 h before FUAS, and assayed in a central laboratory^{4, 5}.

MRI-based classifications for adenomyosis

Imaging system by a 1.5 T MRI system informed the images information of pelvic-enhanced MRI patients. Based on the professional opinion, adenomyosis was also divided according to ultrasound-based classification system (C1, the morphological features of C1 were also assessable by MRI imaging^{11, 14}) and the MRI findings (C2-C5 ¹⁰,¹¹⁻¹⁴). Based on the five classification criteria, imaging physicians (ZJ, 10 years of experience; JZ, with 10 years of experience) and a gynecologist (YT, with 11 years of experience) were individually invited to reclassify adenomyosis¹. Different classification standard criteria are listed in Supplementary Table 1. The classification parameters were used if the results were consistent between two readers, the third reader was invited to discuss the final classification parameters in the case of ambiguous or controversial results¹.

Statistical methods

Analysis were performed in total cohort and stratified by the lesion size of uterine wall based on MRI: Group A, the lesion size of uterine wall ≥ 2/3, MRI-based severity group; Group B, the lesion size of uterine wall<2/3, MRI-based non-severity group. Continuous variables were summarized by the mean and standard deviation or median (P25, P75). In addition, interquartile range (IQR) and categorical variables were shown to be counts and percentages. This study adopted χ2 test, t test or Mann-Whiney U test for examining the differences of demographic and clinical factors between patients with and without dysmenorrhea in total cohort and subgroups. A logistic regression mode was used to explore the correlation between clinicopathlogical features (age, the lesion volume, the uterine volume, subcutaneous fat thickness, serum CA125) and dysmenorrhea by odds ratios (ORs) with 95% confidence intervals (95% CIs) in total cohort and subgroups. Using a Receiver Operating Characteristic (ROC) curve, the optimal cut-off of CA125 levels for dysmenorrhea before FUAS in adenomyosis were investigated. The logistic regression model was used for establishing the associations between elevated CA125 and dysmenorrhea before FUAS in adenomyosis in total cohort and subtype groups. To investigate the factors (age, the lesion size) influencing CA125 level before FUAS, multivariate logistic regression model was employed. GraphPad Prism 7.0 (Version X; La Jolla, CA, USA) was used for image editing. SPSS 22.0 (IBM, Armonk, NY) was adopted for the statistical analysis, and p < 0.05 was thought to be of significance. The data was reviewed by the Data Survilliance and Monitoring Committee of the State Key Laboratory of Ultrasound in Medicine and Engineering. This committee is consisted of multidisciplinary experts in the clinical research.

Clinicopathlogical features in the total cohort

The baseline characteristics, which included age, body mass index (BMI), serum CA125, uterine position and volumes, lesion position and volumes, distribution of dysmenorrhea and menorrhagia and symptom recurrence were summarized in Table 1.

Table 1

Clinicopathlogical features in total cohort
Variable	Total cohort
Age (years)	43.8 ± 5.2
BMI (kg/m2)	23.6 ± 2.8
Parity	1 (1, 2)
Uterus position (n(%))
Anteverted	292 (58.2%)
Retroverted	192 (38.2%)
Neutral	18 (3.6%)
Uterus volume(cm3)	231.3 ± 124.5
Adenomyosis location (n(%))
Anterior	148 (29.5%)
Posterior	263 (52.4%)
Fundus	38(7.6%)
Lateral (left or right)	27(5.4%)
Anterior/Posterior/ Fundus/ Lateral	26(4.2%)
Lesion volume (cm3)	54.6 ± 56.8
Subcutaneous fat thickness (mm)	19.1 ± 8.2
Distance (mm)	22.0 ± 14.8
Serum CA125 (U/ml)	55.9 (30.0, 106.4)
Dysmenorrhea (n(%)
Yes	381(75.9%)
No	121(24.1%)
Menorrhagia (n(%))
Yes	272 (54.2%)
No	230 (45.8%)
Symptom recurrence (n(%))
Yes	133 (26.5%)
No	369 (73.5%)
BMI, body mass index; CA125, cancer antigen 125; distance, distance from the posterior surface of the adenomyosis lesion to the sacrum.

The magnitude of classifications associated with the CA125 of adenomyosis

Table 2 showed χ2 value in C4, considered as the suitable one for CA125, was higher than those in other classification criteria (χ2 = 22.003, P<0.001). In C1, serum CA125 levels in subtype-2 (60.0 U/ml (30.2 U/ml, 124.8U/ml)) were higher than those in subtype-1 (52.2 U/ml (31.1 U/ml, 81.3 U/ml), p = 0.007). In C2, serum CA125 levels in subtype-4 (106 U/ml (47 U/ml, 182.5 U/ml) were higher than those in other subtypes (P = 0.006). In C4, no matter intrinsic or external subtype, serum CA125 of Group A was higher than that of Group B (Z = 22.003, P<0.001). In C5, serum CA125 in subtype-6 was higher when compared with that in other subtypes (P = 0.006). There existed no significant differences for CA125 in C3 (P>0.05) .

Table 2

The identification of different classifications based on MRI for serum CA125.
Variable	Subtype-1	Subtype-2	Subtype-3	Subtype-4	Subtype-5	Subtype-6	χ²	P-value
Classification ¹⁴	52.2 (31.1, 81.3)	60.0 (30.2, 124.8)					7.380	0.007
Classification 2¹⁰	55 (27.5,98.5)	57(30.3,104.8)	45(24,67.5)	106(47,182.5)			12.395	0.006
Classification 3¹¹	55 (28.8,108.5)	45(28.0,69.0)	60(33,123)				4.444	0.108
Classification 4¹²	20 (12.0,42.0)	33.5(13.7,61.8)	55(30,108)	93(51-)	35(26.3,67.8)	59(34,123)	22.003	<0.001
Classification 5¹³	50.5 (27.0,93.5)	72.5(23.3,121.8	58(31,108)	45(29.5,67.5)	94(41.8, 173)	123(51,213.5)	16.265	0.006
* p<0.05
14.Hulka CA, Hall DA, McCarthy K, Simeone J. Sonographic findings in patients with adenomyosis: can sonography assist in predicting extent of disease? AJR American journal of roentgenology 2002;179(2):379 − 83.
10.Kishi Y, Suginami H, Kuramori R, Yabuta M, Suginami R, Taniguchi F. Four subtypes of adenomyosis assessed by magnetic resonance imaging and their specification. American journal of obstetrics and gynecology 2012;207(2):114.e1-7.
11. Bazot M, Daraï E. Role of transvaginal sonography and magnetic resonance imaging in the diagnosis of uterine adenomyosis. Fertility and sterility 2018;109(3):389 − 97.
12. Kobayashi H, Matsubara S. A Classification Proposal for Adenomyosis Based on Magnetic Resonance Imaging. Gynecologic and obstetric investigation 2020;85(2):118 − 26.
13. Gong C, Wang Y, Lv F, Zhang L, Wang Z. Evaluation of high intensity focused ultrasound treatment for different types of adenomyosis based on magnetic resonance imaging classification. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 2022;39(1):530-8.

Clinicopathlogical features according to Classification criterion 4

According to the results of priority study, dysmenorrhea and menorrhagia rates were different upon the size of uterine wall based on C4. Patients were included into the lesion size of uterine wall ≥ 2/3 group (Group A, N = 446, 88.8%, and 68% failure with gonadotrophin-releasing hormone agonist (GnRH-a) or levonorgestrel within 2 years) and the lesion size of uterine wall<2/3 group (Group B, N = 56,11.2%, and 35.7% failure with GnRH-a or levonorgestrel within 2 years). The uterine volumes(236.9 ± 125.6 cm3), lesion volumes (56.1 ± 55.7 cm3) and CA125 57.9 U/ml (31.1 U/ml, 111.1 U/ml) in Group A were higher than those in Group B (P<0.001, Table 3).

Table 3

Patient characteristics in subtype groups.
Variable Variable	MRI-based severity group (n = 446, 88.8%)	MRI-based non-severity group (n = 56, 11.2%)	Test value	P-value
Age (years)	43.9 ± 5.2	42.6 ± 5.6	1.777	0.076
BMI (kg/m2)	23.6 ± 2.8	24.1 ± 2.8	-1.337	0.182
Parity	1 (1, 2)	1 (1, 1)	-0.901	0.368
Uterus position			1.115	0.572
Anteverted	263(59.0%)	29 (51.8%)
Retroverted	167 (37.4%)	25 (44.6%)
Neutral	16 (3.6%)	2 (3.6%)
Uterine volume(cm3)	236.9 ± 125.6	185.0 ± 105.0	2.889	0.004
Adenomyosis location			2.117	0.714
Anterior	135 (30.3%)	13(23.2%)
Posterior	231 (51.8%)	32(12.2%)
Fundus	33 (7.4%)	5 (8.9%)
Lateral (left or right)	25(5.6%)	2 (3.6%)
Anterior/Posterior/undus/ Lateral	22(4.9%)	4 (7.2%)
Adenomyotic lesion	56.1 ± 55.7	32.3 ± 51.6	3.067	0.003
(cm3)
Subcutaneous fat	19.2 ± 8.0	20.5 ± 15.3	-0.637	0.527
thickness (mm)
Distance (mm)	23.9 ± 14.7	25.1 ± 15.7	-0.504	0.614
Hemoglobin (g/dl)	97.7 ± 19.3	100.2 ± 24.7	-0.397	0.694
CA125 (U/ml)	57.9(31.1, 111.1)	35.1(16.8, 67.0)	-3.236	0.001
Dysmenorrhea(n(%))			2.227	0.136
Yes	343(76.9%)	38(67.9%)
No	103 (23.1%)	18(32.1%)
Menorrhagia(n(%))			2.333	0.127
Yes	247(55.4%)	23(44.2%)
No	199 (44.6%)	29(55.8%)
Symptom recurrence(n(%))			9.883	0.002
Yes	125 (28.0%)	8 (15.4%)
No	321 (72.0%)	66 (84.6%)
Group A, the lesion size of uterine wall ≥ 2/3; Group B, the lesion size of uterine wall<2/3; BMI, body mass index; CA125, cancer antigen 125; distance from the posterior surface of the adenomyosis lesion to the sacrum.

We further explored the relationship between CA125 and dysmenorrhea in different groups, as shown in Fig. 1. CA125 levels in patients suffering from dysmenorrhea were higher when compared with those in patients without dysmenorrhea in total cohort(Z=-3.597, P<0.001, Fig. 1A)and Group A (Z=-3.150, P = 0.002, Fig. 1B), while no significant difference was found in Group B (Z=-1.350, P = 0.177, Fig. 1C). In terms of those with dysmenorrhea, CA125 levels of Group A were higher than those in Group B (Z=-2.503, P = 0.012).

The factors influencing dysmenorrhea in total cohort and subtypes subgroups

In total cohort, univariate logistic regression demonstrated that age (OR = 0.909, 95% CI 0.869 ~ 0.951, P < 0.001), CA125 (OR = 1.004, 95% CI 1.001 ~ 1.017, P = 0.012) and subcutaneous fatthickness (OR = 0.97, 95% CI 0.94–0.99, P = 0.007) were related to dysmenorrhea of patients with adenomyosis. However, there were no associations between BMI, the lesion size of uterine wall(≥2/3 vs.<2/3) and dysmenorrhea (P>0.05). According to multivariate logistic regression, age (OR = 0.900, 95% CI 0.855 ~ 0.947, P = 0.007), and CA125 (OR = 1.004, 95% CI 1.001 ~ 1.007, P = 0.018) were correlated with dysmenorrhea of patients with adenomyosis, while subcutaneous fatthickness showed no significant association with dysmenorrhea (P = 0.073) (Table 4).

Table 4

Binary logistic regression analysis of factors impacting dysmenorrhea of adenomyosis in total cohort.
Variable	Univariate			Multivariate
	OR	95%CI	P	OR	95%CI	P
Age (years)	0.909	0.869 ~ 0.951	<0.001	0.900	0.855 ~ 0.947	<0.001
BMI (kg/m2)	0.940	0.873 ~ 1.012	0.098	1.015	0.927 ~ 1.111	0.753
Menorrhagia	1.162	0.774 ~ 1.748	0.468	1.144	0.727 ~ 1.801	0.561
(Yes vs. No)
The volume of uterine wall	1.577	0.864 ~ 2.881	0.138	1.299	0.644 ~ 2.622	0.465
(≥ 2/3 vs.<2/3)
Serum CA125 (U/ml)	1.004	1.001 ~ 1.017	0.012	1.004	1.001 ~ 1.007	0.018
Subcutaneous fatthickness (mm)	0.967	0.944 ~ 0.991	0.007	0.975	0.948 ~ 1.002	0.073
CA125, cancer antigen 125; BMI, body mass index

In severity group (Group A) based on MRI, multivariate logistic regression showed that age (OR = 0.897, 95% CI:0.849 ~ 0.948, P<0.001) and CA125 (OR = 1.004, 95% CI 1.001 ~ 1.008, P = 0.021) were related to dysmenorrhea of patients with adenomyosis, while did not significantly associated with dysmenorrhea in Group B (P = 0.073) (Table 5).

Table 5

Binary logistic regression analysis of factors for dysmenorrhea of adenomyosis in subgroups.
Variable	The volume of uterine wall ≥ 2/3(Group A)			The volume of uterine wall<2/3(Group B)
	OR	95%CI	P	OR	95%CI	P
Age (years)	0.897	0.849 ~ 0.948	<0.001	0.887	0.763 ~ 1.031	0.119
BMI (kg/m2)	1.019	0.924 ~ 1.124	0.701	0.983	0.750 ~ 1.289	0.903
Menorrhagia	1.272	0.783 ~ 2.066	0.331	0.494	0.123 ~ 1.985	0.320
(Yes vs. No)
Serum CA125(U/ml)	1.004	1.001 ~ 1.008	0.021	0.999	0.987 ~ 1.012	0.908
Subcutaneous fatthickness (mm)	0.976	0.943 ~ 1.011	0.173	0.967	0.914 ~ 1.023	0.246
CA125, cancer antigen 125; Group A, the lesion size of uterine wall ≥ 2/3; Group B, the lesion size of uterine wall<2/3; BMI, body mass index.

Identification of CA125 for dysmenorrhea in MRI-based severity group

ROC curves were employed to assess the magnitude of CA125 for dysmenorrhea in Group A. Sensitivity, specificity, optimal value, area under the curve, 95 CIs and p-value were 59.2%, 59.2%, 44.8, 0.594, 0.547 ~ 0.640, P = 0.002.

The factors impacting CA125 level in MRI-based severity group

Then, we investigated the factors causing the increased CA125 levels in MRI-based severity group by multivariate logistic regression. Based on the results, the lesion volume positively related to elevated CA125 levels (OR = 1.016, 95%: 1.008–1.025, P < 0.001), while the ages exhibited a negative correlation with elevated CA125 levels (OR = 0.943, 95%༚0.898–0.991, P = 0.021) (Table 6).

Table 6

Multivariate binary logistic regression analysis of factors for CA125 in MRI-based severity group.
Variable	B	S.E.	Wald	OR	95%CI	P
Age (years)	-0.058	0.025	5.342	0.943	0.898–0.991	0.021
BMI (kg/m2)	-0.037	0.046	0.643	0.964	0.880–1.055	0.423
Menorrhagia	-0.137	0.236	0.336	0.872	0.549–1.386	0.562
(Yes vs. No)
Uterine volume (cm3)	0.000	0.001	0.058	1.000	0.998–1.003	0.810
Lesion volume (cm3)	0.016	0.004	15.408	1.016	1.008–1.025	<0.001
Subcutaneous fatthickness (mm)	0.007	0.017	0.195	1.007	0.975–1.041	0.659
CA125, cancer antigen 125; BMI, body mass index

Our study showed that C4 based on MRI was the suitable classification criterion for CA125 in patients with adenomyosis before FUAS. For those with dysmenorrhea, CA125 levels in MRI-based severity group were shown to be higher than those of the non-severity group, while they showed no significant difference in those without dysmenorrhea. CA125 level of 44.8 U/ml was found to be the optimal cut-off point of dysmenorrhea in severity group based on MRI. When we extended the study to investigate the factors related to the elevated CA125 in MRI-based severity group, the lesion volume was considered as the positively one, while the ages negatively one.

Consist with the results that adenomyosis is actually related to expression of uterine inflammatory mediators and cytokines^{3, 4}, including tumor necrosis factor-α, β (TNF- α, β), interleukin (IL)-1β, IL-18 and CA125, our results again demonstrated that elevated CA125 level was associated with dysmenorrhea secondary to adenomyosis in patients without uterine fibroids and endometriosis⁴. It indicated the higher level of serum CA125, the higher possibilities of dysmenorrhea secondary to adenomyosis⁴. Classification criterion based on MRI also could inform the severity of dysmenorrhea. In the previous study, we found the severity disease was different considered the lesion size of uterine wall. In this study, we found that the C4 was the suitable classification criterion for CA125. Furthermore, we explored the association between CA125 and dysmenorrhea based on C4. While the lesion size of uterine wall ≥ 2/3, CA125 was positively associated with the severity of dysmenorrhea. In the previous study, we confirmed the commonly used diagnosis value, and 35 U/ml was the optimal cut-point for dysmenorrhea²⁰. In this study, we further investigated CA125 as 48.4 U/ml was the optimal cut-point for dysmenorrhea in the patients whose lesion size of uterine wall ≥ 2/3. Meanwhile, no matter what is the cut-off point of CA125 for dysmenorrhea, elevated CA125 level was positively associated with the lesion volume, and negatively associated with the age.

As the main symptom of adenomyosis, dysmenorrhea is probably the results of inflammation, neurogenesis, angiogenesis, and contractile abnormalities in the endometrial and myometrial components³. Dysmenorrhea can be adjusted by abnormal genetic, including CYP1A1 and A2, catechol-O-methyltransferas, Cytochrome P450, lipoxygenase-5 and Cyclooxygenase-2^{3, 21, 22}, involving the key processes in adenomyosis development. Dysmenorrhea could be illuminated by myometrial hypercontractility, and indicated by higher expression of oxytocin receptors and increased contractile amplitude of uterine smooth muscle cells (uSMCs) in adenomyotic uteri, resulting in hyperestrogenism, progesterone resistance, and inflammatory microenvironment³. Then, inflammatory microenviroment promoted the ectopic endometrium secretion of significantly higher CA125 level compared with the normal endometrium²³. The high expression of IL-1β, CRH, and UCN observed in adenomyotic lesions may mediate prostaglandins synthesis and stimulate peritoneal irritation and peritoneal stretch, and therefore CA125 reached the blood circulation through changing endothelial permeability^{3, 24}. Furthermore, our study attempted to explore the combined value of MRI and CA125 for dysmenorrhea secondary to adenomyosis. The results showed that when the MRI imaging informing the invasion wall ≥ 2/3, the larger areas of lesion, the higher levels of CA125 in adenomyosis. Meanwhile, CA125 may aggravate inflammation through promoting ectopic endometrium migration and adhesion in the surrounding myometrium in adenomyosis development⁶, which might result in a relatively severity level of the disease. While the MRI imaging informing the invasion lesion of uterus wall, the patients have higher possibilities of dysmenorrhea before FUAS. These findings might offer clues for investigating the pathogenesis of dysmenorrhea based on MRI and CA125. The suitable classification criterion based on MRI for CA125 might be beneficial for exploring the possible mechanisms with disease development.

Limitations and Strengths

The strength of the current retrospective study was that we informed a suitable classification criterion based on MRI for CA125, further showing that CA125 was associated with dysmenorrhea secondary to adenomyosis upon severity disease based on MRI with a relatively large sample size. This might be of interest to researchers to study pathogenesis of dysmenorrhea based on MRI and CA125. However, this study still had the following limitations. Firstly, patients included in this study were those who received FUAS, which had potential limitation for selection bias and might limit the interpretation of our results to the general patient population. We will include the patients with non FUAS treatment and compare the predictive value of MRI and CA125 for clinic symptom of patients between the FUAS group and non-FUAS group in the future. Secondly, we could not conclude that CA125 was a risk factor of dysmenorrhea in MRI -based severity group in adenomyosis for the retrospective design. However, we demonstrated that CA125 is associated with dysmenorrhea secondary to adenomyosis in MRI -based severity group. Thirdly, although a few patients without complete data were excluded for the retrospective design, the clinicopathologic features of our cohort showed no significant difference from epidemiology of adenomyosis²⁵. Finally, CA125 results might be interfered by sample collection and test. We collected and measured CA125 within one day before FUAS, aiming to minimize interference factors for the findings. Meanwhile, we will assess the severity level of dysmenorrhea by Numerical Rating Scale, not just by describing dysmenorrhea as yes or no with design prospective and multicenter studies.

In summary, this study informed that C4 based on MRI was the suitable one for CA125. Patients with increased CA125>44.8 U/ml were prone to suffer from dysmenorrhea secondary to adenomyosis in MRI-based severity group. Besides, the lesion volume positively related to elevated CA125 levels, while the ages exhibited a negative correlation with elevated CA125 levels.

Statement of Ethics

The approval of this study was approved by ethics committee of the Affiliated Nanchong Central Hospital of North Sichuan Medical College (permit number. 2021/104). Due to data anonymization and the retrospective nature of the study, the need for consent was waived.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding

This work was supported by the Ministry of Science and Technology of China (Grant No.2022YFE0133100), foundation of State Key Laboratory of Ultrasound in Medicine and Engineering (Grant No. 2020KFKT003, 2021KFKT022), the Bureau of Science and Technology Nanchong City Program (No. 20SXQT0320, 22SXQT0254, 22SXQT034) and university project of North Sichuan Medical College (NO. CBY23-ZDA12, CBY23-QNA11 and CBY23-QNA19).

Author Contributions

This study was designed by YT, HQH, BS, QLS and carried out by YT, JL,WH, JRH and MTY, BS, HNH, WT, ZJJ, and LJZ provided data from medical records. All drafted the first manuscript with help from HQH and YT. All authors contributed to and approved the final version of the article for publication.

Data availability statement

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

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No competing interests reported.

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Magnetic resonance imaging-based Classification criteria combined with Serum CA125 for dysmenorrhea before focused ultrasound ablation surgery in adenomyosis

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Abstract

Figures

INTRODUCTION

MATERIALS AND METHODS

Study design and patients

Assessments

Serum CA125 test before FUAS

MRI-based classifications for adenomyosis

Statistical methods

RESULTS

Clinicopathlogical features in the total cohort

The magnitude of classifications associated with the CA125 of adenomyosis

Clinicopathlogical features according to Classification criterion 4

The factors influencing dysmenorrhea in total cohort and subtypes subgroups

Identification of CA125 for dysmenorrhea in MRI-based severity group

The factors impacting CA125 level in MRI-based severity group

DISCUSSION

Limitations and Strengths

Conclusions

Declarations

References

Additional Declarations

Supplementary Files

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