Characteristics of adenomyosis in secondary infertility patients on MRI and factors associated with fertility recovery after HIFU

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This study identified MRI features of adenomyosis, such as T2WI high-signal spots and type II lesions, associated with secondary infertility and found that younger age improved pregnancy outcomes after HIFU treatment.

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Abstract

OBJECTIVE: To study the MRI characteristics of adenomyosis in secondary infertility patients, and to analyze the factors affecting pregnancy after High-intensity focused ultrasound (HIFU). METHODS: Clinical data of 388 patients with adenomyosis were selected from January 2014 to December 2019 treated with HIFU They were divided into the infertility group and the control group by the presence of secondary infertility. Then the patients in the infertile group who had fertility requirements after HIFU were divided into the postoperative pregnancy group and the non-pregnant group, to assess the MRI characteristics of adenomyosis and the factors affecting infertility and to analyze the factors affecting fertility recovery after HIFU. RESULTS: Seventeen (28.81%) of the patients in the infertile group obtained pregnancy after HIFU. Type II (exogenous) lesions, T2-weighted image(T2WI) high-signal spots more than 30, pelvic adhesions, and dysmenorrhea may be related factors affecting the conception of patients with adenomyosis, among which T2WI high-signal spots more than 30 (OR = 1.810, 95CI%: 1.071-3.058) was an independent risk factor for infertility (p < 0.05). There was no significant effect on whether fertilization in patients with pelvic adhesions, while age (OR = 0.844, 95CI%: 0.719-0.990) was an independent influence on whether pregnancy occurred after HIFU (p < 0.05), and the postoperative conception rate was high when the age was less than 37 years. CONCLUSION: T2WI high-signal spots in lesions more than 30, type II (exogenous) lesions, pelvic adhesions, and dysmenorrhea symptoms are risk factors for secondary infertility in patients with adenomyosis. HIFU treatment has the potential to enhance fertility in some patients with uterine adenomyosis. Age serves as an independent factor significantly influencing pregnancy outcomes following HIFU surgery. Consequently, early intervention is recommended for patients with uterine adenomyosis to optimize their fertility potential.
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Abstract

Objective: To study the MRI characteristics of adenomyosis in secondary infertility patients, and to analyze the factors affecting pregnancy after High-intensity focused ultrasound (HIFU).

Methods

Clinical data of 388 patients with adenomyosis were selected from January 2014 to December 2019 treated with HIFU They were divided into the infertility group and the control group by the presence of secondary infertility. Then the patients in the infertile group who had fertility requirements after HIFU were divided into the postoperative pregnancy group and the non-pregnant group, to assess the MRI characteristics of adenomyosis and the factors affecting infertility and to analyze the factors affecting fertility recovery after HIFU.

Results

Seventeen (28.81%) of the patients in the infertile group obtained pregnancy after HIFU. Type II (exogenous) lesions, T2-weighted image(T2WI) high-signal spots more than 30, pelvic adhesions, and dysmenorrhea may be related factors affecting the conception of patients with adenomyosis, among which T2WI high-signal spots more than 30 (OR = 1.810, 95CI%: 1.071–3.058) was an independent risk factor for infertility (p < 0.05). There was no significant effect on whether fertilization in patients with pelvic adhesions, while age (OR = 0.844, 95CI%: 0.719–0.990) was an independent influence on whether pregnancy occurred after HIFU ( p < 0.05), and the postoperative conception rate was high when the age was less than 37 years.

Conclusion

T2WI high-signal spots in lesions more than 30, type II (exogenous) lesions, pelvic adhesions, and dysmenorrhea symptoms are risk factors for secondary infertility in patients with adenomyosis. HIFU treatment has the potential to enhance fertility in some patients with uterine adenomyosis. Age serves as an independent factor significantly influencing pregnancy outcomes following HIFU surgery. Consequently, early intervention is recommended for patients with uterine adenomyosis to optimize their fertility potential. 1.  Introduction Adenomyosis (AM) is a common gynecological disease and frequentness in which endometrial glands and stroma with growth function invade the myometrium, resulting in localized or diffuse hyperplasia of the myometrium, with an incidence rate of 7–23% [ 1]. In the investigation study of Vercellini [ 2] et  al. compared with normal women, the successful pregnancy rate of patients with adenomyosis using assisted reproductive technology (ART) decreased by 8%. Women with adenomyosis are at increased risk of preterm birth and premature rupture of membranes [ 3], and adenomyosis is associated with decreased pregnancy rates, decreased live birth rates, increased miscarriage rates, and adverse obstetric pregnancy and neonatal outcomes [ 4]. Due to the postponed of women’s childbearing age caused by social devel - opment, the prevalence of adenomyosis complicated with secondary infertility is increasing, which has become the key population of assisted reproduction and has attracted wide clinical attention. © 2025 t he a uthor(s). p ublished with license by taylor & f rancis Group, ll C CONTACT Jinyun Chen [email protected] f rom the State Key laboratory of ultrasound in m edicine and engineering, Chongqing medical university, yixueyuan r oad, yuzhong District, Chongqing, 400016, China https://doi.org/10.1080/02656736.2025.2550633 t his is an o pen a ccess article distributed under the terms of the Creative Commons a ttribution license ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. t he terms on which this article has been published allow the posting of the a ccepted m anuscript in a repository by the author(s) or with their consent. ARTICLE HISTORY Received 26 November 2024 Revised 12 August 2025 Accepted 15 August 2025

Keywords

Adenomyosis; infertility; fertility; high-intensity focused ultrasound (HIFU); MRI; ultrasound ablation 2 Z. YANG ET AL. HIFU is an emerging treatment method for adenomyosis with few complications and no permanent dam - age [ 5]. It makes use of the biological effect of ultrasound to coagulative necrosis of the lesion cells and preserve the integrity of the uterus. There have been reports that the fertility of patients with adenomyosis improved after HIFU ablation [6]. However, there is a lack of research reports on the factors affecting fertility in infertile patients with adenomyosis who receive ultrasound ablation. This study aims to analyze the char - acteristics of infertile patients with adenomyosis and the factors related to the improvement of fertility after HIFU treatment through clinical real-world data research, in order to provide a basis for preoperative evalua - tion, and it is expected to make a breakthrough in the fertility of infertile patients with adenomyosis. 2.  Materials and methods 2.1.  Study subjects Patients with adenomyosis treated in the ultrasound ablation center of the First Affiliated Hospital of Chongqing Medical University from January 2014 to December 2019 were included. The clinical data of the patients were collected from the electronic medical record database. Inclusion criteria:(1) age 25–45 years old, diagnosed with adenomyosis by MRI; (2) the uterine wall where the lesion was located was ≥30 mm; (3) those who met the diagnostic criteria of secondary infertility(Existing history of pregnancy and normal sex without contraception, not pregnant for more than one year.) were included in the infertility group; (4) those who had a history of pregnancy in the last 3 years and were diag- nosed with adenomyosis by MRI before the last pregnancy were included in the control group. Exclusion criteria: (1) combined uterine fibroids ≥20mm, exclued type 0/type I myomas; (2) previous diagnosis of tubal occlusion or hydrosalpinx; (3) use of ovarian hormone modulators (e.g. GnRHa, dienogest, levonorgestrel intra- uterine system (Mirela), etc.) to affect estrogen and progesterone secretion in the 3 months prior to the oper- ation; (4) It is known that male factors contribute to infertility, including azoospermia, oligospermia, and sperm morphology abnormalities, etc;The study was approved by the Ethics Committee of our hospital (HF2023-013) and verbal informed consent was obtained from the patients at the time of follow-up. 2.2.  MRI evaluation and measurement The MR images were evaluated and measured by a radiologist with 5 years of experience using a syngo fastView imaging system (Siemens AG) as follows: ① Typing: According to the MRI-based classification of adenomyosis proposed by Kishi Y [ 7], adenomyosis was typed based on MRI. Type I (endogenous type) The lesion is localized in the endometrium, preserving the external uterine structure. Type II (exogenous type): The lesion is situated in the serosal layer of the uterus, without affecting its internal architecture. Type III (intermuscular type): Lesions exist independently and are not associated with either the outer or inner structures. Type IV (other type): Adenomyopathy that does not con - form to any of the aforementioned classifications. Refer to Figure 1 . ② Volume and ablation rate (NPVR) calculation: the volume of the lesion measured on the preoperative T2WI image was outlined with ITK-SNAP at each level of MR imaging, and the volume was summed up as the value of each level, which was automatically output by the system. The same method was used to obtain the non-perfused volume (NPV) on postoperative enhanced MR images. The non-perfused volume ratio (NPVR) = NPV/lesion volume × 100%. ③ The number of T2WI high-signal spots within the lesion was counted and grouped based on the level with the highest number of high-signal spots, which was classified as 0-10; 11-30; and 30 +. ④ Pelvic adhesions: on MR image, adhesions manifested as lack of a clear interface between adjacent organs, loss of fat layer, pinpoint low-signal tugging sensation between organs, and/or angulation and twisting of adjacent intestinal collaterals [ 8]. The main signs of MRI diagnosis of uterorectal trap closure were uterine retroflexion >180°, fibrous mass between uterorectals, displacement of intra-pelvic fluids, elevation of dome, and intestinal collaterals adherence [ 9]. 2.3.  HIFU ablation The Focused Ultrasound Tumor Therapeutic System (Model-JC, Chongqing Haifu Medical Technology Co., Ltd., China) was used, with a diameter of 20 cm ultrasound transducer. The physical focal region is INTERNATIONAL JOURNAL OF HYPERTHERMIA 3 1.5 × 1.5 × 8 mm and the operating frequency is 0.5-1.5 MHz. The ablation procedure was guided with a fre - quency of 3.5 MHz ultrasonography device (Esao MyLab70, Italy). The patient was placed in the prone posi - tion with the anterior abdominal wall in full contact with the circulating degassed water, and in some patients a degassed water bladder could be placed to assist in pushing the bowel to obtain a safe acoustic pathway. A spot scan is selected and the power is set between 350 and 400 W. The focus was at least 10 mm away from the endometrium and 15 mm away from the extrauterine tissue structure. Intravenous fentanyl midazolam citrate is administered for sedation. Through real-time ultrasound monitoring, the change of gray scale of the mass in the treatment area was used as a marker of ablation, and the treat - ment dose was adjusted according to the patient’s tolerance and the change of gray scale of the target area, and the procedure was completed when the increase of the gray scale in the lesion covered the area to be planned, and the color Doppler flow imaging could assist in determining the disappearance of the blood flow signal in the lesion after the ablation. After the operation, patients were instructed to lie prone for 2 h and return to the ward or be accompanied by family members to return home. 2.4.  Follow-up A gynecologist and obstetrician performed telephone follow-up, including clinical symptoms and preg - nancy status. Loss of follow-up was recognized when multiple attempts to contact the patient failed within 3 days. The follow-up cutoff date was June 2024. Follow-up endpoints: pregnancy and delivery, total hysterectomy, or menopause. 2.5.  Statistical methods SPSSv.29 was used to analyze the data, and the measurements conforming to normal distribution were expressed as (x ± S), and the non-normally distributed measurements were expressed as (M ± Q), using ANOVA and wilcoxon rank sum test, etc., and the count data were analyzed by χ2 test, and the influenc - ing factors were analyzed by logistic regression analysis; p < 0.05 was statistically significant. 3.  Results 3.1.  Patient inclusion A total of 388 patients were included, with a mean age of 40.07 ± 5.44 years, 302 cases were successfully followed up and 86 cases (22.16%) were lost, among which 106 patients had fertility demands, 59 (55.66%) in the infertile group and 47 (44.34%) in the control group, with a median follow-up time of 96 months (72–120 months). The flow chart is shown in Figure 2 . 3.2.  Patient baseline data and HIFU ablation Compared with the control group, patients in the infertile group were younger (38.57 ± 5.80) years Vs. (41.34 ± 4.77) years ( p < 0.001); and more patients had significant dysmenorrhea 73.60% Vs. 63.33% Figure 1. Classification of adenomyosis. t he classification of uterine lesions based on nuclear magnetic resonance showed that a was endogenous type, b was exogenous type, c was intermuscular type, d was other types. 4 Z. YANG ET AL. (p < 0.05). Comparison of NPVR obtained by HIFU ablation between the two groups showed that 43.09% in the infertile group was slightly lower than the control (47.02%) ( p < 0.05). The details of the data are shown in Table 1. The ablation after HIFU is shown in Figure 3 . 3.3.  MRI characterization Compared with the control group, type I (endogenous) lesions were less in the infertile group 23.60% Vs. 42.86%, type II (exogenous) lesions were more in the infertile group 23.60% Vs. 12.86%, the number of lesions with more than 30 high signal spots in T2WI was more in the infertile group 29.78% Vs. 19.04%, and the thickness of the Junction zone (JZ)was less in the infertile group than in the control group 36.90 (IQR 13.20, 47.78) mm Vs. 41.10 (IQR 32.73, 50.38) mm. 13.20, 47.78) mm Vs. 41.10 (IQR 32.73, 50.38) mm, the incidence of pelvic adhesions in the infertile group was 26.40%, which was higher than that of the control group by 14.76%, and the differences present above were statistically significant (p < 0.05). The details of the data are shown in Table 2. 3.4.  Pregnancy after HIFU treatment Successful follow-up was done in 302 cases (77.84%), of which 143 were in the infertile group and 159 in the control group. In the control group, 87 cases were fitted with Mirela and 29 cases underwent hysterectomy. In the infertile group, 41 cases were fitted with Mirela and 16 cases underwent hysterec - tomy. Among patients with fertility demands, the pregnancy rate after HIFU was 36.17% (17/47) in the control group and 28.81% (17/59) in the infertile group. Figure 2. f low chart. INTERNATIONAL JOURNAL OF HYPERTHERMIA 5 3.5.  Analysis of factors affecting secondary infertility The results of logistic regression analysis showed that T2WI high-signal spots in the lesions more than 30, type II (exogenous) lesions, pelvic adhesions, and dysmenorrhea symptoms were the risk factors for secondary infertility in adenomyosis ( p < 0.05). The details of the data are shown in Figure 4 . 3.6.  Analysis of factors affecting pregnancy after HIFU treatment Logistic regression equation analysis showed that age, history of curettage, and NLR were risk factors for pregnancy after HIFU for secondary infertility in adenomyosis ( p < 0.05), and age was an independent influencing factor. The details of the data are shown in Figure 5 . 3.7.  The influence of age on pregnancy after HIFU The relationship between patient’s age and pregnancy after HIFU was analyzed using the Receiver oper - ating characteristic curve (ROC). The details of the data are shown in Figure 6 . The area under the curve (AUC) was 0.793 with a 95% confidence interval of 0.678–0.909, and the cut off value was 0.538 corre - sponding to the age of 37.50 years, with a sensitivity of 0.714 and a specificity of 0.824. That is, the rate Table 1. Baseline information of patients. Variable Infertile group ( n = 178) Control group ( n = 210) z/t/χ2 value p Value Age 38.57 ± 5.80 41.34 ± 4.77 5.08 <0.001* BMI (kg/m 2) 22.53(20.85, 24.61) 22.24(20.70, 24.03) 0.29 0.77 Course of disease 5(2, 10) 5(2, 8.25) 0.72 0.47 History of pregnancy Frequency of vaginal delivery 64(35.96%) 151(74.76%) 50.39 <0.001* Cesarean section 51(28.65%) 60(28.57%) 0.00 0.986 2+ curettage times 56(31.46%) 88(42.11%) 4.66 0.031 Menstrual condition Menstrual clots 119(66.85%) 147(70.00%) 0.25 0.613 Menstrual changes 140(78.65%) 171(81.43%) 0.72 0.397 Change in cycle 71(39.89%) 97(46.19%) 1.55 0.213 Increased menstrual flow 104(58.43%) 129(61.43%) 0.31 0.579 Prolonged periods 77(43.26%) 83(39.52%) 1.04 0.308 Dysmenorrhea 131(73.60%) 133(63.33%) 4.67 0.031 * NRS 6.41 ± 2.62 6.16 ± 2.52 0.95 0.172 Hematologic Indicators WBC (10^9/L) 5.69(4.68, 7.12) 5.46(4.77, 6.82) 1.35 0.178 HGB (g/L) 123.50(105.00, 132.75) 121.00(103.00, 132.00) 2.15 0.032* PLT (10^9/L) 253.00(208.25, 300.75) 250.00(216.00, 316.00) 0.4535 0.651 NLR (%) 2.15(1.74, 2.80) 1.97(1.45, 2.95) 1.0945 0.274 HIFU ablation NPVR (%) 43.09 (29.80,60.56) 47.02 (33.72,64.57) 2.26 0.024* Note. *Indicates a statistically significant difference. Count data are expressed as median and quartiles or mean ± standard deviation, and measure data are expressed as frequency and percentage. Notes on abbreviations . WBC: White blood cell count; HGB: hemoglobin count; plt : platelet count; nlr: neutrophil lymphocyte ratio; plr: platelet lymphocyte ratio; npVr: non-perfused volume ratio; nrS: numerical r ating Scale. Figure 3. a blation after HIfu . Note. a and c preoperative t2WI lesions, b and d postoperative Ce- t1WI non-perfused volume. 6 Z. YANG ET AL. of post-HIFU pregnancy was higher ( p < 0.001) when the age was is lower than 37.5 years, the pregnancy rate after HIFU is higher ( p < 0.001). 4.  Discussion Adenomyosis is an estrogen-dependent disease, the ectopic endometrium between the myometrial wall changes with the cycle, the tissue undergoes cyclic damage repair, platelet aggregation, myofi - broblasts increase, causing myofibroblastic alterations, which shows uneven thickening of the myome - trial layer, enlargement of the uterine cavity, distortion of anatomical morphology, endometrial peristalsis and uterine contractility abnormality, which interferes with the migration of spermatozoa and the transportation of embryos, and affects the rate of embryo implantation [ 10–12 ]. In this study, we investigated the factors affecting secondary infertility in adenomyosis and the factors associated with improved fertility in patients after HIFU treatment by using clinical real-world data, with a view to providing a basis for clinical decision-making in patients with adenomyosis who have fertility requirements. Table 2. p atient mrI assessment and measurements. Variable Infertile group ( n = 178) Control group ( n = 210) z/t/χ2 Value p Value Uterine position ( n, %) Anterior 95(53.37%) 122(58.10%) 2.561 0.278 Posterior 60(33.71%) 71(33.81%) Median 23(12.92%) 17(8.09%) Uterine measurements Volume (cm 3) 203.78(144.98,307.25) 222.17(164.58,298.76) 1.552 0.121 Uterine cavity length (mm) 50.60(41.90,63.60) 49.35(41.20,59.24) 1.393 0.164 JZ max (mm) 36.90(13.20,47.78) 41.10(32.73,50.38) 2.828 0.005* Lesion measurements Lesion thickness (mm) 43.60(35.60,54.63) 43.90(35.45,52.93) 0.159 0.874 Lesion volume (cm 3) 86.33.(51.59,158.15) 94.49(59.51,152.05) 0.619 0.536 Lesion typing (n,%) Type I (endogenous type) 42(23.60%) 90(42.86%) 15.924 <0.001* Type II (exogenous type) 42(23.60%) 27(12.86%) 7.598 0.006* Type III (intermural type) 5(2.80%) 2(0.95%) 1.875 0.171 Type IV (other type) 89(50.00%) 91(43.33%) 1.722 0.189 Number of T2WI high signal spots in the lesion ( n, %) 0–10 67(37.64%) 100(47.62%) 3.913 0.048 11–30 58(32.58%) 70(33.33%) 0.024 0.876 30+ 53(29.78%) 40(19.04%) 7.426 0.007* Pelvic adhesions ( n, %) 47(26.40%) 31(14.76%) 8.13 0.004* Note. Count data are expressed as median and quartiles or mean ± standard deviation, and measure data are expressed as frequencies and percentages. JZ: Junctional zone. Figure 4. l ogistic analysis of infertility in adenomyosis patient. Note. *Indicates significance in multifactorial logistic analysis ( p < 0.05). t2WI high-signal spots more than 30 ( or = 1.810, 95CI%: 1.071–3.058) was an influencing factor in multifactorial analysis of infertility in adenomyosis ( p = 0.027). INTERNATIONAL JOURNAL OF HYPERTHERMIA 7 Adenomyosis has different morphological features and is associated with clinical symptoms due to dif - ferences in the development of adenomyosis. Kishi Y [ 7] staging is currently a common staging of adeno - myosis, which correlates with clinical manifestations and can be used as a reference in the selection of clinical treatments. Comparing the different subtypes of adenomyosis in the present study, the difference between secondary infertility group and control group was not statistically significant for both type III (intermural) and type IV (other) ( p > 0.05), but type I (endogenous) was lower than the control group in the infertility group, and type II (exogenous) was higher than the control group, which was in agreement with the study of Exacoustos [ 13] et  al. Type I (endogenous type) lesions often involve women with a history of uterine cavity surgery, with the majority of localized injuries caused by uterine cavity surgery, which has relatively little effect on sperm migration and embryo transport, uterine contractions, etc [ 7,13–16], and in the present study, the percentage of deliveries and scrapings in the infertility group was lower than that in the control group. Type II (exogenous) adenomyosis is often combined with pelvic endometriosis, which causes abnormalities in the morphology and structure as well as function of the patient’s oocytes, and excessive oxidative stress occurs in the peritoneal fluid, which has a toxigenic effect on the spermatozoa, thus affecting the normal function of the spermatozoa [ 17]. Moreover, adhesions formed by severe endo - metriosis cause changes in the pelvic structure, which may affect the process of ovulation and fertilization if the adhesions occur around the ovaries [ 18–20]. Thus it can lead to pelvic pain, dysmenorrhea and high Figure 5. l ogistic analysis of pregnancy after HIfu for infertility. Note. *Indicates significance ( p < 0.05) in multifactorial binary logistic analysis. a ge ( or = 0.822, 95CI%: 0.691–0.978) was an influential factor in the multifactorial analysis of pregnancy secondary to infertility in adenomyosis after HIfu ( p = 0.027). Figure 6. roC of patient age and pregnancy after HIfu treatment. 8 Z. YANG ET AL. probability of infertility [ 14,21]. The results of this study confirm that type II (exogenous) lesions, pelvic adhesions, and dysmenorrhea symptoms are risk factors for secondary infertility in adenomyosis. Adenomyosis of the uterus leads to ultrastructural changes in the binding zone, abnormal proliferation of myoblasts as well as interruption of myofibrillar structure and disorganization of myofibrils occurs, which

Results

in impairment of the normal function of the JZ zone, thus causing abnormal uterine contractions and alterations of uterine cavity pressure, which reduces the success rate of pregnancy [ 22]. In this study, the thickness of the JZ region in the infertile group with adenomyosis was less than that of the control group, and the incidence of dysmenorrhea in the infertile group was higher than that of the control group, then it is suggested that the clinical symptoms of the patients in the infertile group were more severe. Reinhold et  al. demonstrated that the histological features of uterine adenomyosis can be visualized on MRI, with high-signal lesions potentially representing ectopic endometrial tissue, endometrial cysts, or his - tological bleeding [ 23]. Studies by Gong Chunmei [ 24], Zhang Yan [ 25], and others revealed that the num - ber of high-signal spots on T2WI correlates positively with the difficulty of ablation; specifically, a greater number of high-signal spots is associated with increased ablation complexity. Changes in JZ are accompa - nied by alterations in the uterine immune microenvironment and smooth muscle cell activity, as well as elevated levels of inflammatory factors [ 26]. In this study, the presence of high-signal spots within adeno - myosis lesions may reflect higher cellular activity and invasiveness, leading to a higher incidence of T2WI signals exceeding 30 in the secondary infertility group compared to the control group. Combined with elevated PLT levels, these findings suggest that periodic bleeding of ectopic endometrium may induce a hypercoagulable state, thereby affecting the embryo implantation microenvironment and offering new insights into the pathophysiological mechanisms underlying infertility in uterine adenomyosis. HIFU, as a novel physical therapy modality [ 5], alleviates symptoms such as dysmenorrhea and men - orrhagia through precise thermal ablation technology [ 27], while effectively improving the uterine ana - tomical environment. Leveraging its minimally invasive characteristics and relatively low complication rate [ 5], HIFU has emerged as an innovative treatment option for patients with adenomyosis-associated infertility. Clinical observations indicate that successful pregnancies achieved post-treatment hold sub - stantial clinical significance [ 6]. In the present study, HIFU treatment restored fertility in 28.81% of patients with secondary infertility. Additionally, our findings indicated that lesion type II (exogenous), T2WI high signal spots exceeding 30, pelvic adhesions, and dysmenorrhea did not demonstrate statisti - cally significant associations with pregnancy outcomes following HIFU treatment. In principle, modifying pelvic adhesions and exogenous lesions via HIFU remains challenging. Additionally, many patients expe - rience relief from pain symptoms after HIFU treatment, a finding that has been consistently supported by the published research [ 28]. Therefore, it is hypothesized that improvements in the pathological char - acteristics of the lesion and the pelvic microenvironment after HIFU ablation may contribute to the suc - cessful pregnancy outcomes observed in some infertile patients post-surgery. Age, history of curettage, and NLR are important factors affecting pregnancy after HIFU in patients with infertility secondary to adenomyosis. NLR (Neutrophil Lymphocyte Ratio) is a novel inflammatory factor that represents the balance between the body’s inflammatory response and the immune response [ 29,30], and has been proposed as a factor for assessing the severity of adenomyosis [ 31–33]. In the present study, we found that the higher the NLR, the lower the postoperative conception rate. This suggests that patients with fertility requirements can be treated with medication to reduce the NLR concentration preoperatively, reducing the inflammatory response in the body to provide a basis for postoperative pregnancy. Age is the most important factor affecting conception in HIFU, and it is more difficult to restore fertility at age more than 37.5 years, so it suggests that patients with adenomyosis should be intervened as early as possible to improve fertility. Regarding the parameters of HIFU treatment, the NPVR in the postoperative pregnancy group was relatively lower. However, data analysis demonstrated that HIFU treatment did not adversely affect subsequent pregnancy outcomes. It can be inferred that following successful lesion abla - tion, the high-signal areas on T2WI either decreased or disappeared, indicating alterations in the uterine tissue structure. Therefore, HIFU ablation may significantly enhance fertility in some patients. Nevertheless, excessive ablation could potentially impair endometrial repair or uterine blood perfusion. Thus, achieving an optimal balance between lesion control and fertility preservation is critical. This study is a retrospective analysis. Patient recruitment was non-randomized, and patient attrition may introduce bias into the results. MRI-based classification does not fully capture the histological INTERNATIONAL JOURNAL OF HYPERTHERMIA 9 characteristics of lesions, and high-signal lesions were only quantified in the layer with the strongest signal intensity. This approach may overlook lesions between layers, potentially leading to discrepancies in the number of high-signal spots and introducing result bias. Additionally, this study did not include a comparison group of patients who did not undergo HIFU treatment, precluding definitive conclusions about HIFU’s role in promoting pregnancy. Furthermore, patients with endometriosis were not excluded, which could introduce bias when assessing the impact of HIFU on pregnancy outcomes. In the future, a prospective trial will be conducted to validate the efficacy of HIFU in treating infertility caused by uterine adenomyosis and to provide improved management strategies for enhancing fertility in these patients. 5.  Conclusion The results of this study showed that T2WI high-signal spots in lesions more than 30, type II (exogenous) lesions, pelvic adhesions, and dysmenorrhea symptoms are risk factors for secondary infertility in patients with adenomyosis. The reproductive outcomes of women have shown significant improvement following HIFU treatment for adenomyosis, particularly in those under the age of 37. In conclusion, the develop - ment of secondary infertility in patients with uterine adenomyosis is closely associated with imaging characteristics, lesion types, and pelvic conditions. While HIFU treatment has the potential to improve fertility in some patients, it necessitates a thorough evaluation of the patient’s age, endometrial condi - tion, and systemic inflammatory markers (e.g. NLR), as well as meticulous control of the ablation range to prevent over-treatment.While the observed pregnancy rate may not be deemed high, it nonetheless offers renewed hope for young infertile patients with adenomyosis in their disease management. Disclosure statement No potential conflict of interest was reported by the author(s). Funding This research is supported by the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NSCQ-MSX0140): “Study on the Effect and Mechanism of Focused Ultrasound on Improving Fertility in Infertile Patients with Adenomyosis of the Uterus” .

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Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis

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