{"paper_id":"c3649273-0371-46c6-b6ab-8fdf5460a6bb","body_text":"Vol:.(1234567890)\nCurrent Obstetrics and Gynecology Reports (2024) 13:72–79\nhttps://doi.org/10.1007/s13669-024-00379-w\nREVIEW\nNon‑surgical Treatment of Adenomyosis\nIoannis Dedes1  · Georgios N. Kolovos1  · Michael D. Mueller1 \nAccepted: 12 February 2024 / Published online: 22 February 2024 \n© The Author(s) 2024\nAbstract\nPurpose of Review Uterine-sparing excisional surgical techniques for adenomyosis are complex, carry significant risks, \nand after all have substantial recurrence rates. Consequently, there has been a trend towards adopting non-surgical treat-\nments. This narrative review outlines the latest in non-surgical treatments for adenomyosis, highlighting their significance \nin managing this condition and stresses the importance of further research, especially concerning long-term outcomes and \nfertility implications.\nRecent Findings Emerging evidence suggests that non-surgical techniques for the treatment of adenomyosis offer promising \nalternatives to traditional uterus-conserving surgery.\nSummary LNG-IUS is recommended as the primary management strategy for adenomyosis. In our clinical evaluation, a \npretreatment with GnRH-analogs, HIFU, or UAE prior to LNG-IUS insertion in enlarged uteri may mitigate treatment fail-\nure risks, notably device expulsion. Concurrently, post-intervention LNG-IUS application post non-surgical modalities can \ndiminish recurrence probability. In large uteri with presence of multiple uterine fibroids, UAE may be preferable compared \nto thermal ablation procedures especially if there is no wish for pregnancy or comorbidities not allowing for a hysterectomy. \nFor focal adenomyosis, especially when prioritizing fertility preservation, RFA may be considered due to its precise targeting, \navailable data on pregnancy outcomes, and ease of incorporation into gynecological practice. In cases of localized disease of \nthe anterior wall of the uterus without prior surgeries and no suspicion of concurrent endometriosis, HIFU can be favored.\nKeywords Adenomyosis · Non-surgical treatment · Uterine artery embolization · Levonorgestrel-releasing intrauterine \nsystem · Radiofrequency ablation · High-intensity focused ultrasound\nIntroduction\nAdenomyosis is a chronic, benign disease caused by ectopic \nendometrial glands and stroma leading to the formation of \nill-defined lesions within the myometrium. These lesions \ncan be either focal or diffuse (i.e., dispersed within the \nuterus) and are accompanied by hypertrophy and prolifera-\ntion of neighboring myometrial cells.\nThe main symptoms of adenomyosis are pain (e.g., dysmen-\norrhea and pelvic pain) and abnormal uterine bleeding (AUB). \nAdenomyosis can also be associated with infertility and preg-\nnancy complications, such as preterm delivery, intrauterine \ngrowth restriction, and pregnancy-induced hypertension [1, 2].\nFor decades, the key method for diagnosing adenomyo -\nsis was histological examination post-hysterectomy, which \nrelied on the detection of endometrial glands and stroma \nwithin the myometrium. This reliance on post-surgical diag-\nnosis contributed to an underestimation of the significance \nand prevalence of adenomyosis. Recently, however, the land-\nscape of adenomyosis diagnosis has transformed consider -\nably, thanks to advancements in imaging technologies such \nas transvaginal ultrasound and magnetic resonance imaging \n(MRI) [3]. Consequently, there has been a noticeable shift in \nthe demographic profile of patients diagnosed with adeno-\nmyosis, which now includes younger women of reproductive \nage presenting with a diverse array of symptoms. This shift \nhighlights the prevalence of adenomyosis as more common \nin younger patients than previously recognized. It is esti-\nmated to affect up to 15–20% of women of reproductive \nage and commonly overlaps with endometriosis and uterine \nfibroids [4]. These overlapping conditions should be taken \ninto account when choosing the proper treatment.\n * Ioannis Dedes \n Ioannis.dedes@insel.ch\n1 Department of Obstetrics and Gynecology, University \nHospital of Bern, University of Bern, 3010 Bern, \nSwitzerland\n\n73Current Obstetrics and Gynecology Reports (2024) 13:72–79 \nDespite its clinical significance, adenomyosis remains \nsignificantly understudied compared to endometriosis, \nas evidenced by the disparity in scientific literature. A \nsearch on PubMed reveals this gap, with only 3871 entries \nfor “adenomyosis,” markedly fewer than the 34,523 \nentries for “endometriosis.” These numbers highlight the \nneed for increased research and understanding in the field \nof adenomyosis.\nThe limited understanding of adenomyosis’s nature, cou-\npled with the absence of a standardized classification sys-\ntem, has resulted in a disorganized approach to treating this \ndisease. Unlike endometriosis, there is currently no drug \nspecifically labeled for the treatment of adenomyosis and \nonly recently, have guidelines been developed for its man -\nagement, such as those from the Asian Society of Endome-\ntriosis and Adenomyosis and the Society of Obstetricians \nand Gynecologists of Canada (SOGC) [5, 6].\nGenerally, the symptoms of adenomyosis can be  \ncontrolled through hormonal treatment. For patients  \nwith treatment-refractory or severe symptomatology,  \nhysterectomy is considered standard-surgical treatment. In \ncases where organ preservation is warranted, uterine-sparing  \nsurgical techniques have been proposed [13]. Surgical  \ninterventions range from laparoscopic myomectomy for \nremoval of an adenomyoma to more complex procedures \nsuch as the Osada procedure for diffuse adenomyosis, \ninvolving laparotomy and flap reconstruction of the uterus \n[7]. The reported outcomes of surgical treatments include a \npregnancy rate of 40%, a miscarriage rate of 21%, and a live-\nbirth rate of 70% [8 ]. Surgical resection of adenomyosis is \ngenerally associated with significant perioperative risks and \nrequires a highly advanced surgical skill set. Of particular \nconcern is the risk of uterine rupture during pregnancy after \nsurgery. When choosing such a procedure, one should bear \nin mind the significant recurrence rate, which ranges from 9 \nto 19% depending on the surgical technique used [9].\nGiven these complexities and risks, the past decades \nhave seen a shift towards the development and adoption \nof less invasive treatment modalities for adenomyosis. \nTechniques such as Uterine Artery Embolization (UAE), \nHigh-Intensity Focused Ultrasound (HIFU), Percutane-\nous Microwave Ablation (PMWA), and Radiofrequency \nAblation (RFA) have emerged as promising alternatives \nas reports increase on their efficiency and safety for the \ntreatment of adenomyosis. In addition, pregnancies have \nbeen observed in small case series. In the meta-analysis \n“Pregnancy Outcomes after Uterus-sparing Operative \nTreatment,” the comparison between non-surgical treat-\nments (HIFU, RFA, and UAE) and surgical excision for \nadenomyosis showed no significant difference in preg-\nnancy outcomes. Approximately 40% of women success-\nfully conceived using non-excisional methods, with a 21% \nmiscarriage rate, and the live birth rate was 70%—mirror -\ning the outcomes of surgical excision treatments [8 ].\nThese advancements reflect a significant evolution in \nthe therapeutic approach to adenomyosis, moving away \nfrom highly invasive surgeries toward minimally invasive \ninterventions.\nThis narrative review concentrates on the existing evi-\ndence for non-surgical treatments and their significance in \nthe management of adenomyosis.\nTypes of Adenomyosis\nDifferent classification models for adenomyosis exist. Most \nof these models agree on a focal and disseminated disease, \nas well as adenomyosis of the inner and outer myometria. \nAmong the various classification systems, the most compre-\nhensive and commonly used model is that proposed by Kishi \net al. [10] as follows.\nIntrinsic adenomyosis (Subtype I) affects the uterine inner \nlayer—known as the junctional zone; extrinsic adenomyosis \n(Subtype II) infiltrates the outer shell of the uterus; intramu-\nral adenomyosis (Subtype III) is encapsulated within intact \nmuscular structures of the uterus; and indeterminate adeno-\nmyosis (Subtype IV) is a diffuse type that does not fit into \nthe other three subtypes, making it difficult to categorize.\nData are emerging that the different subtypes—especially \nintrinsic versus extrinsic and diffuse versus focal—seem \nto have different etiologies and clinical profiles, making  \nit important to distinguish between them. For example,  \nintrinsic adenomyosis is more commonly associated with \nAUB and prior uterine surgery. In terms of age, patients with \nintrinsic adenomyosis are generally older compared to those \nwith extrinsic adenomyosis. On the other hand, extrinsic \nadenomyosis is more frequently found in younger, nulligravid \nwomen and is notably associated with deep infiltrating  \nendometriosis. It is found to cause more primary infertility \ncompared to diffuse adenomyosis [11, 12].\nMedical Treatment\nMedical treatment is primarily indicated for patients with \nadenomyosis who wish to preserve their fertility or for those \nnearing menopause. It is also recommended for patients who \nare unsuitable for surgical intervention because of other \nmedical comorbidities. The range of hormonal treatments \navailable for adenomyosis includes combined oral contra-\nceptive (COC) pills, progestins, the levonorgestrel-releasing \nintrauterine system (LNG-IUS), and gonadotropin-releasing \nhormone (GnRH) agonists and antagonists and danazol.\n\n74 Current Obstetrics and Gynecology Reports (2024) 13:72–79\nAvailable guidelines recommend using hormonal treat-\nment as the first-line medical option for managing pain \nand AUB.\nCOCs function by inhibiting follicle-stimulating and lute-\ninizing hormones, suppressing follicular growth and endo-\nmetrial proliferation, thereby relieving AUB and chronic \npelvic pain. However, their impact on adenomyotic lesions \nand uterine volume reduction is not well defined [13].\nDienogest, a synthetic oral progestin, stands out for its \neffectiveness in managing endometriosis-associated pain and \nadenomyosis symptoms. It is comparable or even superior to \nCOCs and GnRH analogs in alleviating dysmenorrhea but \nshows less efficacy in reducing uterine volume and inducing \namenorrhea [13]. The use of dienogest, especially in cases of \nintrinsic adenomyosis, may lead to spotting and unpredict-\nable bleeding [14]. Furthermore, concerns about progester -\none resistance, potentially due to KRAS mutations [15] in \nadenomyotic lesions, pose challenges to its effectiveness.\nGnRH analogs, including agonists and antagonists, work \nby downregulating gonadotropin release, leading to reduced \nestrogen levels and consequent shrinkage of the uterus, thus \nalleviating adenomyosis-related pain. While effective, their \nlong-term use is limited by hypoestrogenic side effects such \nas bone loss. GnRH antagonists, avoiding the initial flare-up \neffect seen with agonists, reduce uterine size and symptoms \nbut face challenges in terms of cost and variable patient \nresponses [13].\nAlthough hormonal treatment provides only symptomatic \nrelief, with symptoms likely to relapse immediately after \ncessation of treatment, it remains of great importance in sup-\npressing the progression of adenomyosis.\nLevonorgestrel‑Releasing Intrauterine System \n(LNG‑IUS)\nLNG-IUS improves the symptoms associated with adeno-\nmyosis by inducing decasualization and atrophy of the endo-\nmetrium and downregulating estrogen receptors through \nincreased progesterone release. It is highly effective in \nreducing pain and AUB and is regarded to be more effica-\ncious than COCs [16].\nRecommended by the National Institute for Health \nand Care Excellence (NICE) in the United Kingdom, the \nAsian Society of Endometriosis and Adenomyosis guide-\nlines (Level of evidence: Ib Grade B), and the Society of \nObstetricians and Gynaecologists of Canada (SOGC), LNG-\nIUS is widely used as the first-line medical treatment for \nadenomyosis.\nIn a randomized controlled trial (RCT) 75 patients with \nAUB and/or dysmenorrhea and imaging-confirmed adeno-\nmyosis, those treated with LNG-IUS demonstrated higher \nscores on quality of life (QoL) measures compared to \npatients who underwent hysterectomy [17].\nIn patients with a lower disease burden of adenomyosis, \nLNG-IUS treatment notably improves health-related qual-\nity of life (HR-QOL), particularly in managing symptoms \nsuch as dysmenorrhea and AUB even reflecting on improved \nblood hemoglobin levels. Conversely, for patients with dif-\nfuse (Subtype IV) and extensive disease, the effectiveness \nof LNG-IUS in enhancing HR-QOL is significantly dimin-\nished. While it still provides some relief in dysmenorrhea \nand HMB, it does not improve blood hemoglobin level [18]. \nAnother limitation in the use of LNG-IUS may be a higher \nexpulsion rate in uteri larger than 150 ml [19].\nNo specific studies are available on the rate of hysterec-\ntomy for the treatment-failure of LNG-IUS in adenomyosis, \nbut in cohorts for HMB, it is reported to be 3.7–6% after five \nyears and longer [20].\nNon‑Surgical Interventions\nAll non-surgical interventions share a common origin in \nthe field of radiology and have progressively integrated into \nthe management of gynecological conditions over the past \ntwo decades. Given the advantages of rapid recovery and \nminimal invasive nature of non-surgical interventions, more \ngynecologists are considering them as a secondary treatment \nto traditional pharmacotherapy.\nNon-surgical interventions for adenomyosis can be cat-\negorized into UAE and image-guided thermal ablation tech-\nniques. UAE, an angiographic technique, utilizes embolic \nagents delivered into uterine arteries to create ischemic \nnecrosis within adenomyotic lesions. Owing to the disease’s \nassociation with increased angiogenesis [21] and hypervas-\ncularity [22], UAE may offer targeted treatment selectivity.\nImage-guided thermal ablations, encompassing HIFU, \nPMWA, and RFA, are minimally invasive methods that pre-\ncisely target adenomyotic tissue under imaging guidance.\nThese ablation techniques utilize heat to differentially \naffect tissue based on temperature thresholds. Cell death \noccurs at temperatures exceeding 60 °C. Between 60 °C and \n99 °C, tissue undergoes desiccation and protein coagula-\ntion. However, surpassing 100 °C can lead to vaporization \nand charring causing the destruction of the cytomolecular \narchitecture of the tissue [23–25].\nThe principal distinction among HIFU, PMWA, and RFA \nlies in the type of energy source utilized the mechanism \nof its application to the adenomyotic lesion and a distinct \nheat-profile.\nHigh‑Intensity Focused Ultrasound HIFU\nHIFU employs focused ultrasonic energy externally \nto thermally ablate adenomyotic lesions beneath the \nskin without surface disruption. This procedure can be \n\n75Current Obstetrics and Gynecology Reports (2024) 13:72–79 \nmonitored using ultrasound or MRI to ensure accuracy. \nHowever, the effectiveness of HIFU is contingent upon \nan unobstructed path for the ultrasound beam; obstacles \nsuch as significant cutaneous scarring, abdominal wall \nthickness exceeding 5 cm, the presence of foreign materi-\nals, or bowel segments interposed due to adhesions can \nimpede treatment efficacy [26]. An MRI-based study \nhighlighted that 38.9% of patients suitable for UAE were \nineligible for MRI-guided HIFU, predominantly due to \nbowel interposition [27].\nThe limited penetration of ultrasonic waves can also \nresult in suboptimal ablation for deeply situated adenomy -\nosis, such as lesions on the posterior uterine wall that often \npresent with more severe pathology. Contrasting lesion \nlocations, HIFU has shown superior efficacy in treating \nadenomyotic tissue located on the anterior uterine wall as \ncompared to the posterior [28].\nHIFU is recommended by the Asian Society of Endo-\nmetriosis and Adenomyosis guidelines (Level of evidence \n2a; Grade of recommendation B) [5 ] and mentioned by \nthe SOGC Clinical Practice Guideline [6 ] (low level of \nevidence, conditional recommendation).\nHIFU presents the largest patient cohort among all the \nabove-mentioned image-guided thermal ablation proce-\ndures. A 2021 meta-analysis by Liu et al., encompassing \n15,123 patients treated with HIFU, revealed a notable \ndysmenorrhea symptom relief rate of 84.2%. This find-\ning aligns with the significant treatment effect observed, \nas indicated by a standardized mean difference (SMD) \nof 2.59 [29], corroborating earlier results reported by \nMarques et al. [26].\nHowever, the available data on QoL did not demonstrate \nimprovements in QoL scores post-HIFU treatment. Notably, \nthere was a substantial reduction in menorrhagia severity \nscores from baseline to follow-up [29].\nAdverse reactions primarily included lower abdominal \npain (reported in 21.6% of patients, n  = 392) and pain or \ndiscomfort in the treated area (12.8%, n = 233). Addition -\nally, moderate adverse events such as superficial first to \nsecond-degree skin burns were resolved within 14 days \nusing local dressing.\nReintervention rate was reported by Liu et al. at 11% after \n24 months and longer for the combined group of HIFU and \nRFA (four studies).\nRegarding fertility outcomes, a systematic review by \nChen et al. assessed 557 patients who sought to conceive \npost-HIFU treatment. The study reported a pooled preg -\nnancy rate of 53.4% and a live birth rate of 35.2% [30]. \nHowever, significant heterogeneity among the included stud-\nies suggests the need for a cautious interpretation of these \nfindings, highlighting the necessity for further research to \nsolidify the evidence regarding HIFU’s effectiveness in fer-\ntility outcomes.\nPercutaneous Microwave Ablation (PMWA)\nPMWA employs electromagnetic energy to rapidly heat tis-\nsue, achieved by agitating water molecules within the tis-\nsue. This heating effect is facilitated by the insertion of a \nprobe (antenna) through the skin under anesthesia. Similar \nto HIFU, PMWA is typically performed through a transab-\ndominal approach, which limits its applicability for treating \nadenomyosis located on the posterior wall of retroverted or \nretroflexed uteri.\nIn comparison to HIFU and RFA, PMWA can generate \nhigher temperatures, often exceeding 100 °C, due to its abil-\nity to propagate electromagnetic energy through dehydrated, \ncharred, or desiccated tissue. Technological advancements, \nsuch as cooling systems, antenna arrays, and optimized \ndelivery methods, have improved the clinical application of \nPMWA, enabling more uniform heat distribution across the \ntarget area. PMWA is mainly applied via transabdominal, \nlaparoscopic, or less commonly, transvaginal approaches.\nIn the guidelines of the Asian Society of Endometriosis \nand Adenomyosis, PMWA is mentioned with a low grade of \nrecommendation (Grade C) [5], and the SOGC advises that \nit should not be used outside a research context (low level \nof evidence, conditional recommendation).\nA meta-analysis consisting of 513 patients across six \nstudies observed symptom relief in 89.7% of cases, a sub-\nstantial effect mirrored in a significant SMD of 4.27 [29]. \nThe study by Li et al. on 107 patients revealed notable reduc-\ntions in uterine volume post-treatment, along with improve-\nments in uterine fibroid symptom and HR QoL scores, dys-\nmenorrhea severity, menstrual volume, and hemoglobin \nlevels. However, a substantial dropout rate was observed at \nthe 12-month follow-up [31].\nAdverse events reported post-PMWA included vaginal \ndischarge, pain in the treatment area, fever, nausea, and \nvomiting, occurring in 51.3–72% of cases, but no signifi-\ncant complications such as uterine perforation or injuries \nto surrounding organs were noted [29, 31]. Information on \npregnancy outcomes following PMWA treatment is cur -\nrently unavailable.\nRadiofrequency Ablation (RFA)\nRFA involves inserting electrodes, directly into the target \nlesion under ultrasound guidance. This can be done during \neither laparoscopic surgery or transcervically under either \ntransvaginal or integrated intrauterine ultrasound guidance. \nRFA utilizes high-frequency alternating electrical currents \nto generate heat, effectively controlling the temperature to \nprevent charring and keep it below 100 °C. This results in \nthermal fixation and coagulative necrosis while preserving \nthe cellular structure of the tissue [23, 24].\n\n76 Current Obstetrics and Gynecology Reports (2024) 13:72–79\nRFA is mentioned in the Asian Society of Endometriosis \nand Adenomyosis guidelines (3b Grade of recommendation \nC) [5] and SOGC states similarly to PMWA that it should \nnot be used outside a research context (low level of evidence, \nconditional recommendation).\nA systematic review involving 396 patients across seven \nstudies reported a 94.7% rate of symptom relief with RFA, \nalong with a significant reduction in dysmenorrhea pain \nscores by 63.4% at 12 months [32]. However, specific data \non QoL parameters are not available. One study showed nor-\nmalization in bleeding patterns in 68.7% of cases with AUB.\nThe overall hysterectomy rate for treatment-failure at \n12 months was 10.8 ± 1.5% in the same study [32]. Liu et al. \nreported an overall reintervention of 11% after 24 months \nand longer in the combined group of HIFU and RFA (four \nstudies) [33].\nIn terms of fertility, the clinical pregnancy rate among \nthose trying to conceive naturally was 42.7%, with an overall \nrate of 35.8%. The data, derived from a study of 31 patients, \nreported 41 pregnancies post-RFA, with a 66.7% delivery \nrate and a notable 62.5% rate of cesarean deliveries. There \nwere no reported cases of uterine rupture following RFA \ntreatment [34].\nUterine Artery Embolization (UAE)\nUAE is an angiographic procedure that uses embolic agents \ninjected into uterine arteries to cause ischemic necrosis in \nadenomyotic lesions. The procedure typically involves vas-\ncular access through the femoral artery in the groin area \nand is performed under sedation and local anesthesia. Given \nthe disease’s association with increased angiogenesis [21] \nand hypervascularity [22], UAE may offer targeted treat-\nment selectivity. The occlusion of blood supply to the lesion \nresults in hypoxia, ischemia, and tissue necrosis, with mini-\nmal impact on surrounding tissue [22].\nThis approach has been explored in recent decades as a \ntreatment option for symptomatic adenomyosis, following \nits success in managing uterine fibroids.\nUAE is recommended by the SOGC Clinical Practice \nGuideline [6] (strong recommendation, moderate evidence), \nNICE UK Interventional procedures guidance (IPG473) and \nthe Asian Society of Endometriosis and Adenomyosis guide-\nlines (Level of evidence 2a; Grade of recommendation B) \nfor managing symptomatic adenomyosis [5]. It is offered to \npatients who have completed child-bearing and would like \nto preserve their uterus.\nThe current state of UAE on adenomyosis is depicted in \na systematic review and meta-analysis by A.M. de Bruin \net al. (2017). In a comprehensive study involving 1049 \npatients across 30 studies, UAE achieved significant symp-\ntom improvement in 83.1% of patients. QoL, particularly in \ncases of adenomyosis with uterine fibroids, also improved.\nComplications were reported in 615 out of 1049 patients, \nwith abdominal pain up to two weeks being the most com-\nmon (87.4–361 out of 413 reported cases).\nThe study noted a short-term hysterectomy rate of 4%, \nwhich rose to 14.2% at 12 months. While the efficacy of \nUAE in the short-term is established, concerns arise regard-\ning its long-term because of high symptom recurrence \nrates. Liu et al. observed a reintervention rate of 16.8% at \n24 months or longer [33].\nNotably, patients undergoing UAE often have larger uteri \nand more severe adenomyosis, indicating a possible selec-\ntion bias. The size of the embolization agent and the blood \nsupply of the lesion [22] are crucial factors influencing \nrecurrence risk, as smaller embolization agents and well-\nvascularized lesions tend to have better outcomes [22]. \nIncreased vascularization is not just seen in adenomyosis \nlesions but also in the eutopic endometrium. This should \nraise concerns in sterility treatment—beyond affecting ovar -\nian vascularization, which was a relevant issue in the early \nphase of UAE treatments.\nThe review of de Bruin reported amenorrhea in 6.3% of \nthe participants, all of whom were over 40 years of age. \nThis complication could be due to the infarction of the \nbasal endometrium with or without Asherman syndrome, \nas reported rates of proven ovarian failure are lower.\nData on pregnancy following UAE are limited. In their \ncohort study, Serres-Cousine et al. [35] reported pregnancy \nrate of 53% among 61 patients with adenomyosis. The dis-\nease represented only 16% of the overall analyzed cohort \nwhich consisted mainly of leiomyoma (n  = 398). Of note \nis a lower pregnancy rate of 29% in isolated adenomyosis, \nwhereas in the group of adenomyosis in the presence of \nfibroids, the pregnancy rate was 75%. Adverse pregnancy \nand neonatal outcomes were not observed.\nIt is important to note that data from the UAE treatment \nof uterine fibroids, such as those from the FEMME Trial \n[36], should not be directly applied to adenomyosis treat-\nment due to differences in vascularization patterns between \nthe two conditions. The anticipated outcomes from the \n“Quality of Life after Embolization vs. Hysterectomy in \nAdenomyosis” (QUESTA) Trial may provide more specific \nRCT data relevant to adenomyosis.\nComparative Analysis\nA closer look at the available literature reveals distinct pro-\nfiles for LNG-IUS, UAE, HIFU, PMWA, and RFA, each \nwith their own set of benefits and constraints. Reading \nthrough the available literature on the different non-surgical \ninterventions in detail, only a narrative comparison can be \nattempted (Table  1). Owing to the high heterogeneity and \nlow quality, the data do not allow for a direct comparison in \n\n77Current Obstetrics and Gynecology Reports (2024) 13:72–79 \nTable 1  Summary highlighting the advantages and disadvantages of the different types of non-surgical treatment of adenomyosis\nNon-surgical procedure Functional Principle Advantages Disadvantages\nLevonorgestrel-releasing intrauterine \nsystem (LNG IUS)\nIntrauterine device, transvaginally inserted \nin office setting. LNG induces endometrial \ndecidualization and atrophy, with anti- \nproliferative and anti-inflammatory effects\nRecommended as first-line treatment\nOffice procedure\nCombination as “adjuvant treatment” after non-\nsurgical and surgical treatment\nLess effective in diffuse adenomyosis, larger \nuteri; higher expulsion rate in large uteri\nUterine artery embolization (UAE) Angiographic procedure under fluoroscopic \nguidance. Synthetic agents are injected \nthrough catheters into the uterine arteries, \nresulting in ischemia of the target tissue. It \ncan be done as an outpatient procedure in \nmost cases under sedation or local anesthesia\nSuitable for large, diffuse adenomyosis, espe-\ncially in the presence of uterine fibroids\nIncreased long-term reintervention rate\nFertility concerns\nHigh-intensity focused ultrasound (HIFU) Concentration of high-intensity sonographic \nwaves to heat and destroy tissue through \ncoagulative necrosis. Requires magnetic \nresonance imaging or sonography to track the \nbeam’s path and monitor thermal response of \ntissue. Performed under conscious sedation \non an outpatient basis\nEffective for focal adenomyosis on the anterior \nwall\nNon-invasive (does not breach the skin)\nTechnical limitations\nLess effective for posterior wall lesions\nProlonged ablation time\nRadiofrequency ablation (RFA) Ultrasound-guided placement of one or more \nRF needle electrodes, which deliver high-\nfrequency alternating electrical currents that \ncreate ionic agitation in target tissue, resulting \nin heat generation and coagulative necrosis. \nIt can be done as an outpatient procedure in \nmost cases under sedation or local anesthesia\nPrecise targeting for smaller lesions\nCompared to HIFU and PMWA, it is imped-\nance controlled and provides better monitor-\ning of tissue during the procedure\nEasy incorporation into gynecological practice\nLess successful for large uteri, diffuse disease\nNo information on quality of life available\nPercutaneous microwave ablation (PMWA) A needle antenna with an exposed tip is \nadvanced percutaneously into the lesion \nunder sonographic guidance. Electromagnetic \nenergy rapidly rotates water molecules in tar-\nget tissue to cause tissue necrosis due to heat\nCompared with HIFU and RFA, PMWA can \nreach higher temperatures ablate larger vol-\numes, shorter ablation times\nNo Information on pregnancies available\nNo information on reintervention rate\n\n78 Current Obstetrics and Gynecology Reports (2024) 13:72–79\nthe mentioned meta-analysis and systematic reviews of the \ndifferent intervention. Currently, there is not a single RCTs \nor comparative studies. Robust long-term data are needed to \nadequately counsel patients regarding the potential necessity \nfor repeat interventions.\nFrom a clinical perspective, LNG-IUS is recommended \nas the initial treatment option for adenomyosis. For patients \nwith enlarged uteri, employing a “pretreatment” strategy \nwith GnRH-analogs, HIFU, or UAE before inserting LNG-\nIUS may reduce the risk of treatment failure, such as device \nexpulsion. Furthermore, implementing the LNG-IUS post \nnon-surgical interventions has been associated with reduced \nrates of recurrence. This approach is recommended to opti-\nmize patient outcomes and minimize the probability of \nsymptomatic relapse and reintervention.\nIn large uteri with presence of multiple uterine fibroids, \nUAE may be preferable compared to thermal ablation proce-\ndures especially if there is no wish for pregnancy or comor-\nbidities not allowing for a hysterectomy.\nFor focal adenomyosis, especially when prioritizing fer -\ntility preservation, RFA emerges as a strategic option due \nto its integration into gynecological procedures like hyst-\neroscopy or laparoscopy. Its unique advantage lies in the \navailability of integrated systems for both trans-cervical and \nlaparoscopic applications, allowing gynecologists to employ \nRFA directly during surgeries. This adaptability is a signifi-\ncant benefit not shared by other non-surgical treatments such \nas HIFU or UAE. In cases of localized disease of the anterior \nwall of the uterus without prior surgeries and no suspicion of \nconcurrent endometriosis, HIFU could be favored. PMWA \ncannot be recommended in cases where childbearing is not \nconcluded, as there are no data on pregnancies available.\nConclusion\nIn the realm of uterine-sparing thermal ablation procedures \nfor adenomyosis, technologies such as HIFU, RFA, and \nPMWA show early promise. Across all mentioned interven-\ntions in patients with adenomyosis, dysmenorrhea relief \nrates are well above 80% [29, 37]. Their effectiveness in \nmanaging adenomyosis-related pain and AUB bleeding is \nincreasingly recognized. Additionally, the reintervention \nrates for these non-surgical methods, ranging from 11 to \n17% [33], are comparable to those of surgical, uterus-sparing \nprocedures, which vary between 9 and 19% [9].\nCurrently, concerns remain about the utility of non-  \nsurgical techniques in women with a pregnancy wish, \ndespite encouraging results from one meta-analysis [8 ]. \nThe limited number of patients treated with these methods,  \ncoupled with the high risk of bias and heterogeneity in  \nstudies, hinders definitive conclusions. Particularly in the  \ncase of UAE, there is a potential concern regarding impaired \nmyometrial and endometrial function, which is crucial for \npregnancy. Nevertheless, substantial uncertainties also per-\nsist for thermal ablation procedures: The current energy set-\ntings for these modalities are extrapolated from their appli -\ncation in fibroid treatment. Given the distinct histological \ncharacteristics of adenomyosis, including increased cellu-\nlarity and less defined borders, there is a need to develop \nadenomyosis-specific parameters to optimize efficacy while \nminimizing thermal injury.\nFurthermore, understanding the healing process post-\ntreatment is vital for pregnancies itself as complications such \nas uterine ruptures have been reported for HIFU [38], RFA \n[39], and UAE [40].\nIn conclusion, while advancements in non-surgical treat-\nments for adenomyosis offer promising alternatives to tra-\nditional surgery, their varying efficacies and potential risks \nunderscore the need for further research and development of \nmore refined techniques. The choice of treatment must be \ntailored to each patient's specific condition, balancing the \nbenefits against potential complications, especially in the \ncontext of future fertility.\nAuthor Contribution All authors contributed to the study conception \nand design. Methodology and data synthesis and analysis were per -\nformed by I.D. and G.K. The first draft of the manuscript was written \nby I.D., and all authors commented on previous versions of the manu-\nscript. Supervision was carried out by M.M. All authors have read and \nagreed to the published version of the manuscript.\nFunding Open access funding provided by University of Bern\nData Availability No datasets were generated or analyzed during the \ncurrent study.\nCompliance with Ethical Standards \nEthics Approval No ethics board approval was requested, as the data \nwere extracted from published papers.\nConflict of Interests The authors declare no conflict of interest and \nthat no funds, grants, or other support were received during the prepa-\nration of this manuscript.\nHuman and Animal Rights and Informed Consent This article does not \ncontain any studies with human or animal subjects performed by any \nof the authors.\nOpen Access This article is licensed under a Creative Commons Attri-\nbution 4.0 International License, which permits use, sharing, adapta-\ntion, distribution and reproduction in any medium or format, as long \nas you give appropriate credit to the original author(s) and the source, \nprovide a link to the Creative Commons licence, and indicate if changes \nwere made. The images or other third party material in this article are \nincluded in the article’s Creative Commons licence, unless indicated \notherwise in a credit line to the material. If material is not included in \nthe article’s Creative Commons licence and your intended use is not \npermitted by statutory regulation or exceeds the permitted use, you will \n\n79Current Obstetrics and Gynecology Reports (2024) 13:72–79 \nneed to obtain permission directly from the copyright holder. To view a \ncopy of this licence, visit http://creativecommons.org/licenses/by/4.0/.\nReferences\n 1. Nirgianakis K, et al. Fertility, pregnancy and neonatal outcomes of \npatients with adenomyosis: a systematic review and meta-analysis. \nReprod Biomed Online. 2021;42(1):185–206.\n 2. Horton J, et al. Reproductive, obstetric, and perinatal outcomes of \nwomen with adenomyosis and endometriosis: a systematic review \nand meta-analysis. Hum Reprod Update. 2019;25(5):592–632.\n 3. Tellum T, Nygaard S, Lieng M. 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Obstet Gynecol. \n2014;123(2 Pt 2 Suppl 2):418–20.\nPublisher's Note Springer Nature remains neutral with regard to \njurisdictional claims in published maps and institutional affiliations.","source_license":"CC0","license_restricted":false}