{"paper_id":"16421f9c-1422-4e79-a100-5be177394228","body_text":" Corresponding author: M Ahmadi \nObstetrics and Gynaecology, West Middlesex University Hospital, Chelsea and Westminster Hospital NHS trust, United Kingdom \nCopyright © 2022 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. \nLiterature Review on the Modern Management of Adenomyosis \nM Ahmadi * and A Al Nakash \nObstetrics and Gynaecology, West Middlesex University Hospital, Chelsea and Westminster Hospital NHS trust, United \nKingdom. \nGSC Advanced Research and Reviews, 2022, 11(02), 023–028 \nPublication history: Received on 06 March 2022; revised on 28 April 2022; accepted on 30 April 2022 \nArticle DOI: https://doi.org/10.30574/gscarr.2022.11.2.0104 \nAbstract \nThis review article discusses the current modern management of adenomyosis. Adenomyosis is common amongst \nwomen of child bearing age and it has many implications on quality of life. These women struggle with symptoms of \ndysmenorrhoea, menorrhagia and infertility. We discuss the medical, interventional and surgical management of \nadenomyosis. There are numerous medical treatments which involve hormonal and non-hormonal methods. The \ninterventional methods consist of High intensity focus ultrasound (HIFU), percutaneous microwave ablation (PWMA) \nand radiofrequency ablation (RA). This paper also discusses the role of surgical technique and whether it has a role in \nthe management of adenomyosis, currently surgical options are not routinely offered to patients. There have been \npromising studies which have identified that surgery has improved fertility, menorrhagia and dysmenorrhea for \npatients with adenomyosis. \nKeywords:  Adenomyosis; Menorrhagia; Dysmenorrhoea; Infertility; Management of Adenomyosis \n1. Introduction\nFigure 1a: Ultrasound image of diffuse adenomyosis (left) [1]. 1b: MRI image of diffuse Adenomyosis (right) [2]. \nAdenomyosis is defined as the presence of endometrial glands and stroma in the myometrium [3]. The invasion can be \naccompanied with hypertrophy and hyperplasia of surrounding muscle cells, forming either diffuse or localised lesions. \n\n\nGSC Advanced Research and Reviews, 2022, 11(02), 023–028 \n24 \nAdenomyosis is very common, and women present with menorrhagia, dysmenorrhoea, infertility and related pregnancy \ncomplications [4]. \nAdenomyosis is commonly diagnosed using pelvic ultrasound and Magnetic Resonance Imaging (MRI). Typical features \non ultrasound are the presence of irregular endometrial -myometrial junction, hyperechoic islands, focal or diffuse \nmyometrial bulkiness and increased vascular flow on doppler [5]. \nIn this review article we will discuss the current modern management of adenomyosis. Management of adenomyosis is \ndependent on the symptoms, severity and fertility desire [4]. \n2. Overview of Modern Management  \nThere are multiple different options for managing symptoms of adenomyosis. In this article we will discuss medical, \ninterventional and surgical management for adenomyosis.  \n2.1. Medical Management \nMedical treatment consists of hormonal and non-hormonal methods. Non-hormonal methods consist of Non-Steroidal \nAnti-Inflammatory drugs (NSAIDs) which would be used to treat symptoms of dysmenorrhoea. Hormonal methods such \nas progestins and oral contraceptives are used to treat dysmenorrhoea and menorrhagia associat ed with \nadenomyosis[6]. Sharara et al. [7], summarised the effectiveness of GnRH antagonists which improved pelvic pain and \nsize of adenomyotic lesions in a few case reports. However more work is required to investigate this further[7]. \nLevonorgestrel releasing - intrauterine system (LNG-IUS) has been used for its non-contraceptive benefits of improving \ndysmenorrhoea and menorrhagia. It has been identified in a few studies that LNG -IUS has been shown to be more \neffective than oral contraceptives. It reduces the uterine volumes, reduces pain scores and haemoglobin levels increased \nwith use of LNG-IUS [7]. \nDanazol, is an androgenic hormone, has also been trialled in adenomyotic patients. Danazol-loaded IUS was used in one \nstudy where it improved dysmenorr hoea and there was a decrease in myometrial thickness in comparison to oral \ndanazol. They also identified better fertility after removal of danazol-IUS [7]. \nAromatase inhibitors (which stop the production of oestrogen) and GnRH agonists were compared for u se in \nadenomyosis and identified that both were effective in reducing uterine and adenomyoma volumes, therefore reducing \nprogression and improving symptoms [7]. \nUlipristal acetate, a potent progesterone receptor modulator, has conflicting results in terms of its use. In some studies, \nit has shown an improvement in symptoms but in others it has identified worsening of symptoms. It also has adverse \nside effect of liver injury requiring liver transplantation, which removed its use from the European market. The refore, \nthis drug is not commonly used as treatment for adenomyosis[7]. \nThere have been some mice studies on antiplatelet therapy for adenomyosis which suppressed myometrial infiltration, \nimproved generalised hyperalgesia and reduced uterine contractility. However, there is no human data on its use [7]. \nDopamine agonists such as bromocriptine is thought to be effective in adenomyosis as prolactin and its receptors are \nfound in adenomyotic tissue. In a study it was identified that the use of dopamine agonist s showed thinner maximal \njunction zone six months post treatment on ultrasound, however the results were insignificant on MRI. Its use has been \nshown in small pilot studies and bigger studies are required to identify if it makes a significant improvement i n \nsymptoms [7]. \nAll the above medical treatments are not definitive treatments but manage the symptoms temporarily and with stopping \nthe treatment, symptoms usually flare back. None the less in patients who would like to conceive and want relief of \nsymptoms outside of pregnancy, medical treatments have been effective and widely used.  \n2.2. Interventional Management   \nThere are newer minimally invasive techniques which use thermal energy sources on adenomyotic lesions to improve \nsymptoms. There are three types: H igh intensity focus ultrasound (HIFU), percutaneous microwave ablation (PWMA) \nand radiofrequency ablation (RA)[8]. \n\nGSC Advanced Research and Reviews, 2022, 11(02), 023–028 \n25 \nHIFU ablation is performed under either ultrasound or MRI. Patients are treated in a prone position and ultrasound \nwaves are directed at a ta rget lesion and causes instant coagulative necrosis. Patients are routinely admitted for one \nday, following a period of observation. During PMWA and RFA patients are supine, and an antenna are directed to the \ntarget lesion. \nPMWA uses electromagnetic energy and RA uses high frequency alternating electrical current. Both these procedures \nproduce heat energy which causes tissue necrosis. HIFU although its less invasive and doesn’t use an electrode, there is \na limitation of penetration of ultrasound for lesions  that are deep. MWA and RFA, was identified to be more \nadvantageous in comparison to HIFU due to shorter operator times, reduction in uterine and adenomyosis volume [8]. \nThe non-invasive methods are desirable for patients and have brought interest amongst clinicians as an alternative for \ninvasive methods. Although there have been short term benefits in improvement of symptoms, long term results are \nlimited and there have been recurrence of symptoms [4]. \n2.2.1. Uterine Artery Embolization (UAE) \nIn a review article by Popovic et al. [9], they looked at the effects of uterine artery embolization (UAE) on adenomyosis \nand identified that there is significant symptomatic relief in women undergoing UAE however the studies they reviewed, \nin some cases there was a combination of women having adenomyosis and leiomyoma, so it was difficult to ascertain if \nthe effects were on leiomyoma or adenomyosis. There was also a lack of standardised method of identifying \nimprovement in symptoms across all the different studies, making it difficult to make effective comparison across the \nstudies. Although this method seems a viable option for treatment, more robust data are required to assess if this would \nbe a potential for first-line treatment [9]. \n2.3. Surgical Management  \nThere are multiple surgical techniques that have been used in adenomyosis with newer techniques which also has come \nto fruition. They can be broadly categorised into laparoscopic and laparotomic techniques.  \n2.4. Laparotomic Techniques: Partial Excision  \n2.4.1. Wedge Resection  \nThe classical technique of wedge resection of the uterine wall entails removal of the focal adenomyoma as well as the \nseromuscular layer in a ‘V’ shape. The wound is closed with remaining muscular and serosal layer. This technique would \nbe suitable for foc al adenomyosis. However there have been limited benefits for symptoms of menorrhagia and \ndysmenorrhoea and high recurrence due to leaving behind some adenomyotic tissue [10]. \n2.4.2. Modified Reduction Surgery  \nIn the 1990s there were a few studies where they performed partial excision of adenomyotic tissue, and 6 women went \non to conceive later and none miscarried. Whereas in another study out of the 28 patients who had this procedure, 50% \nhad live births and 38.8% had a miscarriage [10]. \n2.4.3. Transverse H Incision of the Uterine Wall  \nAnother modified laparotomic procedure has been described whereby a transverse H incision is performed on the \nuterine fundus using electro-surgical scalpel separating the uterine serosa to uterine myometrium and then removing \nadenomyoma tissues. They then completed the procedure by suturing the myometrial edges in one or two layers. In a \nlater study they identified that women who had undergone this procedure 38% achieved clinical pregnancy, 16.1% \nmiscarried and 22.5% had live births [10]. \n2.5. Laparotomic Techniques: Complete Excision  \n2.5.1. Triple Flap Method  \nThis technique is effective in diffuse adenomyosis and has potential to prevent uterine rupture in future pregnancies. \nThis technique involves palpating and identifying the areas of adenomyosis  and performing adenomyomectomy by \nopening the uterine cavity and then reconstruction of the uterine wall resistant to rupture. A study looked into women \nwho had undergone this procedure and identified that in 81.4% the blood flow in the operated area had gone back to \nnormal within six months. Also, out of the 46 who conceived 32 had delivered a healthy baby by elective caesarean \nsection. With no cases of uterine rupture. Over the 27 years of the study, only 3.5% of the cases relapsed and required \n\nGSC Advanced Research and Reviews, 2022, 11(02), 023–028 \n26 \na second surgery. The limitation of this technique is that it has to be done under open technique as it requires the \npalpation of the adenomyosis, and delicate suturing of the hand is required [10]. \n2.5.2. Asymmetric Dissection Method  \nThis technique involves excising the  adenomyoma by opening the uterine cavity in a diagonal manner by inserting an \nindex finger and palpating for the lesion and ensuring to excise >5mm of inner myometrium as well as >5mm of the \nserosal myometrium. The uterine cavity is then reconstructed. Figure 2 shows the step-by-step approach of this method. \nHowever, the main limitation of this technique is the risk of uterine rupture. There was spontaneous uterine rupture \nidentified in 5 cases out of the 1,349 operated on [10]. \n2.5.3. Hysterectomy  \nThis method is the gold -standard treatment for adenomyosis, and it has been used for many years as a treatment of \nadenomyosis. However, this method is not preferrable in patients who wish to preserve their fertility.  \n2.6. Laparoscopic Techniques  \nLaparoscopic techniques should be used for focal adenomyosis as there is limited use of instruments and direction of \nmovement. Moreover, the surgeon cannot palpate to identify adenomyotic lesions.  \n \nFigure 2 The step-by-step method of asymmetric dissection [10] \nThere are several techniques that can be used laparoscopically, a longitudinal or transverse incision is performed across \nthe adenomyoma. The adenomatosis is resected using monopolar needle or laser knife. If there is a breach to the \nendometrial cavity, this is sutured and the area excised is sutured in two or more layers. The adenomyotic mass is \nremoved either by morcellator or a removal bag.  There have been concerns that using a morcellator may disperse \nundetected malignant tumours and therefore spread it throughout the abdominal cavity [10]. \n\n\nGSC Advanced Research and Reviews, 2022, 11(02), 023–028 \n27 \nIn a study performed in 2017, 74 patients who had undergone this surgery 13 (41.9%) had conceived, 4 had a \nmiscarriage and 9 (29.0%) had live births. There were no reports of any uterine rupture. In another study where the y \nlooked at pregnancy’s in <40s and in >40s following laparoscopic adenomyomectomy. Although the rate of pregnancy \nwas higher in women <40 years, from those who conceived in the older age group, two cases ended up with a \nhysterectomy for placenta accrete [10]. There have been benefits of both laparoscopic and laparotomic procedures in \nrelieving symptoms of menorrhagia and dysmenorrhoea without limiting fertility. However, despite these benefits, due \nto the scar on the uterus the risk of uterine rupture incr eases in any women having any surgery to the uterus whether \nthat is laparoscopic or laparotomic. In addition to that, it also poses risk for abnormal placentation in pregnancy. \n2.7. Robot-Assisted Laparoscopic Adenomyomectomy  \nFour cases of robotic assisted lap aroscopy are discussed by Chung et al. 2016  [11], where they used robotic assisted \nlaparoscopy to treat adenomyosis in 4 women who wished to preserve their fertility. They all had improvement in pelvic \npain and no residual adenomyotic tissues were seen pos t-operatively after a pelvic MRI. The advantages of robotic \nsurgery is that it has better visual field, with 3D high definition and the robotic arm has an endowrist with better range \nof movement in comparison to standard laparoscopy, allowing better suturi ng similar to laparotomic suturing. \nTherefore, this method has been suggested to be preferential to standard laparoscopy, however there is limited data on \nits use and bigger trials are required to identify benefits of robotic surgery over laparoscopy [11]. \n2.8. Combining Laparoscopy and Levonorgestrel Releasing-Intrauterine System (LNG-IUS) \nThere was a study performed by Sun et al, 2021 [12] that investigated the efficacy of combining laparoscopic \nadenomyomectomy and insertion of levonorgestrel  releasing-intrauterine system (LNG-IUS). They looked at whether \nthere would be a difference in scores for dysmenorrhea, menorrhagia and uterine volume using ultrasound. They \nidentified that in the 50 women in their study there were clinical effectiveness in pelvic pain amon gst patients where \n98%, 96% and 96% at 3, 12 and 24 months post -operatively, respectively. The clinical effectiveness for menorrhagia \nwere 97.6%, 95.2% and 95.2% at 3, 12 and 24 months postoperatively, respectively. The main adverse effects were \nuterine perforation, which occurred in one case and expulsion which occurred in 2 cases [12]. \nThis study shows that combination therapy could be a beneficial method for patients as there is not one technique that \nhas been proven to be therapeutic, except for the traditional hysterectomy method, therefore this can potentially reduce \nrisk of recurrence and treat symptoms in patients with diffuse adenomyosis who do not wish to have laparotomy.  \n3. Discussion \nAdenomyosis is very common in women of fertile age and is associated with menorrhagia, dysmenorrhoea and \ninfertility which significantly affects quality of life. The traditional treatment has been hysterectomy, but this is not \nfavourable in the younger pop ulation as it is not fertility preserving hence, we looked into the newer techniques \navailable that will enable fertility preservation and which are less invasive. These two qualities would be very appealing \nto our patients and much more favourable if they prove to be beneficial in treating adenomyosis.  \nThere are multiple therapies to treat adenomyosis that has been discussed, medical therapies mainly have symptomatic \nrelief and restricted to duration of treatment for example: NSAIDs, progestins, COCP, GnR H agonists and antagonists, \nLNG-IUS, Danazol, aromatase inhibitors, ulipristal acetate and dopamine agonists. Furthermore, newer less invasive \ntechniques such as HIFU, PWMA, RA and UAE have been used which has shown benefit for symptomatic relief. These \nnewer techniques have shown to be promising, but they come with their risks and side effects and more studies are \nrequired to identify long term benefit and recurrence rates.  There are also multiple surgical techniques which range \nfrom laparotomic, laparosc opic and robot -assisted laparoscopy. Laparotomy unfortunately is associated with longer \nhospital stay, higher estimated blood loss and longer recovery in comparison to laparoscopic techniques. The latter have \nbeen favoured especially in patients with comorbidities and obesity and has therefore broaden the spectrum of patients \nwho could benefit from this technique. \nIn one systematic review by Grace Younes, MD, and Togas Tulandi  [13], where they have   evaluated 27 studies: 10 \nprospective and 17 retrospective studies including a total of 1398 patients. They found that excision of adenomyosis is \neffective for symptom control such as menorrhagia and dysmenorrhea and most probably for adenomyosis -related \ninfertility [13]. For preserving fertility and relieving sym ptoms, medical treatment is usually the first choice, whereas \nexcisional surgery could be performed for refractory adenomyosis. The results show that over three-fourths of women \nwill experience symptom relief after conservative surgery. The pregnancy rates  after conservative surgical treatment \nvary widely. However, three -fourths of them conceived after surgery with or without adjuvant medical treatment. \nDepending on the duration of follow -up, recurrence rates differ from no recurrence to almost one -half of patients. \n\nGSC Advanced Research and Reviews, 2022, 11(02), 023–028 \n28 \nConservative surgery for adenomyosis improves pelvic pain, abnormal uterine bleeding, and possibly fertility but the \nbest method of surgery is yet to be seen.  Robot-assisted laparoscopy has very limited studies in its use but has been \nproposed to  be better than standard laparoscopy for its increased range of movement and enables suturing like \nlaparotomy. In all of these surgical techniques the main advantages were that there was significant improvement in \nsymptoms and patients were able to conceiv e and have healthy live births after surgery. Which is a massive \nbreakthrough in surgery, however there are associated risks, one of which is spontaneous uterine rupture and there \nhave been cases where this has occurred in patients following surgery. There fore, more studies are required to assess \nlong term benefits and risk of recurrence as to whether fertility preserving surgery should become the gold standard. \n4. Conclusion \nAs discussed above the management of adenomyosis is very complex and it has different elements. The most important \nof which that we have identified is that surgical treatment can have a role in the management of difficult cases, therefore, \nit should be considered by the clinician from now on and offered to the patient as an option for managing adenomyosis. \nCompliance with ethical standards \nAcknowledgments \nWe would like to thank the BMA library for providing us the references and resources.  \nDisclosure of conflict of interest \nBoth authors declare that they have no conflict of interest.  \nReferences \n[1] Anan R. Adenomyosis [Internet]. Radiopaedia; 2020 [cited 2022 Feb 20]. Available f rom: \nhttps://radiopaedia.org/cases/adenomyosis-15?lang=gb  \n[2] Stanislavsky, A. Adenomyosis on MRI [ Internet]. Radiopaedia; 2014 [Revised 2022; cited 2022 March 01]. \nAvailable from: https://radiopaedia.org/cases/adenomyosis-on-mri?lang=gb  \n[3] Zhao CZ, Wang B, Zhong Cy et al. 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Int J Hyperthermia. 2021; 38(1): 948-962. \n[9] Popovic M, Puchner S, Berzaczy D, Lammer J, Bucek RA. Uterine  artery embolization for the treatment of \nadenomyosis: a review. J Vasc Interv Radiol. Jul 2011; 22(7):901-9. \n[10] Osada H. Uterine adenomyosis and adenomyoma: the surgical approach. Fertil Steril. Mar 2018; 109(3): 406-417.  \n[11] Chung YJ, Kang SY, Choi MR, Cho HH,  Kim JH, Kim MR. Robot -Assisted Laparoscopic Adenomyomectomy for \nPatients Who Want to Preserve Fertility. Yonsei Med J. 2016; 57(6): 1531-1534.  \n[12] Sun F, Zhang Y, You M, Yang Y, Yu Y, Xu H. Laparoscopic adenomyomectomy combined with levonorgestrel -\nreleasing intrauterine system in the treatment of adenomyosis: Feasibility and effectiveness. J Obstet Gynaecol \nRes. Feb 2021; 47(2): 613-620.  \n[13] Younes G, Tulandi T. Conservative Surgery for Adenomyosis and Results: A Systematic Review. J Minim Invasive \nGynecol. Feb 2018; 25(2): 265-276.","source_license":"CC0","license_restricted":false}