{"paper_id":"4fb1ff79-d6f0-4cc9-ab4c-579adabfb320","body_text":"INNOVATIONS  •  January 2022 EMJ50\nFertility and Pregnancy Outcomes after  \nHigh-Intensity Focused Ultrasound Ablation for \nUterine Fibroids and Adenomyosis: A Review\nAbstract\nHigh-intensity focused ultrasound (HIFU) ablation, also known as focused ultrasound surgery, is the \nlatest advancement in treating uterine fibroids and adenomyosis. Limited evidence, in terms of case \nseries only, suggest that ultrasound-guided focused ultrasound/magnetic resonance-guided focused \nultrasound treatment for fibroids and adenomyosis could be a safe alternative to myomectomy or \nuterine artery embolisation for females who wish to have babies. It also appears that this non-invasive \nHIFU treatment can shorten the treatment to pregnancy interval after HIFU ablation. Further studies \nare needed to confirm such findings. \nINTRODUCTION\nUterine fibroids and adenomyosis are common \namong reproductive-age females. Uterine \nfibroids, particularly large submucosal and \nintramural uterine fibroids, may cause infertility \nand implantation and miscarriage problems. 1,2 \nThey may also increase the risk of complications  \nduring pregnancy and delivery; during  \npregnancy, they may cause inappropriate \nenlargement of the uterus, fetal malpresentation, \nobstructed labour, caesarean delivery, and post-\npartum haemorrhage.\n3,4 \nAdenomyosis, though arising from different \naetiology, may also cause similar problems. \nFurthermore, adenomyosis can interfere with the \nprocess of pregnancy by disrupting implantation.5 \nThey are also the most common cause for heavy \nmenstrual bleeding, leading to anaemia before \ncontemplating pregnancy.6 Medical treatments \nwith hormones or progestogen intrauterine \ncontraceptive devices prevent these patients \nfrom conception and pregnancy. Therefore, \nsurgical treatment is the usual resort to improve \ntheir chance of pregnancy.\n7\nMETHODOLOGY \nMethodology of this study of high-intensity \nfocused ultrasound (HIFU) ablation involved \nliterature search using PubMed as the search \nengine and using keywords such as ‘high-\nintensity focused ultrasound’, ‘HIFU’, ‘fibroid’, \nAuthors: *Kwok To Thomas Li,¹ WS Felix Wong²\n1. Department of Obstetrics and Gynaecology, Queen Mary Hospital, The University\nof Hong Kong, China\n2. Division of Women’s and Children’s Health, The University of New South Wales,\nSydney, Austraila\n*Correspondence to lithomas8@gmail.com\nDisclosure: The authors have declared no conflicts of interest.\nReceived: 28.03.21\nAccepted: 22.10.21\nKeywords: Adenomyosis, high-intensity focused ultrasound (HIFU), pregnancy, uterine fibroid.\nCitation: EMJ Innov. 2021;6[1]:50-54.\n\nCreative Commons Attribution-Non Commercial 4.0 January 2022  •  INNOVATIONS 51\n‘adenomyosis’, and ‘pregnancy’ from 2001 to 2021. \nAdditional literature searches were conducted \nfrom peer-reviewed colleges’ publications and \nguidelines, as well as of references from the \nco-author’s books: Adenomyosis Facts and \nTreatments by Xue et al.8 and Focused Ultrasound \nSurgery in Gynecology by Wong et al.9  \nWHAT IS HIGH-INTENSITY FOCUSED \nULTRASOUND AND HOW IT WILL HELP \nTO IMPROVE FERTILITY?\nHIFU ablation, also known as focused ultrasound \nsurgery (FUS), is the latest advancement \nin treating many benign solid tumours in \ngynaecology and surgical conditions, 10-14 \nincluding, but not limited to, uterine fibroids and \nadenomyosis.12,15-17 It is non-invasive, in which \nthe most striking feature is no cut wound of the \nuterine wall in which the lesions are located. \nHIFU focuses the ultrasound energy on the \ntarget lesions such as uterine fibroids or \nadenomyosis without affecting the surrounding \norgans. The localised temperature to the target \nlesion is 60–90 oC. The surrounding tissue and \nvessels under lower temperature dissipate the \nheat by their blood flow. Therefore, the damage \nto the surrounding tissue and vessels could \nbe minimised when the HIFU heat is applied \nin a pulsed manner. This induces coagulation  \nnecrosis of the uterine fibroids or adenomyosis \nwithout damage to the surrounding organs, \nparticularly the major vessels. Subsequently, \nthe necrotic fibroid or adenomyosis tissues are \nabsorbed and removed, leading to reduced sizes \nof the treated lesions. \nAfter HIFU treatment, either with the use of \nultrasound or MRI to assess the size of fibroids, \nmost of the fibroids reduce at least 50.0% in size \nafter a single treatment. Lyon et al.18 reported a \ncase series of 10 patients, with a 23.3% reduction \nin size at 3 months, 49.3% at 12 months, and \n51.9% at 24 months. A retrospective case series \nof 189 nulliparous females also showed the \nmean reduction in uterine fibroids volume was \n58.0%±31.3% in 12 months after HIFU ablation.19 \nThese reductions in uterine sizes greatly enhance \nthe fertility environment of the uterus for \npregnancy. HIFU also has a strong advantage \nin maintaining the integrity of the uterus. Using \nultrasound focusing on ablating adenomyosis \nlesions can restore the uterus’s anatomy and \nimprove the immune microenvironment; the \npregnancy rate increased after HIFU treatment \nfor adenomyosis.20\nHIGH-INTENSITY FOCUSED \nULTRASOUND TECHNIQUE  \nThe target adenomyosis tissue is identified \nthrough visualisation by comparing ultrasound \nand MRI images during HIFU treatment. HIFU \nablation is performed to ablate the adenomyosis \ntissue point by point, layer by layer, until grey-\nscale changes of the coagulated tissue are \nobvious. Under MRI, it is not too difficult after \nto identify the irregular boundary between \nadenomyosis and normal myometrium. \nImproving static ultrasound technology helps \nto identify adenomyosis; also, using cine clips \n(movie editing function) if available can easily \ndiagnose adenomyosis.8 \nHIGH-INTENSITY FOCUSED \nULTRASOUND ABLATION \nCOMPARED WITH MYOMECTOMY OR \nADENOMYOMECTOMY \nMyomectomy or adenomyomectomy are also \nperformed on patients who wish to retain \ntheir uterus, but fibroid recurrence rates after \nabdominal myomectomy are 12.4% and 46.0% \nat 12 and 24 months, respectively. 21 The need \nfor re-operation for recurrent symptoms in \nadenomyosis is high. The risk of recurrence of \nuterine fibroid after HIFU is 15%, which is lower \nor at least comparable with myomectomy.  \nThese surgical procedures are also  \nassociated with morbidity or even mortality.\nHIFU ablation is a new technology. Its safety \nprofile is best-known in treating space-\noccupying lesions in gynaecology. Furthermore, \nthe reported complications are minor. Chen et \nal.22 demonstrated in a large cohort study that \ncomplications arising from HIFU ablation were \nall Grade A or B but not C or above, according \nto the Society of Interventional Radiology  \n(SIR) Severity Classification standard. 23 In  \nanother safety analysis of 9,988 cases of \nuterine fibroids and adenomyosis treated by \nHIFU ablation, Chen et al. 24 noted that more \nserious complications occurred when treating \n\nINNOVATIONS  •  January 2022 EMJ52\nadenomyoma, reflecting the difference in the \npathology of the two different types of disease. \nHowever, the incidence of complications in HIFU \nablation is comparatively low.25\nAfter HIFU ablation, improvement of symptoms \nand quality of life were significantly better than \nsurgical myomectomy. 26 The improvement \nof haemoglobin level enhances successful \npregnancy and delivery outcomes.\nAfter myomectomy, patients who may \nbecome pregnant have risks of uterine rupture, \nmiscarriage, pre-term birth, and intrauterine \nadhesions that impair pregnancy.27 These patients \nare also advised not to get pregnant within 1–2 \nyears to allow the uterine wound to heal well \nbefore pregnancy. Even if previous surgery \nhad not affected the chance of pregnancy, \nthe mode of delivery is still controversial. \nWhen myomectomy, or uncommonly \nadenomyomectomy, has been performed on \na female with fibroids or adenomyosis, some \nobstetricians may allow a trial of a vaginal \nbirth if there is no endometrial opening of the \nuterine cavity during myomectomy. However, \nsome doctors in some Asian countries, because \nof the unavailable detailed history of previous \nmyomectomy or adenomyomectomy, may \nchoose to offer elective caesarean section to \navoid risk of uterine rupture during labour.\nCOMPARISON WITH UTERINE ARTERY \nEMBOLISATION  \nHIFU ablation is a non-invasive procedure that \nhas often been compared with uterine artery \nembolisation (UAE), which has also been accepted \nas an effective alternative treatment for uterine \nfibroids and adenomyosis instead of surgery.28,29 \nHowever, regarding fertility, pregnancy, and \ndelivery outcomes, major complications \ninclude uterine necrosis and infection leading \nto emergent hysterectomy, ovarian failure, \namenorrhoea, and vaginal dryness related to \nnon-target embolisation or over-embolisation.30,31 \nAt present, there is no definite conclusion about \nthe safety of pregnancy after UAE. There are \nreports of cases of successful pregnancy and \ndelivery after UAE; however, adverse outcomes \nof pregnancy after UAE including spontaneous \nabortion, premature delivery, abnormal placenta, \npre-eclampsia, post-partum haemorrhage, etc., \nhave also been observed, 32,33 and the rate of \ncaesarean section has also increased. Therefore, \nfor females considering future pregnancy, UAE \nshould be carefully considered for its impact \nafter treating fibroids or adenomyosis.28\nCOMPARISION WITH MEDICAL \nTREATMENT  \nThere is no long-lasting, effective medical \ntreatment to reduce the size of uterine fibroids, \nincluding short interval treatment with ulipristal. \nHence it is not advisable to use medical treatment \nalone in the management of pressure symptoms \nsecondary to uterine fibroids. \nOn the other hand, there are many existing \nreports showing that after HIFU ablation \ntreatment for fibroids and adenomyosis there \nwas no adverse impact on fertility, pregnancy, \nand labour outcomes.\nImpact on Fertility\nThere has been concern that HIFU ablation might \naffect the ovarian function or fertility reserve. \nLee et al.34 compared the anti-Müllerian hormone \n(AMH) levels of 70 patients with symptomatic \nadenomyosis and uterine fibroids before and \n6 months after HIFU ablation. They found no \nsignificant difference in AMH levels between \nthe two treatment groups, suggesting that \nHIFU ablation has minimal impact on ovarian \nreserve. No AMH changes after HIFU ablation \nwas also confirmed by Cheung et al. 35 in their \nstudy. Therefore, it appears that HIFU ablation \nis comparatively safer for the fertility of patients \nreceiving treatment.\nSo far, there has not been a study that \ndemonstrates the impact of HIFU sonication, \nparticularly for a submucosal fibroid and its \nadjacent endometrial tissue, causing any \nimpairment of implantation. As a result of \nindirect sonication, the ultrasound energy may \nimpair uterine functions. Direct and excessive \nablation of a submucous fibroid might also cause \nintracavitary adhesions or denuded endometrial \nlining. Nevertheless, despite a lack of case \nreports, this possibility cannot be excluded.\n\nCreative Commons Attribution-Non Commercial 4.0 January 2022  •  INNOVATIONS 53\nImpact on Pregnancy  \nIn the early days of magnetic resonance-\nguided (MRg)-HIFU treatment, case reports \nof pregnancies showed successful vaginal  \ndelivery at term, and none had complications \nduring pregnancy and labour. 36,37 Some larger \nstudies, including individual and multicentre \ncollaborative trials, have also confirmed \nsuccessful pregnancies after HIFU ablation for \nfibroids and adenomyosis.38-41 \nAs many studies were from China, the  \nauthors had reported a high rate of induced \nabortions and miscarriage in pregnancies after \nHIFU treatment for fibroids and adenomyosis. \nHowever, it might be related to the fertility \nregulation in the past. It is also possible that \nmaternal age and sizable fibroids after HIFU may \nalso influence the miscarriage rate in any study, \nas both factors can independently adversely \nimpact miscarriages. Bohlmann et al. 42 showed \nthat the risk of miscarriage after ultrasound-\nguided (USg)FUS/MRgFUS was 17.8%, which did \nnot appear to be higher than a control group of \npatients wanting to have children.\nImpact on Delivery \nFrom the literature, normal pregnancies have been \nreported 3–5 months after HIFU treatment. 43,44 \nThese patients had uneventful vaginal deliveries. \nThere was no uterine rupture during pregnancy \nor labour for those with vaginal delivery at term \nafter HIFU treatment. Therefore, it appears from \nthese limited data that pregnancy can occur \nwithin 1 year after HIFU treatment and a good \npregnancy outcome is possible. Conception is \nadvisable 6 months after HIFU. \nHIFU delivers pulsed HIFU to the target  \nlesion of uterine fibroid, whereas myomectomy \naims to remove the target uterine  \nfibroid. After myomectomy, caesarean section \nis needed if the uterine cavity has been entered \nduring surgery. \nDespite the widespread reassurance that  \nvaginal delivery is safe, the rate of elective \ncaesarean section appeared to be high among \nfemales after HIFU ablation. The caesarean \nsection rate was reported as high as 50–78%.38,44 \nAfter HIFU ablation, all pregnancies that reach \nterm would have a high caesarean section rate \ncompared to term pregnancy without HIFU \nsurgery. The reasons for the high caesarean \nsection rate are not known; this might be due to \na maternal preference. \nCONCLUSION \nThere is currently no systematic study on the \neffects on fertility, pregnancy, and delivery \noutcome for patients after HIFU ablation \ntreatment for fibroids and adenomyosis, but there \nhave been a large number of cases of pregnancy \nand related reports, suggesting that there is little \neffect after HIFU on pregnancy. The number of \npatients requiring continued childbirth is still \nsmall, and there is not enough scientific evidence \nto explain the impact on mother and child  \nduring pregnancy.\nThe current consensus among HIFU doctors,  \nbut with limited evidence, suggests that  \nUSgFUS/MRgFUS treatment for fibroids and \nadenomyosis could be a safe alternative to \nmyomectomy or UAE for females who wish to \nhave babies. It also appears that this non-invasive \nHIFU treatment can shorten the treatment to \npregnancy interval after HIFU ablation. Given \nthe prevalence of females with fibroids and \nadenomyosis before childbearing, addressing \nthese important reproductive issues in a large \nclinical trial is critical.\nReferences\n1. Mirzamoradi M et al. Evaluation \nof pregnancy outcomes in Iranian \nwomen with uterine myomas. Novelty \nin Biomedicine. 2020;8(3):142-5.\n2. Serour AG. Adenomyosis a forgotten \ncause of infertility. The Egyptian \nJournal of Fertility of Sterility. \n2020;24(2):11-21.\n3. Lee HJ et al. Contemporary \nmanagement of fibroids in pregnancy. \nRev Obstet Gynecol. 2010;3(1):20-7.\n4. Mehla S, Singh N. Assessment of \npregnancy outcome in patients \nwith uterine fibroids. JAMDSR. \n2020;8(11):145-8.\n5. Harada T et al. The impact of \nadenomyosis on women’s fertility. \nObstet Gynecol Surv. 2016;71(9):557-\n68.\n6. Halvorson LM. New perspectives on \nadenomyosis. Semin Reprod Med. \n2020;38(2-03):87-8.\n7. Szubert M et al. 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Pregnancy and \nlive birth after focused ultrasound \nsurgery for symptomatic focal \nadenomyosis: a case report. Hum \nReprod. 2006.21(5):1255-9.\n45. Shu Li J et al. Pregnancy outcomes in \nnulliparous women after ultrasound \nablation of uterine fibroids: a single-\ncentral retrospective study. Sci Rep. \n2017;7(1):3977.","source_license":"CC0","license_restricted":false}