© Borgis - Postępy Nauk Medycznych 2/2015, s. 88-94
*Krzysztof Pyra, Tomasz Jargiełło, Anna Drelich-Zbroja, Michał Górnik, Klaudia Karska, Michał Sojka, Łukasz Światłowski, Małgorzata Szczerbo-Trojanowska
Embolizacja tętnic macicznych w leczeniu objawowych mięśniaków macicy
Uterine artery embolisation for the treatment of symptomatic uterine fibroids
Department of Interventional Radiology and Neuroradiology, Medical University, Lublin
Head of Department: prof. Małgorzata Szczerbo-Trojanowska, MD, PhD
Wstęp. Mięśniaki są najczęściej występującymi łagodnymi guzami macicy. W ramach leczenia stosuje się zarówno metody zachowawcze, chirurgiczne, jak i minimalnie inwazyjne. Kluczowym elementem przy embolizacji jest odpowiednia kwalifikacja pacjentek.
Cel pracy. Ocena skuteczności i bezpieczeństwa embolizacji tętnic macicznych mikrocząstkami hydrożelowymi pokrytymi środkiem przeciwzapalnym w zmniejszaniu objętości objawowych mięśniaków macicy.
Materiał i metody. W prospektywnym obserwacyjnym badaniu od stycznia 2011 do grudnia 2013 do embolizacji tętnic macicznych zakwalifikowano 206 pacjentek z objawowymi mięśniakami macicy. Ocenie poddano 118 kobiet w wieku od 32 do 52 lat (średnia 39 lat), które zgłosiły się na wizytę kontrolną po miesiącu i kontrolne badanie rezonansu magnetycznego po 3 miesiącach. Pod względem ilości mięśniaków przeważającą grupą były chore z 2/4 mięśniakami (78 chorych), następnie z pojedynczymi mięśniakami (26 chorych) i z macicą tzw. mięśniakowatą (14 chorych). Ze względu na wielkość/średnicę mięśniaków wyróżniono 4 grupy: < 7 cm u 77 chorych, 7-12 cm u 19 chorych, > 12 cm u 8 chorych, macicę mięśniakową stwierdzono u 14 chorych.
Wyniki. Średnie zmniejszenie objętości mięśniaków w całej badanej grupie wyniosło 62%, poczynając od najmniejszej redukcji 9% u chorej z zeszkliwiałym mięśniakiem, po 100% u chorych z wydzielonym mięśniakiem podśluzówkowym.
Wnioski. UAE jest bezpieczną i skuteczną metodą leczenia objawowych mięśniaków macicy. Oprócz redukcji objawów, prowadzi do znacznego zmniejszenia ich masy. Istotną rolę w procesie leczenia odgrywa odpowiednia kwalifikacja chorych do zabiegu i ścisła współpraca między radiologiem zabiegowym i ginekologiem.
Introduction. Uterine fibroids are the most common benign uterine tumours which can be treated with conservative, surgery or minimally invasive methods. Selection of patients for embolisation seems to be essential.
Aim. Assessment of efficacy and safety of uterine artery embolisation with hydrogel microparticles coated with an anti-inflammatory agent for reduction in symptomatic uterine fibroid volumes.
Material and methods. In the prospective observational study carried out between January 2011 and December 2013, 206 patients with symptomatic fibroids were qualified for uterine artery embolisation. 118 aged 32 to 51 (average 39), who reported for follow-ups 3-4 months after procedures, were evaluated. According to the number of fibroids, patients with 2/4 fibroids predominated (78 patients), followed by those with single fibroids (25) and with myomatous uteri (14 patients). According to fibroid sizes, 4 groups were distinguished: < 7 cm in 77 patients, 7-12 cm in 19, > 12 cm in 8, and myomatous uteri in 14 patients
Results. A mean decrease in fibroid volume in the entire study population was 62%, ranging from 9% in the patient with a hyalinised fibroid to 100% in patients with separated submucosal fibroids.
Conclusions. UAE is a safe and effective treatment for symptomatic uterine fibroids. In addition to reducing the symptoms, significantly reduces their volume. The key to success is proper qualification, as well as cooperation between the radiologist and the gynecologist.
Uterine fibroids are the most common benign uterine tumours, which are also called uterine fibromas; histopathologically they are leiomyomas and are among the most frequently occurring benign neoplasms affecting 20-40% of women above the age of 35 years (1-3). Although some factors affecting their occurrence have been determined, their aetiology remains unknown. They are composed of smooth muscles, the same ones, which build the uterine wall. They assume the form of tumours and can occur individually or in clusters, several or dozen tumours each. Their diameters range from several to 15 cm and more. Generally, their sizes do not exceed 10-12 cm. According to their location, fibroids are divided into subserous (the most common type – 50% of cases), intramural (30%), submucous (much less common) or located in the cervix and the round ligament of the uterus. Every fifth patient with fibroids complains of the accompanying symptoms, such as pain and discomfort in the region of the pelvis minor, profuse and prolonged menstrual bleedings, dysmenorrhoea, fertility disorders and miscarriages. In some cases, due to a mass effect, fibroids can compress the adjacent organs, e.g. the urinary bladder, leading to pollakiuria, incontinence or anuresis. In extreme cases, this benign neoplasm can compress the uterus resulting in urinary retention and hydronephrosis. Only about 20% of patients with fibroids have symptoms qualifying them for treatment.
Uterine fibroids can be treated with conservative and interventional methods. Pharmacological treatment involves hormonally active drugs, mainly gonadoliberin analogues, followed by selective estrogen and progesterone receptor modulators, progesterone antagonists, androgens, pure antiestrogens and aromatase inhibitors. The newest preparation used is ulipristal acetate – a synthetic progesterone receptor modulator approved for preoperative treatment of uterine fibroids. Administered for three months before surgery, ulipristal acetate to reduce the volume of fibroids before their removal. According to literature data, post-conservative treatment recurrences are observed in 30-40% of cases.
The interventional methods include surgical and minimally invasive ones, including embolisation, high--intensity focused ultrasound (HIFU) (sometimes focused ultrasound – FUS), ablation or cryomyolysis (4). The most common surgical procedure is hysterectomy. Depending on the extent of procedure, hysterectomies can be partial (removal of the body of uterus), total, total with tuboovariectomy or radical – in cases with neoplastic lesions.
Hysterectomy is usually associated with suppressed menstruation due to the lack of uterine mucous membrane, which is located in the uterine body. In cases of ovariohysterectomy, premenopausal women develop surgically induced menopause with its typical symptoms.
One of the sparing methods is myomectomy, i.e. removal of fibroid tumours while the uterus is preserved, which is an alternative to hysterectomy. The objective of myomectomy is to preserve the reproductive abilities of women and to alleviate some symptoms, such as profound menstruations, pain or compression-associated symptoms. The fibroids > 6 cm are considered too big to be treated by laparoscopy. During the 10-year post-myomectomy period, recurrences are found in even 27% of cases. The traditional procedures can be performed during laparotomy, laparoscopy or via the transvaginal route (5). At the end of the 20th century, uterine artery embolisation (UAE) was introduced, which is the method of low invasiveness. In the 80ties, during UAE for the treatment of reproductive tract haemorrhages, the procedures were found to stop haemorrhages but also substantially reduce fibroid sizes, which was described for the first time in 1987 (6). The first publication regarding the treatment of fibroids with uterine artery embolisation was published in France in 1994 (7). The major assets of such procedures are their low invasiveness, high efficacy, avoidance of surgical intervention, hence preservation of the uterus. Therefore, women started to be increasingly interested in this method, which success was associated with many positive elements. Today, UAE is one of the most commonly applied methods to treat uterine fibroids (8). It is estimated that in 95% of women with symptomatic fibroids recognised during imaging examinations, there is a technical possibility to perform embolisation. Menstruating women with diagnosed symptomatic fibroids are qualified for UAE, irrespective of tumour size and number. However, the fibroid diameter and location enable to estimate the risks and anticipated outcomes.
Selection for embolisation
The prerequisite of effective and safe embolisation is good cooperation between interventional radiologists and gynaecologists. The gynaecologist first decides whether a particular patient qualifies for any further treatment as only about 20% of patients have symptomatic fibroids, and only they are good candidates for treatment.
The first-line imaging examination is transvaginal US, followed by MRI necessary for radiological evaluation (9). MRI is to exclude pathologies other than fibroids within the pelvis (10). Moreover, the endometrium has to be examined; aspiration biopsy according to the Pipell method is used. Cervical cytology and vaginal bacteriological tests are also recommended.
The main laboratory examinations include blood cell counts, coagulation tests (INR, APTT) and renal (creatinine, urea) concentration of FSH at cycle day 3, SR and CRP, general urine tests and ROMA tests. The procedures of embolisation are performed until cycle day 10 (4).
Indications and contraindications for embolisation
According to the Society of Obstetricians and Gynaecologists of Canada, each patient with symptomatic fibroids without contraindications for embolisation can be a candidate for the procedure in question, if benefits, i.e. post-procedure subsidence of symptoms exceed the risk of complications (11). Noteworthy, minimally invasive embolisation of uterine fibroids is associated with low numbers of serious complications; therefore, benefits exceed risks in the majority of cases.
The key element is to make sure that the symptoms reported are caused by fibroids and not some other pathology. Before the selection for embolisation, the uterine cavity and the source of abnormal bleeding should be accurately assessed. If the bleeding is caused by is a single, small-sized subserous fibroid, hysteroscopic myomectomy should be considered.
MRI is more advantageous for evaluation of uterine fibroids than ultrasound examinations, particularly for the diagnosis of adenomyosis; unfortunately, the major drawback is its poor availability (11).
With the years, the value of UFE in the treatment of adenomyosis has been increasingly high. According to the Canadian guidelines, UFE can be performed in patients with concomitant adenomyosis and fibroids. The number and size of fibroids is not a contraindication for UAE procedures. During one procedure, all lesions are treated. Decisions regarding UFE treatment should be made individually, considering benefits vs. risks. The number of contraindications is relatively low. The absolute contraindications include pregnancy, cancer, infections of the reproduction tract, pelvis or systemic infections. The relative contraindications involve allergy to iodine contrast media, renal failure, fibroids of narrow stalks, and intrauterine devices.
Large, pedunculated fibroids, both subserous and submucosa, carry the risk of necrosis with resultant infection (12). The literature data indicate that in this kind of management surgery is required in 1-5% of such cases (13, 14). According to the German publication, one of relative contraindications is the use of gonadoliberin analogues for more than 3 months (4). The opinions on embolisation in patients with adenomyosis are inconsistent; the majority of them follow the guidelines of the Canadian Society. A special case is women with adenomyosis who want to preserve the uterus. For such patients, UAE is one of few options of non-invasive treatment. Therefore, UAE should be considered in such special situations (15-19).
When UAE procedures are performed without epidural anaesthesia, the majority of patients are likely to develop the post-embolisation syndrome, which is a characteristic reaction of the body associated with acute, transient ischaemia of the uterine muscle. The possible symptoms include pain, nausea and vomiting, moderately elevated temperature not exceeding 37.5°C (7).
The comparison of post-hysterectomy and post--embolisation complications reveals that severe, life-threatening complications develop mainly after hysterectomy (14.8% hyst vs. 4.5% UAE) while the percentage of slight complications is comparable in both groups (23.5% vs. 21.0%); premature menopause occurs in 1.4% of cases in the UFE group compared to 0.2 in the hysterectomy group (20). The incidence of premature menopause depends on age, more precisely on the ovarian reserve. With the extent of potential connections between the uterine and ovarian artery determined, embolisation materials of larger diameters are used, which ensure a wider margin of safety. The embolisation particles currently available on the market are characterised by excellent calibration; thus, the most suitable material can be chosen. According to the current findings, premature menopause occurs in 15% of women aged > 45 years and < 1% in women aged < 45 years (21). One of the studies evaluated the ovarian reserve in 36 women over the period of 5 years. All patients were of reproductive age who reported symptoms associated with uterine fibroids and were qualified for uterine artery embolisation. The study demonstrated that embolisation procedures affected accelerated decreases in ovarian reserves (22).
In another study assessing the treatment outcomes in 177 women, the conclusions were different. The study included only women before menopause (the mean age – about 40 years). The authors evaluated the effect of uterine artery embolisation (88 women) and hysterectomy (89 patients) on the ovarian reserve. The 24-month observations revealed a significant increase in FSH in both methods. Additionally, the level of anti-Mullerian hormone (AMH) was determined in 30 patients after UAE and in 33 after hysterectomy. A significant decrease in AMH was observed in patients after UAE. The above data led to the conclusion that both methods affect the ovarian reserve, which can result in premature (iatrogenic) menopause (23). Many studies evaluated the percentage and types of connections between the uterine and ovarian artery. In the study by Razavi et al. (24) of 2002, the uterine-ovarian connections were classified into 3 types: type I (21.6%) – inflow through the ovarian artery to the uterine artery via anastomoses, type II (3.9 %), in which the ovarian artery directly supplies the fibroid and type III, in which the ovaries are mainly supplied by the uterine artery. In type I and II, unless the procedure is carefully carried out, embolisation can be incomplete, whereas in type II, inattentive embolisation can lead to ovarian injury. Once the statistical extentof those connections is known, a suitably larger material can be used, which will minimise the percentage of complications (fig. 1A, B).
Fig. 1. Uterine artery embolisation in the treatment of massive symptomatic uterine fibroids. Angiography before (A) and after (B) treatment.
Powyżej zamieściliśmy fragment artykułu, do którego możesz uzyskać pełny dostęp.
Płatny dostęp do wszystkich zasobów Czytelni Medycznej
1. Poręba R: Współczesne trendy w leczeniu mięśniaków macicy. Lekarz 2011; 3: 4-6.
2. Reroń A: Nowotwory trzonu macicy. [W:] Opala T (red.): Ginekologia. Podręcznik dla położnych, pielęgniarek i fizjoterapeutów. Wydawnictwo Lekarskie PZWL, Warszawa 2003: 260-265.
3. Markowska A: Epidemiologia. [W:] Markowska J (red.): Mięśniaki macicy. Wydawnictwo MedPharm Polska, Wrocław 2008: 9-13.
4. Sieroń D, Wiggermann P, Skupiński J et al.: Przeznaczyniowa embolizacja oraz leczenie falami ultradźwiękowymi mięśniaków macicy. Polish Journal of Radiology 2011; 76(2): 40-42.
5. Emerich J: Operacyjne leczenie mięśniaków. [W:] Markowska J (red.): Mięśniaki macicy. Wydawnictwo MedPharm Polska, Wrocław 2008: 73-83.
6. Greenwood LH, Glickman MG, Schwartz PE et al.: Obstetric and nonmalignant gynecologic bleeding: treatment with angiographic embolization. Radiology 1987; 164(1): 155-159.
7. Ravina JH, Merland JJ, Herbreteau D et al.: Embolisation pre-operatoire des fibromesuterins. Resultats preliminaires (10 cas). Presse Med 1994; 23: 1540.
8. Woźniakowska E, Milart P, Paszkowski T et al.: Embolizacja tętnic macicznych – zagadnienia kliniczne. Ginekol Pol 2013; 84(12): 1055-1058.
9. Lupattelli T, Basile A, Garaci FG, Simonetti G: Percutaneous uterine artery embolization for the treatment of symptomatic fibroids: current status. Eur J Radiol 2005; 54(1): 136-147.
10. Gajewska M, Panek G: Nowotwory złośliwe macicy u kobiet leczonych z powodu mięśniaków metodą embolizacji tętnic macicznych – opis trzech przypadków. Ginekol Pol 2013; 84(3): 229-233.
11. SOGC Clinical Practice Guidelines. Uterine Fibroid Embolization (UFE) No. 150, October 2004.
12. Pelage J-P, de Dref O, Soyer P et al.: Fibroid related menorrhagia: treatment with superselective embolization of the uterine arteries and midterm follow-up. Radiology 2000; 215(2): 428-431.
13. Mehta H, Saudku C, Matson M, Belli M: Review of readmissions due to complications from uterine fibroid embolization. Clin Radiol 2002; 57(12): 1122-1124.
14. Andersen PE, Lund N, Justesen P et al.: Uterine artery embolization of symptomatic uterine fibroida. Initial success and short-term results. Acta Radiol 2001; 42(2): 234-238.
15. Siskin GP, Tublin ME, Stainken BF et al.: Uterine artery embolization for the treatment of adenomyosis: clinical response and evaluation with MR imaging. Am J Roentgenol 2001; 177(2): 297-302.
16. Kim MD, Won JW, Lee DY, Ahn CS: Uterine artery embolization for adenomyosis without fibroids. Clin Radiol 2004 ; 59(6): 520-526.
17. Pelage JP, Jacob D, Fazel A et al.: Midterm results of uterine artery embolization forsymptomatic adenomyosis: initial experience. Radiology 2005; 234(3): 948-953.
18. Liang E, Brown B, Kirsop R et al.: Efficacy of uterine artery embolisation for treatment ofsymptomatic fibroids and adenomyosis – an interim report on an Australian experience. Austr N Z J Obstet Gynaecol 2012; 52(2): 106-112.
19. Rabinovici J, Stewart EA: New interventional techniques for adenomyosis. Best Pract Res Clin Obstet Gynaecol 2006; 20(4): 617-636.
20. Hirst A, Dutton S, Wu O et al.: A multi-centre retrospective cohort study comparing the efficacy, safety and cost-effectiveness of hysterectomy and uterine artery embolisation for the treatment of symptomatic uterine fibroids. The HOPEFUL study. Health Technol Assess 2008 Mar; 12(5): 1-248, iii.
21. Spies JB, Scialli AR, Jha RC et al.: Initial results from uterine fibroid embolization for symptomatic leiomyomata. J Vasc Interv Radiol 1999; 10(9): 1149-1157.
22. Tropeano G, Di Stasi C, Litwicka K et al.: Uterine artery embolization for fibroids does not haveadverse effects on ovarian reserve in regularly cycling women younger than 40 years. Fertil Steril 2004; 81(4): 1055-1061.
23. Hehenkamp WJ, Volkers NA, Donderwinkel PF et al.: Uterine artery embolization versus hysterectomy in the treatment of symptomatic uterine fibroids (EMMY trial): peri- and postprocedural results from a randomized controlled trial. Am J Obstet Gynecol 2005; 193(5): 1618-1629.
24. Razavi MK, Wolanske KA, Hwang GL et al.: Angiographic classification of ovarian artery-to-uterine artery anastomoses: initial observations in uterine fibroid embolization. Radiology 2002; 224: 707-712
25. Rashid S, Khaund A, Murray LS et al.: The effects of uterine artery embolization and surgicaltreatment on ovarian function in women with uterine fibroids. BJOG 2010; 117(8): 985-989.
26. Pietura R: Embolizacja tętnic macicznych w leczeniu mięśniaków macicy – gdzie jesteśmy po 10 latach doświadczeń? Przegląd Menopauzalny 2011; 4: 309-315.
27. Gupta JK, Sinha A, Lumsden MA, Hickey M: Uterine artery embolization for symptomatic uterinefibroids. Cochrane Database Syst Rev 2012; 16: 5.
28. Toor SS, Jaberi A, Macdonald DB et al.: Complication rates and effectiveness of uterine artery embolization in the treatment of symptomatic leiomyomas: a systemic review and metaanalysis. AJR Am J Roentgenol 2012; 199 (5): 1153-1163.
29. Tropeano G, Di Stasi C, Amoroso S et al.: Incidence and risk factors for clinical failure of uterine leiomyoma embolization. Obstet Gynecol 2012; 120: 269-276.
30. Kotarski J: Małoinwazyjne metody leczenia objawowych mięśniaków macicy. [W:] Markowska J (red.): Mięśniaki macicy. Wydawnictwo MedPharm Polska, Wrocław 2008: 57-71.
31. Pisco JM, Duarte M, Bilhim T et al.: Pregnancy after uterine fibroid embolization. Fertil Steril 2011 Mar 1; 95(3): 1121.e5-8. doi: 10.1016/j.fertnstert.2010.08.032. Epub 2010 Sep 25.
32. Toor SS, Jaberi A, Macdonald DB et al.: Complication rates and effectiveness of uterine artery embolization in the treatment of symptomatic leiomyomas: a systematic review and meta-analysis; AJR-American Journal of Roentgenology 2012; 199(5): 1153-1163. Doi: 10.2214/AJR.11.8362.