*Professor M. A. Lumsden, Division of Developmental Medicine, North Glasgow University Hospitals, Glasgow Royal Infirmary, Queen Elizabeth Building, 10, Alexandra Parade, Glasgow G31 2ER, UK.
Objective To evaluate the effect of uterine artery embolisation (UAE) on menstrual blood loss (MBL) and uterine volume in women with symptomatic uterine fibroids.
Design Prospective observational study.
Setting West of Scotland gynaecology and radiology departments.
Population Fifty women (mean age 43 years) with symptomatic fibroids undergoing UAE between January 1999 and June 2003.
Methods Women collected sanitary protection from one menses pre-embolisation and at regular intervals thereafter. This allowed objective measurement of MBL using the alkaline haematin technique. Uterine volume was calculated using magnetic resonance imaging (MRI) before and six months following embolisation. Interventional radiologists performed bilateral UAE. The Wilcoxon's signed rank test was used for statistical analysis of data.
Main outcome measures Post-embolisation MBL and uterine volume changes.
Results Median pretreatment MBL was 162 mL (mean 234, range 9–1339). The median MBL decreased to 60 mL at 3 months (n= 34, range 0–767, P < 0.001), 70 mL at 6–9 months (n= 34, range 0–1283, P < 0.001), 37 mL at 12–24 months (n= 25, range 0–265, P < 0.001), 18 mL at 24–36 months (n= 17, range 0–205, P < 0.001) and 41 mL at 36–48 months (n= 6, range 0–66, P < 0.05). The median reduction in uterine volume was 40% (n= 46, 95% CI 33.0–49.7, P < 0.001).
Conclusions UAE causes a statistically significant reduction in objectively measured MBL. UAE is also associated with a statistically significant reduction in uterine volume at six months. There was no relationship between the changes in uterine volume and MBL.
Uterine leiomyomata are the most common benign tumours of the female genital tract arising from neoplastic transformation of smooth muscle cells.1 They occur in 25% of women during reproductive life and as many as 40% of women beyond the age of 50 years who are still menstruating.2 While many women with fibroids are asymptomatic, those who do come to our attention typically present with bulk-related symptoms (e.g. urinary frequency and constipation), reproductive dysfunction and in particular, excessive menstrual blood loss (MBL).
Traditionally, treatment for symptomatic fibroids has been surgical although medical therapies have been used as a short term measure. These treatments, however, are not without drawbacks, and alternative management options are being sought. Uterine artery embolisation (UAE) is a well established, minimally invasive radiological technique that has been used for more than two decades in the management of acute pelvic haemorrhage. Its use, however, in the treatment of symptomatic fibroids was first reported in 1995 by the French gynaecologist, Ravina et al.3 Since then, preliminary observational studies carried out in both Europe and the United States suggest that UAE is effective in relieving fibroid-associated symptoms in 80–94% of women.4–13 To date, none of these studies include objective measurements of MBL pre- and post-embolisation but instead, rely on subjective assessment of symptoms. Since the correlation between objective and subjective assessment of MBL is poor, it is important to obtain objective information where possible.14,15
The definition of objective menorrhagia is an MBL exceeding 80 mL/cycle.16 To make such a diagnosis accurately, precise measurement of MBL is required. We therefore decided to carry out a prospective observational study to evaluate the effect of UAE on MBL using an objective measurement technique. With the use of magnetic resonance imaging (MRI), we also aimed to evaluate the effect of UAE on uterine volume and thus, fibroid shrinkage.
Local ethics committee approval was obtained prior to commencing this study. Women with an established diagnosis of symptomatic uterine fibroids were referred for consideration for UAE from hospital gynaecology outpatient clinics in the west of Scotland. They had to have experienced either excessive MBL, pelvic pain or pressure symptoms thought to be due to fibroids; some women had a combination of symptoms. The latter was confirmed by a gynaecologist on history taking. The women were given detailed written information on the risks, benefits and complications of embolisation prior to signing a written consent form agreeing to participation in our study.
The study group was requested to collect all sanitary protection from one menses prior to embolisation and at regular intervals thereafter (3, 6–9, 12–24, 24–36 and 36–48 months). Objective measurement of MBL was performed using the alkaline haematin technique, a method regarded as the gold standard for quantification of MBL.16 By soaking menstrual protection in a 5% sodium hydroxide solution (for 24 hours), haemoglobin was extracted from menstrual blood. The optical density of the alkaline haematin supernatant was then measured using spectophotometry and compared with that of the patient's own venous blood; the ratio of the ODs facilitated calculation of MBL.
Prior to UAE, women underwent a pelvic MRI scan, firstly to confirm the diagnosis of fibroids (and provide detail of number, site and size), and secondly, to exclude other pelvic pathology such as adenomyosis and ovarian disease (Fig. 1a,b). This was repeated at six months post-procedure in 46 women (Fig. 2a,b). Imaging included transverse and sagittal T1- and T2-weighted images. During the latter part of the study, a T1-gadolinium-enhanced sequence was also added to assess uterine vascularity. Uterine volume estimations were made in each case, by taking uterine measurements in three dimensions. Using the prolate ellipse equation formula (D1 × D2 × D3) × 0.5 where D1, D2 and D3 were the transverse, oblique and vertical axes measurements of the uterus, respectively, the volume was calculated. Measurements were calculated by four experienced radiologists, each based in one of the four Glasgow city hospitals.
Bilateral UAE was performed by appropriately trained interventional radiologists using a standard technique. With the use of local anaesthesia, intravenous sedation, analgesia and anti-emetics, percutaneous catheterisation of the right femoral artery was achieved. Thereafter, both internal iliac arteries were selectively catheterised in turn, allowing catheterisation of their respective uterine arteries. Angiography confirmed catheter position and demonstrated the vascular supply to the fibroids and uterus (Fig. 3a). Polyvinyl alcohol particles (500–710 um in diameter) were then injected into the circulation to embolise both uterine arteries. Embolisation was considered complete when there was virtually no demonstrable flow in the distal uterine artery (Fig. 3b). Individual procedures took approximately 45 minutes to complete, and every effort was made to keep the total fluoroscopy time and number of image sequences taken to a minimum. In the latter part of the study, the technique of simultaneous catheterisation of both femoral arteries and synchronous embolisation of the uterine arteries was used to further reduce the duration of the procedure and thus, radiation penalty.
Since the data for MBL are positively skewed, non-parametric statistical tests (Wilcoxon signed rank test) were used for analysis. Data are expressed as medians and ranges. P < 0.05 is considered statistically significant.
Patients were aged between 29 and 54 years (n= 50, 44 years). Of 40 women who complained of menorrhagia, 36 (90%) had a loss ≥80 mL/cycle. The 10 women who did not complain of menorrhagia presented with pressure and/or pain symptoms alone. The median MBL was lower at all post-treatment time intervals when compared with pretreatment levels (Table 1).
Table 1. MBL (in mL) pre- and post-embolisation.
The median reduction in MBL at 3, 6–9, 12–24, 24–36 and 36–48 months was 85, 59, 123, 136 and 186 mL (95% CI 67–218, 41–158, 67–236, 93–305 and 93–683), respectively. Figure 4 expresses these data as percentages.
All post-embolisation reductions in MBL were statistically significant when compared with pretreatment levels (3 months, P < 0.001; 6–9 months, P < 0.001; 12–24 months, P < 0.001; 24–36 months, P < 0.001; 36–48 months, P < 0.05).
All but three women experienced reductions in uterine volume following embolisation (Fig. 5). The median reduction in uterine volume at six months post-treatment was 40% (n= 46, 95% CI 33.0–49.7, P < 0.001). This did not correlate with the change in MBL at that time (Spearman's rank correlation coefficient ρ= 0.116, P= 0.513).
Six (12%) women have undergone elective hysterectomy during the follow up period; four for inadequate reduction of MBL, one for persistent pressure symptoms with insufficient fibroid shrinkage and one for a combination of both persistent menorrhagia and pressure symptoms. Although a significant reduction in MBL occurred in three cases (median 61%, range 43–64%), the post-embolisation blood loss was still above the upper limit of normal in two of these cases. Two women have undergone myomectomy for insufficient relief of their pelvic pressure symptoms, despite good uterine volume reduction.
Seven (14%) women have become amenorrhoeic, six of whom have menopausal hormone profiles. The median age at the time of menopause was 46 years (range 40–54 years), while the median ‘treatment–menopause’ time interval was 4.5 months (range 3–36 months). One patient who became amenorrhoeic despite having a normal hormone profile was presumed to have developed post-infective intrauterine adhesions, thus mimicking the clinical picture of Asherman's syndrome. None of these women desired a pregnancy in the future.
Two women have conceived spontaneously at the age of 45 and 39 years, respectively. The first woman conceived 21 months following UAE, and after an uneventful pregnancy, she delivered a healthy term baby vaginally. This particular patient experienced a 50% reduction in her MBL 12–18 months after treatment and a 51% reduction in her uterine volume at six months post-UAE. The second woman conceived 2.5 years after her embolisation procedure. In this instance, UAE was performed for bulk-related symptoms only. After an initial 35% reduction in uterine volume, her fibroids grew in excess of their pre-embolisation dimensions. In view of the risk of major peripartum haemorrhage, elective caesarean section with prophylactic placement of balloon catheters in the uterine arteries was performed, culminating in an uneventful delivery of a healthy, but small for gestational age infant.
The mechanisms whereby fibroids are thought to cause heavy menstrual loss are poorly understood. Early studies speculated that ulceration over submucous tumours may be responsible for abnormal bleeding while other theories suggest that menorrhagia may occur when the surface area of the uterine cavity is increased by the presence of submucous or intracavity fibroids.1,2 However, excessive MBL frequently occurs in the absence of submucous fibroids and thus alternative theories have been postulated. These include abnormalities in local venous drainage and prostaglandin production.17 In the former situation, fibroids are thought to impinge upon and thus cause congestion and dilation of endometrial plexuses; the resultant obstruction may cause endometrial venular ectasia, which may have a role in enhanced uterine bleeding.2,18 Alternatively, fibroid-associated menorrhagia may be due to either increased vascularity of the uterus or anovulatory cycles.18
While hysterectomy, the traditional treatment for symptomatic fibroids, ensures permanent relief of symptoms, it is associated with significant morbidity and guarantees infertility. It is the most common major gynaecological operation in the world for which fibroids are the most common indication.19
Myomectomy is usually reserved for those women who wish to conceive in the future. There are no randomised controlled trials assessing the effect of this procedure on menorrhagia although data studying symptoms before and after myomectomy suggest that it is effective in many cases.20 With this type of surgery, there is a risk that new fibroids will form following treatment.1
There is no long term medical treatment for fibroids and standard medical preparations for menorrhagia are less effective in the presence of these benign growths. Gonadotrophin-releasing hormone agonists (GnRH analogues), by suppressing the ovaries, can induce amenorrhoea and fibroid shrinkage. Their long term use, however, is limited by their side effect profile and fibroids usually regrow to their original dimensions on cessation of treatment.1 The currently available treatments are therefore less than ideal and UAE appears to provide an efficacious alternative for women with symptomatic fibroids.
In the past, MBL has been assessed with the use of pictorial blood loss assessment charts21 and more recently, using menstrual pictograms.22 Previous studies assessing the efficacy of UAE have used menstrual diaries and questionnaires to determine changes in menstrual symptoms. Most of these report a significant subjective improvement in such symptoms following embolisation.7–17 Walker and Pelage,4 who have published the largest prospective study evaluating UAE to date, report 84% and 79% rates of improvement in menstrual bleeding and menstrual pain, respectively. It is important to remember, however, that there is little or no correlation between objective measurement and subjective assessment of blood loss.14,15 This emphasises the need for objective tests such as the alkaline haematin technique, for the accurate assessment of menstrual bleeding. The problem with the latter method, however, is that it is cumbersome and time-consuming for both patient and laboratory investigator. Bearing in mind these impracticalities, it is usually reserved for use in a research setting, such as the one we present here, and more commonly, subjective assessment of fibroid symptomatology is relied upon. Ideally, two menstrual collections would have been collected pre-embolisation in our study, but for the reasons stated above, we thought it would be reasonable to collect sanitary protection from one menses, prior to treatment. At present, the alkaline haematin technique is the only practical means by which an accurate diagnosis of menorrhagia can unequivocally be established. However, a precise, but simpler method of MBL quantification requires to be developed in the future.
The incidence of ovarian failure was high in our group of predominantly perimenopausal women. All but one who became amenorrhoeic were over the age of 45 years and all had completed their family prior to treatment. Nonetheless, this is an important issue that must be discussed with all women considering embolisation, particularly those who wish to maintain their fertility. In fact, owing to the significant risk of ovarian failure following UAE, some gynaecologists and radiologists may feel that fibroid embolisation should not be offered to those women who desire future fertility.
Elimination of clinical symptoms is the main objective of UAE with uterine volume reduction and thus fibroid shrinkage being an additional benefit of treatment. It is important to note, however, that symptom relief can occur after embolisation in the absence of fibroid shrinkage. In this study, there was no relationship found between changes in MBL and uterine volume. Our observation reinforces the lack of understanding of the pathophysiology of fibroid-associated menorrhagia.
We have shown that UAE is a useful technique for treating uterine fibroids in terms of relief of menorrhagia. However, continuing studies with objective MBL assessments are required to establish the long term efficacy of this treatment.
UAE causes a statistically significant reduction in MBL, which in maintained up to 48 months following treatment. It is also associated with a statistically significant reduction in uterine volume at six months. This study suggests that embolisation may prove to be an excellent long term alternative to both surgical and medical treatments currently available to some women with symptomatic uterine fibroids.
The authors would like to thank Dr R. Edwards, Dr G. Urquhart, Dr A. Reid, Dr A. Downie, Dr L. Murray and Sister D. Lyons.