Key words embolization - fibroids - preoperative embolization - fertility
Background
Uterine fibroids are the most common benign tumors of the female genital tract [1 ]. The prevalence of fibroids is highly age-dependent, while they are almost never
observed in women under the age of 20, they are detectable in 33 – 66 % of women between
45 and 50 years of age [2 ]. Their size and number can vary greatly. Gennaro Della Rossa et al. have suggested
defining myomas larger than 9 cm or more than 800 g in weight as “giant” [3 ].
The quality of life can be severely impacted by fibroid-related symptoms [4 ]
[5 ], although such symptoms do not necessarily correlate with the size of the myoma.
Only symptomatic myomas or those affecting fertility should be treated. The therapy
of uterine fibroids is primarily aimed at alleviating symptoms and improving the patient’s
quality of life. When pursuing uterus-preserving treatment measures, however, the
preservation or improvement of fertility must always be included in the therapy decision.
In 2008, Klatsky et al. carried out a systematic review and were able to document
an increased risk of abortion, a two-and-a-half times increase in the risk of abnormal
fetal presentation and a doubled risk of placental previa in patients with a uterine
myomatosus compared to patients without fibroids [6 ]. Parazzini et al. confirmed these results in 2016 [7 ].
Surgical removal and hysterectomy are still the most widely used methods of treating
myomas. A very large uterine myomatosus (for example extending above navel level)
always presents a challenge for the surgeon. Because of the size of the uterus, laparoscopic
access is not useful in this case. In addition, there is a risk of heavy bleeding
from the myoma wound bed and the risk that the uterus can no longer be preserved or
reconstructed [3 ]
[8 ].
Since the initial report of successful treatment of uterine myomas via embolization
of uterine arteries [9 ], uterine artery embolization (UAE) has established itself, especially in developed
industrialized countries, as part of the spectrum of modern uterus-preserving therapies
for myoma-associated disorders.
In recent years, a few working groups have reported on planned preoperative uterine
artery embolization (PUAE), particularly with regard to large uterine myomas, to improve
the surgical outcome of subsequent myoma enucleation and to reduce intraoperative
blood loss [8 ]
[10 ].
After an interval of hours or a few days, uterine artery embolization is followed
by operative myoma enucleation by laparoscopy or by a transverse or longitudinal incision.
The aim of these “hybrid interventions” is to reduce the risk of hysterectomy and
substantial intraoperative blood loss requiring subsequent transfusion in women whose
uterus is enlarged due to individual or multiple very large myomas, but who explicitly
wish to preserve their uterus.
In the following, we present peri- and post-procedural experiences from our own case
series (21 patients) and provide an overview of the current international literature
on preoperative embolization of patients with myomas.
Methodology
A retrospective analysis reviewed the data pertaining to 21 consecutive patients who,
between January 2011 and March 2016, underwent preoperative uterine artery embolization
(PUAE) followed by an open abdominal myoma enucleation. After presenting in a university
gynecological outpatient clinic, all patients were informed in detail regarding the
various treatment options for large uterus myomatosus. Since the surgeon considered
surgery alone without prior embolization to be too risky, all patients with a uterus
myomatosus that could be detected at navel height or higher were offered the option
of combined treatment using UAE and surgery. For all patients treated in this way,
uterine preservation was a “conditio sine qua non”, regardless of an existing desire
for children.
The patients were hospitalized and initially received bilateral embolization of the
uterine artery (UAE) after probing with a microcatheter. As a rule (20/21) unilateral
femoral access was chosen; in one case bilateral access was required due to a contralateral
non-accessible outflow of the internal iliac artery. The type of particle used was
up to the examining physician: depending on the anatomic situation, microspheres were
employed (Embosphere, Meritmedical/Biosphere, Roissy, France) with sizes of 500 – 700 µm
or 700 – 900 µm; or non-spherical particles (PVA, Contour, BostonScientific, Natick,
MA, USA) were selected with sizes of 500 – 710 µm. Three patients expressed the desire
that resorbable gelatin sponge particles should be used instead of non-degradable
embolization particles for their embolization. They felt that the safety, effectiveness,
and temporary character of this embolizate were proven and they would not accept nonabsorbable
particles [11 ].
The radiation exposure during the procedure was determined based on the fluoroscopy
time and the dose area product using Dose Watch (GE Health Care, Chalfont St. Giles,
UK). The patients’ effective dose was calculated using XL Dose, Version 2.12 (Stamm
et al., Hannover, Germany). All patients received adequate opioid-based pain medication
[12 ].
After 24 to 48 hours post-embolization, the patients underwent a longitudinal incision
with the goal of preserving the uterus [Fig. 1 ].
Fig. 1 shows a T2 weighted MRI scan in sagittal view A through the pelvis of a 37 year old patient with a very large leiomyoma (*) affecting
both the fundus and the dorsal wall of the uterus. The cavity of the uterus (arrow)
is very narrow and close to the uterine bladder. 24 hours before fibroid resection
transarterial embolization of the uterine arteries was performed B using spherical particles with a size of 500 – 700 µm. The large peritumoral plexus
are well depicted. Open resection of the large fibroid C proceeded without problems without a need to transfusion demanding loss of blood.
Between June and August 2016, all 21 patients were surveyed using a mailed questionnaire
we developed regarding post-surgical progression, complications, scar length, satisfaction
and improvement in symptoms.
For the literature review, in March 2017 we performed a search using Google Scholar,
Pubmed and Livivo using the keywords “fibroid”, “myoma”, “preoperative” and “uterine
artery embolization” (medical subject heading, MeSH). Those articles providing at
least an English or German abstract were considered.
Results
[Table 1 ] contains data regarding the patients and the findings of fibroids. The removed fibroids
were primarily situated intramurally; some exhibited a broad submucosal component.
The UAE was performed without complication on all 21 patients (performed by TK and
DS).
Table 1
Patient characteristics and fibroid data.
patient profile
mean value (standard deviation)
age (in years)
42.1 (23 – 52)
BMI (in kg/m2 )
25.4 ± 4.7
largest diameter of dominant fibroid in resectate (in cm)
12.7 ± 3.2
total weight of removed fibroid (in g)
1143.3 ± 615.5
surgery duration (in min.)
84.2 ± 24.3
intraoperative blood loss (estimated in ml)
487.5 ± 306
hospitalization time (in days)
10.2 ± 2.6
Hb value in g/dl
preoperatively
12.4 ± 1.7
postoperatively
9.9 ± 1.4
The median fluoroscopy time was 11.7 minutes (mean 13.7 ± 8.72 minutes), the median
effective whole-body dose was 3.49 mSv (mean 9.65 ± 14.4 mSv), the median uterine
dose was 6.02 mSv (Mean 16.68 ± 24.48). The mean dose area product was 959.1 cGy*cm2 (mean 2704 ± 3935 cGy*cm2 ).
Primary uterus preservation was achieved in all 21 fibroid patients. All interventions
were performed by the same surgeon (MD). One patient underwent hysterectomy 14 days
postoperatively in another hospital due to heavy vaginal bleeding that could not be
otherwise controlled.
A benign leiomyoma was histologically confirmed in all operated women.
None of the 21 planned myoma enucleations required the administration of erythrocyte
concentrates (EC) immediately after UAE. With an average blood loss of 475 ml (aspirator
contents plus subjective estimate of surgeon based on sponges used, swabs, etc.),
there was an average drop in serum hemoglobin from 12.9 g/dl preoperatively to 9.5 g/dl
postoperatively (first and second postoperative day). One patient received a postoperative
transfusion of two ECs after hemoglobin declined from 12.6 g/dl to 7.3 g/dl.
The mean hospitalization time of the 21 patients treated with PUAE was 10 days (8 – 11).
Of the 21 patients, 11 responded to the questionnaire sent to them. The interval between
the surgery and patient survey was on average 16 months (10 – 44). Ten of 11 patients
indicated a subjective improvement in symptoms, and 9 would recommend the combined
intervention of embolization and surgery. The mean reported duration of postoperative
“impairment of daily life” was 42 days (min. 20, max. 98). The mean sick leave reported
by the women was 31 days (min. 24, max. 47).
The mean scar length measured by the patients themselves was 12 cm (mean; min. 10,
max. 15). Ten of 11 patients were satisfied with the postoperative result of the incision.
Recurrence of fibroids was reported by 3/11 patients.
Amenorrhea did not occur in any of the queried patients as a result of embolization.
At the time of the survey, one patient was in the second trimester of pregnancy.
Discussion
The first planned removal of a fibroid was probably performed by Kimball in 1853.
By the end of the 19th century, this approach established itself as a standard gynecological-surgical
method [13 ]. Today uterine artery embolization is a world-wide established procedure for treating
fibroids as an alternative to surgery. However, the combination of both procedures
is still subject to discussion. Embolization as preparation for surgical myoma enucleation
was the original intention of Ravina’s Paris working group, which was the origin of
this transarterial method of fibroid treatment in the early 1990s [14 ].
According to a study by Unger et al. (2002), hysterectomy patients with a uterine
weight of more than 1.000 g have a significantly increased risk of perioperative complications
and the need for blood transfusion [15 ]. This may also be applicable to interventions during which fibroids of similar weight
or volume are removed.
Likewise, the latest common consensus recommendation of German-speaking gynecological
and radiological societies holds that uterine artery embolization is only considered
in exceptional cases as an option in the context of fertility treatment [16 ]. This is justified in particular by the possible risk of ovarian damage with subsequent
amenorrhea or ovarian dysfunction after embolization.
Guo et al. observed 6 cases amenorrhea (1.23 %) after embolization of 487 patients
[17 ]. Katsumori et al. treated 211 patients and demonstrated an age-related occurrence
of amenorrhea. Patients who were under 40 years of age at the time of treatment did
not report amenorrhoea 6 years after UAE, whereas patients who were older than 45
years at the time of embolization exhibited amenorrhea in 19.7 % of cases 3 years
after the procedure [18 ].
From our point of view, this supports embolization in the context of fertility treatment
in patients under 40 years of age.
Therefore, in special cases we also consider a combination of preoperative UAE and
subsequent uterus-preserving removal of fibroids as a viable option for women with
an explicit desire for children. According to our literature research, between January
2000 and March 2017 three case histories were published [19 ]
[20 ]
[21 ] as well as 8 case series [8 ]
[10 ]
[22 ]
[23 ]
[24 ]
[25 ]
[26 ]
[27 ] each describing patient cohorts similar to those presented here who were treated
with the combined procedure of embolization and myoma surgery. The results of these
articles are summarized in [Table 2 ].
Table 2
Preoperative uterine artery embolization in the international literature (only case
series, sorted by the year of publication).
first author
publication year
pat.
(n)
control group
interval between UAE and surgery (in days)
study type
surgical mode (n)
essential results
Ngeh
2004 [10 ]
5
yes
n. a.
prospective
(case control)
laparatomy (5)
blood loss lower in PUAE group; transfusion only in control group; fever in 20 % vs
57 % in control group; operation time and duration of hospitalization similar in both
groups
Dumousset
2008 [22 ]
22
no
n. a.
retrospective
laparoscopy (12)
laparatomy (9)
hysterectomy (1)
easier fibroid removal after PUAE; no blood transfusion; average Hb value pre-/postoperative
12.3 vs 10.3 g/dl
Üstünsöz
2007 [26 ]
15
yes
1
prospective (case control)
laparatomy (15)
in group with PUAE Surgery time shorter; less blood loss; no transfusion, no hysterectomy
Goldman 2012 [23 ]
12
yes
0.5
retrospective
laparoscopy
in PUAE group larger fibroids/uteri; less intraoperative blood loss; longer hospitalization
time
Malartic
2012 [24 ]
12
no
0.5 to 2 days
retrospective
laparoscopy (6)
laparotomy (3)
hysteroscopy (3)
Hb difference pre-/postoperatively –0.97 g/dl; no transfusion; no serious complications
Tixier
2010 [25 ]
30
yes
n. a.
retrospective
laparotomy (25)
laparoscopy (5)
blood loss; surgery time; pre-postoverative Hb difference in PUAE compared to control
group lower; hospitalization longer
Butori
2011 [21 ]
33
no
6 h (n = 20)/ 48 h (n = 13)
retrospective
laparotomy (25)
laparoscopy (8)
easier fibroid removal in PUAE group; no blood transfusion; average Hb value change
pre-/postoperative 12.9 vs 11.4 g/dl; no hysterectomy
McLucas
2015 [8 ]
20
no
7
retrospective
laparotomy (20)
no hysterectomy, no transfusion, no significant postoperative complications
PUAE = Preoperative Uterine artery embolization, Hb = hemoglobin, n. a. = not available.
The literature review demonstrates that preoperative UAE can reduce bleeding complications
and that a technically easier removal of fibroid nodes will succeed. The need for
blood transfusions especially differed between pre-embolized patients and control
groups. Ngeh et al. did not transfuse any patients in the PUAE group, whereas in the
group of patients without prior embolization, 3 of 5 patients required administration
of 4 to 6 units of erythrocyte concentrates [10 ]. Üstünsöz et al. did not transfuse any PUAE patient; however, 13 % of non-pre-embolized
patients required transfusion [27 ]. In 2011 Butori et al. confirmed these results [22 ]; no patients receiving prior embolization required transfusion. The hospitalization
time of both groups was the same in these studies.
In the view of the authors, preoperative embolization should be used for those patients
who wish to preserve their uterus and for those expected to be at an increased risk
of bleeding postoperatively, due to very large and/or multiple fibroids, difficult
to remove myomas or those in an unfavorable location. The interval between embolization
and surgery is still unclear. In the majority of the comparisons, a time interval
of 0 to 24 h was chosen, only McLucas et al. performed embolization 7 days before
myoma enucleation [8 ]; no difference was found in the results.
In our cohort, uterus preservation was achieved in the majority of cases (90.5 %).
A blood transfusion was very rarely necessary, which otherwise would have been expected
given the size of the fibroids [10 ]
[15 ]
[23 ].
The results presented here as well as the data from the literature review show that
bleeding complications can be significantly reduced with preoperative UAE. The radiation
exposure of 3.49 mSv is reasonable in our view and does not imply a significant malignancy
risk, especially against the background of natural radiation exposure in Germany of
2 mSv per year [30 ]. Three patients with a large or severely convoluted uterus with arteries that were
difficult to probe with ultrasound had whole-body dose values of 38, 43 and 46, which
explains the wide standard deviation of the indicated mean whole-body dose of 9.65 ± 14.4 mSv.
Amenorrhea resulting from embolization was not observed in the treated cohort.
[Fig. 2 ] shows pedunculated fibroids with a broad base to the uterus. In our case series
pedunculated fibroids do not represent a contraindication, since considering current
literature, there is no known increased risk of complications of uterine artery embolization
due to pedunculated fibroids [28 ]
[29 ].
Fig. 2 shows in A , B the MRI scan of a 42 year old patient with an uterus fully layered with leiomyomas
(*). The cavity of the uterus is highly altered and stretched by the multiple fibroids.
The patient wanted to get pregnant and due to the number and location of the fibroids
a fibroid induced infertility was assumed. C Before operative resection transarterial embolization was performed and the fibroids
(*) could be resected during open surgery with only low amount of blood loss D , E .
Especially in the case of fertility treatment of patients with a myomatous uterus,
preoperative uterine artery embolization seems to be a useful therapy option. Due
to their altered anatomical situation, these patients have a significant risk of significant
fertility limitation and a significantly higher risk of abortion [6 ]
[7 ], so that surgical restoration of a normal uterine cavity not constricted by fibroid
tissue is the objective of treatment. The risk of hysterectomy due to intraoperatively
unavoidable bleeding should be reduced as much as possible in women who wish to have
children. Furthermore, in the view of the authors, PUAE supports a uterus-preserving
procedure even for those patients who refuse blood transfusions, such as Jehovah’s
Witnesses.
The economic effects of PUAE are difficult to quantify or interpret. The additional
expense of embolization itself with a more favorable intra- and postoperative result
should take into account partial or complete sparing of blood transfusions and resulting
reduced risk of infection as well as high satisfaction on the part of the patient.
Preoperative uterine artery embolization with the goal of retaining the uterus or
preserving fertility requires a concerted combination of interventional radiology
and gynecology. Well-coordinated interdisciplinary clinical structures and workflows
are needed to address these complex cases.
