Gynecology and Minimally Invasive Therapy 4 (2015) 149e153

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Gynecology and Minimally Invasive Therapy

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Case report

A case of severe uterine arteriovenous malformation treated with

danazol followed by a transarterial embolization of unilateral uterine
and ovarian arteries
Hiroyuki Yazawa a, *, Syu Soeda b, Tsuyoshi Hiraiwa a, Masayo Takaiwa a, Keiya Fujimori b
a
Department of Obstetrics and Gynecology, Fukushima Red Cross Hospital, Fukushima, Japan
b
Department of Obstetrics and Gynecology, Fukushima Medical University, School of Medicine, Fukushima, Japan

a r t i c l e i n f o a b s t r a c t

Article history: Uterine arteriovenous malformation (AVM) is a potentially life-threatening condition characterized by
Received 1 October 2015 abrupt and profuse uterine bleeding from abnormal connections between arteries and veins in the
Received in revised form myometrium. It is commonly associated with prior pregnancy or uterine trauma. We present a case of
5 October 2015
severe uterine AVM treated with danazol and transarterial embolization (TAE). A 38-year-old patient
Accepted 14 October 2015
Available online 29 October 2015
with a history of two abortions and a myomectomy was referred to our hospital for intermittent massive
uterine bleeding. She was diagnosed with uterine AVM by transvaginal color Doppler ultrasonography
and helical computed tomography (CT). Diagnostic three-dimensional CT (3D-CT) angiography clearly
Keywords:
3D-CT angiography
demonstrated hypervascular tangles of uterine vessels, feeding arteries, remarkably dilated draining
color Doppler ultrasonography veins, as well as early filling of the internal iliac vein and the inferior vena cava, indicating massive
danazol arteriovenous shunting in the uterus. Danazol was administrated for 10 months to reduce the shunting of
transarterial embolization the uterine AVM before TAE with N-butyl-cyanoacrylate of the left ovarian artery and left uterine artery
uterine arteriovenous malformation was successfully performed. After the procedure, we confirmed that shunting through the uterine AVM
was markedly reduced. The patient has not experienced any severe uterine bleeding since the treatment.
Copyright © 2015, The Asia-Pacific Association for Gynecologic Endoscopy and Minimally Invasive
Therapy. Published by Elsevier Taiwan LLC. All rights reserved.

Introduction Case report

Although uterine arteriovenous malformations (AVMs) are
thought to be rare, the true incidence of this condition has not been
documented in the literature. We recently performed a prospective
study examining the incidence of uterine hypervascular lesions
named ‘uterine vascular malformations’ (U-VM) including uterine
AVMin patients after abortion, after delivery, and as outpatients for
2 years. During the study period while we were screening for UVMs,
we observed one case of severe uterine AVM among ~1000 patients.
The current report presents a detailed clinical course and clear
diagnostic imaging of the case.
Conflicts of interest: The authors declare no conflicts of interest.
* Corresponding author. Department of Obstetrics and Gynecology, Fukushima
Red Cross Hospital, 11-31 Irie-cyo, Fukushima 960-8530, Japan. Tel.: þ81 24 534
6101; fax: þ81 24 531 1721.
E-mail address: ikyoku12@fukushima-med-jrc.jp (H. Yazawa).
The patient is a 38-year-old gravida 2, para 0, abortus 2 woman.
Her first pregnancy, which occurred 7 years previously, ended in
spontaneous abortion during the early stages of pregnancy and did
not require dilation and curettage (D&C). She also had undergone
myomectomy 4 years previously. Based on magnetic resonance
imaging (MRI) findings at the time, she was diagnosed with a
uterine leiomyoma of ~6 cm in diameter in the posterior uterine
body. Myomectomy was commenced with a laparoscopically
assisted approach. The total intraoperative blood loss was 1330 mL
and transfusion with 2 units of packed red blood cells was required.
Post operative histopathological examination revealed a diagnosis
of cellular leiomyoma of uterus. After the operation, a 1.88 mg
monthly dose of a gonadotropin releasing hormone analogue
(GnRHa), leuprorelin acetate, was administrated subcutaneously
for 6 months. Two years later, the patient presented to our hospital
with positive urinary pregnancy test. A gestational sac was
confirmed to be in the uterine cavity but fetal heart movements

http://dx.doi.org/10.1016/j.gmit.2015.10.001
2213-3070/Copyright © 2015, The Asia-Pacific Association for Gynecologic Endoscopy and Minimally Invasive Therapy. Published by Elsevier Taiwan LLC. All rights reserved.
Figure 1. Color Doppler ultrasonography and enhanced CT. (A, B) Color Doppler ultrasonography demonstrated a hypervascular lesion of tortuous vessels with a colored mosaic pattern of
irregular turbulent flow in the entire posterior myometrium; (C, D) enhanced CT demonstrated a highly enhanced effect in the posterior myometrium. CT ¼ computed tomography.
 H. Yazawa et al. / Gynecology and Minimally Invasive Therapy 4 (2015) 149e153 151

Figure 3. Transarterial angiography and embolization of the right ovarian artery. The main feeding arteries of the uterine AVM were identified by angiography. (A, B) The left and
right ovarian and uterine arteries contributed to the uterine AVM; (C, D) embolization with N-butyl-cyanoacrylate was performed in the left ovarian artery. AVM ¼ arteriovenous
malformation.

were not detected at 7 weeks of gestation. She was diagnosed with
a missed abortion, and D&C was performed but abnormal uterine
bleeding was not documented during the procedure.
Eighteen months later, the patient experienced massive vaginal
bleeding and she was referred to our hospital due to continuous
vaginal bleeding. Abnormal active vessel flow with a colored
mosaic pattern was detected with color Doppler ultrasonography,
and we suspected a uterine AVM (Figures 1A and 1B). We then
performed three-dimensional computed tomography (3D-CT)
angiography, which demonstrated early-filling hypervascular tan-
gles of uterine vessels fed by the uterine and ovarian arteries
bilaterally, and diagnosed severe uterine AVM. Remarkable dilata-
tion of the uterine and ovarian veins bilaterally as well as early
filling of the internal iliac vein and the inferior vena cava was
observed, indicating massive arteriovenous shunting in the myo-
metrium (Figure 2).
Given the severity of the uterine AVM and the risks involved
with transarterial embolization (TAE) at this time, danazol was
administrated (200e400 mg daily) orally. The uterine AVM was
monitored with monthly color Doppler ultrasonography. Although
abnormal vessel flow did not resolve after 10 months of danazol
therapy, we confirmed that the abnormal flow had reduced slightly,
and TAE was undertaken as a secondary treatment. After con-
firming with angiography that the main feeding arteries were the
bilateral ovarian and uterine arteries, embolization with N-butyl-
cyanoacrylate was performed in the left ovarian and uterine ar-
teries (Figure 3). Embolization of the right side was not performed
to preserve the patient's ovarian function because she desired
future childbearing.
We confirmed the TAE results using color Doppler ultrasonog-
raphy and 3D-CT angiography. The abnormal vessels of the AVM
had almost disappeared on the left side of the posterior myome-
trium whereas the vessels on the right side were persistent with
slight improvement (Figure 4).
The patient resumed menstruation 1 month after the procedure,
because danazol was stopped prior to TAE. Although slight hyper-
menorrhea was observed, it ended within 1 week without massive
blood loss or a decrease in hemoglobin levels. Preservation of her

Figure 2. 3D-CT angiography. Diagnostic 3D-CT angiography clearly demonstrated hypervascular tangles of uterine vessels, feeding arteries, and remarkably dilated draining veins.
The hypervascular tangles of tortuous vessels were fed by the uterine and ovarian arteries bilaterally, consistent with a true uterine AVM. Remarkable dilatation of the uterine and
ovarian veins bilaterally, as well as early filling of the internal iliac vein and the inferior vena cava, were observed, indicating massive arteriovenous shunting in the myometrium
[(A) anterior/posterior view; (C), posterior/anterior view]. AVM ¼ arteriovenous malformation; 3D-CT ¼ three-dimensional computed tomography.
152 H. Yazawa et al. / Gynecology and Minimally Invasive Therapy 4 (2015) 149e153

Figure 4. Color Doppler ultrasonography and 3D-CT angiography after TAE. (A) Color Doppler ultrasonography demonstrated that the abnormal vessel flows of the AVM had almost
disappeared on the left side of the posterior myometrium whereas; (B) the vessels on the right side were persistent with slight improvement. (C, D) 3D-CT angiography
demonstrated same findings. Circles indicate the abnormal vessels of left side of myometrium treated by TAE. AVM ¼ arteriovenous malformation; 3D-CT ¼ three-dimensional
computed tomography; TAE ¼ transarterial embolization.

ovarian function was confirmed by the occurrence of regular
menstrual cycles, 2-phase basal body temperature measurements,
and follicular stimulating hormone level (3.80 mIU/mL, Archtect
FSH, Abbott Japan).
Discussion
An AVM can be defined as a tangle of abnormal connections
between an artery and a vein without an intervening capillary
network.1,2 In general, AVMs are most commonly seen in the brain
and the lungs. Although most AVMs found in the brain and the
lungs are congenital, AVMs in the uterus are more commonly ac-
quired.1,3 Congenital uterine AVMs arise as a result of a defect in
embryonic vascular differentiation or developmental arrest of the
primitive capillary plexus between the 4th and 10th weeks of
embryonic life, and typically involve other organs. Acquired uterine
AVMs frequently develop after uterine trauma, which can induce
the formation of abnormal vascular communications between ar-
teries and veins during healing.1e3 Although uterine trauma asso-
ciated with pregnancy such as D&C, prostaglandin E1 (PGE1)-
induced abortion, cesarean section, and vaginal delivery have all
been listed as primary causes of acquired uterine AVMs, a small
number of cases have also been reported from the insertion of in-
trauterine contraceptive devices, uterine tumors (endometrial
carcinoma or cervical carcinoma), gestational trophoblastic disease,
and uterine infections.1,4e6
Uterine AVM can lead to profuse, life-threatening uterine
bleeding, typically diagnosed by imaging techniques including ul-
trasonography, helical CT, or angiography in patients suffering from
severe vaginal bleeding. Although this condition is thought to be
rare, the true incidence of uterine AVM remains unclear. We
recently performed a prospective evaluation of the incidence of
uterine vascular abnormalities (defining the lesion as uterine
“vascular malformation” according to Timmerman et al6) in pa-
tients after abortion or delivery and in outpatients. We identified
six cases of U-VM among 959 patients observed.7 One of the six
cases was a patient with severe “true uterine AVM” and is pre-
sented in this manuscript. The study is ongoing and so far we have
evaluated over 1000 patients, and have detected only one true case
of AVM. We estimate from the study that the incidence of true
uterine AVM is < 0.1%.
Although the patient was first referred to our hospital over
4 years ago and myomectomy and D&C were performed in our
hospital, her uterine AVM was only diagnosed after we started
screening for U-VMs in 2011. We retrospectively checked her clin-
ical records and past grey-scale ultrasonography findings, and
found that the hypoechoic lesion and dilated veins in the posterior
myometrium were already evident after myomectomy. From these
 H. Yazawa et al. / Gynecology and Minimally Invasive Therapy 4 (2015) 149e153
retrospective ultrasonography findings, we estimated that her AVM
was formed after myomectomy and not after the earlier D&C. As
her uterine myoma was a hypervascular cellular leiomyoma and
massive blood loss occurred during the operation, it was possible
that abnormal arteriovenous connections leading to a severe AVM
were formed during the wound healing process postmyomectomy.
The management of patients with uterine AVMs depends on the
degree of uterine bleeding, hemodynamic stability, and desire for
future fertility. Although hysterectomy is the definitive treatment
for patients who do not desire future fertility, a more conservative
approach is typically required because most AVMs occur in women
of reproductive age. Since the first report of TAE as a treatment for
AVM was made by Forssman et al8 in 1982, this technique has been
increasingly used as an effective treatment for uterine AVM, as it is
preferable for the preservation of uterine function and reproductive
capability. Due to a high clinical success rate and low complication
rate for TAE in the literature,1,3,9 it has been proposed that TAE
should be the first choice for the treatment of uterine AVM in all
women,10 whereas hysterectomy should be reserved for cases with
recurrence of heavy uterine bleeding or the failure of alternative
treatments.11 Although several successful pregnancies and de-
liveries after TAE for uterine AVM have been reported, an increased
risk of pregnancy-associated complications such as spontaneous
abortion, fetal growth restriction, stillbirth, uterine rupture, and
uterine atony after birth, which are associated with poor vascu-
larization, remains a concern.10,12e14
In our patient, because the AVM flow was very active, large, and
involved the entire posterior myometrium at the time of diagnosis
without uncontrolled profuse bleeding, we selected danazol as a
primary conservative treatment to control her intermittent vaginal
bleeding, correct her anemia, and reduce AVM flow,15 thereby
reducing the risks associated with TAE such as embolization
through the AVM shunt to the lung. As danazol only partially
reduced the abnormal flow, we performed TAE as a secondary
conservative treatment, and embolization of the left ovarian and
uterine arteries was successfully performed. Embolization of the
right uterine artery was not performed although this artery
contributed as a feeding artery to the uterine AVM, because we took
into account the risk of losing ovarian function.
153
Although the patient's uterine AVM has been successfully
treated by danazol and TAE with N-butyl-cyanoacrylate, strict
follow-up to monitor for the reactivation of the uterine AVM and
recurrence of profuse uterine bleeding is necessary. If it reappears,
immediate and appropriate management will be needed as the
patient desires to become pregnant in the near future.
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