Ultrasonographic technique to differentiate enhanced myometrial vascularity/arteriovenous malformation from retained products of conception

Abstract

Purpose

To objective of this study is to discuss the ultrasonographic technique to diagnose uterine enhanced myometrial vascularity/arteriovenous malformation (EMV/AVM) and differentiate it from retained products of conception. The study also reviews the management and outcome of EMV/AVM.

Methods

We present a series of three women who developed EMV after early pregnancy loss and a control case of incomplete abortion, where colour Doppler ultrasound was used to distinguish retained products of conception from features of EMV. Clinical status and imaging findings, including peak systolic velocity (PSV), were used for the initial risk stratification of the patients. All cases with EMV/AVM were managed expectantly with serial ultrasound imaging and trending human chorionic gonadotropin levels. The patient with retained products of conception was managed by hysteroscopy and curettage.

Results

In all cases, presentation was suggestive of incomplete abortion with retained products of conception. However, colour Doppler ultrasound demonstrated hypoechoic areas within the endometrium extending into the myometrium with a high maximum PSV. In the control case, colour Doppler ultrasound noted a heterogeneous area in the left uterine cavity; however, vascular flow in this area was distinct from the endometrium, suggesting retained products of conception. All three women with EMV were managed expectantly with close monitoring and good outcomes.

Conclusion

In patients with early pregnancy loss and bleeding or persistently elevated human chorionic gonadotropin levels, clinical status and appropriate use of ultrasound imaging with colour Doppler, including PSV measurement, can assist in recognition of EMV/AVM. Expectant management with serial ultrasound evaluation is a safe treatment option for EMV/AVM with low PSV and can minimise complications such as need for blood transfusion, uterine artery embolization, and hysterectomy.

Introduction

Development of uterine enhanced myometrial vascularity (EMV), also known as acquired arteriovenous malformations (AVM), is a rare but potentially life-threatening event [1, 2]. Although this condition can be congenital or acquired, it usually develops after a previous uterine trauma due to surgery, delivery, abortion, curettage, or infection [2]. Most commonly, EMV is the term used recently to describe acquired uterine AVM, regardless of the presence or absence of products of conception [1]. Some authors collectively name the acquired vascular structures of the uterus identified by colour Doppler as EMV/AVM [1]. The clinical significance of this finding and its management, particularly in asymptomatic women, is not well established. The natural history is variable, with some cases slowly reverting to normal circulation and the condition disappearing over several weeks to months, although others persist without regression, which puts a woman at higher risk for haemorrhage. Given the low incidence of this condition, early recognition and detection remain a challenge for the inexperienced provider. Additionally, vaginal bleeding is a common presentation. Given the proclivity to presume incomplete abortion in the case of vaginal bleeding and concern for retained products of conception (RPOC) on transvaginal ultrasound (TVUS) imaging, dilation and curettage (D&C) is often offered as a treatment. However, for patients with an EMV, D&C may exacerbate the bleeding, and is not recommended. If D&C is performed in unrecognised cases, catastrophic bleeding may ensue, even requiring hysterectomy as a definitive form of treatment [3, 4]. In women with significant bleeding in the context of EMV, uterine artery embolisation is the preferred treatment method. While angiography is the gold-standard method for diagnosis of EMV, colour Doppler ultrasound has become the preferred diagnostic method in the last 2 decades, and represents a non-invasive means of diagnosis and determination of management [1, 3].

The ultrasonographic features of EMV are the presence of ill-defined inhomogeneous mass with multiple myometrial and endometrial hypoechoic cystic or tubular-like structures of variable sizes, along with focal or asymmetric endometrial and myometrial thickening [2, 5]. Colour Doppler ultrasound offers a more specific image, and presents as a colour mosaic with thickened vessels and flow reversals. The spectral evaluation of the vessels within the lesion exhibits high peak systolic velocity (> 20 cm/sec), low-resistance (mean resistive index: 0.3) flow, and low pulsatility of the arterial waveform [6, 7]. Peak systolic velocity is an index measured on spectral Doppler ultrasound, where the Doppler shift of red blood cells in a vessel is converted to a velocity tracing as a peak [8]. The imaging characteristics of increased uterine vascularity on sonography and Doppler are not characteristic of EMV, as they can be seen in RPOC, making the diagnosis difficult [9]. However, unlike in EMV, the vascular areas of RPOC should not have abnormal fistulous communications between arteries and veins [5]. The most sensitive finding of RPOC at gray-scale TVUS is a thickened endometrium. The detection of vascularity with colour Doppler in a thickened endometrium or endometrial mass and no myometrial involvement is likely to represent RPOC [10]. Differentiation between EMV/AVM and retained products of conception is relevant in clinical practice, and it currently represents a challenge.

In this paper, we present a case series of women who developed this complication after early pregnancy loss. We describe in detail the use and technique of colour Doppler ultrasound as a tool for the early diagnosis and appropriate approach to treatment of women presenting with EMV/AVM. We also present a case involving a woman with retained products of conception in which colour Doppler ultrasound showed no evidence of EMV/AVM, to discuss distinguishing features of EMV from retained products of conception.

Materials and methods

Case 1

A 30-year-old G1P0 woman presented to a reproductive endocrinology and infertility practice. During the fertility evaluation, she conceived naturally. However, she was diagnosed with a missed abortion at 7 weeks. Serum beta-human chorionic gonadotropin (HCG) level was 7550 IU/L. Within 1 month, the patient reported passage of tissue. TVUS following the loss was suggestive of retained products of conception. The endometrial stripe measured 16 mm, with heterogeneous material within the endometrial cavity. Serum HCG level was not done. The patient opted for medical management with misoprostol administration. Follow-up TVUS 1 month later showed a 10 mm thick, irregular endometrial stripe with heterogeneous appearance, again raising concern for retained products. The patient declined surgical management with D&C and elected for a follow-up ultrasound after her next menstrual period. TVUS performed nearly 4 months after her initial 7-week TVUS revealed a well-circumscribed 2.5 × 1.5 cm mass arising from the anterior wall of the uterus. There were irregular cavernous areas in the mass, with extensive blood flow on Doppler. The anterior border of the mass was not well defined, with Doppler signals coming from the anterior myometrium into the mass. These findings were concerning for EMV versus molar pregnancy. She was referred to the Maternal Fetal Medicine unit for further management. Serum HCG level was 11.2 IU/ L. Grayscale images of the mass were obtained, and showed an anechoic vascular lake within the structure measuring approximately 8.8 × 7.22 mm (Fig. 1a). Doppler 3D imaging displayed a network of tortuous vessels, with a maximum peak systolic velocity (PSV) of 97 cm/s (Fig. 1a), altogether suggesting EMV. Pelvic magnetic resonance imaging (MRI) showed an intrauterine soft-tissue mass within the endometrial cavity measuring 1.9 × 1.1 cm, demonstrating heterogeneous T2 hyperintensity with avid enhancement. Due to associated risks for haemorrhage in the context of elevated PSV, intervention radiology pelvic angiography was recommended, with consideration of embolisation if indicated. Bilateral uterine angiogram demonstrated multiple foci of contrast pooling in the mid-portion of the uterus, the majority from the left uterine artery, corresponding to an area of abnormal soft tissue seen on ultrasound and MRI and consistent with EMV (Fig. 1b). On angiography, no major arteriovenous anastomoses amenable to embolisation were present; therefore, embolisation was not performed. Given the stable nature of vaginal bleeding, expectant management was continued. The patient was monitored by serial TVUS. Two weeks later, ultrasound showed a complex area within the endometrial canal measuring 2.2 × 1.4 cm. Some vascularity was noted, and PSV was decreased since the previous exam (33.9 cm/s). Repeat TVUS was consistent with resolving EMV, with reductions in the size and vascularity of the mass, and PSV declined to 3 cm/s (Fig. 1c). Patient continued expectant management until the spontaneous resolution of EMV.

Fig. 1.

Ultrasound (a, c) and angiography (b) images of a 30-year-old patient with diagnosis of EMV. Colour Doppler ultrasound revealed a 2.5 × 1.5 cm mass arising from the anterior wall of the uterus with a maximum PSV of 97 cm/s (a). IR pelvic angiography displayed small abnormal vascular pooling in the mid-portion of the uterus, largely supplied by the left uterine artery (yellow dash circle), corresponding to area of abnormal soft tissue seen on ultrasound and MRI consistent with EMV (b). Spontaneous resolution was present on colour Doppler ultrasound with PSV 3 cm/s (c) 4 months after initial diagnosis

Case 2

A 32-year-old G4P3003 woman presented to the emergency department at 8 week 5 day gestation, with significant vaginal bleeding associated with incomplete abortion. Initial ultrasound imaging displayed a gestational sac without the presence of an embryo. Serum HCG level was 3012 IU/L. She was symptomatic for haemorrhage, with unstable vital signs and declining hemoglobin, which prompted emergent suction D&C. The patient’s bleeding resolved following this intervention, and she was discharged home in stable condition the following day. Approximately 3 weeks later, the patient followed up in the outpatient setting and was noted to have an elevated HCG level of 265 IU/L. TVUS revealed an endometrial thickness of 27 mm, with diffuse heterogeneity, areas of increased echogenicity and hypoechogenicity with prominent vascular flow. Some of the vascular areas appeared within the myometrium and some extended into the endometrium with both arterial and venous flow, prompting concern for EMV (Fig. 2a, b). A CT angiogram revealed the heterogeneous appearance of the endometrium, which measured 10 mm. There were multiple serpiginous arteries throughout the fundus, with the enlargement of the early draining vein on the right side highly suspicious for EMV (Fig. 2c). The HCG level was persistently elevated, so the patient was given intramuscular methotrexate. She was referred to the Maternal Fetal Medicine unit for further management. HCG levels were continuously trended and noted to decline (from 109 down to 55 IU/L) following methotrexate administration. Doppler 3D imaging performed 2 months after initial presentation revealed a 4.0 × 3.83 × 1.89 cm irregular, hypoechogenic, tortuous, and tubular structure within the endometrial cavity, and a PSV measurement of 30.6 cm/s (Fig. 2d). HCG level had decreased to 21 IU/L. Given the low PSV, patient was expectantly managed with TVUS every 2 weeks until her HCG declined to non-detectable levels nearly 3 months after she had initially presented. She did not follow up until nearly 7 months from her last US, which showed full resolution of the previously identified EMV (Fig. 2e).

Fig. 2.

Ultrasound (a, b, d, e) and CT angiogram (c) images of a 32-year-old patient with a diagnosis of EMV. Ultrasound with heterogeneous myometrium and abnormal colour flow Doppler (a, b). CT angiogram demonstrated serpiginous arteries throughout the fundus with enlargement of an early draining vein on the right side (c). Colour Doppler ultrasound approximately 2 months from initial presentation revealed an irregular, hypoechogenic, tortuous, and tubular endometrial structure with PSV 30.6 cm/s (d). Complete resolution of EMV (e) was noted by 7 months

Case 3

The patient was a 34-year-old G8P4034 female who presented to the emergency department at 11 week gestation with vaginal bleeding and incomplete abortion. Her HCG level was 7232 IU/L, which had decreased from 23,368 IU/L 1 week prior at an outside hospital system. TVUS imaging demonstrated heterogeneous endometrium with concern for retained products of conception. The patient was hemodynamically stable and elected to have expectant management after counseling regarding options for management. She was seen in follow-up 2 days later. At that time, she was noted to have a 1 cm sac protruding from the external os, which was not amenable to manual removal. Her HCG measured 3460 IU/L. She chose medical management and received three doses of 800 mcg vaginal misoprostol. The patient followed up in the outpatient setting 1 week later, reporting passage of tissue, and her HCG declined to 514 IU/L. TVUS displayed an endometrium measuring 3.9 mm, with fluid and hypoechoic material, and the anterior myometrium demonstrated a hyper-vascular focal area in the lower uterine segment, with venous and arterial waveforms on Doppler flow, raising concerns for EMV (Fig. 3a). She was referred to the Maternal Fetal Medicine unit for further management. Repeat 2D and 3D ultrasound imaging performed 2 weeks later revealed a vascular ‘lake’ measuring 3.4 × 2.1 × 3.4 cm. Power Doppler imaging showed a tortuous network of vessels with PSV 32 cm/s, suggestive of EMV. The patient had a history of one prior cesarean delivery, and the EMV was noted in close proximity to the prior cesarean scar (Fig. 3b). At that time, HCG was 514 IU/L. Given the PSV and the fact that the patient did not have any vaginal bleeding, expectant management with weekly serial ultrasound imaging and trending HCG was recommended. The EMV persisted on subsequent imaging at 2 months from initial imaging, despite HCG trending down to 8 IU/L. At this time, the mass was similar to the size it had been on prior imaging, with PSV 32.2 cm/s. However, 1 month later, there was marked reduction in size of the previously-seen area, with an absence of vascular flow, and the patient’s HCG level was undetectable (Fig. 3c). Finally, 4 months from initial imaging, the EMV had completely resolved on imaging, with no further associated complications.

Fig. 3.

Ultrasound (a, b, c) images show a hyper-vascular focal area in the lower uterine segment myometrium with venous and arterial waveforms on Doppler flow (a). A 3.4 × 2.1 × 3.4 cm tortuous network of vessels with PSV 32 cm/s was identified in close proximity to the prior cesarean scar (b). Complete resolution of EMV occurred after 4 months (c)

Control case

A 37-year-old G1P0 woman was diagnosed with a missed abortion at 8 weeks gestation, following ovarian stimulation with FSH and intrauterine insemination due to a history of infertility (chronic anovulation and endometriosis). She elected to proceed with D&C, which was without complications. However, her HCG remained elevated following this procedure, at 350 IU/L. Ultrasound 2 weeks following D&C revealed a focal area of echogenicity in the left cornua with increased vascularity, measuring 1.0 × 1.4 cm (Fig. 4a). Due to concern for possible EMV, the patient was seen by a maternal fetal medicine specialist who performed repeat imaging. 3D ultrasound imaging demonstrated arcuate uterus (also noted on prior imaging) with a heterogeneous area measuring 1.2 cm in the left cornua. This area was distinct from the rest of the endometrium. Colour Doppler revealed vascular flow surrounding the area, but not extending into the myometrium, suggesting retained products of conception rather than EMV (Fig. 4b). The patient elected to proceed with medical management with misoprostol to avoid repeat surgery. Two rounds of misoprostol were unsuccessful in inducing passage of the retained products. Approximately 1 month from diagnosis of the missed abortion, the patient underwent hysteroscopy D&C. Operative findings included retained tissue obscuring the left ostium, which was successfully resected hysteroscopically (Fig. 4c). Repeat TVUS imaging 1 month after the hysteroscopy revealed a normal-appearing uterus and endometrial lining. The patient had no further sequelae and proceeded with further treatment of infertility.

Fig. 4.

Ultrasound (a, b, c) images revealing an area of increased vascularity in the left uterine cornua. (a). 3D ultrasound imaging demonstrated arcuate uterus, with a heterogeneous area measuring 1.2 cm in the left cornua (b). Operative hysteroscopy with findings of retained tissue obscuring the left ostium (c)

Discussion

In the present study, we report three cases of EMV/AVM associated with retained products of conception. The diagnosis in all of these cases was established due to a high index of suspicion and careful ultrasonographic evaluation with colour Doppler. As previously described by Ilan Timor and others [3, 4], we obtained a broad 2D gray-scale image of the uterus, followed by a spectral pulse wave Doppler image that focused on the areas of interest. We then increased the pulse repetition frequency until only a few vessels were seen to identify the vessels with the highest blood flow velocity. In a final step, the highest PSV was measured by angle correction. Importantly, the ultrasonographic features of EMV on gray scale include irregular, hypoechoic, tubular, tortuous anechoic structures concentrated in small areas of the myometrium [11]. On colour Doppler evaluation, the lesions ‘light up’, demonstrating high-velocity blood flow within the vascular web, with PSV > 20 cm/s. 3D renderings may show main feeding and draining vessels [4, 6, 11]. This is in contrast to ultrasonographic features of retained products of conception, where an echogenic or hyperechoic mass or complex endometrial fluid may be seen within the endometrial cavity [10]. A thick endometrial stripe is noted (> 8–10 mm). Even though colour Doppler flow may be detected in retained products of conception, there are no or minimal blood vessels. Overall, the main differentiating feature present in EMV/AVM is the presence of focal areas of marked endometrial vascularity extending into the myometrium. The severity of the vascular malformation is expressed by the velocity of the blood flow, measured as the PSV [3, 4].

Other modalities for diagnosis of EMV/AVM include digital subtraction angiography, which remains the diagnostic gold standard [12]. However, pelvic angiography is reserved for cases in which the need for therapeutic embolisation is anticipated. Findings with angiography include bilateral hypertrophy of uterine arteries that feed a tortuous, hypertrophic arterial mass with large accessory feeding vessels, and early drainage into enlarged hypertrophic veins. However, digital subtraction angiography is rarely performed for diagnosis alone due to its invasive nature, and as mentioned above, it is reserved for patients requiring surgical intervention or embolisation [12].

Additional imaging modalities, including MRI and CT, may assist in diagnosing EMV. MRI findings suggestive of EMV include a bulky uterus, ill-defined mass, focal or diffuse disruption of the junctional zone, serpiginous flow-related signal voids, and prominent parametrial vessels [5]. The absence of a defined mass and the presence of multiple tortuous and serpiginous flow-related signal voids in the myometrium and parametrium, corresponding to the hyper-vascular areas on colour Doppler sonography, are hallmarks of EMV. On the other hand, CT scan may depict an enlarged uterus with enhancing and enlarged vessels in a thickened myometrium with associated early enhancing para-uterine veins. CT is also useful for describing the anatomy and extension of the EMV [5]. However, given its absence of ionising radiation, low cost, and availability, ultrasonography is the preferred imaging technique to evaluate patients with suspected vascular lesions [5]. The role of hysteroscopy in the diagnosis of EMVs should be individualised and considered when ultrasound and other supportive imaging findings are inconclusive. Implementation of an invasive procedure such as hysteroscopy for diagnosis carries an increased risk of bleeding and haemorrhage; accordingly, the introduction of the hysteroscope should be performed under careful video visualisation to avoid injury. Hysteroscopy is also a useful diagnostic and therapeutic tool in cases where there is still a high index of suspicion for retained products of conception [13]. Hysteroscopy can also be employed to follow up with patients who had to undergo suction D&C or uterine artery embolisation to ensure resolution of EMV [13].

To identify an EMV/AVM, a high index of suspicion is required during routine initial ultrasound evaluation in patients presenting with vaginal bleeding, particularly in the context of any unsuccessful pregnancy event or treatment procedure (including uterine D&C, cesarean delivery, cesarean scar pregnancy, and gestational trophoblastic disease) is required. Therefore, it is important for obstetrics and gynecology practitioners to be acquainted with the diagnosis and optimal management of acquired AVM/EMV. Consistent with other research, we advocate for an initial risk stratification of patients that takes into consideration their clinical status and ultrasound findings, including PSV measurement, to triage them for either expectant or surgical management [4, 11]. We also propose that the measurement of PSV levels is a useful tool for the identification of patients with more extensive anomalies that could potentially put them at a higher risk for complications if disrupted [3, 4, 6, 11]. In the absence of acute vaginal bleeding and haemodynamic instability, treatment can be guided by PSV [6]. The clinical course is considered less dangerous, and expectant management can be considered with a PSV below 40 cm/s. However, when the PSV is more than 60–70 cm/s, uterine artery embolisation may be considered as the treatment of choice. PSV levels are also useful measurement guidance to utilise during follow-up as an outpatient, and to eventually confirm the resolution of the malformation. Complete disappearance can usually take up to 15 or 16 weeks, as in our cases.

When persistent bleeding and hemodynamically instability are demonstrated, the surgical management of EMVs is indicated. Some reports have described the role for suction D&C in the treatment of acquired EMV/AVM [1]. Although this treatment method can be utilised, with this series of cases, we aim to illustrate that since most of the acquired malformations may result in spontaneous resolution, expectant management with serial ultrasound evaluation is a safe treatment option [6]. The significant risk for harm with D&C is particularly relevant in the group of patients with cesarean scar pregnancies and molar pregnancies, which are at increased risk for haemorrhage and subsequent need for hysterectomy.

To highlight this point, we describe Case 3, in which an EMV complicated a cesarean scar pregnancy. Implantation of a pregnancy within the scar from a prior cesarean delivery occurs in 1 in 1.800 to 1 in 2.200 pregnancies [14]. In cesarean scar pregnancy, the gestational sac is surrounded by myometrium and scar tissue, separated from the endometrial cavity. Potential complications of cesarean scar pregnancy include haemorrhage and uterine rupture [10]. More recently, the association between EMV and cesarean scar pregnancy has gained more attention, because the uteroplacental neovascularisation pattern in the cesarean scar pregnancy may lead to the development of an EMV [15]. However, the optimal management of cesarean scar pregnancy with uterine EMV has not been determined. In Case 3, the gestational sac was left in place after a missed abortion in cesarean scar pregnancy, presenting a risk for the development of an EMV. We treated the patient expectantly with weekly colour Doppler ultrasound and measurement of the PSV until resolution. We understand that further prospective studies are warranted to determine the best treatment modality in cases of EMV resulting from a cesarean scar pregnancy, which is of particular importance given current rates of cesarean delivery.

The strengths of our study include a standardised approach to evaluation of EMV/AVM through greyscale and colour Doppler ultrasound with objective measurement of PSV in the area and confirmation of the EMV/AVM with other diagnostic modalities. The limitation of the study is that none of our patients presented with acute bleeding or haemodynamic instability, and expectant treatment was therefore feasible. Future studies could look at pregnancies after resolution of this rare vascular malformation.

In conclusion, we describe the diagnosis and management of three cases with EMV/AVM. Early diagnosis and high index of suspicion for EMV allowed for determination of treatment with the intent to reduce risk. Expectant management was ultimately selected for all three cases, and prevented more invasive treatments that included D&C or as a last resort, hysterectomy, assuring patients’ fertility preservation, and potential.

Author contributions

All authors of this paper made substantial contribution to the conception of the study, collection of the data, and drafting of this manuscript. The authors approve this manuscript in the current form and are accountable for the accuracy of this work.

Funding

The authors did not receive any funding to assist with preparation of this manuscript.

Declarations

Conflict of interest

The authors have no conflict of interest to declare that are relevant to the content of this article.

Ethical approval

The study was approved by the institutional review board SH IRB#: 2019-549.

Informed consent

Informed consent was obtained from all individual participants included in the study.