About uterine enhanced myometrial vascularity: Doppler ultrasound could reduce misdiagnosed life-threatening vaginal bleeding after pregnancy and guide the management

Abstract

Enhanced myometrial vascularity is a rare entity in which an abnormal communication between vessels of the myometrial wall, potentially derived from all pregnancies, increases bleeding risk. Spontaneous regression is possible, but often, it is not foreseeable in which cases it’s better to adopt a waiting behaviour and in which others a treatment is required. We reported three cases of enhanced myometrial vascularity: two occurring after vaginal delivery, and the third one after a scar pregnancy. The first case was successfully treated by embolization, the second one was subjected to curettage complicated by uterine perforation; the third one underwent embolization as well, but subsequently required hysterctomy for persistent methrorragia. As we treated these similar cases in three different ways, we decided to perform a mini review of the literature in the aftermath. Considering literature data, we strongly believe that the detection of peak systolic speed by colour-Doppler ultrasound together with a careful evaluation of clinical symptoms, could be a good guide to the best treatment of each patient.

Introduction

Uterus arteriovenous malformations (AVM) are rare high-flow vascular lesions, due to abnormal anastomoses between arteries and veins. AVM involve the uterine myometrium, but can also extend into the endometrium. In literature, the term AVM is sometimes used for different lesions, which can cause misunderstanding in management and diagnosis. For this reason, in recent years, uterine AVM classification and terminology have been revised [1]. Uterine enhanced myometrial vascularity (EMV) is a condition, as acquired AVM but not true AVM, correlated to an increment of normal vascularity associated with subinvolution of the placental bed site, retained products of conception, or other forms of uterine pathology, such as gestational trophoblastic disease [1–4]; in this case EMV are caused by neoangiogenesis phenomena between the tumor mass and the myometrium [4].

In addition, uterine EMV can follows uterine procedures (dilation and curettage, cesarean delivery, myomectomy), or pregnancy-related complications [1, 2].

The most common clinical manifestation is irregular vaginal bleeding after the term of pregnancy; however, some cases are asymptomatic [1].

Diagnosis is made by transvaginal-ultrasound, associated with colour-Doppler evaluation showing unusual, tubular, tortuous, anechoic structures, high vascularized, with a peak systolic velocity (PSV) over 20 cm/s. In case of vascularized retained product of conception, Akiba et al. have drawn-up a classification according to Doppler evaluation. They took into account the depth of vascularity of the endometrium extending towards the myometrium. They claimed that high degrees of vascularity were related to an higher risk of bleeding. The authors defined the lesions as type1: vascularity confined to endometrium, type 2: vascularity reaching < 1/2 myometrium, or type 3: vascularity reaching ≥ 1/2 myometrium [5].

Possible management were expectation of a spontaneous resolution, uterine artery embolization, or hysterectomy. Curettage was usually contraindicated because it could exacerbate the bleeding [2].

Although a spontaneous regression is possible, it is often not foreseeable in which cases it’s better to adopt a waiting behaviour and in which others a treatment is required due to high risk of bleeding [2].

Some authors propose the evaluations of ultrasonographic parameters such as endometrial thickness < 10 mm, avascular endometrium, and absence of EMV, which are associated with successful non-invasive management in case of vaginal bleeding and retained product of conception [6]. However, in case of EMV, considering that few and not univocal information were reported in literature about how to personalize therapy [3, 5–7], we would like to share our experience. In less than one year we treated three EMV cases, we described them and share our conclusions completed with the review of literature data. We hope our case series could help other physicians in the same situation in the future. Our aim is to help to define the diagnosis and the management of patients trying to decrease the potential risk of life-threatening bleeding and potential fertility reduction.

Case reports

Case 1

38-year-old woman Gravida 4 Para 0 (2 previous miscarriage and 1 caesarean section) was evaluated for heavy vaginal bleeding at 7.5 weeks. A miscarriage was diagnosed, and a curettage was performed. The patient was discharged in good clinical conditions. Four days later, she showed up in the Emergency Room with a metrorrhagia. Tranexamic acid, antibiotics, progesterone and blood transfusion were administrated. The office ultrasound in the Emergency Room described a linear endometrium at the uterine fundus, while a dishomogeneous neoformation of 54 × 54 mm was detected into the uterine isthmus. Colour Doppler evaluation was not performed. A computerized tomography (CT)-scan confirmed the neoformation and the contrast reported a hypervascularization (Fig. 1). The patient was transferred to a tertiary centre and underwent uterine embolization. After discharge, at post-surgical evaluation, smelly vaginal bleeding persisted, and beta-HCG remain elevated. Pelvic infection was suspected, and the patient was admitted to perform intravenously antibiotics and transfusions. At magnetic resonance, a residual of a scar pregnancy miscarriage was suspected, and the patient received Methotrexate. The patient was discharged but 2 weeks later, she complained of metrorrhagia and we had to proceed to hysterectomy. The subsequent follow-up was regular one month after surgery.

Fig. 1.

CT scan image of our first clinical case which confirmed the presence of a vascolarized dishomogeneous neoformations (arrow) of 5 cm detectable into the uterine isthmus

Case 2

36-year-old woman. Gravida 2 Para 0 (1 previous miscarriage). Pregnancy course was regular. She came to our department in labour at 41 weeks. An operative vaginal delivery was performed with vacuum for prolonged second stage. She gave birth to a healthy baby of 3700 gr; the third stage was spontaneous. Vaginal bleeding was 450 ml. At ultrasound before discharge a 3 × 4 cm residual in the uterus was detected, suspected for clotted blood. She returned to Emergency room for metrorrhagia a few days later. A vascularized (type 2 for Akiba et al.) [5] dishomogeneous neoformation of 2 × 3 cm was detected into the uterus, extending into myometrium (Fig. 2). Considering the suspect of placental residual, the patient underwent a curettage, complicated by uterine perforation, and required a laparotomic reparation. Blood loss was 1000 ml and transfusions were administered. She is in regular follow-up.

Fig. 2.

An ultrasound examination, with colour Doppler evaluation of our second case, performed in the emergency room, which demonstrate a 3 cm vascularized dishomogeneous formation (arrow) into the uterus

Case 3

24-year-old woman. Primigravida. Pregnancy course was regular. She came to our department for premature rupture of membrane at 39.5 weeks. Labour was induced and a baby girl of 3500 gr in wellbeing was born with regular vaginal delivery. The third stage of labour was spontaneous. Vaginal bleeding was 700 ml, treated with uterine massage, oxytocin and tranexamic acid perfusion. Considering persistent and discrete lochia rubra, an ultrasound was performed, which reported a linear endometrium in the uterine fundus, while a dishomogeneous formation was detected in the isthmus. A cervical laceration was detected and sutured with a reduction of bleeding. A week after discharge a control visit was scheduled and at colour-Doppler ultrasound an EMV/AVM was reported, described as a neoformation of 3 cm with rich vascularization (type 3 for Akiba et al.) [5]. PSV was not calculated (Fig. 3A). The patient has been placed in close clinical and imaging follow-up. She came back for metrorrhagia. A magnetic resonance (Fig. 3B) described the presence of vascularized tissue into the uterus, suspect of placental residual. A uterine embolization was performed in the tertiary centre and the bleeding stopped. The patient underwent a regular follow-up.

Fig. 3.

A Ultrasound evaluation with colour Doppler of our third case, which described a neoformation of 3 cm, with Doppler type 3 vascularization, according to the Akiba score (arrow). B The magnetic resonance confirmed the presence of vascularized tissue (arrow) into the uterus, suspect for placental residual

Discussion

Uterine EMV is a rare entity in which there is an abnormal communication between uterine vessel branches, derived potentially from all pregnancies [8, 9]. Spontaneous regression was possible, but in our cases, we faced the doubt whether to intervene or wait. Specifically, we reported limitation in EMV diagnosis in two cases. Even when a vascularized residual was found, we didn’t have guidelines to define the best treatment. Actually, in case 3 embolization was a good solution, while in case 1 an hysterectomy was required despite embolization. Probably, also in case 2, embolization, performed instead of curettage, could be a valid alternative to avoid uterine perforation; however, considering we did not value colour Doppler, we can only hypothesized that the patient would have no complications if this therapy was chosen. Colour-Doppler ultrasound was not performed at first evaluation in all cases, but was evaluated only at the second access of patient 2 and 3; PSV was not calculated in our cases. Certainly, ultrasound is cheap, always available, and usually sufficient to diagnose EMV, however not all physicians are confident with spectral Doppler analysis and PSV calculation, especially in Emergency room. Specifically, we had some difficulties in defining a correct diagnosis, whereas in the Emergency room the colour-Doppler was not performed; also in the literature (as shown in Table1), some cases have highlighted the need to add CT-scan or magnetic resonance.

Table 1.

Summary of clinical case reports of AVM/EMV find in literature from January 2011 to March 2022

References	Patient characteristics	Clinical symptoms	Diagnosis	Management	Follow up
Vandenbroucke et al. [12]	22 years old	Persistent vaginal bleeding after abortion	US + MR	UE	Irregular but not abundant period; negative US one month after embolization
	24 years old G4P3	Vaginal bleeding and pain after abortion	US	UE	US was normal after procedure, no persistence of symptoms
	38 years old G5P3, 1 mole	Persistent vaginal bleeding (for one month, pejorative in the last days) after curettage for miscarriage	Colour Doppler US	UE	Regression of bleeding three days after procedure MR after three months was regular
Kim et al. [13]	32 year old G3P2	Persistent and painless vaginal bleeding after miscarriage. 4 weeks after MTX haemorrhagic shock	Colour Doppler US CT after haemorrhagic shock	Uterine curettage Persistent level of betaHCG + a vascularized mas:s MTX. Decrease of betaHCG. Heamorrhagic shock UE + subsequent curettage	CT images 7 months postoperatively was regular The patient reported a regular and normal menstruation cycle
Moulder et al. [14]	32 year old 3 previous pregnancies	2 episodes of vaginal bleeding in 6 weeks after dilation and curettage for scar pregnancy	Angiography	UE Hysterectomy due to placenta percreta	–
Guan et al. [15]	37 years old G4,2 previous caesarean section, 1 previous miscarriage	Prolonged and abundant vaginal bleeding after cornual pregnancy with placenta accreta	Colour Doppler US	Emergency hysterectomy	The patient successfully recovered following the surgery
Delplanquea et al. [16]	31 years old Two previous caesarean section	Heavy bleeding 3 months after intraamniotic MTX for a dichorionic diamniotic twin scar pregnancy	US + MR	Blood transfusion + UE	No short-term complications
Songa et al. [17]	32 years old Gravida 3, 3 caesarean sections	Vaginal bleeding 12 days after the last caesarean section for low lying placenta with pathological adhesion	Colour Doppler US	Total hysterectomy	–
Harzif et al. [18]	35 years old Two previous pregnancies	Haemorrhagic shock 25 days after a caesarean section for preeclampsia	US + angiography	Blood transfusion + UE; hysterectomy for persistent bleeding after 30 days	–
	27 years old	Haemorrhagic shock 60 days after a caesarean section for cardiotocography alteration	Colour Doppler US + angiography	Blood transfusion + UE	Resolution of symptoms
	18 years old	Haemorrhagic shock 49 days after a caesarean section for premature rupture of membranes	US	Blood transfusion + UE	Resolution of symptoms
	32 years old One previous vaginal delivery	Haemorrhagic shock 131 days after caesarean section for placenta previa	US	Blood transfusion + UE	Resolution of symptoms
Gingold and Bradley [19]	22 years old G2P1	Heavy vaginal bleeding following a first-trimester termination of pregnancy	Colour Doppler US (without PVS) + hysteroscopy	Blood transfusion + UE	Resolution, follow up thanks to hysteroscopy
Youssef et al. [20]		Post-partum hemorrage 25 days after vaginal delivery	US	UE	No short-term complications

US ultrasound, MR magnetic resonance, CT computerized tomography, UE uterine embolization

We think that all physicians should be skilled to perform a colour-Doppler ultrasound with PVS evaluation. In the aftermath, we would like to know, if in case 1 the PVS value could predict the risk of hysterectomy, but only further studies will help us to have an answer.

Since we reported difficulties in our experience and those similar limitations were also encountered in the tertiary centre to which we sent our patients, we decided to perform a mini review of the literature, in the aftermath, and to share our cases in order to find a guide for the future, to diagnose EMV and to choose the best therapy for each patient.

Peitsidis et al., conducted a systematic review on AVM/EMV, which led to the conclusion that ultrasound imaging with colour-Doppler minimized the misdiagnosis and suggested that uterine artery embolization is an effective treatment. They did not evaluate which patients were candidate to embolization [10]. Subsequently also Zhu et al. reported a centre experience on these conditions, without explanation as to how they opted for the management they chose [11]. We found 9 case reports in literature after Peitsidis review in 2011 summarized in Table 1: they described their experiences of possible diagnosis and/or treatments, with possible errors, but we found no suggestions or guidelines to help us to customize the management of each patient [12–20].

Timmerman [8] and later Timor-Tritsch [2, 9] suggested that intrauterine alterations should always be investigated with a colour-Doppler examination, studying the flow with a narrow sampling windows of 2 mm, highest PSV frequencies 2–12 MHz and with pulse repetition frequencies of 600–900 MHz. Measurements should be taken at least at 5–10 different sites, and the higher PSV must be taken into account as a guide to decisions to be taken. In case of AVM/EMV with weak bleeding and PSV below 40 cm/s, the risk of bleeding was low, while the possibility of spontaneous resolution was high, and it was possible to choose a conservative treatment with a strict ultrasound follow-up. In case of important vaginal bleeding and/or PSV above 60-70 cm/s uterine artery embolization was strictly suggested. Within 40–60 cm/s the management is variable [2]: Timmerman suggested a treatment if PSV > 50 cm/s in order to reduce the risk of life-threatening bleeding [8]. No PSV cut-off was suggested to opt for hysterectomy.

A subsequent series of three cases was proposed in 2021 that supported the possibility of stratifying AVM/EMV due to clinical conditions and ultrasound, using PSV [21].

In recent years, more attention has been paid to EMV, due to its risk of bleeding. Even if embolization could be a safe option, hysterectomy can be the choice under specifical conditions [7, 22], and we stressed the importance of customizing. Probably, thanks to colour-Doppler ultrasound with PSV, in the future, we will have the opportunity to avoid demolitive surgery in emergency [2, 8] and to choose in which patients a sparing fertility treatment was available.

In conclusion

• The association of 2D-transvaginal ultrasound and colour-Doppler evaluation, particularly in case of prolonged vaginal bleeding after pregnancy, avoid misdiagnosis of EMV.

• All physicians should be trained to perform this imaging technique even in Emergency room.

• The combination of colour-Doppler ultrasound and PSV evaluation associated with clinical evaluation can allow for a better management of each patient.

We would also like to propose a further study to assess whether PSV calculation by spectral analysis besides colour-Doppler evaluation [2, 8, 9] could be a guide for the management of patients, even in a gynaecological Emergency room of a first level hospital and with the aim to look for a PSV cut-off that could give indications to hysterectomy as a treatment of choice considering that embolization is sometimes not enough.

Author contributions

All authors contributed to the study. Material preparation, data collection were performed by MDS and AV. The first draft of the manuscript was written by PA and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Declarations

Funding

The authors declare that no funds, grants, or other support were received during the writing of this manuscript.

Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This is a case report, no ethical approval is required.

Consent to participate

Written informed consent was obtained from the patient.

Consent to publish

The authors affirm that patient provided informed consent for publication of the images.