Transvaginal Ultrasound As a First-Line Approach in Deep Endometriosis: a Pictorial Essay

diagnostics

Article Transvaginal Ultrasound as a First-Line Approach in Deep Endometriosis: A Pictorial Essay

Bogdan Doroftei 1,2,3 , Radu Maftei 1,2,3,*, Ovidiu-Dumitru Ilie 4,* , Gabriela Simionescu 1,2,3, Emil Anton 1,2, Theodora Armeanu 1,2,3, Ana-Maria Dabuleanu 1,2,3, Elena Mihalceanu 1,2,3, Constantin Condac 5 and Ciprian Ilea 1,2

1 Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, no 16, 700115 Iasi, Romania; [email protected] (B.D.); [email protected] (G.S.); [email protected] (E.A.); [email protected] (T.A.); [email protected] (A.-M.D.); [email protected] (E.M.); [email protected] (C.I.) 2 Clinical Hospital of Obstetrics and Gynecology “Cuza Voda”, Cuza Voda Street, no 34, 700038 Iasi, Romania 3 Origyn Fertility Center, Palace Street, no 3C, 700032 Iasi, Romania 4 Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University, Carol I Avenue, no 20A, 700505 Iasi, Romania 5 Faculty of Medicine, “Lucian Blaga” University, Victoriei Avenue, no 10, 550024 Sibiu, Romania; [email protected] * Correspondence: [email protected] (R.M.); [email protected] (O.-D.I.)

Abstract: Endometriosis (EMS) is a benign condition characterized by a systemic inﬂammation that

affects fertile women at reproductive age. Ultrasound became, in recent years, the method of choice for both effective diagnostic and preoperative planning. Therefore, accurate characterization and

Citation: Doroftei, B.; Maftei, R.; Ilie, mapping of endometriotic lesions is imperative in such circumstances to enable optimal approach of O.-D.; Simionescu, G.; Anton, E.; treatment, whether surgical or non-surgical based on the severity of the ﬁndings. This pictorial essay Armeanu, T.; Dabuleanu, A.-M.; outlines a practical approach to evaluating patients with deep endometriosis by means of transvaginal Mihalceanu, E.; Condac, C.; Ilea, C. ultrasound. The technical aspects are in conjunction with both consensus of the International Transvaginal Ultrasound as a Deep Endometriosis Analysis (IDEA) group and the hands-on experience acquired through daily First-Line Approach in Deep clinical practice. Endometriosis: A Pictorial Essay. Diagnostics 2021, 11, 444. https:// Keywords: deep endometriosis; diagnosis; ultrasound; adenomyosis doi.org/10.3390/diagnostics11030444

Academic Editor: Stefano Guerriero 1. Introduction Received: 12 January 2021 Accepted: 1 March 2021 Endometriosis (EMS) is a chronic disease deﬁned by the presence of endometrial-like Published: 4 March 2021 tissue outside the uterine lining. Women at reproductive age are at higher risk because it causes physiological changes that are directly correlated with fertile status. EMS incidence

Publisher’s Note: MDPI stays neutral was estimated to be between 5 and 10% [1,2], but a series of other aspects should be taken with regard to jurisdictional claims in into consideration such as the use of combined oral contraceptives, lack of routine checks published maps and institutional affil- at the doctor, or even misdiagnosis. Cumulatively, all those mentioned early led to a still iations. challenging and hard to diagnose disorder. Retrospectively, the first paper that signaled the use of ultrasound in the diagnosis of endometriosis was published in 1978 [3]. Since then, numerous studies have focused on ultrasound findings in deep endometriosis (DE) and a consensus was reached in 2016

Copyright: © 2021 by the authors. regarding the nomenclature, definitions and measurements of endometriotic lesions de- Licensee MDPI, Basel, Switzerland. pending on their localization [4]. This article is an open access article Ultrasound for these specific lesions is a topic that has been the promoter of many distributed under the terms and other articles published. Furthermore, the objective was to test through the prism of conditions of the Creative Commons specificity and sensibility with other protocols involving magnetic resonance imaging Attribution (CC BY) license (https:// (MRI) and laparoscopy. From our point of view, ultrasound should become routine for DE creativecommons.org/licenses/by/ diagnosis. Unfortunately, it is still limited to diagnosis of ovarian endometrioma [5–7]. 4.0/).

Diagnostics 2021, 11, 444. https://doi.org/10.3390/diagnostics11030444 https://www.mdpi.com/journal/diagnostics Diagnostics 2021, 11, 444 2 of 14

This paper aims to reiterate the importance of ultrasound in the diagnosis of DE. It should become mandatory for gynecologists to be familiar with the ultrasound aspects of DE and use this diagnostic tool in daily practice following the steps proposed in the IDEA (International Deep Endometriosis Analysis group) consensus statement.

2. Materials and Methods The transvaginal ultrasound technique used for detecting DE was performed according to IDEA guidelines [4].

2.1. Study Participants A total of twenty-one women (mean 33.6, range 25–43 years) participated, each one reporting painful symptoms associated with endometriosis for at least 12 months (dysmenorrhea, dyspareunia or dysuria).

2.2. Protocol Prior to the actual procedure, each woman underwent an MRI investigation. En- dometriotic lesions were subsequently conﬁrmed following a histologic examination and surgery. All patients suspected were kindly advised to follow a low residue diet between 2 and 3 days and to take oral laxatives a few hours before the intervention. We further recommend patients partially empty their bladder for better visualization of endometriotic lesions. The images with endometriosis-like symptoms were obtained from patients by using a Voluson E8 expert ultrasound machine (GE Healthcare, Chicago, IL, USA) at the Origyn Fertility Center, Iasi, Romania.

2.3. Procedure At the beginning of the ultrasound examination, the uterus and adnexa were evaluated to identify and describe separately every endometriotic lesion. The presence of “soft markers” was assessed by bimanual examination: a transvaginal probe was gently pushed towards the ovary and transabdominal pressure was applied with the other to notice if the ovary would glide freely along the pelvic sidewall and uterus. The status of the Douglas pouch was appraised using the “sliding-sign” technique. If the rectum glided freely against the uterus and the posterior vaginal fornix, this would be considered as a positive “sliding sign”. The examination concluded with a survey of deep endometriosis in the anterior and posterior compartments.

2.4. Follow-Up Patients were under continuous postoperative follow-up for at least 1 year to evaluate the evolution of symptoms. It should be also mentioned that were placed under standard treatment for at least 3 months on postoperative hormones (dienogest or combined oral contraceptive (COC) in continuous administration between 90–120 days, respectively).

2.5. Ethical Approval The study was approved by the Ethical Committee of the Origyn Fertility Center (no 117/565/January/25/2021). Additionally, all patients gave their signed consent for ultrasound images presented in this paper to be used for research and publication purposes.

3. Results and Discussions 3.1. ADNEXA The assessment of the adnexa involves the evaluation of ovaries, fallopian tubes and the detection of “soft markers”. A clear mapping of the left and right side should be performed especially in the cases of patients with ovaries kissing and important anatomic distortion; also, the examiner must try to establish the origin of the lesion, weather ovary, Diagnostics 2021, 11, x 3 of 16

3. Results and Discussions 3.1. ADNEXA

Diagnostics 2021, 11, 444 The assessment of the adnexa involves the evaluation of ovaries, fallopian tubes3 of and 14 the detection of “soft markers”. A clear mapping of the left and right side should be performed especially in the cases of patients with ovaries kissing and important anatomic distortion; also, the examiner must try to establish the origin of the lesion, weather ovary, uterus,uterus, fallopian fallopian tube tube or or other other organs. organs. For For the the description description of of ovarian ovarian lesions, lesions, we we used used the the terminologyterminology proposed proposed by by the the International International Ovarian Ovarian Tumor Tumor Analysis Analysis (IOTA) (IOTA) group group [8 [8].]. EndometriomaEndometrioma oror ovarianovarian endometriosisendometriosis isis oneone ofof thethe mostmost commoncommon formsforms ofof en-endometriosisdometriosis with with characteristic characteristic aspects aspects of of a cystica cystic lesion lesion with with “ground-glass” “ground-glass” echogenicity echogenic- (Figureity (Figure1) and 1) lowand Dopplerlow Doppler signal. signal.

FigureFigure 1. 1.Typical Typical aspect aspect of of an an endometrioma. endometrioma. Unilocular Unilocular cyst cyst with with “ground-glass” “ground-glass” echogenicity. echogenicity.

AccordingAccording to to a recenta recent study, study, the the ultrasound ultrasound appearance appearance of endometrioma of endometrioma changes changes with thewith patient’s the patient’s age [9]. Whileage [9]. in premenopausalWhile in premenopausal women 75% women of lesions 75% have of a “ground-glass”lesions have a echogenicity,“ground-glass” only echogenicity, 62% of lesions only in peri- 62% andof lesions post-menopausal in peri- and women post-menopausal have this aspect. women In additionhave this to theaspect. typical In appearanceaddition to of the unilocular typical cystsappearance with “ground-glass” of unilocular echogenicity, cysts with Diagnostics 2021, 11, x atypical“ground-glass” forms of echogenicity, endometrioma atypical can also forms be found, of endometrioma such as multilocular can also be cysts found, (Figure such4 of2 ),as16

papillarymultilocular projections cysts (Figure or solid 2), areas papillary (Figures projections3 and4). or solid areas (Figures 3 and 4).

Figure 2. Multilocular endometrioma with “ground-glass” appearance. Figure 2. Multilocular endometrioma with “ground-glass” appearance.

Figure 3. Ovarian endometrioma containing a hyperechoic area (S). Paraovarian multiple adhesions and free fluid (yellow arrow).

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Figure 2. Multilocular endometrioma with “ground-glass” appearance.

Diagnostics 2021, 11, x FigureFigure 3. 3.Ovarian Ovarian endometrioma endometrioma containing containing a a hyperechoic hyperechoic area area (S). (S). Paraovarian Paraovarian multiple multiple adhesions adhe-5 of 16 sions and free fluid (yellow arrow). and free ﬂuid (yellow arrow).

FigureFigure 4. 4.Ovarian Ovarian endometrioma endometrioma containing containing a hyperechoica hyperechoic area area (white (white arrow) arrow) without without Doppler Doppler signal. signal. In the presence of endometrioma, due to adhesions, the fallopian tubes can be affected, resultingIn the in hydrosalpinxpresence of endometrioma, or hematosalpinx. due to In adhesions, one study, the ovarian fallopian endometrioma tubes can be was af- linkedfected, to resulting the severity in hydrosalpinx of deep endometriosis, or hematosalpinx. thus having In one the study, potential ovarian to serve endometrioma as a marker andwas alinked warning to the sign severity of gynecologists of deep endometriosis, [10]. In addition, thus having the surrounding the potential ovarian to serve bowel as a shouldmarker be and carefully a warning checked sign for of thegynecologists presence of [10]. endometriotic In addition, lesions the surrounding (Figure5). ovarian bowelThe should evaluation be carefully of soft markerschecked forfor endometriosisthe presence of detected endometriotic by transvaginal lesions (Figure ultrasound 5). includes ovarian mobility and site-speciﬁc tenderness (SST). The assessment of ovarian mobility is made by applying light pressure with the vaginal transducer in the direction of the ovary. In some cases, the operator can use his/her left hand to apply pressure on the iliac fossa region for a better evaluation of ovarian mobility. Normally, the ovary should glide freely along the pelvic sidewall and uterus. The assessment of the SST consists of applying pressure with the probe and asking the patient about the onset and site of pain. We recommend that the assessment of SST be done at the end of the examination to reduce the patient’s physical and psychological discomfort.

Figure 5. Left ovary with an endometrioma having a typical appearance. Right behind the ovary, a loop of the small intestine with an endometriotic nodule is very adherent to the ovary.

The evaluation of soft markers for endometriosis detected by transvaginal ultrasound includes ovarian mobility and site-specific tenderness (SST). The assessment of ovarian mobility is made by applying light pressure with the vaginal transducer in the direction of the ovary. In some cases, the operator can use his/her left hand to apply pressure on the iliac fossa region for a better evaluation of ovarian mobility. Normally, the ovary should glide freely along the pelvic sidewall and uterus. The assessment of the SST consists of applying pressure with the probe and asking the patient about the onset

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Figure 4. Ovarian endometrioma containing a hyperechoic area (white arrow) without Doppler signal.

In the presence of endometrioma, due to adhesions, the fallopian tubes can be affected, resulting in hydrosalpinx or hematosalpinx. In one study, ovarian endometrioma Diagnostics 2021, 11, 444 was linked to the severity of deep endometriosis, thus having the potential to serve as 5a of 14 marker and a warning sign of gynecologists [10]. In addition, the surrounding ovarian bowel should be carefully checked for the presence of endometriotic lesions (Figure 5).

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Figure 5. Left ovary with an endometrioma having a typical appearance. Right behind the ovary, a Figure 5. Left ovary with an endometrioma having a typical appearance. Right behind the ovary, loopand ofsite the of small pain. intestine We recommend with an endometriotic that the assessment nodule is very of adherentSST be doneto the ovary.at the end of the a loop of the small intestine with an endometriotic nodule is very adherent to the ovary. examination to reduce the patient’s physical and psychological discomfort. 3.2. AdenomyosisThe evaluation of soft markers for endometriosis detected by transvaginal ultra- sound3.2. Adenomyosis includes ovarian mobility and site-specific tenderness (SST). The assessment of ovarianThe mobility uterine evaluationis made by shouldapplying be light done pr accordingessure with to the Morphologicalvaginal transducer Uterus in the Sono- graphicThe Assessment uterine evaluation (MUSA) should consensus be done for according better characterization to the Morphological of lesions, Uterus especially So- directionnographic of Assessment the ovary. (MUSA)In some consensuscases, the foroperator a better can characterization use his/her left of hand lesions, to applyespe- whenpressure in theon the case iliac of fossa associated region pathologyfor a better like evaluation myoma of [ 11ovarian]. Adenomyosis mobility. Normally, is a benign conditioncially when deﬁned in the case by theof associated presence pathol of endometrialogy like myoma glands [11]. and Ad stromaenomyosis at the is a level benign of the thecondition ovary shoulddefined glide by the freely presence along ofthe endometrial pelvic sidewall glands and and uterus. stroma The atassessment the level of thethe uterine muscle wall. The existence of endometrial-like tissue in the uterine wall induces SSTuterine consists muscle of applyingwall. The pressureexistence with of endometrial-like the probe and asking tissue thein the patient uterine about wall the induces onset hypertrophy and hyperplasia of the surrounding myometrium, creating a globose aspect hypertrophy and hyperplasia of the surrounding myometrium, creating a globose aspect of the uterus and an increased uterine volume. of the uterus and an increased uterine volume. Based on the histologic and ultrasonographic aspects, we can distinguish three types of Based on the histologic and ultrasonographic aspects, we can distinguish three types adenomyosis: diffuse adenomyosis (Figures6 and7), focal adenomyosis (Figures8 and9) of adenomyosis: diffuse adenomyosis (Figures 6 and 7), focal adenomyosis (Figures 8 and and adenomyoma. 9) and adenomyoma.

Figure 6. Ultrasound image of diffuse adenomyosis showing an enlarged uterus with fan-shaped Figure 6. Ultrasound image of diffuse adenomyosis showing an enlarged uterus with fan-shaped shadowing: enlarged uterus with loss of the normal aspect of the myometrium: multiple myome- shadowing:trial cysts, fan-shaped enlarged uterus shadowing, withloss echogenic of the normalislands and aspect an ofinterrupted the myometrium: junctional multiple zone. myometrial cysts, fan-shaped shadowing, echogenic islands and an interrupted junctional zone.

Figure 7. Ultrasound image of diffuse adenomyosis showing translesional blood flow in Doppler mode.

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and site of pain. We recommend that the assessment of SST be done at the end of the examination to reduce the patient’s physical and psychological discomfort.

3.2. Adenomyosis The uterine evaluation should be done according to the Morphological Uterus So- nographic Assessment (MUSA) consensus for a better characterization of lesions, especially when in the case of associated pathology like myoma [11]. Adenomyosis is a benign condition defined by the presence of endometrial glands and stroma at the level of the uterine muscle wall. The existence of endometrial-like tissue in the uterine wall induces hypertrophy and hyperplasia of the surrounding myometrium, creating a globose aspect of the uterus and an increased uterine volume. Based on the histologic and ultrasonographic aspects, we can distinguish three types of adenomyosis: diffuse adenomyosis (Figures 6 and 7), focal adenomyosis (Figures 8 and 9) and adenomyoma.

Diagnostics 2021, 11, 444 6 of 14 Figure 6. Ultrasound image of diffuse adenomyosis showing an enlarged uterus with fan-shaped shadowing: enlarged uterus with loss of the normal aspect of the myometrium: multiple myometrial cysts, fan-shaped shadowing, echogenic islands and an interrupted junctional zone.

Figure 7. Ultrasound image of diffuse adenomyosis showing translesional blood flow in Doppler Figure 7. Ultrasound image of diffuse adenomyosis showing translesional blood ﬂow in Diagnostics 2021, 11, x mode. 7 of 16 Doppler mode. Diagnostics 2021, 11, x 7 of 16

FigureFigure 8. 8. UltrasoundUltrasound aspects aspects of focal of focal adenomyosis: adenomyosis: myometrial myometrial cysts surrounded cysts surrounded by echogenic by rim echogenic rim and blood flow in Doppler mode. andFigure blood 8. Ultrasound ﬂow in Doppler aspects of mode. focal adenomyosis: myometrial cysts surrounded by echogenic rim and blood flow in Doppler mode.

Figure 9. Focal adenomyosis in 3D coronal view showing cystic lesions.

3.3.Figure Posterior 9. Focal Compartment adenomyosis in 3D coronal view showing cystic lesions. Figure 9. Focal adenomyosis in 3D coronal view showing cystic lesions. The last step of the IDEA approach consists of assessing the posterior compartment, which3.3. Posterior includes: Compartment the uterosacral ligaments (USLs), the posterior vaginal fornix, the recto- vaginalThe septum last step and of thethe IDEAbowel. approach We recommend consists ofstarting assessing this theevaluation posterior with compartment, the bowel becausewhich includes: 9–22% of the all uterosacralwomen with ligaments proven endometriosis (USLs), the posterior will have vaginal this type fornix, of lesions the recto- [12]. Withvaginal the septum probe orientedand the inbowel. the direction We recommend of the sacrum starting bone, this the evaluation pressure withis applied the bowel gen- tlybecause on the 9–22% entrance of all into women the vagina. with proven Once the endometriosis bowel wall willis identified, have this slow type progressionof lesions [12]. is madeWith thefollowing probe orientedthe bowel in curves. the direction Most commonly, of the sacrum the bone, lesions the are pressure located isin applied the anterior gen- walltly on of the the entrance bowel, butinto sometimes the vagina. it Once may thebe possiblebowel wall to findis identified, an endometriotic slow progression nodule inis themade lateral following wall orthe even bowel in curves. the posterior Most commonly, wall of the the bowel. lesions This are islocated the reason in the whyanterior we suggestwall of theassessing bowel, the but bowel sometimes in the itlongitudinal may be possible and transversal to find an planes. endometriotic nodule in the lateralThe normal wall orthickness even in of the the posterior rectosigmoid wall wallof the is 1–2bowel. mm This (Figure is the 10). reason why we suggest assessing the bowel in the longitudinal and transversal planes. The normal thickness of the rectosigmoid wall is 1–2 mm (Figure 10).

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3.3. Posterior Compartment The last step of the IDEA approach consists of assessing the posterior compartment, which includes: the uterosacral ligaments (USLs), the posterior vaginal fornix, the rectovaginal septum and the bowel. We recommend starting this evaluation with the bowel because 9–22% of all women with proven endometriosis will have this type of lesions [12]. With the probe oriented in the direction of the sacrum bone, the pressure is applied gently on the entrance into the vagina. Once the bowel wall is identiﬁed, slow progression is made following the bowel curves. Most commonly, the lesions are located in the anterior wall of the bowel, but sometimes it may be possible to ﬁnd an endometriotic nodule in the lateral wall or even in the posterior wall of the bowel. This is the reason why we suggest assessing the bowel in the longitudinal and transversal planes. Diagnostics 2021, 11, x 8 of 16 The normal thickness of the rectosigmoid wall is 1–2 mm (Figure 10).

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Figure 10. Ultrasound appearance of a normal bowel loop. Figure 10. Ultrasound appearance of a normal bowel loop.

Any focal thickening of the bowel wall that suggests an endometriotic nodule FigureshouldAny 10. be Ultrasound followed focal thickening byappearance gentle pressure of of a thenormal with bowel bowel the wallloop.probe that to elongate suggests the intestinal an endometriotic loop and nodule should beto followedexclude an byartifact gentle or superposition pressure with of images. the probe Another to elongate helpful tip the is intestinalto observe the loop and to exclude Any focal thickening of the bowel wall that suggests an endometriotic nodule anperistalsis artifact of or the superposition surrounding bowel of images. because Anotherthe nodule helpful will remain tip isimmobile. to observe Any thele- peristalsis of the shouldsions detected be followed during by thegentle ultrasound pressure examinwith theation probe should to elongate be described the intestinal under theloop IDEA and surroundingtoconsensus exclude statementan artifact bowel (Figures or because superposition 11–15). the nodule of images. will Another remain helpful immobile. tip is to Any observe lesions the detected during theperistalsis ultrasound of the surrounding examination bowel should because be the described nodule will underremain immobile. the IDEA Any consensus le- statement (Figuressions detected 11–15 during). the ultrasound examination should be described under the IDEA consensus statement (Figures 11–15).

Figure 11. Ultrasound image showing the bowel with an endometriotic nodule (white arrow, “pulling sleeve sign”) adherent to the uterine torus, in extrinsic retraction. In this case the sliding sign was absent. Figure 11. Ultrasound image showing the bowel with an endometriotic nodule (white arrow, Figure“pulling 11. sleeveUltrasound sign”) adherent image to the showing uterine torus, the bowel in extrinsic with retraction. an endometriotic In this case nodulethe sliding (white arrow, “pulling sleevesign was sign”) absent. adherent to the uterine torus, in extrinsic retraction. In this case the sliding sign was absent.

Diagnostics 2021, 11, 444 8 of 14 Diagnostics 2021, 11, x 9 of 16

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Figure 12. (A) Ultrasound image showing a deep infiltrating endometriosis (DIE) nodule with a Figureregular outline 12. (A (absence) Ultrasound of “spikes”). image (B) the showing same nodule a deep is viewed inﬁltrating in 3D with endometriosis TUI (tomographic (DIE) nodule with a regularFigureultrasound 12. outline ( Aimaging).) Ultrasound (absence image of showing “spikes”). a deep (B infiltra) the sameting endometriosis nodule is viewed(DIE) nodule in 3Dwith with a TUI (tomographic ultrasoundregular outline imaging). (absence of “spikes”). (B) the same nodule is viewed in 3D with TUI (tomographic ultrasound imaging).

Figure 13. Ultrasound image showing a DIE nodule (+) with progressive narrowing, like a “tail” (white arrow), also known as a “comet” sign. Figure 13. Ultrasound image showing a DIE nodule (+) with progressive narrowing, like a “tail” Figure(white arrow), 13. Ultrasound also known as image a “comet” showing sign. a DIE nodule (+) with progressive narrowing, like a “tail” Diagnostics 2021, 11, x 10 of 16 (white arrow), also known as a “comet” sign.

Figure 14. Ultrasound image showing a DIE nodule (+) with prominent spikes towards the bowel Figurelumen (white 14. Ultrasound arrow, “Indian image headdress showing sign”). a DIE nodule (+) with prominent spikes towards the bowel lumen (white arrow, “Indian headdress sign”).

Figure 15. Ultrasound image showing a big DIE nodule with some spikes towards the bowel lumen, in extrinsic retraction. In this case, the sliding sign was absent.

When evaluating intestinal endometriotic nodules, the 3D ultrasound has demon- strated its usefulness, because such imagery allows for better visualization of lesion borders (Figure 16).

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Diagnostics 2021, 11, 444 9 of 14 Figure 14. Ultrasound image showing a DIE nodule (+) with prominent spikes towards the bowel lumen (white arrow, “Indian headdress sign”).

FigureFigure 15. 15.Ultrasound Ultrasound image image showing showing a a big big DIE DIE nodule nodule with with some some spikes spikes towards towards the the bowel bowel lumen, lumen, in extrinsic retraction. In this case, the sliding sign was absent. in extrinsic retraction. In this case, the sliding sign was absent.

WhenWhen evaluatingevaluating intestinalintestinal endometrioticendometriotic nodules,nodules, thethe 3D3D ultrasoundultrasound hashas demon-demon- Diagnostics 2021, 11, x stratedstrated its its usefulness, usefulness, because because such such imagery imagery allows allows for better for visualizationbetter visualization of lesion of borders11 lesion of 16

(Figureborders 16 (Figure). 16).

FigureFigure 16. 16.Three-dimensional Three-dimensional ﬁndings findings of of a a rectosigmoid rectosigmoid nodule nodule in in the the coronal coronal plane. plane.

AnotherAnother importantimportant regionregion thatthat needsneeds toto bebe checkedchecked for for DE DE is is the the rectovaginal rectovaginal septum septum (RVS).(RVS). This This is is located located in in the the retroperitoneum, retroperitoneum, between between the the posterior posterior wall wall of of the the vagina vagina and and thethe anterioranterior wallwall of of the the rectum. rectum. This This structure structure establishes establishes aa strong strong connection connection between between the the vaginavagina andand thethe rectum, rectum, containing containing collagen,collagen, elasticelastic ﬁbers,fibers, smallsmall vessels, vessels, smooth smooth muscle muscle cellscells andand nervesnerves from the inferior hypogastri hypogastricc plexus. plexus. The The ultrasound ultrasound examination examination of the of theRVS RVS is made is made with with the theprobe probe oriented oriented in the in thesame same manner manner as for as forbowel bowel evaluation. evaluation. Ac- Accordingcording to tothe the IDEA IDEA group group definition, deﬁnition, the the no noduledule should be visualizedvisualized belowbelow thethe lineline passingpassing alongalong thethe lowerlower borderborder ofof the posteriorposterior lip of the cervix cervix (Figure (Figure 17)17)[ [4].4].

Figure 17. Ultrasound image depicting an endometriotic nodule of the RVS. (+) the vaginal wall as a hypoechogenic line and an endometriotic nodule (*) with discreet vaginal wall infiltration.

It is very important to use this landmark for better differentiation between RVS endometriosis and retrocervical endometriosis. In the former case, the anterior wall of the rectum is usually infiltrated, which implies bowel resection during surgery, while in the case of retrocervical endometriosis, the bowel wall is not affected, so a local excision or ablation of the lesion is sufficient.

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Figure 16. Three-dimensional findings of a rectosigmoid nodule in the coronal plane.

Another important region that needs to be checked for DE is the rectovaginal septum (RVS). This is located in the retroperitoneum, between the posterior wall of the vagina and the anterior wall of the rectum. This structure establishes a strong connection between the vagina and the rectum, containing collagen, elastic fibers, small vessels, smooth muscle cells and nerves from the inferior hypogastric plexus. The ultrasound examination of the Diagnostics 2021, 11, 444 RVS is made with the probe oriented in the same manner as for bowel evaluation.10 of Ac- 14 cording to the IDEA group definition, the nodule should be visualized below the line passing along the lower border of the posterior lip of the cervix (Figure 17) [4].

FigureFigure 17. 17.Ultrasound Ultrasound image image depicting depicting an an endometriotic endometriotic nodule nodule of of the the RVS. RVS. (+) (+) the the vaginal vaginal wall wall as as a a hypoechogenic line and an endometriotic nodule (*) with discreet vaginal wall infiltration. hypoechogenic line and an endometriotic nodule (*) with discreet vaginal wall inﬁltration.

ItIt isis veryvery important to to use use this this landmark landmark for for better better differentiation differentiation between between RVS RVS en- endometriosisdometriosis and and retrocervical retrocervical endometriosis. endometriosis. In In the the former former case, the anterioranterior wallwall ofofthe the Diagnostics 2021, 11, x rectumrectum isis usuallyusually inﬁltrated,infiltrated, whichwhich impliesimplies bowelbowel resectionresection duringduring surgery,surgery, while while12 in in of the the 16

casecase ofof retrocervicalretrocervical endometriosis,endometriosis, thethe bowelbowel wallwall isis notnot affected,affected, soso aa locallocal excisionexcision oror ablationablation ofof the the lesion lesion is is sufﬁcient. sufficient. TheThe ultrasoundultrasound evaluationevaluation ofof thethe posteriorposterior fornixfornix shouldshouldbe be a a tenderness-guided tenderness-guided examination.examination. The The ultrasound ultrasound beam beam is gentlyis gently placed placed into into the the posterior posterior fornix fornix and and the patientthe pa- istient asked is asked to inform to inform the examiner the examiner about theabout onset the and onset the and site the of any site pain of any experienced pain experienced during the examination. In addition to the size of the lesion, the operator should pay attention to during the examination. In addition to the size of the lesion, the operator should pay at- thetention relationship to the relationship with other endometrioticwith other endometriotic lesions and lesions evaluate and the evaluate mobility the and mobility the status and ofthe the status sliding of the sign slid (Figureing sign 18). (Figure 18).

FigureFigure 18. 18.Ultrasound Ultrasound imageimage showingshowing aa bigbig nodulenodule inﬁltratinginfiltratingthe theposterior posteriorvaginal vaginalfornix fornixand andthe the anterior wall of the rectum. (+) the vaginal wall, (*) the bowel. Diablo-like nodule. anterior wall of the rectum. (+) the vaginal wall, (*) the bowel. Diablo-like nodule.

Normally, uterosacral ligaments are two anatomic structures invisible to ultrasound examination and, according to one meta-analysis [13], the overall pooled sensitivity of transvaginal sonography (TVS) for detection of USL endometriosis was only 53% (95% confidence interval (CI), 35–70%). During the examination, the ultrasound beam is gently placed into the posterior fornix, at the midline, in a sagittal plane and then the probe is swept inferolateral to the cervix. Endometriotic lesions of the USL appear as a hypoechoic thickening and may be isolated or may be included in a big DE nodule (Figures 19 and 20). The nodule should be measured in three orthogonal planes.

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The ultrasound evaluation of the posterior fornix should be a tenderness-guided examination. The ultrasound beam is gently placed into the posterior fornix and the patient is asked to inform the examiner about the onset and the site of any pain experienced during the examination. In addition to the size of the lesion, the operator should pay attention to the relationship with other endometriotic lesions and evaluate the mobility and the status of the sliding sign (Figure 18).

Diagnostics 2021, 11, 444 11 of 14 Figure 18. Ultrasound image showing a big nodule infiltrating the posterior vaginal fornix and the anterior wall of the rectum. (+) the vaginal wall, (*) the bowel. Diablo-like nodule.

Normally,Normally, uterosacral uterosacral ligaments ligaments areare two two anatomic anatomic structures structures invisible invisible to to ultrasound ultrasound examinationexamination and,and, accordingaccording toto oneone meta-analysismeta-analysis [13[13],], thethe overalloverall pooledpooled sensitivity sensitivity ofof transvaginaltransvaginal sonographysonography (TVS)(TVS) forfor detectiondetection ofof USLUSL endometriosisendometriosis waswas onlyonly 53%53% (95%(95% conﬁdenceconfidence intervalinterval (CI),(CI), 35–70%).35–70%). DuringDuring thethe examination,examination, thethe ultrasoundultrasound beambeam is is gently gently placedplaced intointo thethe posteriorposterior fornix,fornix, atat thethe midline,midline, inin aa sagittalsagittal planeplane andand thenthen thethe probe probe is is sweptswept inferolateral inferolateral to to the the cervix. cervix. EndometrioticEndometriotic lesionslesions ofof thethe USL USL appear appear as as a a hypoechoic hypoechoic thickeningthickening and and may may be be isolated isolated or or may may be be included included in in aa big big DEDE nodulenodule (Figures(Figures 19 19 and and 20 20).). TheThe nodule nodule shouldshould bebe measuredmeasured inin threethree orthogonalorthogonal planes.

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Figure 19. Transverse image of the cervix with a uterosacral ligaments (USL) DE hypoechoic nod- Figure 19. Transverse image of the cervix with a uterosacral ligaments (USL) DE hypoechoic nodule (+), with irregular outline. ule (+), with irregular outline.

FigureFigure 20. 20.Sagittal Sagittal imageimage of of the the cervix cervix showing showing a a hypoechoic hypoechoic USL USL DE DE nodule nodule (+) (+) along along with with a a bowel bowel nodulenodule adherent adherent to to a a DE DE nodule nodule of of the the uterine uterine torus torus and and a a USL USL nodule. nodule.

AnotherAnother important important step step in in the the evaluation evaluation of of the the ureter. ureter. Ureteral Ureteral endometriosis endometriosis may may be intrinsicbe intrinsic or extrinsic, or extrinsic, affecting affecting one orone both or both ureters. ureters. Intrinsic Intrinsic ureteral ureteral endometriosis endometriosis is due is todue direct to direct inﬁltration infiltration of the of ureteral the ureteral wall by wa thell by endometrial the endometrial glands glands and stroma. and stroma. Extrinsic Ex- endometriosistrinsic endometriosis is more commonis more common and is a consequenceand is a consequence of an intensive of an ﬁbroticintensive process fibrotic due pro- to cess due to DE. The pelvic portion of the ureters can easily be evaluated by transvaginal ultrasound. The first step is to identify the urethra in a longitudinal section and then the probe should be moved slowly to each part of the lateral pelvic wall. Ureters appear as hypoechoic tubular structures surrounded by a hyperechoic layer, measuring around 1.7 mm at rest and 2.9 mm during peristalsis (Figure 21).

Figure 21. Transvaginal ultrasound of a normal ureter during peristalsis. Notice the flow of urine into the bladder.

As in the case of bowel lesions, if a ureteral nodule is visualized when the probe is fixed, the nodule will remain immobile during peristalsis. Usually, the ureters are nar-

Diagnostics 2021, 11, x 13 of 16

Figure 19. Transverse image of the cervix with a uterosacral ligaments (USL) DE hypoechoic nodule (+), with irregular outline.

Figure 20. Sagittal image of the cervix showing a hypoechoic USL DE nodule (+) along with a bowel nodule adherent to a DE nodule of the uterine torus and a USL nodule.

Diagnostics 2021, 11, 444 Another important step in the evaluation of the ureter. Ureteral endometriosis12 ofmay 14 be intrinsic or extrinsic, affecting one or both ureters. Intrinsic ureteral endometriosis is due to direct infiltration of the ureteral wall by the endometrial glands and stroma. Ex- trinsic endometriosis is more common and is a consequence of an intensive fibrotic pro- DE.cess The due pelvic to DE. portion The pelvic of the portion ureters of can the easily ureters be can evaluated easily be by evaluated transvaginal by transvaginal ultrasound. Theultrasound. ﬁrst step The is to first identify step theis to urethra identify in the a longitudinal urethra in a section longitudinal and then section the probe and then should the beprobe moved should slowly be moved to each slowly part of to the each lateral part pelvicof the wall.lateral Ureters pelvic wall. appear Ureters as hypoechoic appear as tubularhypoechoic structures tubular surrounded structures bysurrounded a hyperechoic by a hyperechoic layer, measuring layer, around measuring 1.7 mm around at rest 1.7 andmm 2.9 at rest mm and during 2.9 peristalsismm during (Figure peristalsis 21). (Figure 21).

FigureFigure 21. 21.Transvaginal Transvaginal ultrasoundultrasound ofof aa normalnormal ureter during peristalsis.peristalsis. Notice Notice the the flow ﬂow of of urine urine into the bladder. into the bladder. Diagnostics 2021, 11, x 14 of 16

AsAs inin thethe casecase ofof bowel lesions, if a a ureteral ureteral nodule nodule is is visualized visualized when when the the probe probe is isfixed, ﬁxed, the the nodule nodule will will remain remain immobile immobile duri duringng peristalsis. peristalsis. Usually, Usually, the theureters ureters are nar- are narrowedrowed by byDE DE at the atthe level level of the of thecrossing crossing with with the theuterine uterine artery. artery. This This is the is reason the reason why whywe recommend we recommend the theinspection inspection of the of theureter ureter unti untill this this level level with with the the ultrasound ultrasound device device in

inDoppler Doppler mode mode (Figure (Figure 22). 22 In). the In thecase case of a ofuret ahral urethral JJ stent, JJ stent, TVS is TVS very is helpful very helpful in evalu- in evaluatingating the position the position and peristalsis and peristalsis (Figure (Figure 23). 23).

FigureFigure 22.22. Transvaginal ultrasound of a a normal normal left left ureter( ureterA ()A and) and of ofthe the crossing crossing of the of the uterine uterine artery when viewed in Doppler mode (B). artery when viewed in Doppler mode (B).

Figure 23. Transvaginal ultrasound of the bladder showing the ureter and the JJ stent in a normal position. (+ sign in the figure plays the role of a pointer to highlight a specific feature)

4. Conclusions Endometriosis is a chronic disease taking a heavy toll on the quality of life and the fertility potential of the women affected by it. Considerable diagnostic delays of up to 8 years from the onset of symptoms add a further economic and social burden [14–16]. Therefore, we should strive towards early and comprehensive diagnosis using all means available, such as by promoting and conducting transvaginal ultrasound examinations on a larger scale. Although the transvaginal ultrasound is known to be an easy, safe and accurate method to diagnose DE, it is yet to become a routine and widely used first-line imagistic approach.

Diagnostics 2021, 11, x 14 of 16

rowed by DE at the level of the crossing with the uterine artery. This is the reason why we recommend the inspection of the ureter until this level with the ultrasound device in Doppler mode (Figure 22). In the case of a urethral JJ stent, TVS is very helpful in evaluating the position and peristalsis (Figure 23).

Diagnostics 2021, 11, 444 13 of 14 Figure 22. Transvaginal ultrasound of a normal left ureter(A) and of the crossing of the uterine artery when viewed in Doppler mode (B).

FigureFigure 23.23. TransvaginalTransvaginal ultrasoundultrasound ofof thethe bladder showing the ureter and the the JJ JJ stent stent in in a a normal normal position. (+ sign in the figure plays the role of a pointer to highlight a specific feature) position. (+ sign in the ﬁgure plays the role of a pointer to highlight a speciﬁc feature).

4.4. ConclusionsConclusions EndometriosisEndometriosis isis aa chronicchronic diseasedisease takingtaking aa heavyheavy tolltoll onon thethe qualityquality ofof lifelife andand thethe fertilityfertility potentialpotential ofof thethe womenwomen affectedaffected by it. Considerable Considerable diagnostic diagnostic delays delays of of up up to to 8 8years years from from the the onset onset of of symptoms symptoms add add a furt furtherher economic and socialsocial burdenburden [[14–16].14–16]. Therefore,Therefore, wewe shouldshould strivestrive towardstowards early early and and comprehensive comprehensive diagnosis diagnosis using using all all means means available,available, suchsuch asas byby promotingpromoting andand conducting conducting transvaginal transvaginal ultrasound ultrasound examinations examinations onon aa largerlarger scale.scale. AlthoughAlthough thethe transvaginaltransvaginal ultrasoundultrasound isis knownknown toto bebe anan easy,easy, safe safe and and accurateaccurate methodmethod toto diagnosediagnose DE,DE, itit isis yetyet totobecome becomea a routine routine and and widely widely used used ﬁrst-line first-line imagisticimagistic approach.approach. A detailed ultrasound examination using the steps of the IDEA consensus statement could detect endometriotic lesions that would otherwise be omitted during laparoscopy (i.e., bowel lesions, ureteral nodules) and contribute to a correct referral of patients suffering from advanced endometriosis to centers of excellence in endometriosis, where they can undergo minimally invasive surgery.

Author Contributions: R.M., O.-D.I., G.S., T.A., A.-M.D. (Conceptualization, Data curation, Investi- gation, Formal analysis, Methodology, Writing—original draft); B.D., E.A., C.I. (Conceptualization, Methodology, Writing—review and editing); B.D., E.M., C.C., C.I. (Supervision, Validation, Project administration). All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Origyn Fertility Center (no 117/565/January/25/2021). Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. Data Availability Statement: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Acknowledgments: The authors wish to thank Simedrea Voicu for his support and helpful advice. Conﬂicts of Interest: The authors declare no conﬂict of interest. Diagnostics 2021, 11, 444 14 of 14

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