- Email: [email protected]
Accuracy of three-dimensional ultrasound in diagnosis and classification of congenital uterine anomalies
TECHNIQUES AND INSTRUMENTATION Accuracy of three-dimensional ultrasound in diagnosis and classification of congenital uterine anomalies Tullio Ghi, M.D., Ph.D., Paolo Casadio, M.D., Marina Kuleva, M.D., Anna Myriam Perrone, M.D., Luca Savelli, M.D., Susanna Giunchi, M.D., Maria Cristina Meriggiola, M.D., Giampietro Gubbini, M.D., Gianluigi Pilu, Professor, Carla Pelusi, Professor, and Giuseppe Pelusi, Professor Department of Obstetrics and Gynecology, University Hospital of Bologna, Italy
Objective: To assess the accuracy of three-dimensional (3D) ultrasound in the diagnosis of congenital uterine anomalies. Design: Prospective study. Setting: University hospital. Patient(s): Nulliparae with three or more consecutive miscarriages. Intervention(s): All women underwent 3D transvaginal ultrasound study of the uterine cavity. Main Outcome Measure(s): Women with negative ultrasound findings subsequently underwent office hysteroscopy, whereas a combined laparoscopic-hysteroscopic assessment was performed in cases of suspected M€ ullerian anomaly. Result(s): A specific M€ullerian malformation was sonographically diagnosed in 54 women of the 284 included in the study group. All negative ultrasound findings were confirmed at office hysteroscopy. Among the women with abnormal ultrasound findings, the presence of a M€ ullerian anomaly was endoscopically confirmed in all. Concordance between ultrasound and endoscopy around the type of anomaly was verified in 52 cases, including all those with septate uterus and two out of three with bicornuate uterus. Conclusion(s): Volume transvaginal ultrasound appears to be extremely accurate for the diagnosis and classification of congenital uterine anomalies and may conveniently become the only mandatory step in the assessment of the uterine cavity in patients with a history of recurrent miscarriage. (Fertil Steril 2009;92:808–13. 2009 by American Society for Reproductive Medicine.) Key Words: Three-dimensional ultrasound, congenital uterine anomalies, recurrent miscarriage, office hysteroscopy and laparoscopy
M€ ullerian anomalies include a wide group of congenital uterine malformations whose prevalence in the general population is around 3%–4% (1, 2). Most of them are reported to increase the risk of infertility or adverse pregnancy outcome (2–6). The reproductive outcome and treatment options depend on the type of uterine malformation. As the most common classification of M€ ullerian anomalies is in accordance with either the external or internal morphology of the uterus (7), assessment of both is mandatory for a correct diagnosis of the type of malformation. Despite being invasive, a combined hysteroscopic and laparoscopic evaluation of uterine morphology and contour has traditionReceived January 16, 2008; revised May 22, 2008; accepted May 27, 2008; published online August 11, 2008. T.G. has nothing to disclose. P.C. has nothing to disclose. M.K. has nothing to disclose. A.M.P. has nothing to disclose. L.S. has nothing to disclose. S.G. has nothing to disclose. M.C.M. has nothing to disclose. G.G. has nothing to disclose. G.P. has nothing to disclose. C.P. has nothing to disclose. G.P. has nothing to disclose. Reprint requests: Tullio Ghi, M.D., I Clinica Ostetrica-Ginecologica, Policlinico S.Orsola-Malpighi, Via Massarenti, 13, 40100 Bologna (FAX: 39-051-636-4411; E-mail: [email protected]).
808
ally been the most widely used method in the differential diagnosis of M€ullerian malformations (8). Recently, thanks to the introduction of volume ultrasound, a comprehensive evaluation of uterine morphology has become feasible at transvaginal ultrasound (9). At volume ultrasound, both the external contours and internal morphology of the uterus may be displayed on the coronal plane, and the presence and type of uterine anomaly may be accurately detected. The purpose of this study was to evaluate in a selected group of women the accuracy of volume ultrasound in the diagnosis and classification of M€ullerian anomalies.
MATERIALS AND METHODS From January 2004 to December 2006, all women consecutively referred to our infertility clinic who were nulliparae with a history of recurrent miscarriage (three or more consecutive abortions by 12 weeks of gestation) were prospectively enrolled in the study and submitted to a volume ultrasound evaluation of the uterine cavity in the midluteal phase of the cycle. Patients were excluded if uterine fibroids or
Fertility and Sterility Vol. 92, No. 2, August 2009 Copyright ª2009 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/09/$36.00 doi:10.1016/j.fertnstert.2008.05.086
endometrial polyps were incidentally detected at ultrasound. For each patient, a control of uterine cavity by office hysteroscopy was arranged in the early follicular phase of the subsequent cycle. Hysteroscopy and ultrasound were performed by different operators (hysteroscopy by PC, ultrasound by TG) with selective competence for each technique. Ultrasound findings were not made available to the operator doing the hysteroscopy. Whenever a specific uterine malformation was sonographically diagnosed, a combined laparoscopichysteroscopic evaluation instead of office hysteroscopy was proposed to the patient and arranged within a month from ultrasound. The study was approved by the Institutional Review Board of our hospital. In addition, a signed declaration of no conflict of interest has been provided by all the authors involved in the study. Ultrasound scan was performed using a Voluson 730 Expert and a Voluson 730 Pro machine (GE, Milan, Italy) equipped with a multifrequency volume endovaginal probe. The insonation technique was standardized according to the following criteria: probe frequency set at 9 mHz, a midsagittal view of the uterus filling 75% of the screen, three-dimensional (3D) box size including the uterus from fundus to the cervix, sweep angle of 90 , and sweep velocity adjusted
to maximum quality. Each volume data set was stored on the hard disk of the ultrasound machine and made available for offline analysis by one of authors (TG or MK). As shown in Figure 1, the volume reconstruction technique was standardized according to the following criteria: the volume rendering box as narrow as possible in the sagittal plane and adjusted on the uterine corpus in the coronal plane, cut plane scrolled in anterior-posterior fashion with slice thickness set at 1 cm, transparency low (<50%), and volume rendering by a mix of surface and maximum mode. The analysis of uterine morphology was performed in a standardized reformatted section with the uterus in the coronal view using the interstitial portions of fallopian tubes as reference points. Specific ultrasound diagnosis of uterine anomalies was based on the classification system originally proposed by the American Fertility Society and subsequently modified according to 3D ultrasound landmarks (10) (Table 1). RESULTS During the study period, 312 nulliparae attending our center with a history of recurrent abortions were submitted to transvaginal volume ultrasound. In 28 cases, women were considered not eligible for the study owing to incidental detection of uterine fibroids (n ¼ 19) or endometrial polyps (n ¼ 9) at
FIGURE 1 Multiplanar imaging of a normal uterus at volume ultrasound: the volume rendering box is as narrow as possible in the sagittal plane (panel B) and adjusted on the uterine corpus in the coronal plane (panel A). A rendered image of the normal uterus on the coronal plane is displayed on panel D.
Ghi. 3D ultrasound in M€ ullerian anomalies. Fertil Steril 2009.
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TABLE 1 Classification of congenital uterine anomalies according to volume transvaginal ultrasound (10). Uterine morphology
Fundal contour
Normal
Straight or convex
Arcuate
Concave fundal indentation with central point of indentation at obtuse angle (>90 ) Presence of septum, which does not extend to cervix, with central point of septum at an acute angle (<90 ) Presence of uterine septum that that completely divides cavity from fundus to cervix Two well-formed uterine cornua
Subseptate
Septate
Bicornuate Unicornuate with or without rudimentary horn
External contour Uniformly convex or with indentation <10 mm Uniformly convex or with indentation <10 mm Uniformly convex or with indentation <10 mm Uniformly convex or with indentation <10 mm Fundal indentation >10 mm dividing the two cornua
Single well-formed uterine cavity with a single interstitial portion of Fallopian tube and concave fundal contour
Ghi. 3D ultrasound in M€ ullerian anomalies. Fertil Steril 2009.
ultrasound scan. The remaining 284 women agreed to participate in the study protocol. The median age of the patients was 34 years (range, 26–44), and their ethnicity was distributed as follows: Caucasian, n ¼ 272 (95.8%); Afrocaribbean, n ¼ 10 (3.5%); and Asian n ¼ 2 (0.7%). The quality of volume ultrasound was satisfactory in all cases. Offline analysis of uterine morphology was successfully carried out within 5 minutes in each case. A normal uterine cavity was demonstrated at ultrasound in 230 (81%) patients, whereas a specific diagnosis of uterine anomaly was sonographically performed in 54 cases (19%). Unicornuate uterus (one case) was sonographically diagnosed when an asymmetric laterally deviated uterine corpus of tubular shape with an accessory noncommunicating rudimental horn was demonstrated on the coronal plane. A single tubal ostium was detectable on this section. Bicornuate uterus (n ¼ 9) was sonographically diagnosed when two separated uterine cornua with external fundal indentation R10 mm dividing the cornua were demonstrated on the coronal plane (Fig. 2A). Septate uterus (n ¼ 35) was sonographically diagnosed when a septum dividing the endometrial cavity was demonstrated on the coronal plane and the external uterine surface was normal or showed a sagittal notch of <1 cm (Fig. 2B). Septate uterus was further classified as complete (n ¼ 14) or incomplete (subseptate uterus, n ¼ 21) as far as the septum itself bridged or did not bridge the fundus to the internal os of the uterine cervix. In subseptate uterus, the fundal indentation at the central point of the septum appeared as an acute angle (Fig. 2D). Arcuate uterus (n ¼ 9) was sonographically diagnosed when normal external uterine contour and concave fun810
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3D ultrasound in M€ullerian anomalies
dal indentation of the endometrial cavity were demonstrated on the coronal plane. In these cases, the fundal indentation at the central point appeared as an obtuse angle (Fig. 2C). After volume ultrasound, office hysteroscopy was performed in the 230 (81%) patients with negative ultrasound findings, and combined hysteroscopy-laparoscopy under general anesthesia was carried out in the 54 (19%) cases with a M€ullerian anomaly suspected at ultrasound. The diagnostic accuracy of 3D ultrasound is summarized in Table 2. All women with negative ultrasound findings showed normal uterine cavity at office hysteroscopy. A complete list of the 54 abnormal cases detected at ultrasound with the volume ultrasound diagnosis and corresponding findings subsequently achieved at endoscopy is provided in the table. At endoscopy, the presence of a M€ullerian anomaly was confirmed in all cases. Exact concordance between ultrasound and endoscopy around the type of anomaly was verified in 52 cases, including all those with septate uterus (partial and complete) and two out of three with bicornuate uterus. Ultrasound diagnosis proved inaccurate in two cases, including an arcuate and a bicornuate uterus that at endoscopy were, respectively, classified as a subseptate and a complete septate uterus. DISCUSSION Our data seem to confirm in a large series of cases that in a selected group of patients volume transvaginal ultrasound is extremely accurate for the diagnosis and classification of congenital uterine anomalies. All women sonographically classified as normal in fact showed no evidence of M€ ullerian anomaly at office hysteroscopy. On the other hand, in all patients sonographically classified as abnormal, a M€ ullerian Vol. 92, No. 2, August 2009
FIGURE 2 (A) Rendered image of a bicornuate uterus at volume ultrasound: on the coronal plane, two divergent cornua divided by a sagittal cleft >10 mm (arrow) are noted. (B) Rendered image of a septate uterus at volume ultrasound: on the coronal plane, a septum dividing the endometrial cavity and extending to the cervix with a normal external uterine surface is demonstrated. (C) Rendered image of an arcuate uterus at volume ultrasound: on the coronal plane, normal external uterine contour and concave fundal indentation of the endometrial cavity at obtuse angle are demonstrated. (D) Rendered image of a subseptate uterus at volume ultrasound: on the coronal plane, the septum is noted not to extend to the cervix, and fundal indentation at its central point appears as an acute angle.
Ghi. 3D ultrasound in M€ ullerian anomalies. Fertil Steril 2009.
anomaly was subsequently confirmed at combined hysteroscopy-laparoscopy. Furthermore, volume ultrasound proved highly valuable in suggesting the type of uterine anomaly, as ultrasound classification was endoscopically confirmed in 52 out of 54 abnormal cases (92.3%). Adequate ultrasound imaging of the uterine cavity was obtained within a few minutes in all cases. According to other investigators (11), all women with concurrent uterine abnormalities such as polyps or fibroids were excluded from the study group, so that only the effect of a malformation on the uterine cavity morphology was subjected to ultrasound evaluation. Owing to the excellent positive (96.3%) and negFertility and Sterility
ative predictive value (100%) registered in this series, volume ultrasound may be proposed as an accurate tool for detecting uterine anomalies in high-risk patients such as those with recurrent abortion. In this group, the option of office hysteroscopy has traditionally been considered as a mandatory step for uterine cavity assessment (12). Being an invasive technique, however, hysteroscopy may cause some discomfort to the patient, and even performed by expert hands, it is certainly more unpleasant than ultrasound for the patient. According to our data, in women with negative ultrasound findings, indication for hysteroscopy certainly becomes debatable, as it does not seem to improve the 811
TABLE 2 Comparison between ultrasound and endoscopic findings in the study group. Ultrasound diagnosis Normal uterus Unicornuate uterus Bicornuate uterus Septate uterus Subseptate uterus Arcuate uterus
n
Confirmed findings at endoscopy
Different findings at endoscopy
230 1 9 14 21 9
230 1 8 14 21 8
— — 1 (septate uterus) — — 1 (subseptate uterus)
Ghi. 3D ultrasound in M€ ullerian anomalies. Fertil Steril 2009.
sensitivity of volume ultrasound in detecting uterine anomalies. On the other hand, because of the high precision of volume ultrasound in characterizing uterine anomalies, women diagnosed with a specific malformation that may be treated by means of resectoscope may be conveniently addressed to an operative hysteroscopy rather than to a diagnostic endoscopic step. Owing to the high accuracy of 3D ultrasound for the diagnosis of bicornuate uterus, patients diagnosed with this condition can avoid further diagnostic steps, as operative hysteroscopy is not useful for treating such an abnormality. As mentioned above, in two of our cases, 3D ultrasound diagnosis proved to be inaccurate, and a specific comment on that is certainly required. In the first case, a woman with ultrasound suspicion of bicornuate uterus was endoscopically diagnosed as having a complete septate uterus. This is certainly a major mistake, but it was made at the beginning of the study when experience in volume reconstruction was still limited. The same volume data set has been subsequently reassessed by the same operator, and performing a volume reconstruction of the uterus on a different plane led to the correct ultrasound picture of a septate uterus. We believe that misdiagnosis was due to an incorrect angle of scrolling through the uterine fundus. In fact, if the section cut through the fundus of a septate uterus is not perpendicular to that due to an excessive rotation of the volume, a false impression of a cleft in the fundal contour compatible with the diagnosis of bicornuate uterus may be raised. The use of a combination of rendered and mutiplanar images in interpreting the pictures should make the differential diagnosis between the two conditions more accurate. In the second case, ultrasound diagnosis of arcuate uterus was endoscopically changed to subseptate uterus. This is a mild inaccuracy as a certain variability in distinguishing between these two forms of uterine anomalies is not uncommon even among experienced endoscopists because the diagnosis is based on subjective impression rather than on objective criteria. Furthermore, as far as the clinical management is concerned, patients with both arcuate and subseptate uteri with a history of recurrent miscarriage are usually treated by means of resectoscopic metroplasty, as was the case for our 812
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3D ultrasound in M€ullerian anomalies
patient. However, ultrasound impression of arcuate uterus has been possibly favored by the presence of synechiae at the level of tubal ostia due to repeated uterine curettages. Before metroplasty, synechiae have been hysteroscopically removed, and this has permitted a more reliable evaluation of fundal indentation. The use of volume ultrasound in the noninvasive diagnosis of uterine anomalies has been previously suggested. Most relevant studies have compared the accuracy of 3D ultrasound to laparoscopy supported by hysterosalpingography (13) or hysteroscopy (14), showing a high agreement between the different techniques. On the other hand, as demonstrated by other investigators (15), compared with conventional two-dimensional ultrasound, volume ultrasound has a higher specificity in detecting uterine anomalies. Furthermore, as reported by other investigators, the reproducibility of 3D ultrasound in the diagnosis and classification of congenital uterine anomalies is extremely high (16). In our study, all women were submitted at least to office hysteroscopy, which is considered the most valuable method to detect congenital anomalies of the uterine cavity (12). However, a combined hysteroscopic and laparoscopic evaluation has been proposed for all cases with abnormal findings at ultrasound. This policy has been judged reasonable to achieve in a single step the final diagnosis and, when indicated, the appropriate treatment. Some M€ullerian anomalies such as bicornuate or septate uterus in fact are not amenable to be differentiated at hysteroscopy only and may be confidently classified when laparoscopic view of the fundus is simultaneously available. Furthermore, when the diagnosis of uterine anomalies that may benefit from metroplasty is laparoscopically ascertained, under the external control of the fundus, resectoscopic surgery may be more safely undertaken. As shown by our series, M€ullerian anomalies may be detected and correctly classified by volume ultrasound thanks to its ability to provide a simultaneous reconstructed view of the internal and external surface of the uterus itself on the coronal plane. On this basis, women may be treated with a combined laparoscopic-hysteroscopic approach only when a curative step is clinically indicated and not for Vol. 92, No. 2, August 2009
diagnostic purposes as previously recommended. Furthermore, in cases with septate uterus undergoing metroplasty, the width of the septum or the thickness of the free uterine wall above the septum may be measured by volume ultrasound before surgery to make the resectopic procedure safer. In our study population, the prevalence of M€ ullerian anomalies is higher than what was reported in previous ultrasound series as one out of five patients turned out to be abnormal. However, among women with recurrent abortion, such a high prevalence of uterine anomalies had been previously documented (11, 12, 17). Accurate detection of uterine malformations in women with recurrent miscarriage is of critical importance since the clinical management and obstetric outcome of such patients are greatly influenced by the presence and type of the anomaly itself. In women with recurrent miscarriage who have a uterine malformation that may be surgically amended, the risk of a recurrent abortion or adverse perinatal outcome is dramatically decreased after metroplasty (6, 18–21). In contrast, in women with recurrent abortion, even discovering a M€ ullerian anomaly that is not treatable is clinically relevant, as this may provide a reasonable explanation of the infertility and may be looked at as a permanent risk factor for adverse pregnancy outcome and not simply as a miscarriage for the individual patient herself. In pregnant women with bicornuate uterus not experiencing first trimester miscarriage, the risks of preterm delivery, preeclampsia, or placental insufficiency (22) are reported to be significantly increased. In conclusion, our data demonstrate that volume transvaginal ultrasound is an accurate and simple method to detect and classify uterine M€ ullerian anomalies and should become the first diagnostic step in the assessment of the uterine cavity of patients with a history of recurrent miscarriage. REFERENCES 1. Simon C, Martinez L, Pardo F, Tortajada M, Pellicer A. Mullerian defects in women with normal reproductive outcome. Fertil Steril 1991;56: 1192–3. 2. Raga F, Bauset C, Remochi J, Bonilla-Musoles F, Simon C, Pellicer A. Reproductive impact of congenital Mullerian anomalies. Hum Reprod 1997;2:2277–81. 3. Buttram CV. Mullerian anomalies and their management. Fertil Steril 1983;40:159–63. 4. Golan A, Schneider D, Avrech O, Raziel A, Bukovsky I, Caspi E. Hysteroscopic findings after missed abortion. Fertil Steril 1992;58:508–10. 5. Acien P. Incidence of Mullerian defects in fertile and infertile women. Hum Reprod 1997;12:1372–6.
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6. Grimbizis G, Camus M, Clasen K, Tournaye H, De Munck L, Devroey P. Hysteroscopic septum resection in patients with recurrent abortions and infertility. Hum Reprod 1998;13:1188–93. 7. American Fertility Society. The American Fertility Society Classification of adnexal adhesions, distal tubal occlusion, distal tubal occlusion secondary to tubal ligation, tubal pregnancies. Mullerian anomalies and intrauterine adhesions. Fertil Steril 1988;49:944. 8. Fayez JA, Mutie G, Schneider PJ. The diagnostic value of hysterosalpingography and hysteroscopy in infertility investigation. Am J Obstet Gynecol 1987;156:558–60. 9. Jurkovic D, Aslam N. Three dimensional ultrasound for diagnosis of congenital uterine anomalies. In: Merz E, ed. 3-D Ultrasound in Obstetrics and Gynaecology. Philadelphia: Lippincott Williams & Wilkins, 1998: 27–9. 10. Woelfer B, Salim R, Banerjee S, Elson J, Regan L, Jurkovic D. Reproductive outcomes in women with congenital uterine anomalies detected by three-dimensional ultrasound screening. Obstet Gynecol 2001;98: 1099–103. 11. Salim R, Regan L, Woelfer B, Bacos M, Jurkovic D. A comparative study of the morphology of congenital uterine anomalies in women with and without a history of recurrent first trimester miscarriage. Hum Reprod 2003;18:162–6. 12. Raziel A, Arieli S, Bucovsky I, Caspi E, Golan A. Investigation of the uterine cavity in recurrent aborters. Fertil Steril 1994;62:1080–2. 13. Raga F, Bonilla-Musoles F, Blanes J, Osborne NG. Congenital Mullerian anomalies: diagnostic accuracy of three-dimensional ultrasound. Fertil Steril 1996;65:523–8. 14. Wu MH, Hsu CC, Huang KE. Detection of congenital mullerian duct anomalies using three-dimensional ultrasound. J Clin Ultrasound 1997;25:487–92. 15. Jurkovic D, Geipel A, Gruboeck K, Jauniaux E, Natucci M, Campbell S. Three-dimensional ultrasound for the assessment of uterine anatomy and detection of congenital anomalies: a comparison with hysterosalpingography and two-dimensional sonography. Ultrasound Obstet Gynecol 1995;5:233–7. 16. Salim R, Regan L, Woelfer B, Bacos M, Jurkovic D. Reproducibility of three-dimensional ultrasound diagnosis of congenital uterine anomalies. Ultrasound Obstet Gynecol 2003;21:578–82. 17. La Sala GB, Montanari R, Dessanti L, Ciqarini C, Sartori F. The role of diagnostic hysteroscopy and endometrial biopsy in assisted reproductive technologies. Fertil Steril 1998;70:378–80. 18. Grimbizis GF, Camus M, Tarlatzis BC, Bontis JN, Devroey P. Clinical implications of uterine malformations and hysteroscopic treatment results. Hum Reprod Update 2001;7:161–74. 19. Heinonen PK. Reproductive performance of women with uterine anomalies after abdominal or hysteroscopic metroplasty or no surgical treatment. J Am Assoc Gynecol Laparosc 1997;4:311–7. 20. Marabini A, Gubbini G, Stagnozzi R, Stefanetti M, Filoni M, Bovicelli A. Hysteroscopic metroplasty. Ann N Y Acad Sci 1994;734: 488–92. 21. Pace S, Cipriano L, Pace G, Catania R, Montanino G. Septate uterus: reproductive outcome after hysteroscopic metroplasty. Clin Exp Obstet Gynecol 2006;33:110–2. 22. Leible S, Munoz H, Walton R, Sabaj V, Cumsille F, Sepulveda W. Uterine artery blood flow velocity waveforms in pregnant women with Mullerian duct anomaly: a biologic model for utero-placental insufficiency. Am J Obstet Gynecol 1998;178:1048–53.
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Objective: To assess the accuracy of three-dimensional (3D) ultrasound in the diagnosis of congenital uterine anomalies. Design: Prospective study. Setting: University hospital. Patient(s): Nulliparae with three or more consecutive miscarriages. Intervention(s): All women underwent 3D transvaginal ultrasound study of the uterine cavity. Main Outcome Measure(s): Women with negative ultrasound findings subsequently underwent office hysteroscopy, whereas a combined laparoscopic-hysteroscopic assessment was performed in cases of suspected M€ ullerian anomaly. Result(s): A specific M€ullerian malformation was sonographically diagnosed in 54 women of the 284 included in the study group. All negative ultrasound findings were confirmed at office hysteroscopy. Among the women with abnormal ultrasound findings, the presence of a M€ ullerian anomaly was endoscopically confirmed in all. Concordance between ultrasound and endoscopy around the type of anomaly was verified in 52 cases, including all those with septate uterus and two out of three with bicornuate uterus. Conclusion(s): Volume transvaginal ultrasound appears to be extremely accurate for the diagnosis and classification of congenital uterine anomalies and may conveniently become the only mandatory step in the assessment of the uterine cavity in patients with a history of recurrent miscarriage. (Fertil Steril 2009;92:808–13. 2009 by American Society for Reproductive Medicine.) Key Words: Three-dimensional ultrasound, congenital uterine anomalies, recurrent miscarriage, office hysteroscopy and laparoscopy
M€ ullerian anomalies include a wide group of congenital uterine malformations whose prevalence in the general population is around 3%–4% (1, 2). Most of them are reported to increase the risk of infertility or adverse pregnancy outcome (2–6). The reproductive outcome and treatment options depend on the type of uterine malformation. As the most common classification of M€ ullerian anomalies is in accordance with either the external or internal morphology of the uterus (7), assessment of both is mandatory for a correct diagnosis of the type of malformation. Despite being invasive, a combined hysteroscopic and laparoscopic evaluation of uterine morphology and contour has traditionReceived January 16, 2008; revised May 22, 2008; accepted May 27, 2008; published online August 11, 2008. T.G. has nothing to disclose. P.C. has nothing to disclose. M.K. has nothing to disclose. A.M.P. has nothing to disclose. L.S. has nothing to disclose. S.G. has nothing to disclose. M.C.M. has nothing to disclose. G.G. has nothing to disclose. G.P. has nothing to disclose. C.P. has nothing to disclose. G.P. has nothing to disclose. Reprint requests: Tullio Ghi, M.D., I Clinica Ostetrica-Ginecologica, Policlinico S.Orsola-Malpighi, Via Massarenti, 13, 40100 Bologna (FAX: 39-051-636-4411; E-mail: [email protected]).
808
ally been the most widely used method in the differential diagnosis of M€ullerian malformations (8). Recently, thanks to the introduction of volume ultrasound, a comprehensive evaluation of uterine morphology has become feasible at transvaginal ultrasound (9). At volume ultrasound, both the external contours and internal morphology of the uterus may be displayed on the coronal plane, and the presence and type of uterine anomaly may be accurately detected. The purpose of this study was to evaluate in a selected group of women the accuracy of volume ultrasound in the diagnosis and classification of M€ullerian anomalies.
MATERIALS AND METHODS From January 2004 to December 2006, all women consecutively referred to our infertility clinic who were nulliparae with a history of recurrent miscarriage (three or more consecutive abortions by 12 weeks of gestation) were prospectively enrolled in the study and submitted to a volume ultrasound evaluation of the uterine cavity in the midluteal phase of the cycle. Patients were excluded if uterine fibroids or
Fertility and Sterility Vol. 92, No. 2, August 2009 Copyright ª2009 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/09/$36.00 doi:10.1016/j.fertnstert.2008.05.086
endometrial polyps were incidentally detected at ultrasound. For each patient, a control of uterine cavity by office hysteroscopy was arranged in the early follicular phase of the subsequent cycle. Hysteroscopy and ultrasound were performed by different operators (hysteroscopy by PC, ultrasound by TG) with selective competence for each technique. Ultrasound findings were not made available to the operator doing the hysteroscopy. Whenever a specific uterine malformation was sonographically diagnosed, a combined laparoscopichysteroscopic evaluation instead of office hysteroscopy was proposed to the patient and arranged within a month from ultrasound. The study was approved by the Institutional Review Board of our hospital. In addition, a signed declaration of no conflict of interest has been provided by all the authors involved in the study. Ultrasound scan was performed using a Voluson 730 Expert and a Voluson 730 Pro machine (GE, Milan, Italy) equipped with a multifrequency volume endovaginal probe. The insonation technique was standardized according to the following criteria: probe frequency set at 9 mHz, a midsagittal view of the uterus filling 75% of the screen, three-dimensional (3D) box size including the uterus from fundus to the cervix, sweep angle of 90 , and sweep velocity adjusted
to maximum quality. Each volume data set was stored on the hard disk of the ultrasound machine and made available for offline analysis by one of authors (TG or MK). As shown in Figure 1, the volume reconstruction technique was standardized according to the following criteria: the volume rendering box as narrow as possible in the sagittal plane and adjusted on the uterine corpus in the coronal plane, cut plane scrolled in anterior-posterior fashion with slice thickness set at 1 cm, transparency low (<50%), and volume rendering by a mix of surface and maximum mode. The analysis of uterine morphology was performed in a standardized reformatted section with the uterus in the coronal view using the interstitial portions of fallopian tubes as reference points. Specific ultrasound diagnosis of uterine anomalies was based on the classification system originally proposed by the American Fertility Society and subsequently modified according to 3D ultrasound landmarks (10) (Table 1). RESULTS During the study period, 312 nulliparae attending our center with a history of recurrent abortions were submitted to transvaginal volume ultrasound. In 28 cases, women were considered not eligible for the study owing to incidental detection of uterine fibroids (n ¼ 19) or endometrial polyps (n ¼ 9) at
FIGURE 1 Multiplanar imaging of a normal uterus at volume ultrasound: the volume rendering box is as narrow as possible in the sagittal plane (panel B) and adjusted on the uterine corpus in the coronal plane (panel A). A rendered image of the normal uterus on the coronal plane is displayed on panel D.
Ghi. 3D ultrasound in M€ ullerian anomalies. Fertil Steril 2009.
Fertility and Sterility
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TABLE 1 Classification of congenital uterine anomalies according to volume transvaginal ultrasound (10). Uterine morphology
Fundal contour
Normal
Straight or convex
Arcuate
Concave fundal indentation with central point of indentation at obtuse angle (>90 ) Presence of septum, which does not extend to cervix, with central point of septum at an acute angle (<90 ) Presence of uterine septum that that completely divides cavity from fundus to cervix Two well-formed uterine cornua
Subseptate
Septate
Bicornuate Unicornuate with or without rudimentary horn
External contour Uniformly convex or with indentation <10 mm Uniformly convex or with indentation <10 mm Uniformly convex or with indentation <10 mm Uniformly convex or with indentation <10 mm Fundal indentation >10 mm dividing the two cornua
Single well-formed uterine cavity with a single interstitial portion of Fallopian tube and concave fundal contour
Ghi. 3D ultrasound in M€ ullerian anomalies. Fertil Steril 2009.
ultrasound scan. The remaining 284 women agreed to participate in the study protocol. The median age of the patients was 34 years (range, 26–44), and their ethnicity was distributed as follows: Caucasian, n ¼ 272 (95.8%); Afrocaribbean, n ¼ 10 (3.5%); and Asian n ¼ 2 (0.7%). The quality of volume ultrasound was satisfactory in all cases. Offline analysis of uterine morphology was successfully carried out within 5 minutes in each case. A normal uterine cavity was demonstrated at ultrasound in 230 (81%) patients, whereas a specific diagnosis of uterine anomaly was sonographically performed in 54 cases (19%). Unicornuate uterus (one case) was sonographically diagnosed when an asymmetric laterally deviated uterine corpus of tubular shape with an accessory noncommunicating rudimental horn was demonstrated on the coronal plane. A single tubal ostium was detectable on this section. Bicornuate uterus (n ¼ 9) was sonographically diagnosed when two separated uterine cornua with external fundal indentation R10 mm dividing the cornua were demonstrated on the coronal plane (Fig. 2A). Septate uterus (n ¼ 35) was sonographically diagnosed when a septum dividing the endometrial cavity was demonstrated on the coronal plane and the external uterine surface was normal or showed a sagittal notch of <1 cm (Fig. 2B). Septate uterus was further classified as complete (n ¼ 14) or incomplete (subseptate uterus, n ¼ 21) as far as the septum itself bridged or did not bridge the fundus to the internal os of the uterine cervix. In subseptate uterus, the fundal indentation at the central point of the septum appeared as an acute angle (Fig. 2D). Arcuate uterus (n ¼ 9) was sonographically diagnosed when normal external uterine contour and concave fun810
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3D ultrasound in M€ullerian anomalies
dal indentation of the endometrial cavity were demonstrated on the coronal plane. In these cases, the fundal indentation at the central point appeared as an obtuse angle (Fig. 2C). After volume ultrasound, office hysteroscopy was performed in the 230 (81%) patients with negative ultrasound findings, and combined hysteroscopy-laparoscopy under general anesthesia was carried out in the 54 (19%) cases with a M€ullerian anomaly suspected at ultrasound. The diagnostic accuracy of 3D ultrasound is summarized in Table 2. All women with negative ultrasound findings showed normal uterine cavity at office hysteroscopy. A complete list of the 54 abnormal cases detected at ultrasound with the volume ultrasound diagnosis and corresponding findings subsequently achieved at endoscopy is provided in the table. At endoscopy, the presence of a M€ullerian anomaly was confirmed in all cases. Exact concordance between ultrasound and endoscopy around the type of anomaly was verified in 52 cases, including all those with septate uterus (partial and complete) and two out of three with bicornuate uterus. Ultrasound diagnosis proved inaccurate in two cases, including an arcuate and a bicornuate uterus that at endoscopy were, respectively, classified as a subseptate and a complete septate uterus. DISCUSSION Our data seem to confirm in a large series of cases that in a selected group of patients volume transvaginal ultrasound is extremely accurate for the diagnosis and classification of congenital uterine anomalies. All women sonographically classified as normal in fact showed no evidence of M€ ullerian anomaly at office hysteroscopy. On the other hand, in all patients sonographically classified as abnormal, a M€ ullerian Vol. 92, No. 2, August 2009
FIGURE 2 (A) Rendered image of a bicornuate uterus at volume ultrasound: on the coronal plane, two divergent cornua divided by a sagittal cleft >10 mm (arrow) are noted. (B) Rendered image of a septate uterus at volume ultrasound: on the coronal plane, a septum dividing the endometrial cavity and extending to the cervix with a normal external uterine surface is demonstrated. (C) Rendered image of an arcuate uterus at volume ultrasound: on the coronal plane, normal external uterine contour and concave fundal indentation of the endometrial cavity at obtuse angle are demonstrated. (D) Rendered image of a subseptate uterus at volume ultrasound: on the coronal plane, the septum is noted not to extend to the cervix, and fundal indentation at its central point appears as an acute angle.
Ghi. 3D ultrasound in M€ ullerian anomalies. Fertil Steril 2009.
anomaly was subsequently confirmed at combined hysteroscopy-laparoscopy. Furthermore, volume ultrasound proved highly valuable in suggesting the type of uterine anomaly, as ultrasound classification was endoscopically confirmed in 52 out of 54 abnormal cases (92.3%). Adequate ultrasound imaging of the uterine cavity was obtained within a few minutes in all cases. According to other investigators (11), all women with concurrent uterine abnormalities such as polyps or fibroids were excluded from the study group, so that only the effect of a malformation on the uterine cavity morphology was subjected to ultrasound evaluation. Owing to the excellent positive (96.3%) and negFertility and Sterility
ative predictive value (100%) registered in this series, volume ultrasound may be proposed as an accurate tool for detecting uterine anomalies in high-risk patients such as those with recurrent abortion. In this group, the option of office hysteroscopy has traditionally been considered as a mandatory step for uterine cavity assessment (12). Being an invasive technique, however, hysteroscopy may cause some discomfort to the patient, and even performed by expert hands, it is certainly more unpleasant than ultrasound for the patient. According to our data, in women with negative ultrasound findings, indication for hysteroscopy certainly becomes debatable, as it does not seem to improve the 811
TABLE 2 Comparison between ultrasound and endoscopic findings in the study group. Ultrasound diagnosis Normal uterus Unicornuate uterus Bicornuate uterus Septate uterus Subseptate uterus Arcuate uterus
n
Confirmed findings at endoscopy
Different findings at endoscopy
230 1 9 14 21 9
230 1 8 14 21 8
— — 1 (septate uterus) — — 1 (subseptate uterus)
Ghi. 3D ultrasound in M€ ullerian anomalies. Fertil Steril 2009.
sensitivity of volume ultrasound in detecting uterine anomalies. On the other hand, because of the high precision of volume ultrasound in characterizing uterine anomalies, women diagnosed with a specific malformation that may be treated by means of resectoscope may be conveniently addressed to an operative hysteroscopy rather than to a diagnostic endoscopic step. Owing to the high accuracy of 3D ultrasound for the diagnosis of bicornuate uterus, patients diagnosed with this condition can avoid further diagnostic steps, as operative hysteroscopy is not useful for treating such an abnormality. As mentioned above, in two of our cases, 3D ultrasound diagnosis proved to be inaccurate, and a specific comment on that is certainly required. In the first case, a woman with ultrasound suspicion of bicornuate uterus was endoscopically diagnosed as having a complete septate uterus. This is certainly a major mistake, but it was made at the beginning of the study when experience in volume reconstruction was still limited. The same volume data set has been subsequently reassessed by the same operator, and performing a volume reconstruction of the uterus on a different plane led to the correct ultrasound picture of a septate uterus. We believe that misdiagnosis was due to an incorrect angle of scrolling through the uterine fundus. In fact, if the section cut through the fundus of a septate uterus is not perpendicular to that due to an excessive rotation of the volume, a false impression of a cleft in the fundal contour compatible with the diagnosis of bicornuate uterus may be raised. The use of a combination of rendered and mutiplanar images in interpreting the pictures should make the differential diagnosis between the two conditions more accurate. In the second case, ultrasound diagnosis of arcuate uterus was endoscopically changed to subseptate uterus. This is a mild inaccuracy as a certain variability in distinguishing between these two forms of uterine anomalies is not uncommon even among experienced endoscopists because the diagnosis is based on subjective impression rather than on objective criteria. Furthermore, as far as the clinical management is concerned, patients with both arcuate and subseptate uteri with a history of recurrent miscarriage are usually treated by means of resectoscopic metroplasty, as was the case for our 812
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3D ultrasound in M€ullerian anomalies
patient. However, ultrasound impression of arcuate uterus has been possibly favored by the presence of synechiae at the level of tubal ostia due to repeated uterine curettages. Before metroplasty, synechiae have been hysteroscopically removed, and this has permitted a more reliable evaluation of fundal indentation. The use of volume ultrasound in the noninvasive diagnosis of uterine anomalies has been previously suggested. Most relevant studies have compared the accuracy of 3D ultrasound to laparoscopy supported by hysterosalpingography (13) or hysteroscopy (14), showing a high agreement between the different techniques. On the other hand, as demonstrated by other investigators (15), compared with conventional two-dimensional ultrasound, volume ultrasound has a higher specificity in detecting uterine anomalies. Furthermore, as reported by other investigators, the reproducibility of 3D ultrasound in the diagnosis and classification of congenital uterine anomalies is extremely high (16). In our study, all women were submitted at least to office hysteroscopy, which is considered the most valuable method to detect congenital anomalies of the uterine cavity (12). However, a combined hysteroscopic and laparoscopic evaluation has been proposed for all cases with abnormal findings at ultrasound. This policy has been judged reasonable to achieve in a single step the final diagnosis and, when indicated, the appropriate treatment. Some M€ullerian anomalies such as bicornuate or septate uterus in fact are not amenable to be differentiated at hysteroscopy only and may be confidently classified when laparoscopic view of the fundus is simultaneously available. Furthermore, when the diagnosis of uterine anomalies that may benefit from metroplasty is laparoscopically ascertained, under the external control of the fundus, resectoscopic surgery may be more safely undertaken. As shown by our series, M€ullerian anomalies may be detected and correctly classified by volume ultrasound thanks to its ability to provide a simultaneous reconstructed view of the internal and external surface of the uterus itself on the coronal plane. On this basis, women may be treated with a combined laparoscopic-hysteroscopic approach only when a curative step is clinically indicated and not for Vol. 92, No. 2, August 2009
diagnostic purposes as previously recommended. Furthermore, in cases with septate uterus undergoing metroplasty, the width of the septum or the thickness of the free uterine wall above the septum may be measured by volume ultrasound before surgery to make the resectopic procedure safer. In our study population, the prevalence of M€ ullerian anomalies is higher than what was reported in previous ultrasound series as one out of five patients turned out to be abnormal. However, among women with recurrent abortion, such a high prevalence of uterine anomalies had been previously documented (11, 12, 17). Accurate detection of uterine malformations in women with recurrent miscarriage is of critical importance since the clinical management and obstetric outcome of such patients are greatly influenced by the presence and type of the anomaly itself. In women with recurrent miscarriage who have a uterine malformation that may be surgically amended, the risk of a recurrent abortion or adverse perinatal outcome is dramatically decreased after metroplasty (6, 18–21). In contrast, in women with recurrent abortion, even discovering a M€ ullerian anomaly that is not treatable is clinically relevant, as this may provide a reasonable explanation of the infertility and may be looked at as a permanent risk factor for adverse pregnancy outcome and not simply as a miscarriage for the individual patient herself. In pregnant women with bicornuate uterus not experiencing first trimester miscarriage, the risks of preterm delivery, preeclampsia, or placental insufficiency (22) are reported to be significantly increased. In conclusion, our data demonstrate that volume transvaginal ultrasound is an accurate and simple method to detect and classify uterine M€ ullerian anomalies and should become the first diagnostic step in the assessment of the uterine cavity of patients with a history of recurrent miscarriage. REFERENCES 1. Simon C, Martinez L, Pardo F, Tortajada M, Pellicer A. Mullerian defects in women with normal reproductive outcome. Fertil Steril 1991;56: 1192–3. 2. Raga F, Bauset C, Remochi J, Bonilla-Musoles F, Simon C, Pellicer A. Reproductive impact of congenital Mullerian anomalies. Hum Reprod 1997;2:2277–81. 3. Buttram CV. Mullerian anomalies and their management. Fertil Steril 1983;40:159–63. 4. Golan A, Schneider D, Avrech O, Raziel A, Bukovsky I, Caspi E. Hysteroscopic findings after missed abortion. Fertil Steril 1992;58:508–10. 5. Acien P. Incidence of Mullerian defects in fertile and infertile women. Hum Reprod 1997;12:1372–6.
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