Original Article
Fundus Thickness Assessment by 3D Transvaginal Ultrasound Allows Metrics-Based Diagnosis and Treatment of Congenital Uterine Anomalies Die Fundusdickenmessung mittels 3D-Transvaginalsonografie ermöglicht eine metrische Diagnostik und Therapie kongenitaler uteriner Anomalien Authors
M. Bajka1, S. Badir2
Affiliations
1
Department OB/GYN, University Hospital Zurich, 8091 Zurich, Switzerland Institute of Mechanical Systems, Swiss Federal Institute of Technology Zurich, 8092 Zurich, Switzerland
Key words
Abstract
Zusammenfassung
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!
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Purpose: The development of a metric fundus assessment and definition of the uterine fundus thickness (FTH) for supporting objective diagnosis and treatment of congenital uterine anomalies (CUAs). Materials and Methods: A) In a prospective cohort study, FTH was systematically assessed by 3 D transvaginal ultrasound (TVS) in patients, who presented a normal uterus. B) The mean normal FTH recorded was applied to uteri with fundal protrusions and septations, and compared to two CUA classification systems (ASF and ESHRE/ESGE). C) FTH was studied for preoperative metric planning and evaluation of the postoperative outcome. Results: A) From August 2013 to January 2014, FTH was assessed in 100 normal uteri. An FTH of 12.02 +/- 2.03 mm (mean +/- SD) was recorded. B) Evaluating the 8 detected abnormal uteri, excellent correlation with the new ESHRE/ESGE classification system was observed, taking an FTH of 12 mm as the overall normal FTH equivalent to the individual normal wall thickness (WTH) stipulated in the classification and an FTH of 18 mm as the WTH + 50 %, serving as a cut-off value of (abnormal) septation. C) Metric fundus assessment was initially applied before and after septum resection and the following pregnancy could be monitored. Conclusion: An FTH measurement in 3 D TVS paves the way for metric fundus diagnostics. This objectively distinguishes normal from abnormal fundi. It also has the potential to support accurate septum resection planning and objective postoperative evaluation. The value of the fundus assessment and metrics proposed in this study is not known. It should be investigated in prospective randomized controlled trials.
Ziel: Entwicklung einer metrischen Beurteilung des uterinen Fundus mit Messung der uterinen Fundusdicke (FTH) zur Unterstützung einer objektiven Diagnostik und Therapie angeborener Uterusfehlbildungen (CUAs). Material und Methoden: A) In dieser prospektiven Kohortenstudie wurde bei Frauen mit normalem Uterus die FTH in der 3D-Transvaginalsonografie (TVS) standardisiert gemessen. B) Der erarbeitete FTH-Mittelwert wurde auf Uteri mit fundalen Protrusionen oder Septen angewendet und mit zwei CUA-Klassifikationen verglichen. C) Die FTH wurde als metrisches Instrument in der präoperativen Planung und Beurteilung des postoperativen Ergebnisses erstmalig untersucht. Ergebnisse: A) Von August 2013 bis Januar 2014 konnte die FTH an 100 normalen Uteri bestimmt werden. Sie maß 12,02 +/- 2,03 mm (mean +/- SD). B) In der Beurteilung der 8 entdeckten abnormalen Uteri wurde eine ausgezeichnete Übereinstimmung mit der ESHRE/ESGE Klassifikation gefunden, wenn 18 mm FTH (12 mm + 50 %) der ESHRE/ESGE-Regel individuelle Wanddicke (WTH) + 50 % gleich gesetzt und als Grenzwert zur Diagnose eines Septums angenommen wurde. C) In einem ersten Fall konnte die FTH-Messung vor und nach Septumresektion eingesetzt und die folgende Schwangerschaft begleitet werden. Schlussfolgerung: Die 3D-TVS-Messung der FTH eröffnet die metrische Fundusdiagnostik. Diese ermöglicht eine einfache und objektive Unterscheidung zwischen normalen und abnormalen Fundi. Sie besitzt zudem das Potential, eine exakte präoperative Planung einer Septumresektion durchzuführen und das operative Ergebnis objektiv zu beurteilen. Der Stellenwert der vorgestellten Messmethode wie auch der vorgeschlagenen Messgrößen ist nicht bekannt. Diese sollten in prospektiv randomisierten kontrollierten Studien überprüft werden.
● congenital uterine anomalies ● fundus thickness ● 3 D ultrasound ● hysteroscopy ● uterine septum resection " " " "
received accepted
4.9.2014 12.3.2015
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1399701 Published online: 2015 Ultraschall in Med © Georg Thieme Verlag KG Stuttgart · New York · ISSN 0172-4614 Correspondence Prof. Michael Bajka Department OB/GYN, University Hospital Zurich Frauenklinikstrasse 10 8091 Zurich Switzerland [email protected]
Bajka M, Badir S. Fundus Thickness Assessment … Ultraschall in Med
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2
Original Article
Introduction !
Methods !
A. In a prospective single center cohort study, starting August 2013, patients consecutively visiting our private OB/GYN office because of abnormal uterine bleeding, pain in the lower abdomen, sterility, infertility, or for a Levonorgestrel Containing Intrauterine System (LNG-IUS) (Mirena®, Bayer Healthcare Pharmaceutical, Germany) check-up underwent clinically indicated diagnostic TVS. Informed consent was obtained in accordance with the regulations set by the Ethics Committee of the Canton of Zurich on how to use medical images for scientific and teaching purposes. If the uterus appeared as a normal healthy organ with no congenital or acquired morphological pathology on ultrasound, it was deemed to contribute to the determination of normal FTH. We used a Voluson E8 ultrasound system (GE Medical System, Zipf, Austria) with an RIC5 – 9-D endocavitary volume transducer. FTH was measured by one investigator (MB) as fol" Fig. 1): A complete 3 D TVS representation of the uterine lows (● corpus and fundus, not necessarily showing the cervix as well,
Bajka M, Badir S. Fundus Thickness Assessment … Ultraschall in Med
Fig. 1 Three-dimensional transvaginal ultrasound for correct fundus thickness measurement (broad double arrow): exactly in the prolongation of the central cavity axis (line) from the inner myometrial border (endometrial-myometrial junction) to the outer border (myometrial-serosal junction). Inner interostial distance (thin double arrow). Abb. 1 3D-TVS zur korrekten Fundusdickenmessung (breiter Doppelpfeil): exakt in der Verlängerung der Zentralachse des Cavums (Linie) von der inneren Myometriumgrenze (Endometrium-Myometrium-Übergang) zur äußeren Myometriumgrenze (Myometrium-Serosa-Übergang). Innere interostiale Distanz (dünner Doppelpfeil).
was acquired as proposed by Bermejo [7]. In the plane which showed the complete cavity and the inner tubal openings, the FTH was captured strictly as part of the central axis through the cavity from the inner myometrial border to the outer border. B. In the next step, the aforementioned fundus assessment and the resulting overall normal FTH were used to assess uteri from the same time period but with pathological fundus protrusions or septations according to the ASF classification system [8], and to compare it to the new ESHRE/ESGE classification system [12]. C. Finally, in the case of HSR, FTH should be further investigated for its role in supporting preoperative planning and the postoperative evaluation of the result. Statistical analysis was performed with the statistical computing environment R: A Language and Environment for Statistical Computing, Open Source Software, 2012. Two-way anova analysis was used to test the effect of parity and LNG IUS status on FTH, parous women (P) versus nulliparous women (0P), and the LNG IUS carriers versus non-LNG IUS carriers. Model assumptions were checked in QQ-plots. Post-hoc tests were Bonferroni corrected.
Results !
A. By January 2014, FTH could be assessed in 100 examined premenopausal patients with a normal uterus according to the ESHRE/ESGE Genital Tract Anomalies (GTA) classification system (U0, no outer fundus indentation or inner fundus protrusion in more than 50 % of the wall thickness (WTH) individually defined as normal), 99 Caucasian and 1 Asian, from 18 to 51 years of age, presenting a body mass index between 18 and 42 kg/m^2. Neither an early day in the cycle nor other possible hormonal influences such as LNG IUS-induced endometrial suppression impeded fundus measurement. We found an FTH of 12.02 +/- 2.03 mm (mean +/- SD) in the entire study group, 12.95 +/- 1.90 mm in P, and 10.92 +/-1.86 mm in 0P. The minima, maxima, means and standard
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Congenital uterine anomalies (CUAs) are a common inborn pathology. They carry a significant potential to worsen pregnancy initiation and outcome. In a comprehensive review on 89 861 women in 94 observational studies, Chan et al. [1] found 5.5 % CUA prevalence in the normal population, 8.0 % in infertility, 13.3 % in miscarriage, and 24.5 % in women who had experienced both infertility and miscarriage. These data strongly support an earlier extensive review by Saravelos et al. [2]. Several studies have revealed septate and arcuate uteri followed by bicornuate uteri to be the dominant malformations in infertility and/or recurrent miscarriage [1 – 6], representing up to more than 90 % of all CUAs found [7]. However, the reported CUA prevalence and frequency depend greatly on the classification system used [8 – 12], the precise definition of the subclasses, and whether these were applied in the mind of the creators or were adapted by later investigators, together with which diagnostics were used. The most accurate diagnostics are thought to be combined hysteroscopy and laparoscopy, sonohysterography and, with huge potential, 3 D transvaginal ultrasound (TVS) [2, 7]. Sophisticated fundus diagnostics may lead to meaningful hysteroscopic septum resection (HSR), which has significantly improved fertility and pregnancy outcome [13, 14]. Grimbizis et al. [15] found a virtually restored term delivery rate (~75 %) when compared to a population without CUA (~80 %). Indeed, with regard to CUA class frequency, reproductive difficulties and possible improvement in pregnancy initiation and outcome, the strong myometrial layer in the fundus is the most therapeutically important region of the uterus. Since 1996, highresolution 3 D TVS has been investigated for use in CUA diagnosis, especially for assessing the fundus, and results have been consistently positive [3 – 5, 7, 16 – 20]. It may therefore be surprising to learn that there is currently no generally accepted metric fundus assessment, for normal anatomy, the classification of CUAs, or for corrective surgery, even though Letterie [21] proposed fundal measurement as a possible diagnostic aid many years ago. In this study, metric assessment and definition of the normal fundus thickness (FTH) by 3 D TVS is presented and its potential role in supporting CUA diagnosis and hysteroscopic fundus correction is highlighted.
Original Article
n
FTH μ +/– SD
p-value
[mm] all
100
12.02 +/–2.03
parous
55
12.95 +/–1.90
nulliparous
45
10.92 +/–1.86
FTH minima
FTH maxima
[mm]
[mm]
6.16
19.43
8.27
19.43
6.16
18.72
Table 1 Fundus thickness (FTH) measurements.
groups < 0.0001*
sub-groups according to parity P No-LNG-IUS
28
12.4 +/–1.90
P LNG-IUS
27
13.38 +/–1.89
0P No-LNG-IUS
35
10.90 +/–2.07
0P LNG-IUS
10
11.02 +/–1.34
1.08
8.27
17.48
10.48
19.43
6.16
18.72
5.4
8.04
13.74
8.27
17.48
< 0.0001*
6.16
18.72
10.48
19.43
8.04
13.74
sub-groups according to LNG IUS status P No-LNG-IUS
28
12.4 +/–1.90
0P No-LNG-IUS
35
10.90 +/–2.07
P LNG-IUS
27
13.38 +/–1.89
0P LNG-IUS
10
11.02 +/–1.34
0.02*
" Table 1. deviation for groups and sub-groups are presented in ● The two-factor analysis of variance showed that parity and LNG IUS status have a significant main effect, but there is no significant interaction between factors. Post hoc comparisons revealed that parity has a significant effect on FTH (regardless of the LNG IUS status), and LNG IUS status has no significant effect on FTH in the " Table 1). same parity group (P or 0P) (● B. Application of the proposed fundus assessment to all eight " Fig. 2) highCUAs detected using the ASF classification system (● lighted an excellent correlation between the FTH measurement and the new EHSRE/ESGE classification system taking a total FTH of 18 mm (12 mm + 50 %) as the cut-off value between normal uteri (U0) and septate uteri (U2, U3) [12]. In three cases, " Fig. 2f, g) or HSR was indicated due to recurrent miscarriage (● " Fig. 2 h). Two patients extreme preterm delivery at 27 weeks (● " Fig. 2f, h). In one of the underwent HSR in the study period (● " two cases undergoing surgery (● Fig. 2f), a pregnancy occurred immediately after the three-month mandatory waiting period. " Fig. 2f), based on the 3 D TVS, the surgeon (MB) C. In this case (● stipulated the need for the resection of a septum with a length of 13 mm. This led to a remaining FTH of 12 mm (total FTH of 25 mm " Fig. 3), which is in perfect accordance – septum of 13 mm) (● with the 12 mm normal FTH determined in this study. Based on " Fig. 4), we were able to confirm the onethe surgical outcome (● to-one transformation of preoperative planning in this case. Fortunately, we also had the opportunity to monitor the result in the " Fig. 5). patient’s next pregnancy (●
Discussion !
The advantages of 3 D TVS CUA diagnosis are multifold. They are mainly based on the following: imaging of the entire uterus with its inner and outer fundus contour; its sub-millimeter resolution; the easy access to the region of interest in 3 D regardless of the day in the cycle; the fact that it is well tolerated by the patients; the avoidance of narcosis for purely diagnostic purposes; the service from diagnosis to treatment offered by one doctor or clinic; the reliability of the measurement; and finally the correlation to MRI results [3 – 5, 7, 16 – 20]. There is undoubtedly a need for reasonable CUA diagnosis and classification as a basis for meaningful therapeutic approaches
with the restoration of anatomical conditions being the ultimate goal. The 1988 ASF (ASRM) CUA classification system [8] has been the gold standard for many years, not only for the majority of scientific work on CUA diagnosis, but also for therapeutic studies. Despite the huge acceptance gained, there are substantial inherent drawbacks, e. g. the normal uterus per se was not defined, and verbatim definitions of the outer or the inner fundus contour are completely missing for all classes. Only drawings exist, unfortunately leaving considerable scope for interpretation. Consequently, many studies rely on the same ASF classification, but differ substantially in their understanding of the fundus, thereby leading to reduced comparability of the results. The latest developments in the GTA classification arise from the ESHERE/ESGE [12]. The system comes with fundamental changes and innovations, such as the defining of the normal uterus and the abandoning of the very heterogeneously interpreted arcuate uterus. Smaller inner protrusions in up to 50 % of the individual wall thickness (WTH) are considered as normal (class U0). Only uteri with a septum of more than 50 % of the WTH are considered septate uteri (class U2 or U3). Since its publication in August 2013, we have successfully applied this new classification system, e. g. to clearly distinguish between normal uteri and CUA warranting cor" Table 2, " Fig. 6). Firstly, many minor insignificant interrection (● ● nal fundal protrusions are not diagnosed as arcuate uterus " Fig. 2a–c) and secondly, the septate uterus diagnosis can al(● ready be applied in situations where the cavity impression ends " Fig. 2d–e), not necessarily reaching the with an obtuse angle (● " Fig. 2f–h) [4, 21]. larger dimensions of an acute angle septum (● Unfortunately, this new classification system does not incorporate the high metric precision offered by 3 D TVS. ESHRE/ESGE [12] argue in favor of an individual determination of WTH on each uterus and work only with relative values. However, in the important septate uterus, abnormal protrusion is part of the median fundus, and cannot be separated from the normal myometrial layer. In this study, we included LNG IUS carriers to test the presence of LNG IUS as a geometrically well-known foreign body for its role in " Fig. 7c, d). On one hand, LNG IUS usually reducFTH assessment (● es the contrast between cavity and myometrium by thinning the endometrium over time. On the other hand, however, it clearly defines the inner fundus. However, LNG IUS status had no significant " Table 1). effect on FTH in the same parity group (P or 0P) (● Bajka M, Badir S. Fundus Thickness Assessment … Ultraschall in Med
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Mean (μ), standard deviation (SD), minima and maxima are presented for all groups and sub-groups. Data are grouped in parous (P) and nulliparous women (0P), into sub-groups of parous LNG IUS carriers (P LNG-IUS), nulliparous LNG IUS carriers (0P LNG-IUS), parous non-LNG IUS carriers (P No-LNG-IUS), and nulliparous non-LNG IUS carriers (0P No-LNG-IUS). Significant values are marked with * (p < 0.05).
Fig. 2 a–h The 8 CUAs in this study diagnosed using the AFS classification system presented in ascending order of FTH. The white lines with white circles at the ends mark an FTH of 18 mm, the proposed cut-off between normal and enlarged FTH. The broader section of the white line represents 12 mm, the mean FTH found in this study, also representing a potential anatomical goal in terms of hysteroscopic septum resection (HSR). D1 shows the inner interostial distance on the Trojano-McCarthy-Line (TML) ( " Fig. 6) [23], D2 the part of the FTH above the TML and D3 the part of the FTH below the TML. A comparison of FTH with the two classification systems [8, 12] shows an excellent correlation between the FTH measurement and the ESHRE/ESGE classification system, whereby the first 3 uteri a–c are diagnosed as normal, and uteri d–h as abnormal. In contrast, the ASF classification system already combines the first three uteri with the diagnosis arcuate uteri, and stays with this in cases 4 and 5 d, e with substantial septation due solely to its obtuse angle towards the cavity. Case 7 g was diagnosed as a bicorporeal septate uterus (U3c) based on the ESHRE/ESGE classification, opening the discussion as to whether this patient might not benefit from HSR, even if the ASF classification diagnosis of partial bicornuate uterus (IVb) is maintained. Case 8 h is presented with less contrast due to its thin endometrial layer during lactation and C-section scar.
●
Abb. 2 a–h Die 8 CUA dieser Studie nach ASF-Klassifikation, nach steigender FTH angeordnet. Die weiße Linie mit den Endpunkten markiert 18 mm FTH, den vorgeschlagenen Grenzwert zwischen normaler und verbreiteter FTH. Der breitere Anteil der weißen Linie zeigt 12 mm an, den Mittelwert für die FTH erarbeitet in dieser Studie. Er zeigt auch das mögliche anatomische Ziel bei der hysteroskopischen Septumresektion (HSR) an. D1 steht für die innere Distanz zwischen den Tubenwinkeln auf der Trojano-McCarthy-Linie (TML) (" Abb. 6) gelegen [23], D2 steht für den äußeren Anteil der FTH, D3 für den inneren Anteil. Der Vergleich der FTH mit den beiden Klassifikationen [8, 12] zeigt eine sehr gute Übereinstimmung mit der ESHRE/ESGE-Klassifikation, wobei die ersten 3 Uteri a–c als normal bezeichnet werden, d–h als abnormal. Im Gegensatz dazu bezeichnet die ASF-Klassifikation schon die ersten drei Uteri a–c als arcuatus, vergibt auch für den vierten und fünften Uterus d, e mit deutlicher, aber noch stumpfwinkliger Septumbildung dieselbe Diagnose. Der siebte Uterus g wurde durch die ESHRE/ESGE als bicorporeal septierter Uterus klassiert, womit die Diskussion nach Sinn und Möglichkeit einer HSR auch bei einem offensichtlichen Uterus bicornis nach ASF vorzunehmen, eröffnet wird. Der achte Fall h wird mit wenig Kontrast dargestellt, wozu der niedrige Aufbau des Endometriums in Stillzeit und die Narbe nach Sektio wesentlich beitragen.
●
Fig. 3 Preoperative planning for septum resection. a Two-dimensional median sagittal plane. b Threedimensional transvaginal rendered image. With a fundal thickness of 25 mm, 13 mm would be resected as a pathological septum leaving a normalized fundus thickness of 12 mm. Abb. 3 Präoperative Planung der Septumresektion. a 2D-TVS im medianen Sagittalschnitt. b 3D-TVS Nativbild. Von der gemessenen Fundusdicke von 25 mm sollen 13 mm pathologisches Septum reduziert werden, um die angestrebte „normalisierte“ Fundusdicke von 12 mm zu erreichen.
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Original Article
Original Article
Fig. 4 Postoperative evaluation after septum resection (same patient as " Fig. 3). a Two-dimensional median sagittal plane, new fundus thickness measures 12.3 mm. b Three-dimensional transvaginal image, new fundus thickness measures 13.5 mm. Both images show successful surgical implementation of preoperative planning.
●
Abb. 4 Postoperative Evaluation nach Septumresektion (gleiche Patientin wie " Abb. 3). a 2D medianer Sagittalschnitt, die neue Fundusdicke misst 12,3 mm. b 3D-TVS, die neue Fundusdicke misst 13,5 mm. Beide Bilder zeigen übereinstimmend eine erfolgreiche Umsetzung der geplanten Septumresektion.
Fig. 5 Comparison of the gravid uterus at 6 weeks of gestation before and after fundus correction (same patient as " Fig. 3, 4). a Before septum resection was performed – taken in patient’s 2nd pregnancy, which ended in miscarriage. b After fundus correction – taken in patient’s 3 rd pregnancy, which reached week 38 without any signs of preterm delivery.
●
Table 2 Attempt to correlate the ESGE classification with the metric fundus thickness (FTH) assessment and possible consequences.
EHSRE/ESGE
FTH
classification
assessment
possible consequences
U0 normal uterus
mean 12 mm, maxima 18 mm
no intervention
U2 septate uterus U3c bicorporeal septate uterus
> 18 mm
HSR, goal: new FTH of 12 mm (septum resection is completed) or resection level has reached the inner interostial line (flat inner fundus is achieved)
During hysteroscopic septum resection (HSR), we follow this simple rule to end the procedure when either the FTH is reduced to 12 mm (septum resection completed), or at most, when the resection level has reached the level of the inner interostial line (flat inner fundus achieved).
" Table 1). As We found 12 mm (mean) for FTH in normal uteri (● expected, the results show a significantly larger FTH in P than in 0P [22], but the difference between P (mean 12.94 mm) and 0P (mean 10.92 mm) is small and could be negligible from a clinical
Abb. 5 Vergleich desselben graviden Uterus bei jeweils sechs Schwangerschaftswochen vor und nach Septumresektion (dieselbe Patientin wie in " Abb. 3, 4). a Vor Septumresektion – aufgenommen in der zweiten Schwangerschaft der Patientin, welche in einem spontanen Abort endete. b Nach Septumresektion – aufgenommen in der dritten Schwangerschaft, in welcher die Patientin ohne Anzeichen für eine Frühgeburt die 38. Schwangerschaftswoche problemlos erreichte.
●
perspective. We assume that HSR may be carried out with an intraoperative precision of +/- 1 mm at best. Pragmatically, to work with 12 mm as an overall normal FTH could help facilitate preoperative planning and the calculation of the part of FTH defined as the pathological septum for resection (total FTH measured – " Table 2). Neverthe12 mm = length of septum to be resected) (● less, the ESHRE/ESGE GTA classification system [12] defines the normal uterus with up to 150 % of the individual WTH. If we combine our FTH metric results with the ESHRE/ESGE definitions ap" Fig. 2), the outer plied to the eight CUAs found in the study (● " Table 2). This is clearly limit of normal FTH can be set at 18 mm (● in line with the largest FTH of 19.43 mm, which we deemed to be normal in this study. Gubbini et al. [5] proposed an innovative approach using 3 D TVS to sub-classify uteri of ASF class V and VI [8]. They defined FTH as simply the part above the “intercornual distance” or “interostial line”, “using the interstitial portions of the Fallopian tubes as reference points”. However, we find it difficult to follow this definition, since in our 3 D TVS study, we were able to constantly describe the inner tubal angles, but were often unsure about the " Fig. 7b, d). Furcorrect position of the outer tubal openings (● thermore, the intramural portion of the Fallopian tubes, if detect-
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●
Fig. 6 Comparison of different classification systems on congenital uterine anomalies in a septate uterus. a The system proposed by Trojano and McCarthy 2004 [23] based on the 1988 ASF classification [8]. b The classification used in this study based on the ESHRE/ESGE GTA classification from 2013 [12]. The reference and starting line is the Trojano-McCarthy-Line (TML, red), connecting the inner tubal openings (white points), followed by an upward evaluation of the outer fundus contour (blue), then downwards to the inner contour (green), culminating in the classification of CUA. WTH = wall thickness.
Abb. 6 Vergleich zweier Klassifikationen angeborener Uterusfehlbildungen, dargestellt anhand eines Uterus subseptus. a Das von Trojano und McCarthy 2004 [23] vorgeschlagene Vorgehen, basierend auf der ASFKlassifikation [8] von 1988. b Die dieser Studie zugrunde liegende Klassifikation zu den Anomalien des Genitaltraktes der ESHRE/ESGE von 2013 [12]. Referenzlinie und Ausgangspunkt ist die Trojano-McCarthy-Linie (TML, rot), die die beiden Tubenwinkel (weiße Punkte) miteinander verbindet, gefolgt von der Lagebestimmung der äußeren Funduskontur (blau) und anschließend der inneren Funduskontur (grün). Beide Zuordnungsschritte führen schließlich zur jeweiligen Klassifikation der vorliegenden CUA. WTH = Wanddicke.
Fig. 7 Three–dimensional TVS image, not enhanced, to define tubal openings. a, c – Fundus showing only the inner tubal angles (arrows), c with LNG IUS in situ. b, d – Occasionally the complete intramural portion of both tubes might be followed through the myometrial layer up to the external tubal openings (arrows), d with LNG IUS in situ. Abb. 7 3D-TVS, Nativbild zur Visualisierung des intramuralen Tubenverlaufs. a, c Es können nur die inneren Tubenwinkel dargestellt werden (Pfeile), c mit LNG-IUS in situ. b, d Nur gelegentlich kann der vollständige intramurale Verlauf beider Tuben bis zu den äußeren Tubenöffnungen (Pfeile) dargestellt werden, d mit LNG-IUS in situ.
able, was always a line as opposed to a horn or a point. Based on their definition, Gubbini et al. [5] advise keeping the FTH at HSR to no less than 15 mm. However, for the complete FTH, we found 15 mm or more in only 10 % of normal uteri, meaning that Gubbi-
Bajka M, Badir S. Fundus Thickness Assessment … Ultraschall in Med
ni’s rule would obviously lead to a substantially less than anatomical correction of a uterus with a septum. In the case of the patient with a partial septate uterus (U2a) [12] " Fig. 2f, 3), postoperative 2 D and 3 D TVS undergoing HSR (●
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Original Article
" Fig. 4). Moreover, proved successful implementation of HSR (● following the metric approach, septum resection could be judged as complete, even if there was a clear remaining protrusion into the cavity, accentuated by the cavity horns reaching now the external tubal openings. Three months later, the patient became " Fig. 5). For the first time, she reached week 37 pregnant again (● under favorable conditions without any signs of preterm delivery and gave vaginal birth to a healthy child at term.
Conclusion !
In summary, despite the ongoing debate regarding the most appropriate CUA classification system, we believe that the new ESHRE/ESGE GTA classification system [12] represents a substantially improved basis for reasonable assignment to either normal or abnormal in terms of treatment or non-treatment. The 3 D TVS metric fundus assessment applied in this study led to the determination of 12 mm as a suitable overall normal FTH. This value could also serve as a targeted FTH upon HSR with an FTH of 18 mm as the cut-off between normal and septate uteri, qualifying for HSR. This assessment could represent the metric and therefore objective basis for the ESHRE/ESGE classification system. It also paves the way for metric preoperative planning and metric postoperative evaluation and therefore for supporting and optimizing HSR. The value of fundus assessment and metrics proposed in this study is not known. Hence it should be further investigated in prospective randomized controlled trials.
References 01 Chan YY, Jayaprakasan K, Zamora J et al. The prevalence of congenital uterine anomalies in unselected and high-risk populations: a systematic review. Human Reproduction Update 2011; 17: 761 – 771 02 Saravelos SH, Cocksedge KA, Li TC. Prevalence and diagnosis of congenital uterine anomalies in women with reproductive failure: a critical appraisal. Hum Reprod Update 2008; 14: 415 – 429 03 Woelfer B, Salim R, Banerjee S et al. Reproductive outcomes in women with congenital uterine anomalies detected by three-dimensional ultrasound screening. Obstet Gynecol 2001; 98: 1099 – 1103 04 Ghi T, Casadio P, Kuleva M et al. Accuracy of three-dimensional ultrasound in diagnosis and classification of congenital uterine anomalies. Fertil Steril 2009; 92: 808 – 813 05 Gubbini G, Di Spiezio Sardo A, Nascetti D et al. New outpatient subclassification system for American Fertility Society Classes V and VI uterine anomalies. J Minim Invasive Gynecol 2009; 16: 554 – 561 06 Ghi T, De Musso F, Maroni E et al. The pregnancy outcome in women with incidental diagnosis of septate uterus at first trimester scan. Hum Reprod 2012; 27: 2671 – 2675
07 Bermejo C, Martinez Ten P, Cantarero R et al. Three-dimensional ultrasound in the diagnosis of Müllerian duct anomalies and concordance with magnetic resonance imaging. Ultrasound Obstet Gynecol 2010; 35: 593 – 601 08 The American Fertility Society classifications of adnexal adhesions, distal tubal obstruction, tubal occlusion secondary to tubal ligation, tubal pregnancies, Mullerian anomalies and intrauterine adhesions. Fertil Steril 1988; 49: 944 – 955 09 Acien P, Acien M, Sanchez-Ferrer M. Complex malformations of the female genital tract. New Types and revision of classification. Hum Reprod 2004; 19: 2377 – 2384 10 Acien P, Acien M, Sanchez-Ferrer ML. Mullerian anomalies ‘‘without a classification’’: from the didelphys-unicollis uterus to the bicervical uterus with or without septate vagina. Fertil Steril 2009; 91: 2369 – 2375 11 Oppelt P, Renner SP, Brucker S et al. The VCUAM (Vagina Cervix Uterus Adnex-associated Malformation) classification: a new classification for genital malformations. Fertil Steril 2005; 84: 1493 – 1497 12 Grimbizis GF, Gordts S, Di Spiezio Sardo A et al. The ESHRE/ESGE consensus on the classification of female genital tract congenital anomalies. Hum Reprod 2013; 28: 2032 – 2044 13 Pabuçcu R, Gomel V. Reproductive outcome after hysteroscopic metroplasty in women with septate uterus and otherwise unexplained infertility. Fertil Steril 2004; 81: 1675 – 1678 14 Molle A, De Franciscis P, Colacurci N et al. Hysteroscopic resection of the septum improves the pregnancy rate of women with unexplained infertility: a prospective controlled trial. Fertil Steril 2009; 91: 2628 – 2631 15 Grimbizis GF, Camus M, Tarlatzis BC et al. Clinical implications of uterine malformations and hysteroscopic treatment results. Hum Reprod Update 2001; 7: 161 – 174 16 Raga F, Bonilla-Musoles F, Blanes J et al. Congenital Müllerian anomalies: diagnostic accuracy of three-dimensional ultrasound. Fertil Steril 1996; 65: 523 – 528 17 Wu MH, Hsu CC, Huang KE. Detection of congenital Müllerian duct anomalies using three-dimensional ultrasound. J Clin Ultrasound 1997; 25: 487 – 492 18 Letterie GS. Structural abnormalities and reproductive failure: Effective techniques of diagnosis and management. New York: Blackwell Science; 1998 19 Bermejo C, Martinez Ten P, Recio M et al. Three-dimensional ultrasound and magnetic resonance imaging assessment of cervix and vagina in women with uterine malformations. Ultrasound Obstet Gynecol 2014; 43: 336 – 345 20 Imboden S, Müller M, Raio L et al. Clinical significance of 3D ultrasound compared to MRI in uterine malformations. Ultraschall in Med 2014; 35: 440 – 444 21 Jayaprakasan K, Chan YY, Sur S et al. Prevalence of uterine anomalies and their impact on early pregnancy in women conceiving after assisted reproduction treatment. Ultrasound Obstet Gynecol 2011; 37: 727 – 732 22 Verguts J, Ameye L, Bourne T et al. Normative data for uterine size according to age and gravidity and possible role of the classical golden ratio. Ultrasound Obstet Gynecol 2013; 42: 713 – 717 23 Troiano R, McCarthy S. Mullerian duct anomalies: imaging and clinical issues. Radiology 2004; 233: 19 – 34
Bajka M, Badir S. Fundus Thickness Assessment … Ultraschall in Med
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Original Article
Fundus Thickness Assessment by 3D Transvaginal Ultrasound Allows Metrics-Based Diagnosis and Treatment of Congenital Uterine Anomalies Die Fundusdickenmessung mittels 3D-Transvaginalsonografie ermöglicht eine metrische Diagnostik und Therapie kongenitaler uteriner Anomalien Authors
M. Bajka1, S. Badir2
Affiliations
1
Department OB/GYN, University Hospital Zurich, 8091 Zurich, Switzerland Institute of Mechanical Systems, Swiss Federal Institute of Technology Zurich, 8092 Zurich, Switzerland
Key words
Abstract
Zusammenfassung
"
!
!
Purpose: The development of a metric fundus assessment and definition of the uterine fundus thickness (FTH) for supporting objective diagnosis and treatment of congenital uterine anomalies (CUAs). Materials and Methods: A) In a prospective cohort study, FTH was systematically assessed by 3 D transvaginal ultrasound (TVS) in patients, who presented a normal uterus. B) The mean normal FTH recorded was applied to uteri with fundal protrusions and septations, and compared to two CUA classification systems (ASF and ESHRE/ESGE). C) FTH was studied for preoperative metric planning and evaluation of the postoperative outcome. Results: A) From August 2013 to January 2014, FTH was assessed in 100 normal uteri. An FTH of 12.02 +/- 2.03 mm (mean +/- SD) was recorded. B) Evaluating the 8 detected abnormal uteri, excellent correlation with the new ESHRE/ESGE classification system was observed, taking an FTH of 12 mm as the overall normal FTH equivalent to the individual normal wall thickness (WTH) stipulated in the classification and an FTH of 18 mm as the WTH + 50 %, serving as a cut-off value of (abnormal) septation. C) Metric fundus assessment was initially applied before and after septum resection and the following pregnancy could be monitored. Conclusion: An FTH measurement in 3 D TVS paves the way for metric fundus diagnostics. This objectively distinguishes normal from abnormal fundi. It also has the potential to support accurate septum resection planning and objective postoperative evaluation. The value of the fundus assessment and metrics proposed in this study is not known. It should be investigated in prospective randomized controlled trials.
Ziel: Entwicklung einer metrischen Beurteilung des uterinen Fundus mit Messung der uterinen Fundusdicke (FTH) zur Unterstützung einer objektiven Diagnostik und Therapie angeborener Uterusfehlbildungen (CUAs). Material und Methoden: A) In dieser prospektiven Kohortenstudie wurde bei Frauen mit normalem Uterus die FTH in der 3D-Transvaginalsonografie (TVS) standardisiert gemessen. B) Der erarbeitete FTH-Mittelwert wurde auf Uteri mit fundalen Protrusionen oder Septen angewendet und mit zwei CUA-Klassifikationen verglichen. C) Die FTH wurde als metrisches Instrument in der präoperativen Planung und Beurteilung des postoperativen Ergebnisses erstmalig untersucht. Ergebnisse: A) Von August 2013 bis Januar 2014 konnte die FTH an 100 normalen Uteri bestimmt werden. Sie maß 12,02 +/- 2,03 mm (mean +/- SD). B) In der Beurteilung der 8 entdeckten abnormalen Uteri wurde eine ausgezeichnete Übereinstimmung mit der ESHRE/ESGE Klassifikation gefunden, wenn 18 mm FTH (12 mm + 50 %) der ESHRE/ESGE-Regel individuelle Wanddicke (WTH) + 50 % gleich gesetzt und als Grenzwert zur Diagnose eines Septums angenommen wurde. C) In einem ersten Fall konnte die FTH-Messung vor und nach Septumresektion eingesetzt und die folgende Schwangerschaft begleitet werden. Schlussfolgerung: Die 3D-TVS-Messung der FTH eröffnet die metrische Fundusdiagnostik. Diese ermöglicht eine einfache und objektive Unterscheidung zwischen normalen und abnormalen Fundi. Sie besitzt zudem das Potential, eine exakte präoperative Planung einer Septumresektion durchzuführen und das operative Ergebnis objektiv zu beurteilen. Der Stellenwert der vorgestellten Messmethode wie auch der vorgeschlagenen Messgrößen ist nicht bekannt. Diese sollten in prospektiv randomisierten kontrollierten Studien überprüft werden.
● congenital uterine anomalies ● fundus thickness ● 3 D ultrasound ● hysteroscopy ● uterine septum resection " " " "
received accepted
4.9.2014 12.3.2015
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1399701 Published online: 2015 Ultraschall in Med © Georg Thieme Verlag KG Stuttgart · New York · ISSN 0172-4614 Correspondence Prof. Michael Bajka Department OB/GYN, University Hospital Zurich Frauenklinikstrasse 10 8091 Zurich Switzerland [email protected]
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2
Original Article
Introduction !
Methods !
A. In a prospective single center cohort study, starting August 2013, patients consecutively visiting our private OB/GYN office because of abnormal uterine bleeding, pain in the lower abdomen, sterility, infertility, or for a Levonorgestrel Containing Intrauterine System (LNG-IUS) (Mirena®, Bayer Healthcare Pharmaceutical, Germany) check-up underwent clinically indicated diagnostic TVS. Informed consent was obtained in accordance with the regulations set by the Ethics Committee of the Canton of Zurich on how to use medical images for scientific and teaching purposes. If the uterus appeared as a normal healthy organ with no congenital or acquired morphological pathology on ultrasound, it was deemed to contribute to the determination of normal FTH. We used a Voluson E8 ultrasound system (GE Medical System, Zipf, Austria) with an RIC5 – 9-D endocavitary volume transducer. FTH was measured by one investigator (MB) as fol" Fig. 1): A complete 3 D TVS representation of the uterine lows (● corpus and fundus, not necessarily showing the cervix as well,
Bajka M, Badir S. Fundus Thickness Assessment … Ultraschall in Med
Fig. 1 Three-dimensional transvaginal ultrasound for correct fundus thickness measurement (broad double arrow): exactly in the prolongation of the central cavity axis (line) from the inner myometrial border (endometrial-myometrial junction) to the outer border (myometrial-serosal junction). Inner interostial distance (thin double arrow). Abb. 1 3D-TVS zur korrekten Fundusdickenmessung (breiter Doppelpfeil): exakt in der Verlängerung der Zentralachse des Cavums (Linie) von der inneren Myometriumgrenze (Endometrium-Myometrium-Übergang) zur äußeren Myometriumgrenze (Myometrium-Serosa-Übergang). Innere interostiale Distanz (dünner Doppelpfeil).
was acquired as proposed by Bermejo [7]. In the plane which showed the complete cavity and the inner tubal openings, the FTH was captured strictly as part of the central axis through the cavity from the inner myometrial border to the outer border. B. In the next step, the aforementioned fundus assessment and the resulting overall normal FTH were used to assess uteri from the same time period but with pathological fundus protrusions or septations according to the ASF classification system [8], and to compare it to the new ESHRE/ESGE classification system [12]. C. Finally, in the case of HSR, FTH should be further investigated for its role in supporting preoperative planning and the postoperative evaluation of the result. Statistical analysis was performed with the statistical computing environment R: A Language and Environment for Statistical Computing, Open Source Software, 2012. Two-way anova analysis was used to test the effect of parity and LNG IUS status on FTH, parous women (P) versus nulliparous women (0P), and the LNG IUS carriers versus non-LNG IUS carriers. Model assumptions were checked in QQ-plots. Post-hoc tests were Bonferroni corrected.
Results !
A. By January 2014, FTH could be assessed in 100 examined premenopausal patients with a normal uterus according to the ESHRE/ESGE Genital Tract Anomalies (GTA) classification system (U0, no outer fundus indentation or inner fundus protrusion in more than 50 % of the wall thickness (WTH) individually defined as normal), 99 Caucasian and 1 Asian, from 18 to 51 years of age, presenting a body mass index between 18 and 42 kg/m^2. Neither an early day in the cycle nor other possible hormonal influences such as LNG IUS-induced endometrial suppression impeded fundus measurement. We found an FTH of 12.02 +/- 2.03 mm (mean +/- SD) in the entire study group, 12.95 +/- 1.90 mm in P, and 10.92 +/-1.86 mm in 0P. The minima, maxima, means and standard
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Congenital uterine anomalies (CUAs) are a common inborn pathology. They carry a significant potential to worsen pregnancy initiation and outcome. In a comprehensive review on 89 861 women in 94 observational studies, Chan et al. [1] found 5.5 % CUA prevalence in the normal population, 8.0 % in infertility, 13.3 % in miscarriage, and 24.5 % in women who had experienced both infertility and miscarriage. These data strongly support an earlier extensive review by Saravelos et al. [2]. Several studies have revealed septate and arcuate uteri followed by bicornuate uteri to be the dominant malformations in infertility and/or recurrent miscarriage [1 – 6], representing up to more than 90 % of all CUAs found [7]. However, the reported CUA prevalence and frequency depend greatly on the classification system used [8 – 12], the precise definition of the subclasses, and whether these were applied in the mind of the creators or were adapted by later investigators, together with which diagnostics were used. The most accurate diagnostics are thought to be combined hysteroscopy and laparoscopy, sonohysterography and, with huge potential, 3 D transvaginal ultrasound (TVS) [2, 7]. Sophisticated fundus diagnostics may lead to meaningful hysteroscopic septum resection (HSR), which has significantly improved fertility and pregnancy outcome [13, 14]. Grimbizis et al. [15] found a virtually restored term delivery rate (~75 %) when compared to a population without CUA (~80 %). Indeed, with regard to CUA class frequency, reproductive difficulties and possible improvement in pregnancy initiation and outcome, the strong myometrial layer in the fundus is the most therapeutically important region of the uterus. Since 1996, highresolution 3 D TVS has been investigated for use in CUA diagnosis, especially for assessing the fundus, and results have been consistently positive [3 – 5, 7, 16 – 20]. It may therefore be surprising to learn that there is currently no generally accepted metric fundus assessment, for normal anatomy, the classification of CUAs, or for corrective surgery, even though Letterie [21] proposed fundal measurement as a possible diagnostic aid many years ago. In this study, metric assessment and definition of the normal fundus thickness (FTH) by 3 D TVS is presented and its potential role in supporting CUA diagnosis and hysteroscopic fundus correction is highlighted.
Original Article
n
FTH μ +/– SD
p-value
[mm] all
100
12.02 +/–2.03
parous
55
12.95 +/–1.90
nulliparous
45
10.92 +/–1.86
FTH minima
FTH maxima
[mm]
[mm]
6.16
19.43
8.27
19.43
6.16
18.72
Table 1 Fundus thickness (FTH) measurements.
groups < 0.0001*
sub-groups according to parity P No-LNG-IUS
28
12.4 +/–1.90
P LNG-IUS
27
13.38 +/–1.89
0P No-LNG-IUS
35
10.90 +/–2.07
0P LNG-IUS
10
11.02 +/–1.34
1.08
8.27
17.48
10.48
19.43
6.16
18.72
5.4
8.04
13.74
8.27
17.48
< 0.0001*
6.16
18.72
10.48
19.43
8.04
13.74
sub-groups according to LNG IUS status P No-LNG-IUS
28
12.4 +/–1.90
0P No-LNG-IUS
35
10.90 +/–2.07
P LNG-IUS
27
13.38 +/–1.89
0P LNG-IUS
10
11.02 +/–1.34
0.02*
" Table 1. deviation for groups and sub-groups are presented in ● The two-factor analysis of variance showed that parity and LNG IUS status have a significant main effect, but there is no significant interaction between factors. Post hoc comparisons revealed that parity has a significant effect on FTH (regardless of the LNG IUS status), and LNG IUS status has no significant effect on FTH in the " Table 1). same parity group (P or 0P) (● B. Application of the proposed fundus assessment to all eight " Fig. 2) highCUAs detected using the ASF classification system (● lighted an excellent correlation between the FTH measurement and the new EHSRE/ESGE classification system taking a total FTH of 18 mm (12 mm + 50 %) as the cut-off value between normal uteri (U0) and septate uteri (U2, U3) [12]. In three cases, " Fig. 2f, g) or HSR was indicated due to recurrent miscarriage (● " Fig. 2 h). Two patients extreme preterm delivery at 27 weeks (● " Fig. 2f, h). In one of the underwent HSR in the study period (● " two cases undergoing surgery (● Fig. 2f), a pregnancy occurred immediately after the three-month mandatory waiting period. " Fig. 2f), based on the 3 D TVS, the surgeon (MB) C. In this case (● stipulated the need for the resection of a septum with a length of 13 mm. This led to a remaining FTH of 12 mm (total FTH of 25 mm " Fig. 3), which is in perfect accordance – septum of 13 mm) (● with the 12 mm normal FTH determined in this study. Based on " Fig. 4), we were able to confirm the onethe surgical outcome (● to-one transformation of preoperative planning in this case. Fortunately, we also had the opportunity to monitor the result in the " Fig. 5). patient’s next pregnancy (●
Discussion !
The advantages of 3 D TVS CUA diagnosis are multifold. They are mainly based on the following: imaging of the entire uterus with its inner and outer fundus contour; its sub-millimeter resolution; the easy access to the region of interest in 3 D regardless of the day in the cycle; the fact that it is well tolerated by the patients; the avoidance of narcosis for purely diagnostic purposes; the service from diagnosis to treatment offered by one doctor or clinic; the reliability of the measurement; and finally the correlation to MRI results [3 – 5, 7, 16 – 20]. There is undoubtedly a need for reasonable CUA diagnosis and classification as a basis for meaningful therapeutic approaches
with the restoration of anatomical conditions being the ultimate goal. The 1988 ASF (ASRM) CUA classification system [8] has been the gold standard for many years, not only for the majority of scientific work on CUA diagnosis, but also for therapeutic studies. Despite the huge acceptance gained, there are substantial inherent drawbacks, e. g. the normal uterus per se was not defined, and verbatim definitions of the outer or the inner fundus contour are completely missing for all classes. Only drawings exist, unfortunately leaving considerable scope for interpretation. Consequently, many studies rely on the same ASF classification, but differ substantially in their understanding of the fundus, thereby leading to reduced comparability of the results. The latest developments in the GTA classification arise from the ESHERE/ESGE [12]. The system comes with fundamental changes and innovations, such as the defining of the normal uterus and the abandoning of the very heterogeneously interpreted arcuate uterus. Smaller inner protrusions in up to 50 % of the individual wall thickness (WTH) are considered as normal (class U0). Only uteri with a septum of more than 50 % of the WTH are considered septate uteri (class U2 or U3). Since its publication in August 2013, we have successfully applied this new classification system, e. g. to clearly distinguish between normal uteri and CUA warranting cor" Table 2, " Fig. 6). Firstly, many minor insignificant interrection (● ● nal fundal protrusions are not diagnosed as arcuate uterus " Fig. 2a–c) and secondly, the septate uterus diagnosis can al(● ready be applied in situations where the cavity impression ends " Fig. 2d–e), not necessarily reaching the with an obtuse angle (● " Fig. 2f–h) [4, 21]. larger dimensions of an acute angle septum (● Unfortunately, this new classification system does not incorporate the high metric precision offered by 3 D TVS. ESHRE/ESGE [12] argue in favor of an individual determination of WTH on each uterus and work only with relative values. However, in the important septate uterus, abnormal protrusion is part of the median fundus, and cannot be separated from the normal myometrial layer. In this study, we included LNG IUS carriers to test the presence of LNG IUS as a geometrically well-known foreign body for its role in " Fig. 7c, d). On one hand, LNG IUS usually reducFTH assessment (● es the contrast between cavity and myometrium by thinning the endometrium over time. On the other hand, however, it clearly defines the inner fundus. However, LNG IUS status had no significant " Table 1). effect on FTH in the same parity group (P or 0P) (● Bajka M, Badir S. Fundus Thickness Assessment … Ultraschall in Med
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Mean (μ), standard deviation (SD), minima and maxima are presented for all groups and sub-groups. Data are grouped in parous (P) and nulliparous women (0P), into sub-groups of parous LNG IUS carriers (P LNG-IUS), nulliparous LNG IUS carriers (0P LNG-IUS), parous non-LNG IUS carriers (P No-LNG-IUS), and nulliparous non-LNG IUS carriers (0P No-LNG-IUS). Significant values are marked with * (p < 0.05).
Fig. 2 a–h The 8 CUAs in this study diagnosed using the AFS classification system presented in ascending order of FTH. The white lines with white circles at the ends mark an FTH of 18 mm, the proposed cut-off between normal and enlarged FTH. The broader section of the white line represents 12 mm, the mean FTH found in this study, also representing a potential anatomical goal in terms of hysteroscopic septum resection (HSR). D1 shows the inner interostial distance on the Trojano-McCarthy-Line (TML) ( " Fig. 6) [23], D2 the part of the FTH above the TML and D3 the part of the FTH below the TML. A comparison of FTH with the two classification systems [8, 12] shows an excellent correlation between the FTH measurement and the ESHRE/ESGE classification system, whereby the first 3 uteri a–c are diagnosed as normal, and uteri d–h as abnormal. In contrast, the ASF classification system already combines the first three uteri with the diagnosis arcuate uteri, and stays with this in cases 4 and 5 d, e with substantial septation due solely to its obtuse angle towards the cavity. Case 7 g was diagnosed as a bicorporeal septate uterus (U3c) based on the ESHRE/ESGE classification, opening the discussion as to whether this patient might not benefit from HSR, even if the ASF classification diagnosis of partial bicornuate uterus (IVb) is maintained. Case 8 h is presented with less contrast due to its thin endometrial layer during lactation and C-section scar.
●
Abb. 2 a–h Die 8 CUA dieser Studie nach ASF-Klassifikation, nach steigender FTH angeordnet. Die weiße Linie mit den Endpunkten markiert 18 mm FTH, den vorgeschlagenen Grenzwert zwischen normaler und verbreiteter FTH. Der breitere Anteil der weißen Linie zeigt 12 mm an, den Mittelwert für die FTH erarbeitet in dieser Studie. Er zeigt auch das mögliche anatomische Ziel bei der hysteroskopischen Septumresektion (HSR) an. D1 steht für die innere Distanz zwischen den Tubenwinkeln auf der Trojano-McCarthy-Linie (TML) (" Abb. 6) gelegen [23], D2 steht für den äußeren Anteil der FTH, D3 für den inneren Anteil. Der Vergleich der FTH mit den beiden Klassifikationen [8, 12] zeigt eine sehr gute Übereinstimmung mit der ESHRE/ESGE-Klassifikation, wobei die ersten 3 Uteri a–c als normal bezeichnet werden, d–h als abnormal. Im Gegensatz dazu bezeichnet die ASF-Klassifikation schon die ersten drei Uteri a–c als arcuatus, vergibt auch für den vierten und fünften Uterus d, e mit deutlicher, aber noch stumpfwinkliger Septumbildung dieselbe Diagnose. Der siebte Uterus g wurde durch die ESHRE/ESGE als bicorporeal septierter Uterus klassiert, womit die Diskussion nach Sinn und Möglichkeit einer HSR auch bei einem offensichtlichen Uterus bicornis nach ASF vorzunehmen, eröffnet wird. Der achte Fall h wird mit wenig Kontrast dargestellt, wozu der niedrige Aufbau des Endometriums in Stillzeit und die Narbe nach Sektio wesentlich beitragen.
●
Fig. 3 Preoperative planning for septum resection. a Two-dimensional median sagittal plane. b Threedimensional transvaginal rendered image. With a fundal thickness of 25 mm, 13 mm would be resected as a pathological septum leaving a normalized fundus thickness of 12 mm. Abb. 3 Präoperative Planung der Septumresektion. a 2D-TVS im medianen Sagittalschnitt. b 3D-TVS Nativbild. Von der gemessenen Fundusdicke von 25 mm sollen 13 mm pathologisches Septum reduziert werden, um die angestrebte „normalisierte“ Fundusdicke von 12 mm zu erreichen.
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Original Article
Original Article
Fig. 4 Postoperative evaluation after septum resection (same patient as " Fig. 3). a Two-dimensional median sagittal plane, new fundus thickness measures 12.3 mm. b Three-dimensional transvaginal image, new fundus thickness measures 13.5 mm. Both images show successful surgical implementation of preoperative planning.
●
Abb. 4 Postoperative Evaluation nach Septumresektion (gleiche Patientin wie " Abb. 3). a 2D medianer Sagittalschnitt, die neue Fundusdicke misst 12,3 mm. b 3D-TVS, die neue Fundusdicke misst 13,5 mm. Beide Bilder zeigen übereinstimmend eine erfolgreiche Umsetzung der geplanten Septumresektion.
Fig. 5 Comparison of the gravid uterus at 6 weeks of gestation before and after fundus correction (same patient as " Fig. 3, 4). a Before septum resection was performed – taken in patient’s 2nd pregnancy, which ended in miscarriage. b After fundus correction – taken in patient’s 3 rd pregnancy, which reached week 38 without any signs of preterm delivery.
●
Table 2 Attempt to correlate the ESGE classification with the metric fundus thickness (FTH) assessment and possible consequences.
EHSRE/ESGE
FTH
classification
assessment
possible consequences
U0 normal uterus
mean 12 mm, maxima 18 mm
no intervention
U2 septate uterus U3c bicorporeal septate uterus
> 18 mm
HSR, goal: new FTH of 12 mm (septum resection is completed) or resection level has reached the inner interostial line (flat inner fundus is achieved)
During hysteroscopic septum resection (HSR), we follow this simple rule to end the procedure when either the FTH is reduced to 12 mm (septum resection completed), or at most, when the resection level has reached the level of the inner interostial line (flat inner fundus achieved).
" Table 1). As We found 12 mm (mean) for FTH in normal uteri (● expected, the results show a significantly larger FTH in P than in 0P [22], but the difference between P (mean 12.94 mm) and 0P (mean 10.92 mm) is small and could be negligible from a clinical
Abb. 5 Vergleich desselben graviden Uterus bei jeweils sechs Schwangerschaftswochen vor und nach Septumresektion (dieselbe Patientin wie in " Abb. 3, 4). a Vor Septumresektion – aufgenommen in der zweiten Schwangerschaft der Patientin, welche in einem spontanen Abort endete. b Nach Septumresektion – aufgenommen in der dritten Schwangerschaft, in welcher die Patientin ohne Anzeichen für eine Frühgeburt die 38. Schwangerschaftswoche problemlos erreichte.
●
perspective. We assume that HSR may be carried out with an intraoperative precision of +/- 1 mm at best. Pragmatically, to work with 12 mm as an overall normal FTH could help facilitate preoperative planning and the calculation of the part of FTH defined as the pathological septum for resection (total FTH measured – " Table 2). Neverthe12 mm = length of septum to be resected) (● less, the ESHRE/ESGE GTA classification system [12] defines the normal uterus with up to 150 % of the individual WTH. If we combine our FTH metric results with the ESHRE/ESGE definitions ap" Fig. 2), the outer plied to the eight CUAs found in the study (● " Table 2). This is clearly limit of normal FTH can be set at 18 mm (● in line with the largest FTH of 19.43 mm, which we deemed to be normal in this study. Gubbini et al. [5] proposed an innovative approach using 3 D TVS to sub-classify uteri of ASF class V and VI [8]. They defined FTH as simply the part above the “intercornual distance” or “interostial line”, “using the interstitial portions of the Fallopian tubes as reference points”. However, we find it difficult to follow this definition, since in our 3 D TVS study, we were able to constantly describe the inner tubal angles, but were often unsure about the " Fig. 7b, d). Furcorrect position of the outer tubal openings (● thermore, the intramural portion of the Fallopian tubes, if detect-
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●
Fig. 6 Comparison of different classification systems on congenital uterine anomalies in a septate uterus. a The system proposed by Trojano and McCarthy 2004 [23] based on the 1988 ASF classification [8]. b The classification used in this study based on the ESHRE/ESGE GTA classification from 2013 [12]. The reference and starting line is the Trojano-McCarthy-Line (TML, red), connecting the inner tubal openings (white points), followed by an upward evaluation of the outer fundus contour (blue), then downwards to the inner contour (green), culminating in the classification of CUA. WTH = wall thickness.
Abb. 6 Vergleich zweier Klassifikationen angeborener Uterusfehlbildungen, dargestellt anhand eines Uterus subseptus. a Das von Trojano und McCarthy 2004 [23] vorgeschlagene Vorgehen, basierend auf der ASFKlassifikation [8] von 1988. b Die dieser Studie zugrunde liegende Klassifikation zu den Anomalien des Genitaltraktes der ESHRE/ESGE von 2013 [12]. Referenzlinie und Ausgangspunkt ist die Trojano-McCarthy-Linie (TML, rot), die die beiden Tubenwinkel (weiße Punkte) miteinander verbindet, gefolgt von der Lagebestimmung der äußeren Funduskontur (blau) und anschließend der inneren Funduskontur (grün). Beide Zuordnungsschritte führen schließlich zur jeweiligen Klassifikation der vorliegenden CUA. WTH = Wanddicke.
Fig. 7 Three–dimensional TVS image, not enhanced, to define tubal openings. a, c – Fundus showing only the inner tubal angles (arrows), c with LNG IUS in situ. b, d – Occasionally the complete intramural portion of both tubes might be followed through the myometrial layer up to the external tubal openings (arrows), d with LNG IUS in situ. Abb. 7 3D-TVS, Nativbild zur Visualisierung des intramuralen Tubenverlaufs. a, c Es können nur die inneren Tubenwinkel dargestellt werden (Pfeile), c mit LNG-IUS in situ. b, d Nur gelegentlich kann der vollständige intramurale Verlauf beider Tuben bis zu den äußeren Tubenöffnungen (Pfeile) dargestellt werden, d mit LNG-IUS in situ.
able, was always a line as opposed to a horn or a point. Based on their definition, Gubbini et al. [5] advise keeping the FTH at HSR to no less than 15 mm. However, for the complete FTH, we found 15 mm or more in only 10 % of normal uteri, meaning that Gubbi-
Bajka M, Badir S. Fundus Thickness Assessment … Ultraschall in Med
ni’s rule would obviously lead to a substantially less than anatomical correction of a uterus with a septum. In the case of the patient with a partial septate uterus (U2a) [12] " Fig. 2f, 3), postoperative 2 D and 3 D TVS undergoing HSR (●
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" Fig. 4). Moreover, proved successful implementation of HSR (● following the metric approach, septum resection could be judged as complete, even if there was a clear remaining protrusion into the cavity, accentuated by the cavity horns reaching now the external tubal openings. Three months later, the patient became " Fig. 5). For the first time, she reached week 37 pregnant again (● under favorable conditions without any signs of preterm delivery and gave vaginal birth to a healthy child at term.
Conclusion !
In summary, despite the ongoing debate regarding the most appropriate CUA classification system, we believe that the new ESHRE/ESGE GTA classification system [12] represents a substantially improved basis for reasonable assignment to either normal or abnormal in terms of treatment or non-treatment. The 3 D TVS metric fundus assessment applied in this study led to the determination of 12 mm as a suitable overall normal FTH. This value could also serve as a targeted FTH upon HSR with an FTH of 18 mm as the cut-off between normal and septate uteri, qualifying for HSR. This assessment could represent the metric and therefore objective basis for the ESHRE/ESGE classification system. It also paves the way for metric preoperative planning and metric postoperative evaluation and therefore for supporting and optimizing HSR. The value of fundus assessment and metrics proposed in this study is not known. Hence it should be further investigated in prospective randomized controlled trials.
References 01 Chan YY, Jayaprakasan K, Zamora J et al. The prevalence of congenital uterine anomalies in unselected and high-risk populations: a systematic review. Human Reproduction Update 2011; 17: 761 – 771 02 Saravelos SH, Cocksedge KA, Li TC. Prevalence and diagnosis of congenital uterine anomalies in women with reproductive failure: a critical appraisal. Hum Reprod Update 2008; 14: 415 – 429 03 Woelfer B, Salim R, Banerjee S et al. Reproductive outcomes in women with congenital uterine anomalies detected by three-dimensional ultrasound screening. Obstet Gynecol 2001; 98: 1099 – 1103 04 Ghi T, Casadio P, Kuleva M et al. Accuracy of three-dimensional ultrasound in diagnosis and classification of congenital uterine anomalies. Fertil Steril 2009; 92: 808 – 813 05 Gubbini G, Di Spiezio Sardo A, Nascetti D et al. New outpatient subclassification system for American Fertility Society Classes V and VI uterine anomalies. J Minim Invasive Gynecol 2009; 16: 554 – 561 06 Ghi T, De Musso F, Maroni E et al. The pregnancy outcome in women with incidental diagnosis of septate uterus at first trimester scan. Hum Reprod 2012; 27: 2671 – 2675
07 Bermejo C, Martinez Ten P, Cantarero R et al. Three-dimensional ultrasound in the diagnosis of Müllerian duct anomalies and concordance with magnetic resonance imaging. Ultrasound Obstet Gynecol 2010; 35: 593 – 601 08 The American Fertility Society classifications of adnexal adhesions, distal tubal obstruction, tubal occlusion secondary to tubal ligation, tubal pregnancies, Mullerian anomalies and intrauterine adhesions. Fertil Steril 1988; 49: 944 – 955 09 Acien P, Acien M, Sanchez-Ferrer M. Complex malformations of the female genital tract. New Types and revision of classification. Hum Reprod 2004; 19: 2377 – 2384 10 Acien P, Acien M, Sanchez-Ferrer ML. Mullerian anomalies ‘‘without a classification’’: from the didelphys-unicollis uterus to the bicervical uterus with or without septate vagina. Fertil Steril 2009; 91: 2369 – 2375 11 Oppelt P, Renner SP, Brucker S et al. The VCUAM (Vagina Cervix Uterus Adnex-associated Malformation) classification: a new classification for genital malformations. Fertil Steril 2005; 84: 1493 – 1497 12 Grimbizis GF, Gordts S, Di Spiezio Sardo A et al. The ESHRE/ESGE consensus on the classification of female genital tract congenital anomalies. Hum Reprod 2013; 28: 2032 – 2044 13 Pabuçcu R, Gomel V. Reproductive outcome after hysteroscopic metroplasty in women with septate uterus and otherwise unexplained infertility. Fertil Steril 2004; 81: 1675 – 1678 14 Molle A, De Franciscis P, Colacurci N et al. Hysteroscopic resection of the septum improves the pregnancy rate of women with unexplained infertility: a prospective controlled trial. Fertil Steril 2009; 91: 2628 – 2631 15 Grimbizis GF, Camus M, Tarlatzis BC et al. Clinical implications of uterine malformations and hysteroscopic treatment results. Hum Reprod Update 2001; 7: 161 – 174 16 Raga F, Bonilla-Musoles F, Blanes J et al. Congenital Müllerian anomalies: diagnostic accuracy of three-dimensional ultrasound. Fertil Steril 1996; 65: 523 – 528 17 Wu MH, Hsu CC, Huang KE. Detection of congenital Müllerian duct anomalies using three-dimensional ultrasound. J Clin Ultrasound 1997; 25: 487 – 492 18 Letterie GS. Structural abnormalities and reproductive failure: Effective techniques of diagnosis and management. New York: Blackwell Science; 1998 19 Bermejo C, Martinez Ten P, Recio M et al. Three-dimensional ultrasound and magnetic resonance imaging assessment of cervix and vagina in women with uterine malformations. Ultrasound Obstet Gynecol 2014; 43: 336 – 345 20 Imboden S, Müller M, Raio L et al. Clinical significance of 3D ultrasound compared to MRI in uterine malformations. Ultraschall in Med 2014; 35: 440 – 444 21 Jayaprakasan K, Chan YY, Sur S et al. Prevalence of uterine anomalies and their impact on early pregnancy in women conceiving after assisted reproduction treatment. Ultrasound Obstet Gynecol 2011; 37: 727 – 732 22 Verguts J, Ameye L, Bourne T et al. Normative data for uterine size according to age and gravidity and possible role of the classical golden ratio. Ultrasound Obstet Gynecol 2013; 42: 713 – 717 23 Troiano R, McCarthy S. Mullerian duct anomalies: imaging and clinical issues. Radiology 2004; 233: 19 – 34
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