Sonographic diagnosis of adenomyosis-ultrasound that cried wolf?

The presence of adenomyosis is traditionally confirmed by histopathologic examination of the uterine specimen. Today, it could be diagnosed by magnetic resonance imaging or ultrasound. Ultrasound diagnosis was previously less precise. However, with the advances in ultrasound technology including 3 dimensional ultrasound, the specificity and sensitivity of ultrasound to diagnose adenomyosis have increased. In addition, it has led to an clear increase in the prevalence of adenomyosis. In 2018, Van den Bosch et al. (1Harmsen M.J. Van den Bosch T. de Leeuw R.A. Dueholm M. Exacoustos C. Valentin L. et al.Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis: results of modified Delphi procedure.Ultrasound Obstet Gynecol. 2022; 60: 118-131Crossref PubMed Scopus (39) Google Scholar) published a sonographic classification and reporting system, based on the consensus opinion of experts, for diagnosing adenomyosis using the Morphological Uterus Sonographic Assessment (MUSA) criteria. This reporting system includes features characteristic of adenomyosis including an enlarged globular uterus, asymmetrical thickening of the myometrium, myometrial cysts, echogenic subendometrial lines and buds, hyperechogenic islands, fan-shaped shadowing, an irregular or interrupted junctional zone, and translesional vascularity on color Doppler ultrasound examination. Such a system was meant to facilitate studies on the prevalence and clinical implications of adenomyosis as well as on the effectiveness of therapy. The investigators rightfully stated that it cannot be used alone to decide on treatment but rather needs to be validated in future studies evaluating the relationship between the sonographic features and the clinical outcomes. Subsequently, the investigators revised their criteria (1Harmsen M.J. Van den Bosch T. de Leeuw R.A. Dueholm M. Exacoustos C. Valentin L. et al.Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis: results of modified Delphi procedure.Ultrasound Obstet Gynecol. 2022; 60: 118-131Crossref PubMed Scopus (39) Google Scholar). The most important update in the revised version is the classifications of sonographic findings into direct (such as cysts in the endometrium and hyperechogenic islands) and indirect features (such as globular uterus and irregular or interrupted junctional zone), acknowledging that in the absence of intramyometrial abnormalities, indirect features are not conclusive for the presence of adenomyosis. In this issue of Fertility & Sterility, Dason et al. (2Dason E.S. Maxim M. Hartman A. Li Q. Kanji S. Li T. et al.Pregnancy outcomes with donor oocyte embryos in patients diagnosed with adenomyosis using the Morphological Uterus Sonographic Assessment (MUSA) criteria.Fertil Steril. 2023; 119: 484-489Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar) retrospectively evaluated the pregnancy outcome of in vitro fertilization (IVF) treatment using donor oocytes in patients with adenomyosis and reported that “ultrasound features of adenomyosis may not be significant in impacting reproductive outcome (2Dason E.S. Maxim M. Hartman A. Li Q. Kanji S. Li T. et al.Pregnancy outcomes with donor oocyte embryos in patients diagnosed with adenomyosis using the Morphological Uterus Sonographic Assessment (MUSA) criteria.Fertil Steril. 2023; 119: 484-489Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar).” The investigators should be applauded for using donor oocytes recipients as the study group, thus focusing on the uterine factor effects adenomyosis might have. In their study, the clinical outcomes of 100 donor oocyte recipient patients receiving 223 embryo transfers were compared. They divided the patients into 3 groups; no adenomyosis, 1 feature, and ≥2 ultrasound features. Adenomyosis was initially diagnosed in 22 patients. Using the MUSA criteria, the number of patients with adenomyosis increased to 69. Over three quarters of patients had one feature specifically, disruption of the junctional zone. Seven patients exhibited one feature only. Whether one feature only is sufficient to diagnose adenomyosis is questionable. Xholly et al. (3Younes G. Tulandi T. Effects of adenomyosis on in vitro fertilization treatment outcomes: a meta-analysis.Fertil Steril. 2017; 108: 483-490.e3Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar) stated that the presence of ≥2 features are necessary for the diagnosis of adenomyosis. The number of ultrasound features is related to age as well as the severity of adenomyosis symptoms. In addition, increase in the number of reported features is associated with reduction in IVF success rate. Apart from the presence of a focal lesion which was associated with a decrease in the odds of live birth, no other sonographic finding was associated with a reduction in live birth. The outcome of first embryo transfer including the number of live births was independent on the number of ultrasound features. Earlier reports comparing the impact of focal versus diffuse adenomyosis on reproductive outcome have been mixed. Another factor that has to be considered is the possible concomitant endometriosis in those patients. Previous studies and meta-analyses have shown deleterious effect of adenomyosis on IVF outcome (4Cozzolino M. Tartaglia S. Pellegrini L. Troiano G. Rizzo G. Petraglia F. The effect of uterine adenomyosis on IVF outcomes: a systematic review and meta-analysis.Reprod Sci. 2022; 29: 3177-3193Crossref PubMed Scopus (15) Google Scholar, 5Xholli A. Scovazzi U. Londero A.P. Evangelisti G. Cavalli E. Schiaffino M.G. et al.Angle of uterine flexion and adenomyosis.J Clin Med. 2022; 11: 3214Crossref PubMed Scopus (2) Google Scholar). It is possible that Dason et al. (2Dason E.S. Maxim M. Hartman A. Li Q. Kanji S. Li T. et al.Pregnancy outcomes with donor oocyte embryos in patients diagnosed with adenomyosis using the Morphological Uterus Sonographic Assessment (MUSA) criteria.Fertil Steril. 2023; 119: 484-489Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar), included cases with “minimal adenomyosis” that did not impact the IVF outcomes. Further, it was a retrospective study with its inherent limitation, the number of cases was relatively small, they included either fresh or frozen embryos and the diagnosis was based on a single baseline 2 dimensional ultrasound. Their study and others showed that the average age of patients was 40. In Aesop’s fable “The boy who cried wolf,” a shepherd boy repeatedly fools villagers into thinking a wolf is attacking his town’s flock. When an actual wolf appears and the boy calls for help, the villagers believe that it is another false alarm, and the sheep are eaten by the wolf. This tale illustrates what a type 1 statistical error resulting in overdiagnosis might cause. Believing the boy every time would result in a waste of resources. Defining every infertile patient with adenomyosis based on the MUSA criteria might result in unnecessary treatment, possibly neglecting other potential diagnosis that could have resulted in treatment failure and not less important in patients’ distress. This study, for the first time, assesses the clinical relevance of the different sonographic features. Only a focal lesion was associated with a reduction in live birth. Whether the magnitude of this reduction is specific to adenomyosis deserves further study. It would also be interesting to know what the results of the study would have been if the study group was limited only to the 22 patients initially diagnosed with adenomyosis to better understand the impact of the proposed MUSA criteria. Aesop’s fable also reminds us of the dangers of ignoring the boy’s cry. Just as we should be aware of the crying wolf with every sonographic feature of adenomyosis, we should be cautious of ignoring a wolf when one does appear. Just as the investigators of this study and of the MUSA classification system propose, further study is needed to better understand the clinical relevance of the sonographic criteria of adenomyosis on fertility and other patient’s symptomatology such as dysmenorrhea, dyspareunia, and abnormal uterine bleeding. Ultimately, as clinicians and scientists, our diagnosis of adenomyosis should take into account the patient’s symptoms, the clinical signs, and the imaging criteria when tailoring the best treatment approach. To date, the impact of adenomyosis on IVF outcome remains unclear. A prospective study in a large number of patients with focal adenomyosis, diffuse adenomyosis, and without adenomyosis to correlate the relationship between the number and different MUSA features on the pregnancy outcome is needed. Pregnancy outcomes with donor oocyte embryos in patients diagnosed with adenomyosis using the Morphological Uterus Sonographic Assessment criteriaFertility and SterilityVol. 119Issue 3PreviewTo use the Morphological Uterus Sonographic Assessment (MUSA) criteria to evaluate the impact of adenomyosis on the live birth rate after donor egg embryo transfer. Full-Text PDF