Diagnosis
The gold standard for diagnosis of adenomyosis is histopathology from hysterectomy specimens, but specific definitions vary. Published criteria include endometrial glands within the myometrial layer greater than 0.5 to 1 low power field from the basal layer of the endometrium, endometrial glands extending deeper than 25% of the myometrial thickness, or endometrial glands a certain distance (ranging from 1-3 mm) from the basalis layer of the endometrium.16 Various methods of non-hysterectomy tissue sampling have been proposed for diagnosis, including needle, hysteroscopic, or laparoscopic sampling, but the sensitivity of these methods is poor.17 Limiting the diagnosis of adenomyosis to specimen pathology relies on invasive methods and clearly we cannot confirm the diagnosis by hysterectomy in patients with a desire for future fertility. It is for this reason that the prevalence of the disease is widely unknown.
The alternative to pathologic diagnosis is to identify radiologic changes that are associated with adenomyosis via either transvaginal ultrasound (TVUS) or MRI. Features suggestive of adenomyosis on MRI overlap with TVUS features, including uterine enlargement, anteroposterior myometrial asymmetry, T1- or T2-intense myometrial cysts or foci, and a thickened JZ.18 A JZ thicker than 12 mm has been thought to be predictive of adenomyosis, whereas a thickness of less than 8 mm is predictive of its absence, although the JZ may vary in thickness with the menstrual cycle.19,20 A 2021 systematic review and meta-analysis comparing MRI diagnosis with histopathologic findings reported a pooled sensitivity and specificity of 60% and 96%, respectively.21 The reported range for sensitivity and specificity is wide: 70% to 93% for sensitivity and 67% to 93% for specificity.22-24
Key TVUS features associated with adenomyosis were defined in 2015 in a consensus statement released by the Morphological Uterus Sonographic Assessment (MUSA) group.25 These include a globally enlarged uterus, anteroposterior myometrial asymmetry, myometrial cysts, fan-shaped shadowing, mixed myometrial echogenicity, translesional vascularity, echogenic subendometrial lines and buds, and a thickened, irregular or discontinuous JZ (FIGURES 3 and 4).25 The accuracy of ultrasonographic diagnosis of adenomyosis using these features has been investigated in multiple systematic reviews and meta-analyses, most recently by Liu and colleagues who found a pooled sensitivity of TVUS of 81% and pooled specificity of 87%.23 The range for ultrasonographic sensitivity and specificity is wide, however, ranging from 33% to 84% for sensitivity and 64% to 100% for specificity.22 Consensus is lacking as to which TVUS features are most predictive of adenomyosis, but in general, the combination of multiple MUSA criteria (particularly myometrial cysts and irregular JZ on 3D imaging) appears to be more accurate than any one feature alone.23 The presence of fibroids may decrease the sensitivity of TVUS, and one study suggested elastography may increase the accuracy of TVUS.24,26 Moreover, given that most radiologists receive limited training on the MUSA criteria, it behooves gynecologists to become familiar with these sonographic features to be able to identify adenomyosis in our patients.
Adenomyosis also may be suspected based on hysteroscopic findings, although a normal hysteroscopy cannot rule out the disease and data are lacking to support these markers as diagnostic. Visual findings can include a “strawberry” pattern, mucosal elevation, cystic hemorrhagic lesions, localized vascularity, or endometrial defects.27 Hysteroscopy may be effective in the treatment of localized lesions, although that discussion is beyond the scope of this review.
Clinical presentation
While many women who are later diagnosed with adenomyosis are asymptomatic, the disease can present with heavy menstrual bleeding and dysmenorrhea, which occur in 50% and 30% of patients, respectively.28 Other symptoms include dyspareunia and infertility. Symptoms were previously reported to develop between the ages of 40 and 50 years; however, this is biased by diagnosis at the time of hysterectomy and the fact that younger patients are less likely to undergo definitive surgery. When using imaging criteria for diagnosis, adenomyosis might be more responsible for dysmenorrhea and chronic pelvic pain in younger patients than previously appreciated.1,29 In a recent study reviewing TVUS in 270 adolescents for any reason, adenomyosis was present in 5% of cases and this increased up to 44% in the presence of endometriosis.30
Adenomyosis often co-exists and shares similar clinical presentations with other gynecologic pathologies such as endometriosis and fibroids, making diagnosis on symptomatology alone challenging. Concurrent adenomyosis has been found in up to 73% and 57% of patients with suspected or diagnosed endometriosis and fibroids, respectively.31,32 Accumulating evidence suggests that pelvic pain previously attributed to endometriosis may in fact be a result of adenomyosis; for example, persistent pelvic pain after optimal resection of endometriosis may be confounded by the presence of adenomyosis.29 In one study of 155 patients with complete resection of deep infiltrating endometriosis, persistent pelvic pain was significantly associated with the presence of adenomyosis on imaging.33
Adenomyosis is increasingly being recognized at the time of infertility evaluation with an estimated prevalence of 30% in women with infertility.3 Among women with infertility, adenomyosis has been associated with a lower clinical pregnancy rate, higher miscarriage rate, and lower live birth rate, as well as obstetric complications such as abnormal placentation.34-36 A study of 37 baboons found the histologic diagnosis of adenomyosis alone at necropsy was associated with a 20-fold increased risk of lifelong infertility (odds ratio [OR], 20.1; 95% CI, 2.1-921), whereas presence of endometriosis was associated with a nonsignificant 3-fold risk of lifelong infertility (OR, 3.6; 95% CI, 0.9-15.8).37
In women with endometriosis and infertility, co-existing adenomyosis portends worse fertility outcomes. In a retrospective study of 244 women who underwent endometriosis surgery, more than five features of adenomyosis on imaging was associated with higher rates of infertility, in vitro fertilization treatments, and a higher number of in vitro fertilization cycles.31 Moreover, in women who underwent surgery for deep infiltrating endometriosis, the presence of adenomyosis on imaging was associated with a 68% reduction in likelihood of pregnancy after surgery.38
Conclusion
As we begin to learn about adenomyosis, our misconceptions become more evident. The notion that it largely affects women at the end of their reproductive lives is biased by using histopathology at hysterectomy as the gold standard for diagnosis. Lack of definitive histologic or imaging criteria and biopsy techniques add to the diagnostic challenge. This in turn leads to inaccurate estimates of incidence and prevalence, as we assume patients’ symptoms must be attributable to what we can see at the time of surgery (for example, Stage I or II endometriosis), rather than what we cannot see. We now know that adenomyosis is present in women of all ages, including adolescents, and can significantly contribute to reduced fertility and quality of life. We owe it to our patients to consider this condition in the differential diagnosis of dysmenorrhea, heavy menstrual bleeding, dyspareunia, and infertility.
CASE Resolved
The patient underwent targeted hysteroscopic resection of adenomyosis (FIGURE 5) and conceived spontaneously the following year. ●
