The management of adenomyosis remains a great challenge to practicing gynaecologists. Until recently, hysterectomy has been the only definitive treatment in women who have completed child bearing. A number of nonsurgical and minimally invasive, fertility-sparing surgical treatment options have recently been developed. This review focuses on three aspects of management, namely, (1) newly introduced nonsurgical treatments; (2) management strategies of reproductive failures associated with adenomyosis; and (3) surgical approaches to the management of cystic adenomyoma.
Adenomyosis is a common benign gynaecological condition but its diagnosis and treatment remain a clinical challenge to physicians. The true incidence of adenomyosis is unknown and the prevalence varies widely due to the lack of a standardized definition and diagnostic criteria. The prevalence from previous retrospective cohort and prospective cohort observational studies is summarized in Tables
Prevalence of adenomyosis after hysterectomy specimens for various gynaecological conditions (from retrospective cohort studies).
Study | Vercellini et al. | Vavilis et al. | Seidman and Kjerulff1996 [ | Parazzini et al. | Bergholt et al. |
---|---|---|---|---|---|
Number of cases ( | 1334 | 594 | 1252 | 707 | 549 |
Adenomyosis (%) | 25 | 20 | 12–58 | 21 | 10–18 |
Uterine fibroid | 23 | 21 | 15 | ||
Genital prolapse | 26 | 26 | 30 | ||
Ovarian cyst | 21 | 18 | 30 | ||
Cervical cancer | 19 | 18 | 25 | ||
Endometrial cancer | 28 | 16 | |||
Ovarian cancer | 28 | 21 |
Prevalence of adenomyosis from previous prospective cohort observational studies.
Study | Number of patients ( | Study characteristics | Diagnostic modality | Definition of adenomyosis | Prevalence% |
---|---|---|---|---|---|
de Souza et al. 1995 [ | 26 | Infertility patients presenting with dysmenorrhea or menorrhagia, all had laparoscopy performed | MRI | Focal adenomyoma: ill-defined lesions within the myometrium | 54 |
Diffuse adenomyosis: diffuse or irregular JZ thickening | |||||
| |||||
Kunz et al. 2005 [ | 227 | Study group ( | MRI | | |
Study subgroup: presence of endometriosis, <36 years old with fertile partners | |||||
Control group ( | |||||
| |||||
Kissler et al. 2008 [ | 70 | Patients with severe dysmenorrhea with laparoscopy performed | MRI | Maximal thickness >8 mm or greater on T2 weighted images | 53 |
Group I: patients with dysmenorrhea < 11 years | |||||
Group II: patients with dysmenorrhea > 11 years | |||||
| |||||
Naftalin et al. 2012 [ | 985 | Consecutive patients attending the general gynaecology clinic | TVS | Asymmetrical myometrial thickening not caused by presence of fibroids, parallel shadowing, linear striations, myometrial cysts, hyperechoic islands, adenomyoma, and irregular JZ | 21 |
MRI: magnetic resonance imaging; TVS: transvaginal ultrasound scan; JZ: junctional zone.
Adenomyosis is best defined by Bird in 1972 as “the benign invasion of endometrium into the myometrium, producing a diffusely enlarged uterus which microscopically exhibits ectopic non-neoplastic, endometrial glands and stroma surrounded by the hypertrophic and hyperplastic myometrium” [
The exact pathogenesis of adenomyosis remains debatable. The diagnosis of adenomyosis is made when ectopic endometrial implants are found within the myometrium of the uterus. The most common and widely accepted theory involves the downward invagination of the endometrial basalis layer into the myometrium due to either myometrial weakness or altered immunologic activity leading to disruption of the endometrial-myometrial interface, also known as the “junctional zone (JZ)” [
Histological examination is the gold standard in the diagnosis of adenomyosis, even though the exact histological criteria have not been universally agreed. One accepted criterion is the presence of endometrial tissue more than 2.5 mm below the endomyometrial junction or a JZ thickness of more than 12 mm [
Apart from the findings of these ectopic endometrial tissues within the myometrium, smooth muscle changes like hyperplasia are often found. Ultrastructural differences between smooth muscle cells from adenomyosis and normal uterus were found with myocytes showing cellular hypertrophy, differences in cytoplasmic organelles, nuclear structures, and intercellular junctions [
Rarely, adenomyosis may present as a cystic lesion lined with endometrial tissue and surrounded by myometrial tissue when it is called “cystic adenomyoma.” Juvenile cystic adenomyoma (JCA) is a subgroup of cystic adenomyoma that commonly occurs in adolescents or women < 30 years of age and is not associated with diffuse adenomyosis. Takeuchi et al. [
The classic presentation of adenomyosis is heavy, painful menstrual bleeding, typically occurring in multiparous women between 40 and 50 years of age [
There is also increasing evidence to show an association between infertility and adenomyosis [
Two-dimensional (2D) transabdominal USG may reveal uterine enlargement or asymmetric thickening of the anterior and posterior myometrial walls. However, transabdominal USG is often not accurate enough in diagnosing adenomyosis as it fails to provide sufficient image resolution for visualization of the myometrium. Therefore, 2D transvaginal USG is often the first-line investigation. In a review performed by Reinhold et al., it was shown that transvaginal USG had a sensitivity of 80–86%, specificity of 50–96%, and an overall accuracy of 68–86% in diagnosing diffuse adenomyosis [
USG features of adenomyosis include the presence of three or more sonographic criteria: heterogeneity, increased echogenicity, decreased echogenicity, and anechoic lacunae or myometrial cysts [
Sonographic diagnosis of adenomyosis is not always easy but the consensus statement and recommendation published by the MUSA (Morphological Uterus Sonographic Assessment) group on how sonographic features of adenomyosis should be described and measured should help to improve the diagnostic accuracy [
Three-dimensional (3D) USG improves diagnostic accuracy of adenomyosis as it allows better imaging of the JZ [
Magnetic resonance imaging (MRI) is the gold standard imaging modality for assessing the JZ in the evaluation of adenomyosis [
Accuracy of TVS and MRI for the noninvasive diagnosis of adenomyosis.
TVS | MRI | |
---|---|---|
Sensitivity | 72% | 77% |
Specificity | 81% | 89% |
Positive likelihood ratio | 3.7 | 6.5 |
Negative likelihood ratio | 0.3 | 0.2 |
TVS: transvaginal ultrasound scan; MRI: magnetic resonance imaging.
A recent study also showed that using Aixplorer (Supersonic Imagine, France) scanner with application of shear wave elastography during transvaginal scanning may improve diagnostic accuracy of adenomyosis [
Hysterosalpingography is seldom used to diagnose adenomyosis. However, in patients undergoing infertility assessment, the occasional finding of spiculations measuring 1–4 mm in length, arising from the endometrium towards the myometrium, or a uterus with the “tuba erecta” finding may be suggestive of adenomyosis [
Several hysteroscopic appearances have been found to be associated with adenomyosis, including irregular endometrium with endometrial defects or superficial openings, hypervascularization, strawberry pattern, or cystic haemorrhagic lesions [
In 1992, McCausland [
In a prospective, nonrandomized study conducted by Jeng et al. [
As in the case of endometriosis, the management strategy of adenomyosis depends primarily on the presenting symptom and whether it is associated with reproductive failure.
Medical treatment for adenomyosis is similar to those given for endometriosis. Apart from symptomatic relief, hormonal treatment mainly works by inhibition of ovulation, cessation of menses, improving the hormonal milieu, and causing decidualization of the endometrial deposits.
LNG-IUD may be used in conjunction with other treatment modalities such as GnRH analogue [
Uterine artery embolization (UAE) has been used to treat symptomatic fibroids since the 1990s. There is increasing evidence to suggest that it is also effective in the treatment of management of adenomyosis. In a review of 15 studies including 511 women with adenomyosis, Popovic et al. found [
High intensity focused ultrasound (HIFU) is another nonsurgical treatment for uterine fibroids that focuses high intensity ultrasound in the target lesion causing coagulative necrosis and shrinkage of the lesion. Both MRI and USG can be used for guidance for the procedure. MRI has better real time thermal mapping during the HIFU treatment. Yet, ultrasound guided HIFU is less costly and offers real time anatomic monitoring imaging and a grey scale change during treatment represents a reliable indicator in treatment response. It is effective in both focal and diffuse lesions [
There is limited report on the use of laparoscopic or hysteroscopic endometrial in treating adenomyosis in the literature. The success rate of myometrial electrocoagulation ranges from 55 to 70% as reported [
Hysterectomy is the definitive treatment option for intractable symptomatic adenomyosis when medical or other conservative treatments have failed to control the symptoms. Patients undergoing hysterectomy for adenomyosis should be advised of an increased risk of bladder injury and persistent pelvic pain. Furuhashi et al. [
Several studies have shown that adenomyosis is associated with a negative impact on the success rate of IVF. In a recent meta-analysis conducted by Vercellini et al. [
Puente et al. [
The use of short-term GnRH agonists to shrink the size of the adenomyosis lesion has been shown to improve conception rate within 6 months of cessation of GnRH agonist therapy [
In women with adenomyosis planning to undergo IVF treatment, the following management strategies should be considered.
Several studies have shown that pretreatment with GnRH analogue before IVF treatment improved pregnancy outcome. Zhou et al. [
In women without pre-IVF GnRH analogue therapy as described above, long GnRH analogue protocol should be considered as it helps to induce decidualization of the adenomyotic deposits rendering the disease inactive. Tao et al. [
In women with adenomyosis, a two-staged in vitro fertilization could be considered. Patients can undergo ovarian stimulation, oocyte retrieval, and fertilization followed by frozen-thawed embryo transfer (FET) at a later stage. Prior to the FET, GnRH analogue suppression therapy for 3 months or so leads to shrinkage of the adenomyosis. FET in the first HRT cycle following GnRH analogue suppression therapy, before the adenomyosis lesion regrows to its pretreatment size and exerts its adverse impact on implantation, may improve the result.
Performing a mock embryo transfer is desirable in women with adenomyosis, as it may help to assess the uterine cavity length and position, choose the correct transfer catheter, and alert the clinicians any extra precautions (e.g., use of tenaculum or cervical dilatation). Mock embryo transfer is particularly desirable in those with an enlarged uterus or distorted uterine cavity.
Adenomyosis has been reported to be associated with increased incidence of preterm delivery, preeclampsia, and second trimester miscarriage when compared with the control group [
GnRH agonist pretreatment to suppress the pituitary ovarian axis prior to hormone replacement therapy to prepare the endometrium in FET cycles appeared to improve the outcome compared with hormone replacement therapy without downregulation. In a study including 339 patients with adenomyosis, 194 received long-term GnRH agonist plus HRT (downregulation + HRT) and 145 with HRT alone. The clinical pregnancy, implantation, and ongoing pregnancy rates in the downregulation and HRT group were significantly higher than that of the HRT alone group, being 51.35% versus 24.83%, 32.56% versus 16.07%, and 48.91% versus 21.38%, respectively [
Several functional studies showed that excessive uterine contractility (>5 contractions per minute) has been demonstrated in approximately 30% of patients undergoing embryo transfer and this may have a significant adverse impact on subsequent embryo implantation and clinical pregnancy rates [
Recurrent implantation failure is diagnosed when there is failure to achieve a clinical pregnancy after transfer of at least four good-quality embryos in a minimum of three fresh or frozen cycles in a woman under the age of 40 years [
Surgery is seldom required for women prior to IVF treatment, the indication being (1) well-defined adenomyoma more than 5 cm and (2) recurrent miscarriage or recurrent implantation failure after IVF. A retrospective cohort study performed by Kishi et al. [
Just as it is now possible to remove intramural myoma with refined hysteroscopic techniques, hysteroscopic adenomyomectomy may also be possible in selected cases, especially when the adenomyoma is <5 cm or when it protrudes into the uterine cavity. However, hysteroscopic adenomyomectomy should always be carried out under USG guidance. A minimal safety margin of 5 mm between the serosa and adenomyoma is considered necessary to avoid the risk of uterine perforation although the safety margin may sometimes increase after part of the lesion has been removed and the uterine contractions which follow help to push the adenomyoma further towards the cavity. Pretreatment with 3-month course of GnRH agonist beforehand can help reduce the vascularity and bleeding during the operation. Sometimes, it may also help to push the adenomyoma towards the uterine cavity due to the reduction of uterine volume.
The location of the adenomyoma should be clearly defined before the start of the procedure. Using a lower perfusing pressure, say at 40 mmHg instead of the usual 90–100 mmHg, may allow a slight bulge of the adenomyoma into the cavity to be visualized. Vasopressin, a potent vasoconstrictor, may be injected into the uterus by using an oocyte retrieval needle [
Cystic adenomyoma is a special category of adenomyoma. Figures
(a) Ultrasound and (b) MRI appearance of a cystic adenomyoma.
(a) Hysteroscopic view at high perfusion pressure. (b) Hysteroscopic view at low perfusion pressure with bulging of cystic adenoma seen. (c) Hysteroscopic dissection of cystic adenomyoma wall away from endometrium. (d) Roller ball ablation of adenomyotic deposits.
Many treatment modalities are now available for the treatment of adenomyosis. The management plan ought to be individualized, depending on the presenting symptom and the desire to achieve a successful pregnancy. Recent development in various nonsurgical and surgical options has significantly improved the prospect of a successful treatment in women wishing to conceive again.
The authors declare that there are no conflicts of interest regarding the publication of this paper.
Jin-Jiao Li and Jacqueline P. W. Chung contributed equally to the manuscript.
This work was supported by grants from the National Natural Science Foundation of China (no. 81270680, no. 81571412) and the Beijing Municipal Administration of Hospital Clinical Medicine, Development of Special Funding Support (ZYLX201406).