Adenomyosis – Causes, Symptoms, Diagnosis, Treatnment

Adenomyosis is a uterine condition that is histologically characterized by the presence of ectopic endometrial glands and stroma within the myometrium, surrounded by hypertrophic and hyperplastic myometrial changes [rx]. For several decades, the diagnosis of adenomyosis was made in hysterectomy specimens either coincidentally, or in women treated surgically for chronic pelvic pain and/or abnormal uterine bleeding[rx].

Adenomyosis is a medical condition characterized by the growth of cells that build up the inside of the uterus (endometrium) atypically located within the cells that put up the uterine wall (myometrium),^[rx] as a result, thickening of the uterus occurs. As well as being misplaced in patients with this condition, endometrial tissue is completely functional. The tissue thickens, sheds, and bleeds during every menstrual cycle.^[rx]

Causes of Adenomyosis

• Adenomyosis and endometriosis are usually regarded as closely related, but
  • Microscopic appearance, and probably their pathogenesis, are somewhat different
  • They may occur independently of each other
  • Adenomyosis mostly is made up of nonfunctional (basal) endometrium and is frequently connected with the mucosa (vs. endometriosis, composed of functional layers)
  • Adenomyosis may represent a unique form of endometrial diverticulosis
• Hypothetical mechanisms include (Crum: Diagnostic Gynecologic and Obstetric Pathology, 2nd Edition, 2011)
  • Instillation of endometrium within the myometrium
  • In situ metaplasia of pluripotent stem cells retained in myometrium or
  • Improper partitioning of the endometrium from the myometrium
• Of note, del(7) (q21.2q31.2), a deletion found in typical leiomyoma, has been found in three cases of adenomyosis, suggesting some pathobiology overlap between leiomyomata and adenomyosis (Cancer Genet Cytogenet 1995;80:118)
• Invasive tissue growth – Some experts believe that endometrial cells from the lining of the uterus invade the muscle that forms the uterine walls. Uterine incisions made during an operation such as a cesarean section (C-section) might promote the direct invasion of the endometrial cells into the wall of the uterus.
• Developmental origins  – Other experts suspect that endometrial tissue is deposited in the uterine muscle when the uterus is first formed in the fetus.
• Uterine inflammation related to childbirth –  Another theory suggests a link between adenomyosis and childbirth. Inflammation of the uterine lining during the postpartum period might cause a break in the normal boundary of cells that line the uterus.
• Stem cell origins – A recent theory proposes that bone marrow stem cells might invade the uterine muscle, causing adenomyosis.

Symptoms of Adenomyosis

Adenomyosis can vary widely in the type and severity of symptoms that it causes, ranging from being entirely asymptomatic 33% of the time to being a severe and debilitating condition in some cases. Women with adenomyosis typically first report symptoms when they are between 40 and 50, but symptoms can occur in younger women.^[rx][rx]

Symptoms and the estimated percent affected may include:^[rx]

• Chronic pelvic pain (77%)
• Heavy menstrual bleeding (40-60%), which is more common in women with deeper adenomyosis. Blood loss may be significant enough to cause anemia, with associated symptoms of fatigue, dizziness, and moodiness.
• Abnormal uterine bleeding
• Painful cramping menstruation (15-30%)
• Painful vaginal intercourse (7%)
• A ‘bearing’ down feeling
• Pressure on bladder
• Dragging sensation down thighs and legs
• Uterine enlargement (30%), which in turn can lead to symptoms of pelvic fullness.
• Tender uterus
• Infertility or sub-fertility (11-12%) – In addition, adenomyosis is associated with an increased incidence of preterm labor and premature rupture of membranes.^[rx][rx]

Women with adenomyosis are also more likely to have other uterine conditions, including:

• Uterine fibroids (50%)
• Endometriosis (11%)
• Endometrial polyp (7%)
• Nonneoplastic condition presenting with palpably enlarged uterus
• Symptoms are nonspecific: dysmenorrhea, menorrhagia, abnormal uterine bleeding, dyspareunia, chronic pelvic pain associated with the menstrual period and infertility (Eur J Obstet Gynecol Reprod Biol 2009;143:103, N Engl J Med 2010;362:2389)
• Associated with deep infiltrating endometriosis, parity, intense dysmenorrhea and increasing age (Eur J Obstet Gynecol Reprod Biol 2014;181:289)
• Tends to regress after menopause (Hum Reprod 2012;27:3432)
• When extensive, it confers a potential risk of infarction and thrombosis and exacerbates menorrhagia via activation of coagulation and fibrinolysis during menstruation (Eur J Obstet Gynecol Reprod Biol 2016;204:99)
• Painful menstrual cramps (dysmenorrhea).
• Heavy menstrual bleeding (menorrhagia).
• Abnormal menstruation.
• Pelvic pain.
• Painful intercourse (dyspareunia).
• Infertility.
• Enlarged uterus.

Diagnosis of Adenomyosis

Histopathology

• The diagnosis of adenomyosis is through a pathologist microscopically examining small tissue samples of the uterus.^[rx] These tissue samples can come from a uterine biopsy or directly following a hysterectomy. Uterine biopsies can be obtained by either a laparoscopic procedure through the abdomen or hysteroscopy through the vagina and cervix.^[rx]
• The diagnosis is established when the pathologist finds invading clusters of endometrial tissue within the myometrium. Several diagnostic criteria can be used, but typically they require either the endometrial tissue to have invaded greater than 2% of the myometrium, or a minimum invasion depth between 2.5 to 8mm.^[rx] Histopathological image of uterine adenomyosis observed in the hysterectomy specimen. Hematoxylin & eosin stain.

Gross Findings

• Enlarged uterus
• Thickened uterine wall with a trabeculated appearance
• Hemorrhagic pinpoint or cystic spaces throughout wall^[rx]

Microscopic Findings

• Endometrial glands and stroma haphazardly distributed throughout the myometrium
• Concentric myometrial hyperplasia frequent around adenomyotic foci
• Variants: Gland-poor, stroma-poor, intravascular^[rx]

Laboratory Evaluation

Laboratory testing is useful to rule out other disease entities included in the differential diagnosis, in addition to identifying certain complicating features such as anemia due to heavy menstruation. While some biomarkers due exist, none are specific for adenomyosis.[rx]

Imaging

Adenomyosis can vary widely in the extent and location of its invasion within the uterus. As a result, there are no established pathognomonic features to allow for a definitive diagnosis of adenomyosis through non-invasive imaging. Nevertheless, non-invasive imaging techniques such as transvaginal ultrasonography (TVUS) and magnetic resonance imaging (MRI) can both be used to strongly suggest the diagnosis of adenomyosis, guide treatment options, and monitor response to treatment.^[rx] Indeed, TVUS and MRI are the only two practical means available to establish a pre-surgical diagnosis.^[rx]

Ultrasound

Transvaginal ultrasound is the preferred diagnostic imaging modality for adenomyosis. The characteristic findings reflect the histopathologic changes of the disease process and can be broken down into three categories:

• Endometrial infiltration – echogenic striations and nodules, myometrial cysts, and “lollipop” diverticula (cystic striations)
• Smooth muscle proliferation – focal or diffuse myometrial thickening with indistinct borders more commonly involving the posterior fundus and heterogenous echotexture manifesting as “Venetian blind” appearance of thin linear shadows
• Vascularity – color Doppler demonstrating an increased number of tortuous vessels throughout the involved myometrium as opposed to leiomyomas which displace vessels

A number of mimics can have similar findings on the ultrasound exam, including tamoxifen use, prior endometrial ablation, endometriosis, uterine contractions, vascular malformations, leiomyomas, and cancer. Certain techniques such as low-frequency, coronal reconstructions, 3-D ultrasound, cine-clips, color Doppler, and saline infusion sonohysterography (SIS) can be used to differentiate between these entities.

MRI

Characteristic findings on MRI parallel the same features seen on ultrasound[rx][rx]:

• On T2-weighted imaging, uterine enlargement characterized by ill-defined, low-signal-intensity regions within the junctional zone is reflective of smooth muscle hyperplasia (junctional zone thicker than 12mm is generally accepted as diagnostic)
• T2 hyperintense myometrial cysts reflecting regions of ectopic endometrial tissue (can also have increased intrinsic T1 signal or increased susceptibility in hemorrhagic foci)
• Contrast enhancement is generally not reliable for assessment of vascularity as compared to a color Doppler ultrasound
• Similar to ultrasound, a variety of mimics ranging from co-existing gynecologic pathologies to physiologic variants exist. Susceptibility weighted imaging, diffusion-weighted imaging, MR spectroscopy, cine MR imaging, and increased 3T field strength are all problem-solving strategies.[rx]
• It is important to obtain the MRI in the late proliferative or secretory phase (days 7 to 28) due to the decreased signal of normal myometrium during the early proliferative phase (days 1 to 6).[rx]

Transvaginal ultrasonography

Common transvaginal ultrasound findings in patients with adenomyosis include the following:^[rx][rx][rx]

• globular, enlarged, and/or asymmetric uterus
• abnormally dense or especially varied density within the myometrium
• myometrial cysts – pockets of fluid within the smooth muscle of the uterus
• linear, acoustic shadowing without the presence of a uterine fibroid
• echogenic linear striations – bright lines or stripes
• anterior/posterior wall asymmetry
• the diffuse spread of small vessels within the myometrium
• Lack of contour abnormality
• Absence of mass effect
• Ill-defined margins between a normal and abnormal myometrium

Others Study

• The power Doppler or Doppler ultrasonography function – can be used during transvaginal ultrasonography to help differentiate adenomyomas from uterine fibroids.^[rx][rx][rx] This is because uterine fibroids typically have blood vessels circling the fibroid’s capsule. In contrast, adenomyomas are characterized by widespread blood vessels within the lesion.^[rx] Doppler ultrasonography also serves to differentiate the static fluid within myometrial cysts from flowing blood within vessels.^[rx]
• The junction zone (JZ) – or a small distinct hormone-dependent region at the endometrial-myometrial interface, may be assessed by three-dimensional transvaginal ultrasound (3D TVUS) and MRI. Features of adenomyosis are disruption, thickening, enlargement or invasion of the junctional zone.^[rx]
• Sagittal MRI of a woman’s pelvis – showing a uterus with adenomyosis in the posterior wall. Gross enlargement of the posterior wall is noted, with many foci of hyperintensity.
• Shear Wave Elastography – A recent study also showed that using Aixplorer (Supersonic Imagine, France) scanner with the application of shear wave elastography during transvaginal scanning may improve the diagnostic accuracy of adenomyosis [rx]. This study found that adenomyosis was associated with a significant increase of the myometrial stiffness estimated with shear wave elastography. Further studies are required to verify the clinical usefulness of such an approach.
• Hysterosalpingography – Hysterosalpingography is seldom used to diagnose adenomyosis. However, in patients undergoing infertility assessment, the occasional finding of speculations 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 [rx].
• Hysteroscopy – 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 hemorrhagic lesions [rx]. Nevertheless, there is limited data available on the diagnostic accuracy of these various features.
• Hysteroscopic and Laparoscopic Myometrial Biopsy – The study found that the depth of adenomyosis was correlated with the severity of menorrhagia. Of the 90 patients studied, 50 patients had normal hysteroscopy in which 55% of them had significant adenomyosis (greater than 1 mm) when compared to controls (0.8 mm).
• Laparoscopic Myometrial Biopsy – In a prospective, nonrandomized study conducted by Jeng et al. [rx] evaluating 100 patients with clinical signs and symptoms strongly suggestive of adenomyosis, the sensitivity of myometrial biopsy were 98% and the specificity 100%; the positive predictive value was 100% and the negative predictive value 80%, which were superior to those of transvaginal sonography, serum CA-125 determination, or the combination of both. The group suggested that a laparoscopy-guided myometrial biopsy is a valuable tool in the diagnosis of diffuse adenomyosis in women presenting with infertility, dysmenorrhea, or chronic pelvic pain.

Treatment of Adenomyosis

Adenomyosis can only be cured definitively with surgical removal of the uterus. As adenomyosis is responsive to reproductive hormones, it reasonably abates following menopause when these hormones decrease. For women in their reproductive years, adenomyosis can typically be managed with the goals to provide pain relief, to restrict progression of the process, and to reduce significant menstrual bleeding.

Medications

• NSAIDs – Nonsteroidal anti-inflammatory drugs, such as ibuprofen and naproxen, are commonly used in conjunction with other therapies for pain relief. NSAIDs inhibit the production of prostaglandins by decreasing the activity of the enzyme cyclooxygenase. Prostaglandins have been shown to be primarily responsible for dysmenorrhea or the cramping pelvic pain associated with menses.
• Analgesic – Nonsteroidal anti-inflammatory drugs (NSAIDs) work by inhibiting the cyclooxygenase (COX-1 and COX-2) and decreasing the production of prostaglandins. NSAIDs have been proved to be effective in the treatment of primary dysmenorrhea by Gambone et al. [rx]. It is usually the first-line treatment for symptomatic pain relief for adenomyosis.
• Oral Contraceptive Pills (OCPs) – Combined oral contraceptive pills work by inhibiting ovulation by suppressing the release of gonadotropins. Many studies have shown that they are effective in the treatment of dysmenorrhea. A prospective observational trial showed that continuous low-dose OCP was more effective than cyclical low-dose OCP in controlling symptoms in patients after surgical treatment for endometriosis [rx].
• Danazol – Danazol is an isoxazole derivative of 12 alpha-ethinyl testosterone. It causes a hypogonadal state and thus is widely used for the treatment of endometriosis and abnormal uterine bleeding [rx]. However, data on its use in adenomyosis remains limited. This may be due to its unwanted adverse effects after systemic treatment.
• Dienogest – Dienogest is a selective synthetic oral progestin that combines the pharmacological properties of 17-alpha-progesterone and 19 nor-progesterone with a pronounced local effect on endometrial tissue. Dienogest has been shown to be effective in the treatment of endometriosis-associated pelvic pain. A prospective clinical trial has shown dienogest to be a valuable alternative to depot triptorelin acetate for the treatment of premenopausal pelvic pains in women with uterine adenomyosis. [rx]
• Levonorgestrel-Releasing Intrauterine Device (LNG-IUD) – LNG-IUD is an intrauterine device, which releases 20 micrograms of levonorgestrel per day. It has been shown to be an effective treatment for abnormal uterine bleeding. LNG-IUD acts locally and causes decidualization of the endometrium and adenomyotic deposits. LNG-IUD alleviates dysmenorrhea by improving uterine contractility and reducing local prostaglandin production within the endometrium. LNG-IUD appears to be an effective method in relieving dysmenorrhea associated with adenomyosis [rx] and more effective than the combined OC pill [rx], improved the quality of life [rx], and appears to be a promising alternative treatment to hysterectomy.
• LNG-IUD – may be used in conjunction with other treatment modalities such as GnRH analog [rx] or transcervical resection of the endometrium (TCRE) [rx]. In the latter study, it was found that TCRE combined with LNG-IUD was more effective in reducing menstrual flow compared with the LNG-IUD alone although there was no significant difference in the amount of pain reduction between the two treatment strategies.
• GnRH Agonists – GnRH agonists are effective in alleviating dysmenorrhea and relieving menorrhagia associated with adenomyosis [rx]. However, due to the undesirable climacteric side effects and risk of osteoporosis, treatment with GnRH agonists is usually restricted to a short duration of 3–6 months although the duration of use may be extended if add-back estrogen therapy is employed [rx]. Discontinuation of treatment usually leads to regrowth of the lesions and recurrence of symptoms.
• Selective Estrogen Receptor Modulator (SERM) – Selective estrogen receptor modulators like tamoxifen or raloxifene have been tried in the treatment of endometriosis [rx] based on observations that SERMs may reduce endometriosis lesion in mouse [rx]; however, their value in the treatment of adenomyoma has not been formally explored.
• Aromatase Inhibitors – Like endometriosis, adenomyotic deposits are estrogen-dependent. Aromatase inhibitors inhibit the conversion of estrogen from androgens, thereby lowering the synthesis of estrogen. A prospective randomized controlled study found that the efficacy of aromatase inhibitors (letrozole 2.5 mg/day) in reducing the volume of adenomyoma as well as improving adenomyosis symptoms was similar to that of GnRH agonists (goserelin 3.6 mg/month) [rx] [rx].
• Ulipristal Acetate – Ulipristal acetate (UPA) is a potent selective progesterone receptor modulator. There is good evidence to suggest that it can be used to shrink fibroid and control menorrhagia [rx, rx]. It is possible that it may be similarly effective in the treatment of adenomyoma but literature data is lacking.
• Antiplatelet Therapy – There is new evidence to suggest the role of antiplatelet therapy in treating adenomyosis. Emerging evidence suggests that endometriotic lesions are wounds undergoing repeated tissue injury and repair (ReTIAR), and platelets induce epithelial-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT), leading ultimately to fibrosis. Adenomyotic lesions are thought to have similar pathogenesis to that of endometriosis. A recent study in mice suggests that antiplatelet treatment may suppress myometrial infiltration, improve generalized hyperalgesia, and reduce uterine hyperactivity [rx].
• Uterine Artery Embolization – 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 the management of adenomyosis. [rx][rx].
• High-Intensity Focused Ultrasound – High intensity focused ultrasound (HIFU) is another nonsurgical treatment for uterine fibroids that focuses high-intensity ultrasound on 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. [rx, rx] [rx].
• Endomyometrial Ablation or Resection – There is a 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 [rx]. [rx]MRI treated with laparoscopic bipolar coagulation, having significant reduction or the resolution of dysmenorrhea or heavy menstrual bleeding.
• GnRH Analogue Therapy before In Vitro Fertilization – Several studies have shown that pretreatment with GnRH analog before IVF treatment improved pregnancy outcome. Zhou et al. [rx] analyzed the clinical efficacy of leuprorelin acetate in the treatment of uterine adenomyosis with infertility. They found that, after 2–6 months of leuprorelin acetate therapy, the mean uterine volume was significantly reduced from 180 ± 73 cm³ to 86 ± 67 cm³, leading to an improvement in embryo implantation and clinical pregnancy rates.
• Stimulation Protocol – In women without pre-IVF GnRH analog therapy as described above, a long GnRH analog protocol should be considered as it helps to induce decidualization of the adenomyotic deposits rendering the disease inactive. Tao et al. [rx] showed that GnRH antagonist protocol appears to be inferior to GnRH agonist long protocol cycle, and the latter appeared to be associated with increased pregnancy and decreased miscarriage rates.
• Two-Staged In Vitro Fertilization – 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 analog suppression therapy for 3 months or so leads to shrinkage of the adenomyosis. FET in the first HRT cycle following GnRH analog suppression therapy, before the adenomyosis lesion regrows to its pretreatment size and exerts its adverse impact on implantation, may improve the result.
• Mock Embryo Transfer – 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.
• Single Embryo Transfer – Adenomyosis has been reported to be associated with an increased incidence of preterm delivery, preeclampsia, and second-trimester miscarriage when compared with the control group [rx]. Consequently, multiple pregnancies should be avoided and so single embryo transfer should be advised. Women who had adenomyomectomy prior to IVF should also be advised to have SET to avoid multiple pregnancies with a view to minimizing the risk of scar rupture.
• HRT Protocol in Frozen-Thawed Embryo Transfer (FET) Cycle – 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. [rx].
• Uterine Contractility and Atosiban Therapy – 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 [rx]. The incidence of abnormal contractility appeared to be higher in women with adenomyosis [rx] which may in part explain the higher incidence of reproductive failure observed in this group of women. Recurrent Implantation Failure – Recurrent implantation failure is diagnosed when there is a failure to achieve a clinical pregnancy after the 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 [rx]. It is known that adenomyosis is associated with recurrent implantation failure [rx]. Women with recurrent implantation failure should be offered a 3D scan or MRI to establish if there is adenomyosis; if adenomyosis is present, the above management strategies should be adopted to improve the outcome.

Hormones and hormone modulators

• Levonorgestrel-releasing intrauterine devices or hormonal IUDs – such as the Mirena, are an effective treatment for adenomyosis.^[rx] They reduce symptoms by causing decidualization of the endometrium, reducing or eliminating menstrual flow.^[rx] Additionally, by helping downregulate estrogen receptors, hormonal IUDs shrink the clusters of endometrial tissue within the myometrium. This leads to reduced menstrual blood flow, helps the uterus contract more properly, and helps to reduce menstrual pain. The use of hormonal IUDs in patients with adenomyosis has been proven to reduce menstrual bleeding, improve anemia and iron levels, reduce pain, and even result in an improvement of adenomyosis with a smaller uterus on medical imaging.^[rx][rx] 
• Oral contraceptives  – reduce the menstrual pain and bleeding associated with adenomyosis. This may require taking continuous hormone therapy to reduce or eliminating menstrual flow. Oral contraceptives may even lead to short-term regression of adenomyosis.
• Progesterone or Progestins – Progesterone counteracts estrogen and inhibits the growth of endometrial tissue. Such therapy can reduce or eliminate menstruation in a controlled and reversible fashion. Progestins are chemical variants of natural progesterone.
• Gonadotropin-releasing hormone (GnRH) – agonists and danazol have been tried in order to relieve adenomyosis related symptoms and show some effect, but the studies are few, mainly with a retrospective study design and have small sample sizes.^[rx] Long-time use of GnRH-analogues is often associated with heavy side effects, loss of bone density and increased risk of cardiovascular events, and therefore not feasible for young women. Furthermore, all present treatment options are irrelevant options for women trying to conceive. Exogenous progestogenic treatments have been found to be ineffective.^[rx] In IVF-settings long down-regulation prior to IVF might have a positive effect on pregnancy rates.^[rx]

Surgery

Uterine-sparing procedures

• Uterine artery embolization (UAE) – In this minimally-invasive procedure, doctors intentionally block two large arteries that supply the uterus, called the uterine arteries. This is performed in order to dramatically reduce the blood supply to the uterus. By doing so, there is insufficient blood and thus oxygen present for the adenomyosis to develop and spread.  57-75% of women who undergo UAE for adenomyosis typically report long-term improvement in their menstrual pain and bleeding. However, there is a recurrence rate of symptoms in 35% of women following a UAE. 
• Myometrium or adenomyoma resection – In this procedure, surgeons remove a focal consolidation of adenomyosis known as an adenomyoma. To be successful this procedure requires that the adenomyosis is relatively focally isolated and with a minimal diffuse spread. Unfortunately, adenomyosis is commonly diffuse and the operation is successful only 50% of the time. The procedure is performed with either a laparoscope or hysteroscope.^[rx]
• Myometrial electrocoagulation^[rx]
• Myometrial reduction^[tx]
• MRI-guided focused ultrasound surgery^[rx]

Endometrial ablation and resection

• Endometrial ablation techniques –  are only for women who have completed their childbearing. The techniques either include physical resection and removal of the endometrium through a hysteroscope or focus on ablating or killing the endometrial layer of the uterus without its immediate removal. Endometrial ablation and resection techniques are most appropriate for shallow adenomyosis. The efficacy of the procedures is reduced if the adenomyosis is too widespread or deep. Furthermore, deep adenomyosis may become trapped behind a scarred region that was ablated, leading to further bleeding and pain. Endometrial resection is also limited to relatively shallow adenomyosis as significant bleeding may result from damage to large arteries that are present 5 mm deep within the myometrium.^[rx]
• Non-hysteroscopic procedures – These techniques do not require a hysteroscope are relatively fast, and many can be performed as an outpatient procedure.
• Thermal balloon – Using a thin expanding balloon placed within the uterus, providers can introduce heated fluid and ablate the endometrium. This procedure has been shown to result in amenorrhea or complete cessation of menstrual bleeding for 12 months in 23% of patients. 16% of patients eventually experience treatment failure with pain or bleeding requiring additional treatments or a hysterectomy. ^[9]
• Cryo-endometrial ablation (CEA) – A form of cryotherapy whereby using a small probe, providers can directly apply sub-zero temperatures within the uterus to freeze and ablate the endometrium.
• Circulating Hot Water – Heated water directly introduced into the uterus is used to thermally ablate the endometrium.
• Microwave ablation – Using a small probe introduced into the uterus, a provider uses microwave energy to ablate the endometrium.
• High-energy radiofrequency ablation – Using a small expandable mesh placed within the uterus, providers use high-energy radio waves to ablate the endometrium.
• Hysteroscopic procedures: These techniques all require the use of a hysteroscope to perform.
  • Wire-loop resection – Under direct visualization through a hysteroscope, a wire loop instrument charged with an electric current permits a provider to carefully remove the endometrium in strips.
  • Laser ablation – Under direct visualization through a hysteroscope, lasers are used to vaporize and ablate the endometrium.
  • Rollerball ablation – Under direct visualization through a hysteroscope, a metallic ball on the end of a probe is charged with electricity and rolled across the surface of the endometrium. This has been shown to have a coagulative effect to the depth of 2–3 mm into the myometrium. This destroys the endometrium and the nearby growth of dysfunctional smooth muscle. Deeper adenomyosis escapes this coagulative effect.^[9]

References