When the endometrial glands and mesenchyme invade the myometrium, it is called adenomyosis. It was previously considered to be an intrinsic endometriosis, but is now considered to be a separate disease. Adenomyosis has become a common gynecological condition with a high incidence and is therefore receiving a lot of attention. In contrast to the normal endometrium, the endometrium located in the myometrium resembles the basal endometrium, which is unresponsive to progesterone and is often in a proliferative phase. The disease is associated with endometriosis in about 20%-50% and uterine fibroids in about 30%, and pelvic adhesions are also common.
Key points of diagnosis and treatment
I. Diagnosis
Dysmenorrhea and menorrhagia are the main symptoms of adenomyosis, and a few patients have infertility. On examination, the uterus is enlarged, mostly homogeneous and hard, usually not more than 12 weeks in size, otherwise, it may be combined with fibroids. If the uterus is adenomyoma, it can also show asymmetric enlargement. MRI is recognized as the most reliable non-invasive method to diagnose adenomyosis at home and abroad, but because of its high cost, it is only done when other non-invasive diagnostic methods still fail to diagnose and affect the decision of surgical treatment. The gold standard for the diagnosis of adenomyosis remains the pathological diagnosis.
Ultrasound is the most commonly used method to assist in the diagnosis of adenomyosis. Vaginal ultrasound is more accurate than abdominal ultrasound, with small cystic echoes within the myometrium being the most specific diagnostic indicator, and the accuracy of vaginal ultrasound in the diagnosis of adenomyosis is even comparable to that of magnetic resonance imaging (MRI) if not combined with fibroids. On transvaginal color Doppler ultrasound (TVCDS), the ectopic lesion between the uterine walls shows a stellate colored flow signal, with low flow velocity detected, and very little regular flow around the lesion. On transvaginal 3-DCPA examination, the vascularity in the uterine lesion is thickened and disorganized, with smooth and clear walls and a high-velocity, high-resistance arterial spectrum, whereas the perfusion in uterine fibroids has a spherical meshwork structure and a high-velocity, low-resistance arterial spectrum. Although ultrasound diagnosis is easy and non-invasive, it cannot confirm the diagnosis. The sensitivity and specificity of vaginal ultrasonography are 82.7% and 67.1% respectively, while the sensitivity and specificity of puncture biopsy are 44.8% and 95.9% respectively, and the positive prediction rate of both methods are 50% and 81.2% respectively.
MRI has better specificity than vaginal ultrasound for the diagnosis of adenomyosis, but is also less effective in diagnosing large uteruses >400 cm3 (>12 gestational weeks in size). Hysteroscopy reveals an enlarged uterine cavity, sometimes with abnormal glandular openings, and can exclude endometrial lesions. Laparoscopy reveals a uniformly enlarged uterus with a more pronounced anterior and posterior diameter, a harder uterus, a grayish or dark purple appearance, and sometimes purple nodules protruding from the plasma membrane. When available, multi-point coarse needle aspiration biopsy is performed to confirm the diagnosis. The CA125 level in patients with adenomyosis is significantly higher, with a positivity rate of 80%, while the CA125 positivity rate for uterine fibroids is only 20%, and the CA125 level in patients with adenomyosis is positively correlated with the size of the uterus.
Treatment
(A) Surgical treatment
1.Hysterectomy
It is the main treatment method and the only evidence-based method that can cure dysmenorrhea or/and excessive menstruation, and is suitable for older patients without fertility requirements. In recent years, the use of negative hysterectomy has been increasing. In simple adenomyosis, the uterus is mostly less than 12 gestational weeks, and there is no difficulty in performing negative hysterectomy, but laparoscopic hysterectomy is feasible in cases of combined endometriosis, ovarian endometriotic cysts or estimated significant adhesions. Although some studies have shown that slightly more than 10% of the uterus with adenomyosis can involve the cervix, some studies have also shown that adenomyosis is mainly seen in the body of the uterus and rarely in the cervix, and secondary hysterectomy can still be considered as long as all of the lower uterine segment is removed.
2.Conservative surgery
The main procedures are excision of the adenomyosis, endometrial ablation and intervention. There are also laparoscopic uterine artery block and lesion ablation (using electrical, radiofrequency and ultrasound energy). The number of reports has increased in recent years, but the effectiveness of these procedures has yet to be confirmed by evidence-based medical studies.
(1) Excision of adenomyotic lesions is indicated for young patients who require preservation of reproductive function. Uterine adenomyoma is usually removed, which can significantly improve symptoms and increase the chance of pregnancy. In limited adenomyosis, most of the lesions can be removed to relieve symptoms. Although the pregnancy rate is lower in diffuse adenomyosis, it still has some therapeutic value. GnRH-a treatment can be used for 3 months before surgery to reduce the size of the lesion and facilitate surgery. Injection of diluted posterior pituitary saline (12u dissolved in 50 ml saline) at the surgical site before excision can significantly reduce bleeding and decrease the difficulty of surgery. We generally use a monopolar electric hook and make a transverse pike incision at the most prominent part of the lesion, taking care to preserve the peripheral muscle tissue, followed by suturing the wound in two layers. The lesion excision is done along with uterine nerve removal or uterine artery blockage to try to increase the efficacy. In recent years, there has been experience with 30 cases, mainly patients who had already given birth but required preservation of the uterus, and the resected lesions were weighed between 15-120 g. The postoperative dysmenorrhea was relieved, and the recurrence rate of dysmenorrhea was about 10% at one-year follow-up, but the pain level was still less than before surgery, and the long-term results are still under observation. Recently, Japanese scholars Takeuchi et al. reported the experience of laparoscopic surgery, in which dilute posterior pituitary saline was injected at the surgical site first, and then a transverse H-shaped incision was made at the lesion, which could dig out most of the lesion and did not easily penetrate into the uterine cavity, and then the muscle layer encircling the lesion was folded and sutured.
(2) Endometrial removal
In recent years, it has been reported that endometrial resection under hysteroscopy was performed to treat adenomyosis, and after the operation, the patient’s menstrual flow was significantly reduced, even amenorrhea, and dysmenorrhea was improved or disappeared. The success rate was 92.86%. The patients’ menstruation improved and anemia was cured. 77.8% of the 18 cases with preoperative dysmenorrhea disappeared and 22.2% were relieved after surgery. Similar reports have been made abroad. However, there are reports of emergency hysterectomy for severe adenomyosis with deeper infiltration of the myometrium. Some authors have reported that immediate postoperative placement of an intrauterine device releasing levonorgestrel (LNG-IUS, Mannedol) in the uterine cavity after TCRE significantly increased the rate of amenorrhea at one year after surgery and reduced the rate of reintervention. Decreased menstruation and disappearance of dysmenorrhea have also been reported in patients with adenomyosis who underwent endometrial removal via hot bulb. As this method is simple and safe, it deserves further study.
(3) Interventional treatment
In recent years, a number of authors have reported the treatment of adenomyosis with arterial embolization therapy (TAE). After super-selective cannulation of both uterine arteries or the anterior trunk of both internal iliac arteries by Seldinger’s technique, embolization with fresh gelatin sponge pellets (1-3mm in diameter) carrying antibiotics is confirmed by imaging. The volume of the uterus and the lesion decreased significantly. In patients with adenomyosis treated with TAE using gelatin sponge as an embolic agent, blood flow was sparse in the normal myometrium and sparse or no blood flow in the lesions 7 days after TAE. However, there are still some complications of TAE treatment that have not yet been solved, the long-term efficacy remains to be observed, and the effect on future reproductive function is still unclear, so the clinical application is still not popular, and further experience has to be accumulated.
(4) Laparoscopic uterine artery block
Wang CJ et al. in Taiwan reported that 20 patients with symptomatic adenomyosis were treated by laparoscopic uterine artery block, and the uterine volume was reduced by 0.4%-74.0% six months after surgery. However, nine patients developed non-cyclic abdominal pain after surgery, and three of them subsequently underwent hysterectomy. Most of the patients were not satisfied with the surgical results because the pain could not be completely relieved.
(II) Pharmacological treatment
The efficacy of pharmacological treatment for adenomyosis is only temporary. For young patients with fertility requirements, near menopause or those who do not undergo surgery, Danazol, endometrium, progesterone or gonadotropin-releasing hormone analog or agonist (GnRH-a) can be tried, with the same dosage and precautions as for endometriosis. Although dysmenorrhea disappears during pseudo-menopausal drug treatment, the pain often returns soon after stopping the drug. Treatment with gonadotropin-releasing hormone agonists (GnRH-a) can also cause uterine shrinkage, amenorrhea, and disappearance of dysmenorrhea.
In recent years, some authors in China have reported the treatment of perimenopausal adenomyosis with mifepristone. Patients took mifepristone (10 mg/d) orally for 3 months from the 1st to the 3rd day of menstruation, and after treatment, the patient stopped menstruation, dysmenorrhea disappeared, and the uterus was significantly reduced in size, and side effects were rare. We have done animal experiments and found that mifepristone not only significantly blocked the onset of adenomyosis in mice, but also reduced the size of the uterus and adenomyosis lesions and reduced the extent of lesions, which is consistent with the results of pharmacological treatment of adenomyosis in humans.
L-18 methacrynic acid can treat perimenopausal adenomyosis, and the rate of relief of dysmenorrhea was 100% after treatment, although the uterus volume was not significantly reduced. It has been reported at home and abroad that the treatment of dysmenorrhea and menorrhagia in perimenopausal adenomyosis with LNG-IUS (Manuel) is effective. Our individual cases have been observed for more than 3 years after the device. Preliminarily, it seems that Mannorrhea is more effective for excessive menstruation and mild to moderate dysmenorrhea, but not effective enough for severe dysmenorrhea, with some side effects. A multicenter prospective study is currently underway in Beijing to investigate the exact efficacy of Mannorrhea in the treatment of adenomyosis.
Conservative treatment of adenomyosis, especially surgical and pharmacological treatment in young patients, will remain a challenge for clinicians in the future, and new conservative treatments proposed in recent years have yet to be validated by evidence-based medical data.
Treatment of Combined Infertility
The management of adenomyosis combined with infertility is usually difficult and there is no clear and effective treatment plan. If the patient also has endometriosis, it may be treated as endometriosis for observation. In simple diffuse adenomyosis, GnRH-a treatment for 3-6 months has been reported, with a certain pregnancy rate after discontinuation of the drug. Surgical excision of the lesion (which may not be complete) may also be considered in limited adenomyosis and has some pregnancy rate after surgery. For those who have failed medication or/and surgical treatment or are older, pregnancy should be promptly facilitated with assisted conception techniques such as intrauterine insemination and IVF-ET. Pre-treatment with GnRH-a can be done before IVF-ET.