Asherman’s Syndrome

Asherman’s syndrome is a rare, acquired, gynecological disorder of the uterus(intrauterine adhesions or intrauterine synechiae) that occurs when scar tissue forms inside the uterus and/or the cervix. It is characterized by the bonding of scar tissue that lines the walls of the uterus, which decreases the volume of the uterine cavity. The bonding of uterine scar tissue (intrauterine adhesions or synechiae) may occur as a result of surgical scraping or cleaning of tissue from the uterine wall (dilatation and curettage [D and C]), infections of the endometrium (e.g., genital tuberculosis), or other factors. Asherman’s syndrome can be severe (greater than 75% of the front and back walls of the uterus can fuse) to moderate and mild, where only smaller portions of the uterine wall fuse. Patients can experience a range of symptoms depending on the severity of the disease, including reduced menstrual flow, increased cramping and abdominal pain, eventual stoppage of menstrual cycles (amenorrhea), and, in some women, infertility. Current treatment options include hysteroscopic surgery as well as preventive (Foley catheter) and restorative therapies (hormone treatment). Newer options like stem cell treatments are also currently being explored to treat severe cases of Asherman’s syndrome.

Causes

Asherman’s syndrome is most commonly caused by trauma to the uterus through surgical scraping or cleaning of the uterine wall (dilatation and curettage, also known as D & C). D & C is generally performed to clear the uterine lining following a miscarriage or abortion or to treat certain uterine conditions such as heavy bleeding. D & C after a miscarriage is one of the highest risk factors for Asherman’s syndrome. The scraping of the uterine lining following this procedure can lead to scar tissue that can adhere, leading to Asherman’s syndrome. Other types of surgery on the uterus such as removal of fibroids or polyps or surgical repair of structural defects in the uterus can cause scar tissue formation which is also a risk factor for Asherman’s syndrome. Factors that trigger inflammation in the uterus known as endometriosis and sporadic inflammation of the uterus have been linked to Asherman’s syndrome. Infection and inflammation of the uterus caused by bacteria (genital tuberculosis) and parasites such as blood flukes are also risk factors for Asherman’s syndrome.

Asherman syndrome occurs primarily after a dilation and curettage performed for elective termination of pregnancy, a missed or incomplete miscarriage, or to treat a retained placenta after delivery. It may occur with or without hemorrhage after delivery or elective termination of pregnancy. Less often, it results after a dilation and curettage for a non-obstetrical procedure for excessive bleeding, sampling for endometrial cancer, or removal of endometrial polyps. It can also occur after surgery to remove uterine fibroids. In patients with persistent excessive uterine bleeding (hypermenorrhea), specific procedures to create these adhesions throughout the uterine cavity is the desired goal to control the bleeding. These procedures are done to ablate the endometrium and create scarring. In the developing world, it may also occur due to infections from schistosomiasis or tuberculosis(genital).

The causes of Asherman’s syndrome can include:

  • Operative hysteroscopy: A surgery where your provider places a camera into your uterus and then cuts off and removes fibroids using an electric instrument.
  • Dilation and curettage (D&C): A type of surgery, dilation, and curettage (D&C) are used to open your cervix (dilate) and then remove tissue from your uterus. This tissue can be the lining of your uterus (endometrium) or tissue from a miscarriage or abortion. During the procedure, a tool is used to scrape away the extra tissue. This typically doesn’t cause scarring unless you have an underlying infection.
  • Cesarean section (c-section): This surgery is used to deliver a baby. In some cases, a c-section can cause scar tissue to form. This can happen when the stitches (sutures) were used to stop bleeding (hemorrhages) during the c-section and you have an infection at the time of the procedure. Otherwise, it’s very rare for a c-section to cause Asherman’s syndrome.
  • Infections: Infections alone don’t typically cause Asherman’s syndrome. But, when you have an infection while you undergo uterine surgery, like a D&C or a c-section, you can develop Asherman’s syndrome. Some infections that could lead to Asherman’s syndrome include cervicitis and pelvic inflammatory disease (PID).
  • Radiation treatment: Sometimes, a treatment option can cause scar tissue to develop in your uterus. Radiation therapy can be used on conditions like cervical cancer, but this can cause adhesions (scar tissue) that lead to Asherman’s syndrome.

Diagnosis

Asherman’s syndrome is usually diagnosed through imaging the size and shape of the uterus. The gold standard for diagnosis is a scope and camera tool called a hysteroscope that is inserted into the uterus to display a real-time view of the uterine cavity. Unfortunately, hyperscopes are not readily available in most gynecologist offices. Consequently, Asherman syndrome may be underdiagnosed since it cannot be effectively detected by routine examinations or by more standard diagnostic scans such as ultrasound. Another common diagnostic method for Asherman’s syndrome is hysterosalpingography which involves the injection of a contrasting fluid into the uterus for an X-ray image to be generated. Hysterosalpingography allows for the imaging of the uterine cavity shape which may be abnormal in the presence of intrauterine adhesions. Other common imaging tools such as ultrasound and magnetic resonance imaging (MRI]) cannot usually detect Asherman’s syndrome and remain supplementary diagnostic tools.

Imaging tests that can be used to diagnose Asherman’s syndrome include:

  • Ultrasound: This type of imaging test uses sound waves to create a picture of your internal organs. An ultrasound can be done externally on your skin or internally with a transvaginal ultrasound. A thin wand is inserted into the vaginal during this version of the test.
  • Hysteroscopy: During this procedure, your healthcare provider uses a thin tool with a camera on the end to look inside your uterus. This is inserted in your vagina and moved up through your cervix and into your uterus. Hysteroscopy allows your provider a very detailed look at the inside of your uterus. It can also be used to treat Asherman’s syndrome.
  • Saline infusion sonography: This imaging test uses ultrasound along with a saline (a mixture of salt and water) solution to create a clear image of the inside of your uterus. The fluid expands your uterus so that your provider can see details of the shape and defects of your uterine cavity. This gives your provider a very detailed look at the inside and outside of your reproductive organs.

Treatment

Therapies for Asherman’s syndrome focus on restoring the uterus to its original size and shape. The therapies can be divided into three primary approaches: treatment – hysteroscopic surgery, re-adhesion prevention, and uterus restoration therapies. Mild cases of Asherman’s syndrome may only require surgical treatment, while more severe cases may require all three approaches. Most cases of Asherman’s syndrome can be cured with treatment.

As I frequently reform after surgery, techniques have been developed to prevent the recurrence of adhesions. Methods to prevent adhesion reformation include the use of mechanical barriers (Foley catheter, saline-filled balloon uterine stents,[rx] gel barriers (Seprafilm, Spraygel, autocrosslinked hyaluronic acid gel Hyalobarrier) and mechanical barrier film (Women Leaf)[rx] to maintain opposing walls apart during healing, thereby preventing the reformation of adhesions. Antibiotic prophylaxis is necessary for the presence of mechanical barriers to reduce the risk of possible infections. A common pharmacological method for preventing the reformation of adhesions is sequential hormonal therapy with estrogen followed by progestin to stimulate endometrial growth and prevent opposing walls from fusing.[rx] However, there have been no randomized controlled trials (RCTs) comparing post-surgical adhesion reformation with and without hormonal treatment, and the ideal dosing regimen or length of estrogen therapy is not known. A recent meta-analysis compared different post-surgical prevention barrier strategies and concluded that there was no single superior treatment.[rx] Furthermore, diagnostic severity and outcomes are assessed according to different criteria (e.g. menstrual pattern, adhesion reformation rate, conception rate, live birth rate). More comparative studies are needed in which reproductive outcomes can be analyzed systematically.

Treatment

The most common treatment for Asherman’s syndrome is hysteroscopic surgery (hysteroscopes plus scissors or other cutting instruments) to cut the adhesions of the uterine wall. The hysteroscope allows the doctor a magnified and direct view of the uterus for precise cutting of the uterine adhesions. Most hysteroscopic surgery can be done in an outpatient setting. The treatment of the severe cases of Asherman’s syndrome can be more challenging, as the cavity may be completely blocked or too narrow to allow the insertion of the hysteroscope inside the cervix.

Re-Adhesion Prevention

Several procedures have been developed to prevent re-adhesion of the uterine wall following hysteroscopic surgery, since the scar tissue may re-adhere. The Foley catheter was one of the first devices developed to separate the uterine walls to prevent recurrent adhesions. A Foley catheter can be inserted in the uterine cavity for 5 to 7 days with a bag for removing drainage from the uterus. Another method to prevent adhesions from reoccurring is a uterine balloon stent made from silicon and shaped to fill the uterine cavity. Finally, the application of certain chemicals such as hyaluronic acid has been shown to help prevent uterine re-adhesion. Although the mechanism is not completely understood, it is believed that hyaluronic acid acts as a temporary barrier to prevent re-adhesion and may also promote tissue repair.

Uterus Restoration Therapy

Hormone therapy such as estrogen supplements has been proposed to help enhance tissue repair and restore the lining of the uterus. While some studies have suggested that estrogen therapy may enhance the repair and growth of cells in the uterine wall, more clinical studies are being performed to confirm the value of estrogen therapy for the treatment of Asherman’s syndrome. Antibiotics are also often prescribed following hysteroscopic surgery. While antibiotics do not directly prevent re-adhesion, they help prevent infections and inflammation that may damage the uterus and trigger re-adhesion of the uterine walls.

Preoperative and postoperative treatment with oral, transdermal, or intramuscular estrogen preparations may help to reduce scarring postoperatively and promote regeneration of the normal endometrium.

Devices to prevent the apposition of the uterine walls may also reduce scar formation. The devices are placed intraoperatively but need to be monitored carefully to reduce the unintended risk of atrophy of the wall due to pressure from the device.

Experimental protocols to rebuild the endometrium by infusing stem cells derived from the patient may provide some promise in the future. These stem cells may be derived from the patient’s blood cells, fresh or freeze-dried amniotic tissue, or other sources. However, further studies are needed to confirm the safety, efficacy, and risks associated with these protocols.

Although adhesive gels containing synthetic hyaluronidase have been studied and show promise in reducing the recurrences of the adhesions, evaluation of these studies has not confirmed their benefit.

Reevaluation one to two weeks postoperatively may allow earlier identification of recurrent adhesions while small and allow resection before these adhesions worsen.

Investigational Therapies

Clinical trials of stem cell therapy are ongoing to determine if this therapy can help rebuild the uterine wall, particularly following severe cases of Asherman’s syndrome. Stem cells are basic cells (undifferentiated) that can be programmed to become almost any cell in the body including cells that line the uterus. Stem cell therapies are focusing primarily on rebuilding the endometrial lining that has become damaged from adhesions and surgery. Early clinical trials have demonstrated that stem cell therapy is safe and may be effective in helping the regeneration of the uterine walls as well as helping resumption of menstruation and improving fertility.

References

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