Continuing Education Activity

Asherman syndrome (intrauterine adhesions or intrauterine synechiae) occurs when scar tissue forms inside the uterus and/or the cervix. These adhesions occur after surgery of the uterus or after a dilatation and curettage with tuberculosis and schistosomiasis being a less common cause. This activity illustrates the evaluation and management of Asherman syndrome and explains the role of the interprofessional team in improving care for patients with this condition.

Objectives:

• Outline the etiology of Asherman syndrome.
• Summarize the American Fertility Society classification of the severity of Asherman syndrome.
• Review the treatment considerations for patients with Asherman syndrome.
• Explain the importance of collaboration and communication among the interprofessional team to routinely monitor the endometrium for evidence of endometrial cancer which will improve outcomes in those with Asherman syndrome.

Introduction

Asherman syndrome, which is also referred to as intrauterine adhesions or intrauterine synechiae, occurs when scar tissue (adhesions) forms inside the uterus and/or the cervix.[1][2][3]

Etiology

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.[3][4] 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).[5]

Epidemiology

Asherman syndrome may go unrecognized in women who are not trying to conceive since they may not recognize or be concerned with the symptoms. These women may have hypomenorrhea. Therefore, Asherman syndrome may be underdiagnosed because it is usually undetectable by routine examinations or diagnostic procedures such as an ultrasound scan. It may occur in up to 13% of women undergoing a termination of pregnancy during the first trimester, and 30% in women undergoing a dilation and curettage (D and C) after a late spontaneous abortion. Women with placental abnormalities (e.g., placenta increta) may have a higher risk of developing Asherman syndrome as the placenta adheres to deeper layers within the uterus and becomes more difficult to remove.[4][6] The incidence may be as high as 23.4% in patients undergoing procedures two to four weeks after the initial procedure for a vaginal delivery or missed abortion. The risk increases for patients undergoing repeated procedures for bleeding or repeated elective termination of pregnancies.

It is found in 1.5% of women evaluated with a hysterosalpingogram (HSG) for infertility, between 5 and 39% of women with recurrent miscarriage. Asherman’s Syndrome may occur in 31% of women after the initial hysteroscopic resection of leiomyoma, and up to 46% after the second hysteroscopic resection.  

Pathophysiology

Asherman syndrome occurs when trauma to or removal of the basal layer of endometrium in opposing areas within the uterine cavity. Such injury to the lining triggers inflammation that allows these adhesive bands to form from one side of the cavity to the other. Abnormalities in placentation where the placental tissue burrows below the basal layer of the endometrium significantly increase the risk of developing Asherman syndrome. The extent of the adhesions defines whether the case is mild, moderate, or severe. The adhesions can be thin or thick, spotty in location, or confluent. The adhesive bands are usually not vascular, an important consideration when discussing treatment options.

History and Physical

Patients with Asherman syndrome may have light or absent menstrual periods (amenorrhea). Still, some patients have normal periods based on the surface area of the cavity that is affected. Others have no periods but have severe dysmenorrhea (pain with menstruation) that may occur around the time of the anticipated menstrual period. The pain may indicate that the endometrial build-up occurs during the cycle, but that menstrual flow is obstructed due to adhesions near or within the cervix. These adhesions can present as recurrent miscarriage and/or infertility due to deficient endometrium and its poor vascularisation.

Evaluation

The failure to induce menses despite stimulating the endometrium with an estrogen-progesterone challenge, in a patient with secondary amenorrhea, with normal hypothalamic-pituitary-ovarian functions and hormone levels, points towards the diagnosis of Asherman's syndrome.[7]

Although two-dimensional sonography may suggest adhesive disease, Asherman syndrome is more often evaluated initially with saline sonography or hysterosalpingography to demonstrate the adhesions. Still, the sensitivity for diagnosis remains only 75% for these modalities. Hysteroscopy remains the gold standard for diagnosing the extent of the disease and allows treatment to occur simultaneously. MRI is needed when there is a total obliteration of the uterine cavity.[8][9][10]

Treatment / Management

Asherman syndrome should be treated by a surgeon experienced with hysteroscopy, sometimes with sonographic or laparoscopic guidance. These surgeons often recommend removing scars with scissors but may also use other modalities with care taken not to create further disease. Preoperative and postoperative treatment with oral, transdermal, or intramuscular estrogen preparations may help to reduce scarring postoperatively and promote regeneration of the normal endometrium.[1][11][12][13]

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.

Differential Diagnosis

• Thyroid disease
• Hypothalamic dysfunction
• Pituitary dysfunction
• Androgen-secreting ovarian/adrenal tumors
• Polycystic ovarian disease
• Pelvic inflammatory disease
• Cervical stenosis
• Premature menopause

Staging

The American Fertility Society classifies the severity of the disease in three stages as follow:

• Mild disease: few filmy adhesions involving less than a third of the uterine cavity with normal menses or hypomenorrhea.
• Moderate disease: filmy and dense adhesions, the involvement of one-third to two-thirds of the cavity, and hypomenorrhea.
• Severe Disease: dense adhesions involving more than two-thirds of the cavity with amenorrhea.

Prognosis

The chances of conceiving and delivery after surgery are lower in patients with moderate to severe disease but may improve after surgery if the cavity can be reconstructed and menses recur. Although a normal-appearing uterine cavity may be seen after repeated surgeries, rebuilding a normal endometrial lining may lag for some time after surgery or may not reoccur. 

Complications

Asherman's syndrome can result in repetitive pregnancy loss/abortions despite surgery and treatment.[5] Recurrence of the adhesions can be seen even after adhesiolysis.[10]

Although the risk of endometrial cancer in women with Asherman syndrome may be lower than the general population, women with Asherman may develop endometrial cancer before or after menopause. Since the signs and symptoms often found in these women (early or abnormal bleeding, thickened endometrium) may be missed due to the scarring or cervical obstruction; therefore, these women may benefit from a routine sonographic evaluation of the endometrium to monitor changes.[2][14]

Asherman's syndrome can result in obstetric complications that include preterm labor, Low birth weight(LBW), and placental complications that include retained placenta and placenta accreta.[10]

Deterrence and Patient Education

Even though the prevention of Asherman syndrome being challenging, patients should be educated regarding the usage of contraception and the contraceptive methods available, which will ultimately play a significant role in reducing the rates of legal abortions, thus minimizing curettage. [10]

Pearls and Other Issues

It has been inferred that Asherman’s syndrome has a constitutional component, explaining why it occurs only in a fraction of the individuals undergoing endometrial instrumentation and also explaining its occurrence in individuals without any preceding endometrial trauma. Besides, there appears to be a vulnerable time in the postpartum period when the process of curettage is likely to incite maximal damage to the endometrium, especially the basalis layer, resulting in a higher rate of adhesion formation. This period includes the second, third, and fourth postpartum weeks.[5][15]

Although Dilatation and curettage (D&C) being the most frequently used intervention for removing Retained products of conception(RPOC), hysteroscopic resection, in comparison, is associated with lower rates of intrauterine adhesion formation. Hysteroscopic resection gives the advantage of direct visualization of the uterine chamber, thus allowing the removal of RPOC with minimal damage to the endometrium.[16]

Enhancing Healthcare Team Outcomes

The diagnosis and management of Asherman syndrome are often difficult and require an interprofessional team that includes an obstetrician, gynecologist, and radiologist. Asherman syndrome should be treated by a surgeon experienced with hysteroscopy, sometimes with sonographic or laparoscopic guidance.

These patients should be closely followed by the nurse practitioner and primary caregiver as they may develop endometrial cancer before or after menopause. 

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References

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Guo EJ, Chung JPW, Poon LCY, Li TC. Reproductive outcomes after surgical treatment of asherman syndrome: A systematic review. Best Pract Res Clin Obstet Gynaecol. 2019 Aug;59:98-114. [PubMed: 30713131]

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Azizi R, Aghebati-Maleki L, Nouri M, Marofi F, Negargar S, Yousefi M. Stem cell therapy in Asherman syndrome and thin endometrium: Stem cell- based therapy. Biomed Pharmacother. 2018 Jun;102:333-343. [PubMed: 29571018]

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Zheng F, Zhu B, Liu Y, Wang R, Cui Y. Meta-analysis of the use of amniotic membrane to prevent recurrence of intrauterine adhesion after hysteroscopic adhesiolysis. Int J Gynaecol Obstet. 2018 Nov;143(2):145-149. [PubMed: 30073656]

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Disclosure: Collin Smikle declares no relevant financial relationships with ineligible companies.

Disclosure: Siva Naga Yarrarapu declares no relevant financial relationships with ineligible companies.

Disclosure: Shailesh Khetarpal declares no relevant financial relationships with ineligible companies.