BASICS
DESCRIPTION
- Asherman syndrome (AS) is the term used to describe infertility or secondary amenorrhea associated with intrauterine adhesions (IUAs) (or development of scar tissue within the endometrium.
- The extent of IUAs can range from mild disease causing thin, filmy adhesions from the anterior uterine wall to the posterior uterine wall to complete obliteration of the intrauterine cavity due to large thick adhesions comprised largely of dense connective tissue.
- The severity to which these adhesions cause symptoms of infertility or abnormal menses will dictate the level of disease.
- The manifestations of IUA include decrease in menstrual flow, infertility, recurrent miscarriage, placenta accreta, amenorrhea, and so forth, which significantly influence the reproductive health.
- The leading risk factor for IUAs and AS is intrauterine trauma associated with a surgical instrumentation or manipulation.
- Treatment is indicated by the extent of disease and consists of lysis of adhesions and preventative measures.
EPIDEMIOLOGY
Incidence
As intrauterine adhesive disease is rare and generally asymptomatic, true incidence and prevalence is difficult to measure.
Prevalence
Prevalence has been cited as
- 0.3% incidental finding in women undergoing intrauterine device placement without gynecologic symptoms (1).
- 21.5% in women who have undergone postpartum curettage (1).
ETIOLOGY AND PATHOPHYSIOLOGY
- The etiology of this disorder is trauma to a pregnant uterus, especially after postpartum curettage or after D&C for missed abortion (2).
- When curettage is done during 2nd, 3rd and 4th postpartum week, a higher incidence of IUA is associated with this procedure (3).
- Endometrial injury from procedures unrelated to pregnancy has also been implicated in the disease process, that is, myomectomy or curettage performed in the nonpregnant uterus.
- Infectious processes have also been found as a cause or adhesive disease within the endometrium. Although studies have shown conflicting evidence, genital tuberculosis is one of the main etiological factors of this condition, whereas chronic endometritis has also been associated with IUA.
- After endometrial injury, impaired endometrial repair is thought to be the pathogenesis behind IUA (4).
- Intrauterine surgery or infection may cause damage to the basal layer of endometrium, leading to the impaired regeneration of epithelial cells (4).
- The basalis layer of endometrium is damaged, causing inactive regeneration of endometrial cells and glands leading to poor endometrial repair signaling and defective angiogenesis.
- The absence of vascular regeneration causing interruption in the endometrium causes formation of fibrous scar and adhesion between anterior and posterior walls (4).
RISK FACTORS
- Endometrial curettage up to 4 weeks postpartum
- Recurrent miscarriages and D&C procedures
- Congenital (septate uterus or bicornuate uterus) and acquired intrauterine abnormalities (polyps or fibroids) have been identified more frequently in woman with IUA (5).
- Women with more than one miscarriage generally have more IUAs compared with women with one miscarriage (5).
GENERAL PREVENTION
- Avoiding repeated intrauterine curettage for early pregnancy loss by opting for expectant and medical management especially in women with history of previous uterine instrumentation.
- Other measures have been proposed, such as routine estrogen therapy, after uterine curettage and using hyaluronic acid as an adhesion barrier; however, no studies have demonstrated clinical benefit from these approaches.
COMMONLY ASSOCIATED CONDITIONS
- Associated with m ĵllerian duct malformations, especially with septate uterus
- Patients with remaining areas of normally functioning endometrium may have increased risk of developing endometrial adenocarcinoma (6)[C].
- Endometriosis from backflow of menstrual fluid
DIAGNOSIS
HISTORY
- History of uterine instrumentation
- Infertility
- Menstrual irregularities
- Recurrent pregnancy loss
- Cyclic pelvic pain
- Rule out systemic endocrine disorders (eating disorders, excess exercising, hypothyroidism, and androgen excess).
PHYSICAL EXAM
- No physical exam findings are considered diagnostic.
- Pelvic exam is normal in most cases.
- Transcervical sounding of the uterus might reveal obstruction (6)[C].
DIFFERENTIAL DIAGNOSIS
- Ovarian dysfunction/anovulation
- Hypothalamic-pituitary axis depression
- Pituitary dysfunction
- Endometriosis
- Polycystic ovarian syndrome (PCOS)
- Pelvic inflammatory disease
- Cervical stenosis
- Obstructive m ĵllerian duct anomalies
- See "Etiology" in "Amenorrhea" and "Infertility."
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Amenorrhea work up:
- Tailored to the initial complaint: UPT or blood hCG, progesterone, testosterone, dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone/follicle-stimulating hormone (LH/FSH), thyroid-stimulating hormone (TSH), prolactin
- Hysteroscopy:
- Directly visualizes cervical canal and uterine cavity
- Allows for biopsy of lesions and treatment/lysis of mild adhesions, with subsequent increased pregnancy rates
- Established as the gold standard for diagnosis of IUA due to low cost, high accuracy, and ability to perform in outpatient setting (7)[B]
- Transvaginal ultrasound (US)
- Lower sensitivity and specificity with high variability between technicians
- Useful with obstruction of lower uterine cavity, where hysterosalpingography (HSG) or sonohysterography (SHG) cannot be used (8)[C]
- May be helpful in predicting prognosis after treatment
Follow-Up Tests & Special Considerations
- Lack of menses after progesterone challenge or exogenous estrogen withdrawal in patients with obstructive amenorrhea
- MRI: can visualize uterine cavity above adhesions; however, MRI signal of adhesions has not been well established.
- Used in research setting; not recommended in general practice due to high cost; unknown sensitivity
Diagnostic Procedures/Other
Use of HSG and SHG is reasonable when hysteroscopy is not available (7)[B].
- HSG:
- Demonstrates shape of uterus and fallopian tubes
- Endometrial lesions are seen as filling defects or uterine wall abnormalities.
- Assesses fallopian tube patency and morphology
- Can have a high false-positive rate (up to 38%)
- SHG:
- Also known as saline infusion hysterography (SIH)
- Transvaginal sonography with intrauterine injection of isotonic saline
- Only useful in cases of partial IUA adhesions
Test Interpretation
- Biopsy of endometrial tissue shows fibrosis, loss of distinction between functional and basal layer; functional layer is replaced with epithelial monolayer.
- Possible calcification or ossification in the stroma
- Tissue usually becomes avascular, but in some cases, vascularity increases with thin-walled dilated vessels.
- Endometrium is affected throughout uterine cavity, even in areas remote from synechiae.
- Histologically similar to samples from uteri with induced adhesions, following resection of endometrium or balloon ablation.
TREATMENT
Operative hysteroscopy is the mainstay of treatment.
GENERAL MEASURES
Expectant management is a reasonable option in women with asymptomatic and mild AS:
- 78% regain menses in 1 to 7 years.
- 45.5% regain fertility in 1 to 7 years (9)[B].
MEDICATION
- Following surgical repair, hormone treatment has demonstrated increased endometrial stripe thickness and endometrial volume; no data are available on the probability of recurrence of adhesions or fertility.
- There is no shared consensus about the type of regimen (8)[B].
SURGERY/OTHER PROCEDURES
- Hysteroscopic adhesiolysis is the treatment of choice:
- Directly visualizes adhesions, which can then be divided with hysteroscopic scissors, blunt lysis with flexible hysteroscope, or laser/diathermy cutting
- Nonthermal methods minimize further trauma to endometrium.
- Dense adhesions require guidance with laparoscopy or US.
- Hysterotomy with myometrial scoring (7)[C]
- Enables widening of uterine cavity, over which endometrium can regenerate
- Should only be considered in severe cases; moderate success in restoring uterine cavity and achieving subsequent pregnancy
- Carries higher risk of complications, including possible need for emergent hysterectomy and uterine rupture during subsequent pregnancies
INPATIENT CONSIDERATIONS
- Antibiotic administration is not indicated during the operative hysteroscopy; specific data about hysteroscopy for AS is lacking (10)[B].
- Prevention of adhesion formation after surgical treatment
- Foley balloon catheter
- 10F Foley catheter balloon, inflated with 3.5 mL of saline, with stem cut above cervix; leave in for 7 to 10 days after operative treatment
- Fresh amnion graft over Foley catheter may reduce reformation of adhesions; no data on fertility outcomes.
- Hyaluronic acid
- Available as a bioresorbable membrane (Seprafilm) or an auto-cross-linked HA (ACP) gel (Hyalobarrier gel)
- Seprafilm provides a protective coating for about 7 days and can be used 24 hours after endometrial trauma for primary prevention.
- ACP gel separates uterine walls for at least 72 hours and can be used immediately after lysis of adhesions to prevent recurrence of adhesion; no data on fertility outcome (7)[A].
- Intrauterine contraceptive device (IUD)
- Inserted immediately after lysis of adhesions
- Loop IUD is more effective than T-shaped and safer than copper; however, it is no longer available in many countries, including the US.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Uterine cavity should be reexamined before patient attempts conception.
- HSG or SHG can be done 2 to 3 months after hysteroscopic adhesiolysis to assess if normal uterine shape has been restored (7)[B].
- Restoration of uterine cavity anatomy does not guarantee resolution of symptoms; there can remain varying degrees of endometrial fibrosis and nonfunctional endometrial tissue.
PATIENT EDUCATION
All patients should be appropriately counseled regarding success rates and risks of surgical interventions:
- High rate of adhesion recurrence
- Potential need for repeat procedures
- Potential for future pregnancy complications
PROGNOSIS
All outcomes vary depending on initial severity of IUA:
- Anatomic outcomes: up to 93% success in long-term maintenance of uterine cavity; recurrence of adhesions in mild (0%), moderate (17.7%), and severe (41.9%) adhesions
- Menstrual outcomes: Between 92% and 96% of amenorrheic women resume normal menstruation after treatment.
- Reproductive outcomes following hysteroscopic management: pregnancy rate, 63%; of those, 75% live birth rate
COMPLICATIONS
- Women with AS, even following treatment, are at increased risk of obstetric complications:
- Up to 50% premature birth rate
- Increased rates of placenta previa and accreta, IUGR, and mid-trimester loss (6)[B]
- Preterm premature rupture of membranes (PPROM), placenta abruptio placenta, and cesarean section for placental malpresentation (11)[B]
- Possible complications of surgical procedures include uterine perforation, hemorrhage, endometrial damage leading to further adhesion formation, pelvic infection, and future obstetric complications due to repeated cervical dilation/increased risk of cervical incompetence (6)[B].
REFERENCES
11 Schenker JG, Margalioth EJ. Intrauterine adhesions: an updated appraisal. Fertil Steril. 1982;37(5):593-610.22 Schenker JG. Etiology of and therapeutic approach to synechia uteri. Eur J Obstet Gynecol Reprod Biol. 1996;65(1):109-113.33 Jensen PA, Stromme WB. Amenorrhea secondary to puerperal curettage (Asherman's syndrome). Am J Obstet Gynecol. 1972;113(2):150-157.44 Chen Y, Chang Y, Yao S. Role of angiogenesis in endometrial repair of patients with severe intrauterine adhesion. Int J Clin Exp Pathol. 2013;6(7):1343-1350.55 Hooker AB, Lemmers M, Thurkow AL, et al. Systematic review and meta-analysis of intrauterine adhesions after miscarriage: prevalence, risk factors and long-term reproductive outcome. Hum Reprod Update. 2014;20(2):262-278.66 Yu D, Wong YM, Cheong Y, et al. Asherman syndrome-one century later. Fertil Steril. 2008;89(4):759-779.77 AAGL Advancing Minimally Invasive Gynecology Worldwide. AAGL practice report: practice guidelines for management of intrauterine synechiae. J Minim Invasive Gynecol. 2010;17(1):1-7.88 Conforti A, Alviggi C, Mollo A, et al. The management of Asherman syndrome: a review of literature. Reprod Biol Endocrinol. 2013;11:118.99 Schenker JG, Margalioth EJ. Intrauterine adhesions: an updated appraisal. Fertil Steril. 1982;37(5):593-610.1010 Nappi L, Di Spiezio Sardo A, Spinelli M, et al. A multicenter, double-blind, randomized, placebo-controlled study to assess whether antibiotic administration should be recommended during office operative hysteroscopy. Reprod Sci. 2013;20(7):755-761.1111 Tuuli MG, Shanks A, Bernhard L, et al. Uterine synechiae and pregnancy complications. Obstet Gynecol. 2012;119(4):810-814.
ADDITIONAL READING
Myers EM, Hurst BS. Comprehensive management of severe Asherman syndrome and amenorrhea. Fertil Steril. 2012;97(1):160-164.
CODES
ICD10
N85.6 Intrauterine synechiae
ICD9
621.5 Intrauterine synechiae
SNOMED
- Asherman syndrome (disorder)
- Intrauterine adhesions (disorder)
CLINICAL PEARLS
- 90% of AS cases are associated with curettage for pregnancy complications.
- Highest risk for development is trauma to endometrium, occurring within first 4 weeks postpartum or postabortion.
- Symptoms depend on the extent of pathologic changes, specifically depth of fibrosis, location of adhesions, and overall changes to uterine cavity.
- Hysteroscopy with mechanical instrumentation is the treatment of choice.
- Restoration of uterine cavity anatomy does not guarantee resolution of symptoms.