Asherman's syndrome

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Editor(s)-in-Chief: C. Michael Gibson, M.S.,M.D. [mailto:mgibson@perfuse.org] Phone:617-632-7753; Canan S Fornusek, Ph.D.; Associate Editor-In-Chief:

Overview
 Asherman's syndrome, also called "uterine synechiae" or intrauterine adhesions, presents a condition characterized by the presence of scars within the uterine cavity.

Causes and features
The cavity of the uterus is lined by the endometrium. This lining is composed of two layers, the functional layer which is shed during menstruation and an underlying basal layer which is necessary for regenerating the functional layer. Trauma to the basal layer, typically after a dilation and curettage (D&C) performed after a miscarriage, or delivery, or for elective abortion can lead to the development of intrauterine scars resulting in adhesions which can obliterate the cavity to varying degrees. In the extreme, the whole cavity has been scarred and occluded. Even with relatively few scars, the endometrium may fail to respond to estrogens and rests. Often, patients experience secondary menstrual irregularities characterized by changes in flow and duration of bleeding (amenorrhea, hypomenorrhea, or oligomenorrhea) and become infertile. Menstrual anomlies are often but not always correlated with severity: adhesions restricted to only the cervix or lower uterus may block menstruation. Pain during menstruation and ovulation are also sometimes experienced, and can be attributed to blockages.

Asherman's syndrome occurs most frequently after a D&C is performed on a recently pregnant uterus, following a missed or incomplete miscarriage, birth, or elective termination (abortion) to remove retained products of conception/placental remains. As the same procedure is used in all three situations, Asherman's can result in all of the above circumstances. It affects women of all races and ages as there is no underlying predisposition or genetic basis to its development. According to a study on 1900 patients with Asherman’s syndrome, over 90% of the cases occurred following pregnancy-related curettage. It is estimated that up to 5% of D&Cs result in Asherman's. More conservative estimates put this rate at 1%. Asherman's results from 25% of D&Cs performed 1-4 weeks post-partum, 30.9% of D&Cs performed for missed miscarriages and 6.4% of D&Cs performed for incomplete miscarriages. In the case of missed miscarriages, the time period between fetal demise and curettage increases the likelihood of adhesion formation to over 30.9% The risk of Asherman's also increases with the number of procedures: one study estimated the risk to be 16% after one D&C and 32% after 3 or more D&Cs.

Depending on the degree of severity, Asherman's syndrome may result in infertility, repeated miscarriages, pain from trapped blood, and high risk pregnancies (see Prognoses below). There is evidence that left untreated, the obstruction of menstrual flow resulting from scarring can lead to endometriosis.

Asherman's can also result from other pelvic surgeries including Cesarean section/ref>, removal of fibroid tumours (myomectomy) and from other causes such as IUDs, pelvic irradiation, schistosomiasis and genital tuberculosis. Chronic endometritis from genital tuberculosis is a significant cause of severe IUA in the developing world, often resulting in total obliteration of the uterine cavity which is difficult to treat.

An artificial form of Asherman's syndrome can be surgically induced by endometrial ablation in women with excessive uterine bleeding, in lieu of hysterectomy.

Incidence
The condition is estimated to affect 1.5% of women undergoing HSG, between 5 and 39% of women with recurrent miscarriage  and up to 40% of patients who have undergone D&C for retained products of conception. The true prevalence of Asherman’s syndrome is unclear as many doctors are unaware of the symptoms or diagnosis. Increased awareness about the condition and its diagnosis is also expected to reveal a higher frequency than previously reported.

Diagnosis
The history of a pregnancy event followed by a D&C leading to secondary amenorrhea is typical. Hysteroscopy is the gold standard for diagnosis. Imaging by sonohysterography or hysterosalpingography will reveal the extent of the scar formation. Hormone studies show normal levels consistent with reproductive function.

Hysterosalpingography
(Images courtesy of RadsWiki)

Ultrasonography
Ultrasonography is not a reliable method of diagnosing Asherman's Syndrome.

Treatment
Fertility can be restored by removal of adhesions. Fluoroscopically guided operative hysteroscopy is used for visual inspection of the uterine cavity and dissection of scar tissue (adhesiolysis). In more severe cases, laparoscopy is used in addition to hysteroscopy as a protective measure against uterine perforation. Microscissors are usually used to cut adhesions. Electrocauterization is not recommended. Sometimes a balloon stent (Foley catheter or Cook stent) filled with saline is inserted in the uterus for up to 3 weeks to keep the walls of the uterus apart as they heal to prevent the reformation of adhesions.

Hormonal therapy with synthetic or conjugated estrogen is usually prescribed following surgery to stimulate endometrial growth thereby preventing the walls of the uterus from re-adhering.

More studies are needed to evaluate which method of treatment is most likely to have a successful outcome.

Follow-up tests (HSG, hysteroscopy or SHG) are necessary to ensure that scars have not reformed. Further surgery may be necessary to restore a normal uterine cavity.

According to a recent study among 61 patients, the overall rate of adhesion recurrence was 27.9% and in severe cases this was 41.9%. Another study found that postoperative adhesions reoccur in close to 50% of severe Asherman's and in 21.6% of moederate cases. Mild IUA unlike moderate to severe synechiae do not appear to reform.

Classification of IUA
As severity of the condition correlates with prognosis, classification of IUA is useful for choosing the treatment method and providing a prognosis relating to fertility outcome following treatment. Several classification systems have been proposed for Asherman’s syndrome, although none of them is currently endorsed universally. The older systems were based on hysterosalpingography findings however with the advent of hysteroscopy modern classification systems are based on hysteroscopic diagnosis of adhesions. Those of the American Fertility Society , the European Society for Hysteroscopy and Nasr's proposed system are the most complex, taking into account several criteria. There is variation between criteria used in these systems but they include type of adhesions, location, extent of the uterine cavity affected, clinical symptoms, menstrual characteristics or history, and/or obstetric history. The precision in these systems may make them difficult to apply in practice because the boundaries between grade subtypes are sometimes subtle. None of these classification systems have been validated by clinical studies, and research reporting treatment outcomes often lack details on exact IUA grades in patients. This adds to the difficulties in comparing study outcomes in patients treated for Asherman's syndrome.

Prognosis
The extent of scar formation is critical. Small scars can usually be treated with success. Extensive obliteration of the uterine cavity or fallopian tube openings (ostia) may require several surgical interventions or even be uncorrectable. In this case surrogacy, IVF or adoption may be advised.

Patients who carry a pregnancy after correction of Asherman's syndrome may have an increased risk of having abnormal placentation including placenta accreta where the placenta invades the uterus more deeply, leading to complications in placental separation after delivery. Premature delivery, second-trimester pregnancy loss , and uterine rupture are other reported complcations. They may also develop incompetent cervix where the cervix can no longer support the growing weight of the fetus, the pressure causes the placenta to rupture and the mother goes into premature labour. Cerclage is a surgical stitch which helps support the cervix if needed.

The overall pregnancy rate after adhesiolysis was 60% and the live birth rate was 38.9% according to one study. Success is related to the severity of the adhesions with 93, 78, and 57% pregnancies achieved after treatment of mild, moderate and severe adhesions, respectively and resulting in 81, 66, and 32% live birth rates, respectively.

Age is another factor contributing to fertility outcomes after treatment of Asherman's. For women under 35 years of age treated for severe adhesions, pregnancy rates were 66.6% compared to 23.5% in women older than 35.

Prevention
Asherman's is not usually caused by an 'over-aggressive' D&C:a properly performed D&C can lead to Asherman’s. Medical alternatives to D&C for evacuation of retained placenta/products of conception exist including misoprostol methotrexate and mifepristone. Studies show this less invasive and cheaper method to be to be efficacious, safe and an acceptable alternative to surgical management for most women. . It was suggested as early as in 1993 that the incidence of IUA might be lower following medical evacuation (eg. Misoprostol) of the uterus, thus avoiding any intra-uterine instrumentation. So far, one study supports this proposal, showing that women who were treated for missed miscarriage with misoprostol did not develop IUA, while 7.7% of those undergoing D&C did. The advantage of misoprostol is that it can be used for evacuation not only following miscarriage, but also following birth for retained placenta or hemorrhaging.

Alternatively, D&C could be performed under ultrasound guidance rather than blind procedure. This would enable the surgeon to end scraping the lining when all retained tissue has been removed, avoiding injury.

Early monitoring during pregnancy to identify miscarriage can prevent the development of, or as the case may be, the reoccurence of Asherman’s as adhesions are more likely to occur after a D&C the longer the period after fetal death. Therefore immediate evacuation following fetal death may prevent IUA.

The use of hysteroscopic surgery instead of D&C to remove retained products of conception or placenta is another alternative, although it could be ineffective if a lot of tissue is present. Also, hysteroscopy is not a widely or routinely-used technique and requires expertise.

There is no data to indicate that suction D&C is less likely than sharp curette to result in Asherman's. A recent article describes three cases of women who developed intrauterine adhesions following manual vacuum aspiration.

History
It was first described in 1894 by Heinrich Fritsch (Fritsch, 1894) and further characterized by the gynecologist Joseph Asherman in 1948.

It is also known as Fritsch syndrome, or Fritsch-Asherman syndrome.