What is Asherman’s syndrome?

Asherman’s syndrome (AS) is an acquired condition, meaning a person is not born with it. Physically, it is characterized by adhesions — bands of fibrous or scar tissue — inside the uterus or cervix. These adhesions are also sometimes referred to as intrauterine synechiae. The most common symptoms include hypomenorrhea (decreased menstrual flow/light periods) or amenorrhea (no periods).ⁱ  Intrauterine adhesions (IUAs) reduce the functional surface of the normal endometrial lining (uterine lining), putting females with AS at risk for fertility-related issues.ⁱⁱ

Like most adhesions or scar tissue, some IUAs are more severe than others and are graded or classified based on that severity.^iii,iv The American Fertility Society has developed the most widely used classification system.^v This classification system categorizes Asherman’s syndrome in three stages:

• Stage I: Mild
• Stage II: Moderate
• Stage III: Severe

Among females with fertility issues, the prevalence of AS ranges from 2.8 to 45.5 percent.^vi This wide range in reported frequency may be due to differences in the population of females involved in studies or differences in the criteria used to define cases of AS.^vii

Females with AS have a higher rate of infertility, miscarriage, abnormal placental development, and poor implantation following in vitro fertilization (IVF).^viii

What causes Asherman’s syndrome?

Asherman’s syndrome is primarily caused by injury or trauma to the uterus during or after pregnancy. The endometrium of a recently pregnant uterus is more susceptible to injury, and those injuries can develop into IUAs.^ix

While AS is considered rare, it is difficult to know just how frequently it occurs, as delays in diagnosis are common. Existing clinical research reports this incidence of IUA formation:^x

• 15 percent in females who have previously had a dilation and curettage (D&C)
• 19 percent in females who have had a miscarriage with the past year
• 21 percent in females who have recently had a first-trimester termination

After uterine surgery such as a D&C, IUAs can develop where endometrial connective tissue has been lost. The IUAs can create tissue bridges between the walls of the uterus that eventually cause the uterine walls to stick together.^xi This sticking results in scarring within the uterine cavity.

Having a D&C after a miscarriage can be a primary cause of AS and IUAs and is the underlying factor for 15 to 40 percent of females with AS. The incidence depends on the characteristics of the patient, as well as how often they have undergone a D&C. For example, for females who have more than one D&C, the likelihood of developing AS is closer to 40 percent.^xii

Surgical treatment for pregnancy termination (such as D&C) can increase the likelihood of AS development. One review study observed that 21 percent of females had developed adhesions following the surgical termination of first trimester pregnancies.^xiii

A meta-analysis of 18 prospective studies showed that within a year post-miscarriage, 19 percent of females assessed with hysteroscopy had IUAs.^xiv The severity of IUAs in these individuals was variable, with most individuals having mild (58 percent) or moderate adhesions (28 percent). Most patients who had IUAs were treated with D&Cs and females with more than one D&C had a higher risk of adhesion formation than those who underwent only one D&C. Females with a history of more than one miscarriage also had a higher rate of IUAs compared to individuals with one loss.

AS is also associated with treatment for retained products of conception. The rate of IUAs is lower when females with retained products of conception are treated with hysteroscopy versus D&C (13 percent vs. 30 percent).^xv,xvi,xvii

Asherman’s syndrome without pregnancy

While most AS cases occur after pregnancy-related surgeries (mainly D&C), it is possible that AS can develop without a previous pregnancy. For example, post-surgical infections after other uterine surgeries can also be the cause of AS.^xviii These procedures include hysteroscopic resection of uterine septum, polyps, or fibroids.

It is also possible (though uncommon in North America) for tuberculosis infection of the female reproductive organs to cause AS.^xix

What are the symptoms of Asherman’s syndrome?

The hallmark symptom of Asherman’s syndrome is a change in menstruation. Females can have either light periods (hypomenorrhea) or absent periods (amenorrhea). Females who develop AS are typically not menopausal and have recently been pregnant. They generally have also undergone a related uterine surgery.

Among patients affected by AS, nearly one third have hypomenorrhea while two thirds have amenorrhea. Approximately 3.5 percent will have recurring dysmenorrhea, which is defined as painful menstrual periods.^xx

An abnormal menstrual flow does not in and of itself assure an AS diagnosis, as there are many other reasons for a light or absent period. Furthermore, roughly 2 to 3 percent of females with severe AS can have regular and painless menstrual periods with normal blood flow and duration.^xxi,xxii

How is Asherman's syndrome diagnosed?

If an individual is experiencing problems with menstruation, such as decreased flow or an absent period, Asherman’s syndrome should be considered. AS should also be suspected if an individual is having issues with fertility and has a history of uterine surgery such as a D&C.^xxiii AS cannot be diagnosed with a simple pelvic examination, but rather requires imaging of the uterine cavity.^xxiv

For AS diagnosis and treatment, hysteroscopy (minor surgery to examine the inside of the uterus with a camera) remains the gold standard.^xxv Hysteroscopy provides a real-time view of the uterine cavity by using a small camera that is inserted from the vagina and through the cervix into the uterus. During the procedure, doctors can identify the area of scarring, observe the extent of the scarring, and determine the characteristics of any uterine adhesions (filmy, dense). Hysteroscopy can be performed in a clinic or office, making it the optimal tool for assessing the endometrium and, if possible, immediately treating the adhesions.^xxvi

Other imaging methods such as hysterosalpingography (HSG) and saline infusion sonohysterography (SIS) can be used to identify uterine adhesions, but they offer only diagnosis and not the option of treatment at the time of diagnosis. HSG uses dye and X-ray, whereas SIS uses saline and ultrasound. One limitation of HSG is that it has a high false-positive rate of up to 39 percent.^xxvii In contrast, SIS has higher diagnostic accuracy for detecting intrauterine abnormalities.^xxviii

While routine 2D ultrasound can show a thin endometrial lining, it is not useful to diagnose AS. Distention of the cavity with fluid, as is done with SIS, is necessary to confirm the presence of uterine adhesions.^xxix

What are the treatment options and how successful are they?

Treatment of intrauterine adhesions/Asherman’s syndrome is only recommended if a patient has clinical symptoms, such as severe pain and/or reproductive issues. The recommended treatment options for AS include surgical removal of adhesions (hysteroscopic adhesiolysis), followed possibly by secondary intervention to help prevent re-development of intrauterine adhesions after hysteroscopic intervention.^xxx,xxxi

Surgical treatment: Hysteroscopy

Hysteroscopy is the gold-standard treatment to remove IUAs and restore the normal shape and volume of the uterine cavity,^xxxii but is generally only recommended for females who want to conceive or have debilitating symptoms (e.g., pain with periods). Hysteroscopic surgery allows providers to directly view adhesions for more precise and safe treatment.

The cutting or breaking up of the adhesions during hysteroscopy is known as hysteroscopic adhesiolysis. In cases where lesions are filmy (thin and translucent), using the top of the hysteroscope (camera) and uterine distension may be enough to break down the adhesions. In these cases, patients may be able to have a “no touch hysteroscopy” in the clinic, without anesthesia or the need for an operating room.^xxxiii The advantages of this approach are that patients can avoid any of the additional risks associated with sedation and the additional cost and time of having surgery in the operating room. Studies have shown that 89 percent of patients only need minor preoperative pain relief such as non-steroidal anti-inflammatory drugs (NSAIDs).^xxxiv

In the situation of more dense adhesions, providers use hysteroscopic scissors to cut the adhesions. This procedure can be done under ultrasound to help guide the surgeon and ensure safety. In the case of these dense adhesions, or if a patient cannot tolerate an office hysteroscopy, the procedure can be done under minimal sedation in an operating room or surgical center and the patient can go home the same day.

According to a 10-year clinical study,^xxxv the outcomes are good for females with AS who have their adhesions surgically removed. Specifically, the rate of successfully restoring normal menstruation and uterine anatomy was 95 percent among the 638 AS patients receiving one to three hysteroscopic adhesiolysis procedures.^xxxvi

Prevention of post-surgical adhesion recurrence

One of the biggest AS treatment challenges is the recurrence of adhesions after hysteroscopic adhesiolysis. The rate of recurrent adhesion formation can be as high as 30 to 66 percent,^xxxvii and is generally higher in individuals with severe AS.^xxxviii

There are several interventions to help prevent adhesion recurrence, including hormone treatment, anti-adhesion barriers, and repeat hysteroscopy. These treatments may help reduce the risk of re-adhesion, but there is a lack of consensus on the best approach.^xxxix

Hormone medications

The most common post-operative medication is estrogen therapy, which is meant to stimulate regeneration of a normal endometrium and help prevent scarring, though its effectiveness is unclear.^xl,xli Daily oral estrogen is often prescribed, with or without progestin medication, and usually for about one to three months. Dosages used in the literature vary between 4 mg to 10 mg per day, but it is unclear whether there is any benefit to higher dosages.^xlii,xliii

Anti-adhesion barriers

There are a few different types of anti-adhesion barriers including intrauterine devices (IUDs), balloon stents, and anti-adhesion hyaluronic acid–based gels.

Intrauterine devices (IUDs)

The first type of physical anti-adhesion barriers to be used were intrauterine devices (IUDs). An IUD is inserted into the uterus directly following hysteroscopic adhesiolysis and act by separating the layers of the endometrium, which helps prevent scarring during endometrial regeneration.^xliv The IUD of choice is a non-hormonal IUD (e.g., Lippes loop); however, it is no longer commercially available in many regions.^xlv Copper and T-shaped IUDs are not recommended. While most studies support a benefit for the post-operative use of IUDs, they likely need to be combined with other adjuvant treatments for maximal benefit.^xlvi

Balloon stent or foley catheter with balloon

Insertion of either a specialized balloon stent, or a foley catheter with inflated balloon, into the uterus following hysteroscopic adhesiolysis is another method to physically separate the uterine wall to help promote healing and prevent adhesion reformation. In a study of 1,240 patients, a balloon stent was introduced following adhesiolysis.^xlvii The pregnancy rate was 61.6 percent; however, they did not report on adhesion recurrence.

It is unclear if balloon stent placement is more effective than IUD at preventing recurrence. One randomized controlled trial comparing intrauterine balloon stent and IUD found that the adhesion recurrence rate was identical between the two treatments. However, other small studies suggest conception rate may be higher if intrauterine stent or foley catheter is used.^xlviii

Nevertheless, the 2017 American Association of Gynecologic Laparoscopists (AAGL) and European Society of Gynaecological Endoscopy (ESGE) guidelines on Asherman’s syndrome state that IUD, uterine stent or balloon all appear to reduce risk of adhesion recurrence. However, they note that limited data are available as to fertility outcomes after these treatments.^xlix

Anti-adhesion hyaluronic acid-based gels

A final option for preventing post-procedural recurrence is the insertion of anti-adhesion hyaluronic acid-based gels following hysteroscopy. These gels (e.g., Hyalobarrier© and Seprafilm©) are believed to physically interfere with adhesion re-formation and promote proliferation of the endometrium.  A meta-analysis of five randomized controlled trials showed that the incidence of post-operative adhesions was significantly reduced in patients who received hyaluronic acid gel compared to individuals who did not receive the gel.^l However, it is unclear if hyaluronic acid gel insertion improves future fertility as there is a lack of long-term follow-up evidence in the literature.^li A study by Lin et al (2013) showed that IUD and intrauterine balloon stents were both more effective than hyaluronic acid gel alone.^lii

Additional research is required to determine what, if any, effect treatment with the barrier methods described above have on future fertility, and which one is the most effective at reducing adhesion recurrence.

Is it possible to get pregnant with Asherman’s syndrome?

While sub-fertility is more common in individuals with Asherman’s syndrome, it does not mean that females with AS will not conceive and have a successful pregnancy.

Infertility in patients with AS may result from adhesions that block transport of sperm from the vagina to the fallopian tubes, preventing sperm movement towards the egg.^liii It may also be caused by adhesions in the uterus that impair normal implantation.  The true prevalence of infertility amongst individuals with AS is unclear, but one study of people with Asherman’s syndrome (2,151 cases) found that 43 percent experienced infertility.^liv

Currently, hysteroscopic removal of intrauterine adhesions (hysteroscopic adhesiolysis, discussed above) is often recommended before trying to conceive^lv since surgical treatment often improves the chance of pregnancy and pregnancy outcomes.

In one study of 357 AS patients receiving hysteroscopic adhesiolysis, the overall conception rate was 48 percent.^lvi When pregnancy rates were analyzed by severity of disease, 60.7 percent of individuals with mild adhesions, 53 percent with moderate adhesions, and 25 percent with severe adhesions, were able to spontaneously get pregnant after treatment. The average time to pregnancy was approximately 9.7 months, with a miscarriage rate below 10 percent.^lvii In other studies, the cumulative live birth rates for females who have hysteroscopic adhesiolysis varies from 25 to 80 percent depending on the study, age of patients, and severity of AS.^lviii

While conception rates are usually high following successful treatment of AS, adhesion recurrence can occur, especially in patients with severe scarring. Post-surgical recurrence is one of the most important factors that can hinder reproductive outcomes after IUA treatment.^lix While it is possible for fertility to be restored after AS treatment, fertility treatment (i.e., IVF) may still be necessary, especially in cases of infertility not due to AS, such as tubal disease or male-factor infertility.^lx

Females who have AS and do conceive may be at increased risk for pregnancy complications, such as placenta-related abnormalities (i.e., placenta accreta), miscarriage, restricted growth of the fetus, and preterm delivery.^lxi,lxii For example, in studies, moderate to severe AS/IUAs was found to carry a 14 percent risk of abnormal placentation (incorrect location of the placenta)^lxiii and an approximately 8 percent risk of post-partum hemorrhage (excessive bleeding).^lxiv Another study showed that females with moderate or severe cases of AS experience a combined 19 percent rate of miscarriage, stillbirth, and preterm delivery.^lxv  While there is an increased risk for these complications, many patients with a history of AS have uncomplicated pregnancies.

Conclusion

Receiving an Asherman’s syndrome diagnosis can be disheartening, particularly because of its potential impact on fertility. Individuals who are trying to conceive should talk to their doctor about available treatment options, including hysteroscopy.