Erica Schipper, Rafael F. Valle, Camran Nezhat
First reported in 1894, intra-uterine adhesions (IUA) were further characterized by the gynecologist Joseph Asherman,1-2 whose name was applied to the syndrome of partial or complete obliteration of the uterine cavity by adhesions with resulting menstrual abnormalities, infertility, or recurrent pregnancy loss.3 The true prevalence of Asherman's syndrome is difficult to determine given that IUA can be entirely asymptomatic; however, the condition has been estimated to affect 1.5% of women undergoing hysterosalpingography, between 5 and 39% of women with recurrent pregnancy loss and up to 40% of patients who have a history of surgical treatment for retained products of conception.4-5 The incidence of uterine synechiae has apparently risen in the past two decades, likely as a result of improved diagnosis or to more uterine surgery (including pregnancy-related curettage), or both.4
ETIOLOGY AND PATHOPHYSIOLOGY
Intrauterine adhesions are scars that result from trauma to the uterus, most commonly in association with recent pregnancy, although any instrumentation of the uterine cavity may predispose to the condition. In over 90% of cases, they are caused by curettage.1-2, 6 Usually, the trauma has occurred because of excessive bleeding requiring curettage 1 to 4 weeks after delivery of a term or preterm pregnancy or after an induced abortion. During this vulnerable phase of the endometrium, any trauma may denude or remove the basalis layer, causing the uterine walls to adhere to each other and form a permanent bridge and distorting the symmetry of the uterine cavity. In a randomized, controlled study comparing conservative, medical, and surgical management of incomplete abortion in 82 women, Tam et al. explored the effect of instrumentation of the uterus associated with recent pregnancy.7 Six months after the initial treatment, diagnostic hysteroscopy showed that conservative management and medical evacuation resulted in no IUA formation, whereas a small number of women (7.7%) in the surgical evacuation group developed thin, filmy synechiae. Surgical treatment of missed abortion is more likely to result in IUA than that for incomplete abortion (30.9% versus 6.4%).8 An increase in the time period between fetal demise and curettage in a missed abortion correspondingly increases the likelihood of adhesion formation, possibly due to fibroblastic activity of the remaining placental tissue.8 Not surprisingly, the risk of IUA also increases with the number of procedures, as demonstrated by a 1993 prospective study which found adhesions in 16% of women who underwent one surgical termination of pregnancy, 14% after two terminations, and 32% after three or more terminations.9 The adhesions were thin and filmy after one dilatation and curettage, but thick after two or more procedures. Hysteroscopic procedures, such as resection of submucosal leiomyomata or uterine septae and endometrial ablation, can also result in IUA formation, as can pelvic irradiation.5, 10 Taskin, et. al observed IUA in 31.3% of patients undergoing hysteroscopy for a single uterine myoma, with an increase to 45.5% in patients diagnosed with multiple myoma prior to hysteroscopy.11 In rare circumstances, conditions such as abdominal metroplasty and abdominal myomectomy may cause intrauterine adhesions, but these adhesions are usually the result of misplaced sutures rather than the true cooptation of denuded areas of myometrium that occurs following postpartum or postabortal curettage.6 The risk from Cesarean section is estimated at approximately 2% to 2.8%.8, 12
The role of infection in the development of IUA continues to be debated, with little definitive evidence of causality.5, 13 As a significant exception, IUA have been strongly associated with genitourinary tuberculosis, particularly in countries where the disease is endemic.13-14 These cases carry a particularly poor prognosis with regard to future fertility.14-15
The type and consistency of the adhesions vary: some are focal, some extensive, some thickened and dense with extensive fibromuscular or connective tissue components. The extent and type of uterine cavity occlusion correlate well with the extent of trauma during the vulnerable phase of the endometrium following a recent pregnancy. Some adhesions are localized, while others completely occlude the cavity. Consistency usually follows duration of adhesions, the older lesions being thicker, denser and composed of connective tissues.10, 16-18
Reproductive outcomes correlate well with the type of adhesions and the extent of uterine cavity occlusion. Therefore, it is useful to have a means of classifying these adhesions as filmy and composed of endometrial tissue, fibromuscular, or composed of connective tissue. The degree of uterine cavity occlusion is also important. Attempts to classify intrauterine adhesions by hysterosalpingography (HSG) give a good appraisal of the extent of uterine cavity occlusion, but it is impossible to determine the type of adhesions that are present. When using hysteroscopy alone, it is difficult to assess the extent of uterine cavity occlusion by visualization because the axis to the hysteroscopist is from the cervix to the fundus, whereas HSG outlines the uterine cavity in a radiographic anterior-posterior view. For this reason, the combination of hysterography and hysteroscopy has been used most commonly to assess not only the extent of uterine cavity occlusion, but also the type of adhesions found by hysteroscopy at the time of treatment. Valle and Sciarra used a three-stage classification of the extent and severity of intrauterine adhesions (mild, moderate and severe) based on the degree of involvement shown on HSG and the extent and type of adhesions found on hysteroscopy.6 Three stages of intrauterine adhesions are defined as follows:
Mild adhesions: filmy adhesions composed of basalis endometrial tissue causing partial uterine cavity occlusion.
Moderate adhesions: fibromuscular adhesions – characteristically thick and still covered with endometrium that may bleed upon division, that partially or totally occlude the uterine cavity.
Severe adhesions: adhesions composed of connective tissue only, lacking any endometrial lining and not likely to bleed upon division. These adhesions may partially or totally occlude the uterine cavity.
In 1988, the American Fertility Society (now the American Society of Reproductive Medicine) proposed a classification of intrauterine adhesions based on the findings at HSG and hysteroscopy and the correlation with menstrual patterns.19 The proposed classification system of Nasr et al. goes further to include obstetric history, as prior pregnancies, including those that end in abortion, may have positive prognostic value.20 March has proposed yet another classification system that also emphasizes types of adhesions and degree of cavity occlusion.13 Unfortunately, with so many different ways to classify IUA and no consensus on a universal system, the comparison of studies on Asherman's syndrome becomes quite difficult.
DIAGNOSIS AND INDICATIONS FOR TREATMENT
The clinical manifestations of IUA include abnormal menstruation or amenorrhea, cyclic pelvic pain, infertility, recurrent pregnancy loss, intrauterine growth restriction, and abnormal placentation.13 Almost one-half of women with Asherman's syndrome suffer from subfertility or infertility, which is the most common presenting concern among patients with IUA.8 The degree of menstrual dysfunction does not necessarily correspond to the intrauterine pathology, and eumenorrheic women with infertility have a higher incidence of Asherman's syndrome compared with women without evidence of infertility.10 Patients with minimal or focal intrauterine adhesions may not demonstrate obvious abnormalities and may continue to have normal menstruation.8
The menstrual abnormalities observed in Asherman's syndrome are caused by the physical obliteration of the cavity by adhesions. Cyclic pelvic pain can occur when the endocervical canal is blocked or when portions of functional endometrium are compartmentalized without an available route of egress. The remaining endometrium, however, is often atrophic due to the poor uterine perfusion that occurs in Asherman’s.21 The impaired blood supply likely results from myometrial fibrosis and vascular occlusion. The resulting poor endometrial development and scarring of the uterine cavity often involve the tubal ostia and endocervical canal, further affecting fertility.
Patients may also exhibit problems during pregnancy, particularly intrauterine growth restriction,22 should the adhesions not totally occlude the uterine cavity. When total amenorrhea and total uterine cavity occlusion exist, the patient will generally be infertile. Other problems associated with intrauterine adhesions include premature labor, fetal demise and ectopic pregnancy. When pregnancy is carried to term, placental insertion abnormalities, such as placenta accreta, increta, or percreta may occur.13, 23
The natural course of IUA is not well understood. Schenker and Margoliath evaluated 292 patients who did not receive treatment for intrauterine adhesions.8 Of these, 133 women (45.5%) conceived, and of these, only 50 (30%) achieved a term pregnancy, 38 (23%) had preterm labor, and 66 (40%) had a spontaneous abortion. Placenta previa, ectopic pregnancy, and abnormal placental insertions were diagnosed in 21 patients (13%).8
The most important clue to the diagnosis of intrauterine adhesions is a history of trauma to the endometrial cavity, particularly following delivery or abortion. Secondary to that is a history of amenorrhea or hypomenorrhea. Because intrauterine adhesions are not related to hormonal events, an intact hypothalamic-pituitary-ovarian axis should result in a biphasic basal body temperature curve demonstrating ovulation. Failure to withdraw from a progesterone challenge test in a patient who has a history of postpartum or postabortal intrauterine manipulation and who is amenorrheic will strengthen the diagnosis. Uterine sounding has been used to ascertain obstruction of the internal cervical os, but this test should be abandoned because of an increased danger of perforation of the uterus as well as inaccuracy of diagnosis.
The most useful screening test for intrauterine adhesions is hysterosalpingogram. It provides evaluation of the internal cervical os and uterine cavity, delineation of the adhesions, and information about the condition of the rest of the uterine cavity if adhesions do not completely occlude this area.24 About 1.5% of hysterosalpingograms will show intrauterine adhesions, and in those performed for repeated abortions, about 5% may demonstrate intrauterine adhesions.23 A history of trauma to the endometrial cavity will increase the yield of HSG for intrauterine adhesions in about 39% of patients.3 These adhesions are typically stellate, irregular shaped filling defects with ragged contours and in variable locations in the uterine cavity. They are most commonly found in the central corporeal cavity and, less frequently, at the cornuae and lower uterine segment.
Despite the usefulness of HSG as a screening method for patients suspected of having intrauterine adhesions, the final diagnosis is determined by direct visualization with hysteroscopy. Approximately 30% of abnormal hysterosalpingograms may be excluded or corrected by hysteroscopy.25 The diagnosis is confirmed by direct visualization, and appropriate treatment can be provided once the adhesions are observed endoscopically.
HSG is useful in determining the extent of uterine cavity occlusion but cannot provide an appraisal of the consistency and the type of intrauterine adhesions. For this reason, hysteroscopy becomes a useful adjunct to HSG by confirming the extent and type of adhesions. Hysteroscopy is considered the gold standard for the diagnosis of IUA. When compared to hysteroscopy-proven diagnosis, sonohysterography and HSG have a sensitivity of 75% with positive predictive values of about 43% and 50%, respectively.26 HSG functions as a good screening test for IUA with the added benefit of its ability to assess tubal patency.24 The limitations of HSG are a result of the inability to determine the etiology of observed filling defects. Like HSG, sonohysterography has limited accuracy in diagnosing IUA and is best utilized as a screening test. Three-dimensional sonohysterography represents a newer diagnostic modality that can not only detect IUA but also estimates endometrial cavity volume, which is decreased in the setting of Asherman's syndrome.27 Makris, et. al demonstrated sensitivity and specificity of 91.9% and 98.8% in using three-dimensional sonohysterography to detect any intrauterine abnormalities, including IUA, myomas, polyps, and mullerian anomalies.28 However, hysteroscopy is still 33% more sensitive in diagnosing IUA.27 Transvaginal ultrasound alone, in the absence of saline infusion, has a low sensivity in the diagnosis of Asherman's syndrome29, although it may be helpful in identifying residual areas of functional endometrium. Use of transvaginal sonography to evaluate endometrial thickness prior to surgery may contribute significant prognostic value in cases of severe Asherman's syndrome, as patients with minimal endometrial thickness respond poorly to treatment.30
Hysteroscopy can be used to evaluate the extent and location of IUA as well as provide a means of treatment. Office hysteroscopy provides a useful diagnostic modality and is often used for second-look hysteroscopy after treatment of IUA. In addition to diagnosis and treatment, hysteroscopy is required for the classification of IUA.
Other techniques such as MRI have been used to make this diagnosis, but their accuracy is not well established and not enough experience exists with these techniques to supplant HSG and hysteroscopy.31 Furthermore, the cost of MRI may be prohibitive.
METHODS OF TREATMENT
Lysis of diagnosed IUA is undertaken in patients with infertility, recurrent pregnancy loss, and pelvic pain. Treatment of intrauterine adhesions is surgical, consisting of removing adhesions by division. In the past blind methods of division were used with curettes, probes or dilators; additionally, hysterotomy-assisted division of adhesions under direct visualization was attempted, but these techniques have failed to produce acceptable results and largely have been abandoned. The introduction of modern hysteroscopy has permitted transcervical division of adhesions under visual guidance; hysteroscopic methods have used mechanical and electrosurgical means, such as hysteroscopic scissors, the resctoscope and lasers.
The goal of hysteroscopic lysis of adhesions is to restore the normal anatomy of the uterus. Hysteroscopy should be performed during the proliferative phase of the menstrual cycle, with the obvious exception of the amenorrheic patient. Patients should be informed that multiple procedures may be required, particularly in the event that dense, extensive adhesions are encountered.
One approach to IUA is the sharp lysis of adhesions with semi-rigid hysteroscopic scissors under direct visualization. The procedure may be initiated using a smaller-diameter hysteroscope with a single port allowing the introduction of semi-rigid hysteroscopic scissors. If adequate for treatment, this can spare the patient the more extensive cervical dilation required to introduce the larger operative resectoscope. Because intrauterine adhesions in general are avascular, they may be divided rather than completely excised; treatment has been similar to that for division of a uterine septum. The adhesions are divided centrally, allowing the uterine cavity to expand upon division of the adhesions. The semi-rigid hysteroscopic scissors, because of their ease of manipulation, are helpful in selectively dividing these adhesions, particularly as adhesions tend to retract upon cutting. Occasionally, thick connective tissue adhesions form very thick stumps and benefit not only from division but also from removal. To achieve this effect, a sharp punch-biopsy forceps becomes most useful to selectively sculpt the uterine cavity in order to achieve a uniform symmetry. This technique is also useful at the cornuae, particularly at the tubal ostia.
Fluids with electrolytes should be used when dividing these adhesions mechanically with scissors, because adhesions are cut close to the myometrial tissue and the extensive area of denudation may predispose to fluid intravasation. Normal saline, dextrose 5% in half normal saline and Ringer’s lactate are most appropriate. Care must be taken to measure the amount of fluid used and the amount recovered when using the hysteroscope. The instrument used in operative hysteroscopy should have both inflow and outflow channels, permitting an estimate of the amount of fluid that has not been recovered. Care also must be taken to ensure that the intrauterine pressure does not exceed the mean arterial pressure of about 100 mmHg. Monitoring both fluid deficit and pressure can significantly reduce the risk of excessive intravasation of fluid.
Depending on the extent of uterine cavity occlusion, division is done under visual control by cutting the adhesions in the middle to avoid damage of the uterine wall. In cases of total uterine cavity occlusion, a selective dissection of the adhesions begins at the internal cervical os until a neocavity is created. Dissection then progresses until the cornuae and tubal ostia are free. When extensive adhesions are present, the hysteroscopist should be alert to perforation. Concomitant laparoscopy or sonography should be strongly considered. Upon completion of the procedure, indigo carmine is injected transcervically to test the patency of the tubes using laparoscopic visualization.6, 32
The advantages of using hysteroscopic scissors for the division of intrauterine adhesions are mechanical. These tools provide excellent landmarks when dividing these adhesions, particularly when approaching the adjacent myometrium. Bleeding may be observed at the myometrium, alerting the surgeon to stop further dissection so as to avoid perforation. No scattering of energy is produced to damage the small areas of healthy endometrium, which are the reservoir for future re-epithelialization. With regard to disadvantages, semi-rigid instruments are sometimes difficult to manipulate, particularly at the lateral walls of the uterine cavity. Scissors may not provide the sharpness or appropriate angle to lyse some adhesions, and scissors often do not close well distally and need to be readjusted and sharpened frequently.
For severe IUA, a possible approach involves inserting a Pratt cervical dilator directed toward each cornua under laparoscopic guidance, thereby converting the obliterated cavity into a uterine septum.33 Each ostium is then identified using a 5mm hysteroscope, and the hysteroscopic scissors are used to divide the ‘uterine septum’.
Treatment of intrauterine adhesions using the resectoscope is an alternative to mechanical tools. The resectoscope can be used to divide intrauterine adhesions either with a resetting loop, a loop bent forward, or specially designed electrodes that can be directly applied to the adhesions dividing them easily. These instruments are in the form of knives or wires that must be specifically and selectively directed to the adhesions, particularly those in the lateral portion uterus or in the cornuae. When using the resectoscope with monopolar cautery, fluids without electrolytes must be used – for example dextrose 5% in water, glycine 1.5%, sorbitol 3.5%, and mannitol 5% -- which provide excellent visualization and are useful distending media. Use of these non-electrolyte fluids has a disadvantage of causing potential organ damage in the event of excessive intravasation. Systems which utilize bipolar energy allow the use of saline as distending medium, which decreases the risk of fluid overload. As an advantage, the use of electrosurgery may decrease bleeding due to coagulation. When dividing adhesions, however, the resectoscope loop may not be the appropriate electrode to use because it designed to resect rather than to selectively divide the adhesions centrally. When the resectoscopic loop has been used for this purpose, several complications have occurred, particularly as result of future sacculations of the uterus, dehiscences and perforations. Ascertaining where adhesions end and where the normal myometrium begins is difficult, and resection may be so deep that portions of the myometrium may be shaved during division of the adhesions. Electrodes such as the knife or wire types that can selectively be directed to the adhesions and divide them systematically have been specifically designed for this purpose. Nonetheless, concern remains about energy scatter and damage to the peripheral healthy endometrium. With use of specific electrodes and appropriate choice of cutting mode where possible, lowest effective power, and limited duration of exposure, this effect may be somewhat decreased. It is important to monitor the operation with concomitant laparoscopy or sonography because the landmarks at the intersection of adhesions and myometrium may be lost, and the coagulating effect this energy on the myometrium may obscure a view of small vessels that, when bleeding, warn the hysteroscopist to stop further dissection. Finally, thermal damage to surrounding organs with or without perforation is a risk.34
Treatment of intrauterine adhesions with fiberoptic lasers, such as the neodymium-doped yttrium aluminum garnet (Nd-YAG), argon and KTP/532 may also be used to divide intrauterine adhesions. Their application, however, has been somewhat limited. The Nd-YAG laser with sculptured or extruded fibers may be a useful tool to selectively divide intrauterine adhesions, particularly those that are lateral and fundal.15 Care must be taken to obliterate these fibers by direct contact and selectively be aware of the overall symmetry of the uterine cavity as the coagulating power of the laser may cause an effect similar to that of electrosurgery, that is, both coagulating and cutting. The landmarks of the adjacent myometrium may be lost while performing division of the adhesions. Small arteries traversing the myometrium may not bleed, so dissection may proceed further than is necessary or safe. The hysteroscopic manipulation of fiberoptic lasers is fairly easy and facilitated by the use of oblique telescopes. The argon and KTP/532 lasers use the sharpest fibers to cut and limit coagulation effect.35
Because lasers are not conductive, fluids with electrolytes should be used. Normal saline, dextrose 5% in half normal saline and ringers lactate provide excellent visualization and contain sodium, which decreases risk of adverse outcomes if excessive fluids are absorbed. The use of these electrolyte-containing fluids will not prevent pulmonary edema but will decrease the risk of hyponatremia; therefore a larger volume of fluid may be used than when using fluids devoid of electrolytes. Ideally, a hysteroscope with a continuous flow system or one with true inflow and outflow measurement should be used to keep an accurate account of the fluid deficit.
Use of the laser is attractive and has the benefit of easy manipulation, but it requires more time than use of mechanical tools, such as hysteroscopic scissors. It is important, therefore, when using this type of energy to expedite the procedure as much as possible so as to prevent excessive fluid from being intravasated.
Vaporizing electrodes have also been used with electrolyte solutions as distending media. Concerns similar to those of electrosurgery apply, particularly with limited evaluation of the penetration and scatter these produce by these electrodes when applied to tissues.36
During hysteroscopy for severe Asherman's syndrome, laparoscopic guidance can be used as a precautionary measure against uterine perforation, although some studies have found this unnecessary. Simultaneous laparoscopy provides the added benefit of identifying other potential infertility factors. Real-time trans-abdominal ultrasound can also facilitate dilatation of the challenging cervix and subsequent hysteroscopy, although resolution of the endometrial cavity may be limited when there is little or no endometrium present.
The treatment of severe adhesions remains a challenge. Other methods have been suggested to simplify the treatment, such as concomitant fluoroscopy, sonography, trans-fundal uterine injection of dyes, coaxial injection of radio-opaque material, vital dyes to distinguish fibrous adhesions from residual endometrium, endometrial electrosurgical scoring, blind lateral sounding of the uterine cavity and hysterotomy for trans-fundal dissection of the adhesions. However, all these methods have been used in a limited fashion and have not consistently proved their efficacy.37-38
INTRA- AND POSTOPERATIVE MANAGEMENT
The principal goal of therapy is to remove the adhesions surgically. A major concern, then, is the recurrence of adhesions following surgery. Postoperative adhesion formation occurs in almost 50% of the most severe of cases and in 21.6% of moderate cases.6 Mild synechiae appear to be the exception in that they tend not to recur.
Because most of these patients have a sclerotic or destroyed endometrium, they need other adjunctive therapy to promote re-epithelialization and a means of continued separation of the uterine cavity walls to prevent the reformation of adhesions. Such adjuncts include mechanical intrauterine barriers, prophylactic antibiotics and estrogens to promote epithelialization. There is little consensus or evidence-based data to recommend a specific regimen for prevention of recurrent adhesions depending on the severity of Asherman's syndrome. Empirically, the more severe cases tend to be managed more aggressively in terms of adhesion prevention.5
Mechanical barriers used to prevent recurrence of adhesions include intrauterine devices (IUD), a pediatric foley catheter,8 or an intrauterine balloon. The IUD is left in place for 1-3 months, but the catheters are removed after 1-2 weeks.15 Previously, the Lippes Loop IUD was favored for prevention of adhesions due to its large surface area and otherwise inert qualities; however, this device is no longer available in the United States. Currently available devices are T-shaped and include those impregnated with progestin, which suppress endometrial proliferation, and copper-containing devices, which are highly inflammatory. Both of these are sub-optimal in preventing intrauterine adhesions. Consideration should instead be given to pediatric foley catheters or dedicated uterine stents such as the Cook Balloon Uterine Stent (Cook Medical, Bloomington, IN), which conforms to the uterine shape.13
There are no data to support the use of prophylactic antibiotics prior to hysteroscopy for Asherman's syndrome, and the American College of Obstetricians and Gynecologists does not recommend this practice for diagnostic or operative hysteroscopy or for IUD placement.39 However, prophylactic antibiotics are frequently used in these patients in view of a traumatized endometrium and the extensive manipulation typically required. Antibiotic choice is most often in the form of cephalosporins: cefazolin 1g intravenously 30 minutes before surgery, followed by cephalexin 500mg four times daily by mouth for a week, should an intrauterine splint be placed. Alternatively, doxycycline 100mg twice daily for the duration of the stent or balloon placement may be used post-operatively. In cases of tuberculous endometritis, adequate antibiotic treatment must be completed prior to proceeding with surgical intervention.
Adjunctive hormonal therapy consists of high dose estrogen for 30-60 days, depending on the extent of uterine cavity occlusion and the type of adhesions found. The more extensive and old the adhesions, more prolonged the hormonal treatment must be. In the last 10 days of this artificial cycle, oral progestin is given to induce withdrawal bleeding.6, 13 Upon completion of the hormonal treatment and once withdrawal bleeding has ceased, HSG and/or office hysteroscopy is performed to assess the results of the operation and decide on further therapy or initiation of attempts at conception.6, 40 Obstetric complications, particularly placenta accreta and its variants, have been observed in patients who conceive prior to documentation of adhesion resolution following synechiolysis.13, 34
Consideration should also be given to applying the above adhesion prevention techniques following other uterine instrumentation, such as dilation and curettage or hysteroscopic myomectomy, in order to prevent IUA in the first place.
Recently, the use of newer adhesion barriers in the prevention of IUA has been explored. Tsapanos et al. performed a randomized, controlled study of postoperative, intrauterine insertion of Seprafilm, a bioresorbable carboxymethylcellulose membrane, to determine whether it would prevent or decrease IUA in women who had undergone surgical treatment for incomplete, missed, or recurrent abortion.41 The Seprafilm group demonstrated increased pregnancy rates and decreased incidence of IUA formation. Guida et al. investigated the use of autocrosslinked hyaluronic acid gel after hysteroscopy in another prospective, randomized, controlled trial and found decreased incidence and severity of de novo IUA formation in patients treated with the gel.42 Additionally, Amer et al. have shown some success in reduction of recurrent IUA with the use of human amnion as a biologic barrier placed after hysteroscopic adhesiolysis.43 Although these results are promising, confirmatory studies are lacking to support the widespread use of any of these products.
RESULTS OF TREATMENT
Surgical management of IUA is generally favorable. The results of hysteroscopic treatment of intrauterine adhesions have correlated well with the extent of uterine cavity occlusions and the type of adhesions present. One hysteroscopy is usually adequate to obtain acceptable anatomy, and very few patients require more than two procedures. Normal menstruation is restored in over 90% of patients.6, 40 On second-look hysteroscopy, Pabuccu, et al. noted recurrence of IUA in 60% of patients treated for severe adhesions with rare or absent recurrence in patients treated for minimal or moderate adhesions.15
Normal menstruation is restored in over 90% of the patients following lysis of IUA.6, 40 In Roge et al.’s study of 102 patients with Asherman’s syndrome, 44% were unable to conceive after treatment. Of these, almost 60% had additional infertility factors, emphasizing the need for a thorough infertility evaluation along with the surgical treatment of IUA.44 This evaluation should include endocrine studies, exclusion of male factor infertility, and assessment of tubal patency.
Reproductive outcomes correlate well with type of adhesions and the extent of uterine cavity occlusion. Of 187 patients treated hysteroscopically by Valle and Sciarra, removal of mild filmy adhesions in 43 cases gave the best result, with 35 (18%) term pregnancies.6 In 97 moderate cases of fibromuscular adhesions, 64 (66%) went on to have term pregnancies. In 47 severe cases of connective tissue adhesions, 15 (32%) had subsequent term pregnancies. Overall restoration of menses occurred in 90% of the patients, and the overall term pregnancy rate was 79.7%. Roy et al. similarly found higher rates of conception following hysteroscopic adhesiolysis in patients with mild Asherman’s (58%) as compared with moderate and severe (30% and 33.3%, respectively).22 Term pregnancy rates following adhesiolysis appear to be better in patients presenting with recurrent pregnancy loss than in those presenting with infertility.6, 15
Results following treatment of intrauterine adhesions using the resectoscope have been similar; however, the reported postoperative complications may be serious and appropriate precautions must be taken when using this type of instrument. A few series reported lysis of adhesions with fiberoptic lasers, and when used appropriately, results with laser therapy should not vary much from those reported with electrosurgery.34 45
SUMMARY AND CONCLUSIONS
Intrauterine adhesions adversely affect menstruation and reproduction. Infertility, recurrent pregnancy loss, or pelvic pain, particularly with a history of uterine instrumentation in association with pregnancy, should raise suspicion of Asherman’s syndrome.
Undoubtedly, the management of intrauterine adhesions has advanced significantly due to the development of operative hysteroscopy. This approach has offered more accurate evaluation and a more refined treatment, with markedly improved surgical results. The hysteroscopic treatment of intrauterine adhesions provides the opportunity for restoration of the uterine cavity’s symmetry, which resolves menstrual abnormalities and leads to improvement of reproductive outcomes with the removal of a major cause of recurrent abortion and infertility. The treatment of intrauterine adhesions can be accomplished by four different methods: scissors, resectoscope, fiberoptic lasers and vaporization with bipolar electrodes. All have advantages and disadvantages and must be used with respect to knowledge of each particular technology and its drawbacks. Each technique should be tailored not only to the anatomy and etiology of each process but also to the experience and knowledge of the operator. The surgeon should select the most appropriate method and technology for each patient. Management may require multiple procedures. Adjuvant measures, such as laparoscopy, ultrasound, or fluoroscopy, can be used to guide the hysteroscopic procedure in the more severely affected patients. Postoperative care should be tailored to the individual patient and procedure. The lysis of moderate to severe adhesions warrants the postoperative use of hormonal therapy to help regenerate the endometrium and an intra-uterine Foley or stent to mechanically separate the walls of the endometrial cavity with the purpose of preventing adhesion reformation. Such measures should also be considered following other types of uterine instrumentation with the goal of preventing Asherman’s syndrome. Given the frequency of adhesion recurrence, second-look hysteroscopy or alternate evaluation, such as HSG or sonohysterography, should be strongly considered, particularly prior to attempting conception.
The goals of therapy should be a successful pregnancy for those patients with impaired reproduction with the least morbidity possible and the diminution of unnecessary cost.19 Versatility plays a significant role in the selection of therapeutic alternatives; the surgeon must intelligently select the best method for each individual patient while considering their own skills and available resources.
1. Asherman JG. Amenorrhoea traumatica (atretica). J Obstet Gynaecol Br Emp 1948;55:23-30.
2. Asherman JG. Traumatic intra-uterine adhesions. J Obstet Gynaecol Br Emp 1950;57:892-6.
3. Klein SM, Garcia CR. Asherman's syndrome: a critique and current review. Fertil Steril 1973;24:722-35.
4. Al-Inany H. Intrauterine adhesions. An update. Acta Obstet Gynecol Scand 2001;80:986-93.
5. Kodaman PH, Arici A. Intra-uterine adhesions and fertility outcome: how to optimize success? Curr Opin Obstet Gynecol 2007;19:207-14.
6. Valle RF, Sciarra JJ. Intrauterine adhesions: hysteroscopic diagnosis, classification, treatment, and reproductive outcome. Am J Obstet Gynecol 1988;158:1459-70.
7. Tam WH, Lau WC, Cheung LP, Yuen PM, Chung TK. Intrauterine adhesions after conservative and surgical management of spontaneous abortion. J Am Assoc Gynecol Laparosc 2002;9:182-5.
8. Schenker JG, Margalioth EJ. Intrauterine adhesions: an updated appraisal. Fertil Steril 1982;37:593-610.
9. Friedler S, Margalioth EJ, Kafka I, Yaffe H. Incidence of post-abortion intra-uterine adhesions evaluated by hysteroscopy--a prospective study. Hum Reprod 1993;8:442-4.
10. March CM, Israel R, March AD. Hysteroscopic management of intrauterine adhesions. Am J Obstet Gynecol 1978;130:653-7.
11. Taskin O, Sadik S, Onoglu A, et al. Role of endometrial suppression on the frequency of intrauterine adhesions after resectoscopic surgery. J Am Assoc Gynecol Laparosc 2000;7:351-4.
12. Roge P, d'Ercole C, Cravello L, Boubli L, Blanc B. [Hysteroscopic treatment of uterine synechias. A report of 102 cases]. J Gynecol Obstet Biol Reprod (Paris) 1996;25:33-40.
13. March CM. Asherman's syndrome. Semin Reprod Med 2011;29:83-94.
14. Sharma JB, Pushparaj M, Roy KK, et al. Hysterosalpingographic findings in infertile women with genital tuberculosis. Int J Gynaecol Obstet 2008;101:150-5.
15. Pabuccu R, Atay V, Orhon E, Urman B, Ergun A. Hysteroscopic treatment of intrauterine adhesions is safe and effective in the restoration of normal menstruation and fertility. Fertil Steril 1997;68:1141-3.
16. Foix A, Bruno RO, Davison T, Lema B. The pathology of postcurettage intrauterine adhesions. Am J Obstet Gynecol 1966;96:1027-33.
17. Siegler AM, Kontopoulos VG. Lysis of intrauterine adhesions under hysteroscopic control. A report of 25 operations. J Reprod Med 1981;26:372-4.
18. Siegler AM, Valle RF. Therapeutic hysteroscopic procedures. Fertil Steril 1988;50:685-701.
19. The American Fertility Society classifications of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, mullerian anomalies and intrauterine adhesions. Fertil Steril 1988;49:944-55.
20. Nasr AL, Al-Inany HG, Thabet SM, Aboulghar M. A clinicohysteroscopic scoring system of intrauterine adhesions. Gynecol Obstet Invest 2000;50:178-81.
21. Polishuk WZ, Siew FP, Gordon R, Lebenshart P. Vascular changes in traumatic amenorrhea and hypomenorrhea. Int J Fertil 1977;22:189-92.
22. Roy KK, Baruah J, Sharma JB, Kumar S, Kachawa G, Singh N. Reproductive outcome following hysteroscopic adhesiolysis in patients with infertility due to Asherman's syndrome. Arch Gynecol Obstet 2010;281:355-61.
23. Dmowski WP, Greenblatt RB. Asherman's syndrome and risk of placenta accreta. Obstet Gynecol 1969;34:288-99.
24. Roma Dalfo A, Ubeda B, Ubeda A, et al. Diagnostic value of hysterosalpingography in the detection of intrauterine abnormalities: a comparison with hysteroscopy. AJR Am J Roentgenol 2004;183:1405-9.
25. Valle RF, Sciarra JJ. Current status of hysteroscopy in gynecologic practice. Fertil Steril 1979;32:619-32.
26. Soares SR, Barbosa dos Reis MM, Camargos AF. Diagnostic accuracy of sonohysterography, transvaginal sonography, and hysterosalpingography in patients with uterine cavity diseases. Fertil Steril 2000;73:406-11.
27. Weinraub Z, Maymon R, Shulman A, et al. Three-dimensional saline contrast hysterosonography and surface rendering of uterine cavity pathology. Ultrasound Obstet Gynecol 1996;8:277-82.
28. Makris N, Kalmantis K, Skartados N, Papadimitriou A, Mantzaris G, Antsaklis A. Three-dimensional hysterosonography versus hysteroscopy for the detection of intracavitary uterine abnormalities. Int J Gynaecol Obstet 2007;97:6-9.
29. Salle B, Gaucherand P, de Saint Hilaire P, Rudigoz RC. Transvaginal sonohysterographic evaluation of intrauterine adhesions. J Clin Ultrasound 1999;27:131-4.
30. Schlaff WD, Hurst BS. Preoperative sonographic measurement of endometrial pattern predicts outcome of surgical repair in patients with severe Asherman's syndrome. Fertil Steril 1995;63:410-3.
31. Confino E, Friberg J, Giglia RV, Gleicher N. Sonographic imaging of intrauterine adhesions. Obstet Gynecol 1985;66:596-8.
32. Neuwirth RS, Hussein AR, Schiffman BM, Amin HK. Hysteroscopic resection of intrauterine scars using a new technique. Obstet Gynecol 1982;60:111-3.
33. McComb PF, Wagner BL. Simplified therapy for Asherman's syndrome. Fertil Steril 1997;68:1047-50.
34. Friedman A, DeFazio J, DeCherney A. Severe obstetric complications after aggressive treatment of Asherman syndrome. Obstet Gynecol 1986;67:864-7.
35. Newton JR, MacKenzie WE, Emens MJ, Jordan JA. Division of uterine adhesions (Asherman's syndrome) with the Nd-YAG laser. Br J Obstet Gynaecol 1989;96:102-4.
36. Loffer FD. Preliminary experience with the VersaPoint bipolar resectoscope using a vaporizing electrode in a saline distending medium. J Am Assoc Gynecol Laparosc 2000;7:498-502.
37. Thomson AJ, Abbott JA, Kingston A, Lenart M, Vancaillie TG. Fluoroscopically guided synechiolysis for patients with Asherman's syndrome: menstrual and fertility outcomes. Fertil Steril 2007;87:405-10.
38. Valle RF. Intrauterine Adhesions (Asherman's Syndrome). In: Marty R BB, deMontgolfier R, ed. Office and Operative Hysteroscopy. New York: Springer-Verlag; 2002:229-42.
39. ACOG practice bulletin No. 104: antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol 2009;113:1180-9.
40. March CM, Israel R. Gestational outcome following hysteroscopic lysis of adhesions. Fertil Steril 1981;36:455-9.
41. Tsapanos VS, Stathopoulou LP, Papathanassopoulou VS, Tzingounis VA. The role of Seprafilm bioresorbable membrane in the prevention and therapy of endometrial synechiae. J Biomed Mater Res 2002;63:10-4.
42. Guida M, Acunzo G, Di Spiezio Sardo A, et al. Effectiveness of auto-crosslinked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic surgery: a prospective, randomized, controlled study. Hum Reprod 2004;19:1461-4.
43. Amer MI, Abd-El-Maeboud KH, Abdelfatah I, Salama FA, Abdallah AS. Human amnion as a temporary biologic barrier after hysteroscopic lysis of severe intrauterine adhesions: pilot study. J Minim Invasive Gynecol 2010;17:605-11.
44. Roge P, D'Ercole C, Cravello L, Boubli L, Blanc B. Hysteroscopic management of uterine synechiae: a series of 102 observations. Eur J Obstet Gynecol Reprod Biol 1996;65:189-93.
45. Intrauterine Adhesions. In: Seigler AM VR, Lindemann HJ, Mencaglia L, ed. Therapeutic Hysteroscopy: Indications and Techniques. St. Louis: CV Mosby; 1990:82-105.