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Adhesions & Asherman's Syndrome
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Scar is an undesirable end product of surgery but scar formation forms a necessary healing process.
When a woman undergoes an open abdominal myomectomy, she is at risks of developing two types of scars after the operation: intra-abdominal (scars at the site of cut (incision) on the abdomen to access the womb and incision on the surface of the womb to access the fibroids) and intrauterine (scars on the walls of the womb inside the uterine cavity where the fibroids attached to the wall prior to the operation). In the case of hysterectomy, the risk is mainly abdominal scar formation.
1. What are adhesions?
Adhesions are internal scars which are made up of strand like fibrous tissues forming abnormal bridges/bonds between two parts of the body after trauma, through complex processes involving the injured tissues and the peritoneum.

Adhesions may occur at the site of a surgical procedure. Surgical procedures most commonly associated with adhesion formation include but not limited to myomectomy, total abdominal hysterectomy, cesarean section, ovarian and tubal surgery and excision of endometriosis.
2. What is Asherman's syndrome?
A condition where scar formation causes the walls of your womb adhere to one another, usually triggered by uterine inflammation due to trauma to the endometrium or gravid uterine cavity. Scar formation begins immediately after uterine trauma and new scars cease to form 7 days after that.
Medical terms: Uterine synechiae, intrauterine adhesions.
History: It was first described by Heinrich Fritsch in 1894 and later studied by Israeli gynaecologist Joseph Asherman in 1948.
Prevalence: It occurs most frequently after incomplete abortion (50%), postpartum haemorrhage (24%) and elective abortion (17.5%). Other less common triggers include myomectomy, hysteroscopic resection, D&C, caesarean section, tuberculosis, caustic abortive agents and uterine packing.
3. What are the causes of Asherman's?
In many cases, Asherman's is associated with a procedure called a D&C (curettage), which is performed following a miscarriage or birth. It is rarely associated with a D&C for diagnostic evaluation of the uterine lining.
Incidence of Asherman's following trauma to a gravid uterine cavity is shown in table below:

Incidence of Asherman's caused by trauma to a gravid uterine cavity
Procedure Rate of Asherman's Reference
Post abortion/miscarriage curettage 66.7 % [a]
Post partum curettage caesarean section 21.5% [a]
Evacuation of a hydatidiform mole 0.6% [a]

Asherman's can also result from intrauterine surgery to remove fibroids, uterine structural defects (septum, bicornuate uterus, large polyps), or at caesarean section infections related to IUD use (or the placement of any foreign object within the cavity of the womb).

Incidence of Asherman's caused by trauma to a nongravid endometrium
Procedure Rate of Asherman's Reference
Diagnostic curettage 1.6% [a]
Abdominal myomectomy 1.3% [a]
Cervical biopsy & polylectomy 0.5% [a]
Infection of an IUD 0.2% [a]
Use of radium 0.05% [a]
Resection of septa 6.7% [b]
Hysteroscopic resection of solitary fibroids 31.3% [b]
Hysteroscopic resection of multiple fibroids 45.5% [b]
UAE 1 case [c]
Uterine devacularisation 1 case [d]
Endometrial ablation by thermal balloon 36.4% [e]
[a] Schenker & Margalioth. Ferility and Sterility 1982; 37: 593-610.
[b] Taskin O et al. J Am Assoc Gynecol Laparosc 2000; 7: 351-354.
[c] Davis C et al. Clin Radiol 2002; 57: 317-318.
[d] Roman H et al. Fertil Steril 2005; 83: 755-757.
[e] Leung PL et al. Fertil Steril 2003; 79: 1226-1228.
4. What are the symptoms of intra-abdominal and intrauterine (Asherman's) adhesions?
The symptoms of adhesions are summarised in the table below:

Symptoms of adhesions
Intra-abdominal Intrauterine (Asherman's)
  • Chronic pelvic pain, which is a major problem accounting for 10% of gynaecological visits and 50% of laparoscopic investigations. Up to 50% of all cases of pelvic pain could be caused by adhesive disease. Pain is thought to be caused by restriction of movement of pelvic organs by the adhesive scars.
  • Nausea.
  • Infertility: Intra-abdominal adhesive disease is responsible for up to 15-20% of all cases of infertility.
  • Small bowel obstruction: 54% to 74% of small bowel obstruction cases are caused by adhesions. Up to 56% of women with adhesion-related small bowel obstruction have had at least one previous pelvic procedure, most commonly hysterectomy. About 5% of women receiving radical hysterectomy develop small bowel obstruction and more than half of these women require surgical management.
  • Intrauterine adhesions are not usually associated with chronic pain except in the case of obstruction occuring at the internal os (the opening of the cervix into the body of the womb) leading to hematometra (menstrual blood accumulating behind the obstructed internal os in the cavity of the womb)
  • No menstrual flow (amenorrhea) or decreased menstrual flow (hypomenorrhea).
  • Infertility: Adhesions involving the uterus and fallopian tubes may cause infertility after myomectomy, which can negate the infertility enhancement desire.
  • Recurrent miscarriages.
These symptoms are more likely to indicate Asherman's syndrome if they occur suddenly after a D&C procedure or other gynaecological surgery.
5. What are scars made of?
The scars are made of fibrous connective tissue bands with or without glandular tissue which may be firmly or dense.
6. How are the scars formed?
Adhesion begins immediately after gynaecological surgery and the process of scar formation continues up to 7 days.
Cellular activity of scar formation
Time after surgery What is happening
Immediately Inflammation causes the macrophages, fibroblasts and fibrin matrix to move the surface of the wound.
Day 3 - Macrophages form the foundation of the advancing adhesions;
- Proliferation of fibroblasts and vasculisation result in fibrin matrix advancement.
Day 5 Scars are increasing in vascular and organised in structure.
Day 7 No new scar formation.
7. How is Asherman's diagnosed?
A pelvic exam is usually normal. Diagnosis usually begins with medical history combined with a degree of suspicion. Before embarking on any confirmatory test, other causes of amenorrhoea and menstrual disturbances should be ruled out. The tests to be carried out include: pregnancy, blood count, FSH, TSH and prolactin.
If Asherman's syndrome is suspected, your doctor may recommend a hysterosalpingogram (an X-ray test of the cavity of the womb) or hysteroscopy (an outpatient surgical procedure) or saline hysterogram or sonogram. These tests may reveal scar tissue partially or completely filling the womb cavity.
7.1. Hysterosalpingography
In this procedure, a radio contrast dye is injected and x-rays are used to assess the womb and fallopian tubes.
Complications of this technique are few but include bleeding, infection and crampy pain. Reaction to the dye material and perforation of the uterus are also rare. Crampy pain is relieved by non-steroidal anti-inflammatories such as ibuprofen. Some doctors prescribe antibiotics to prevent infection.
7.2. Hysteroscopy
This is the gold standard method of diagnosis. During hysteroscopy, a small camera is inserted through the cervix that allows your gynaecologist to look at the inside of your womb under magnification to assess the extent of adhesions.
7.3. saline Hysterography
The saline hysterogram or sonogram (SHG) is a study in which sterile saline is placed into the uterine cavity with a catheter and a transvaginal ultrasound is performed. In the USA, this is can be carried out in an office of a gynaecologist.
8. How is Asherman's treated?
The objective of modern treatments focuses on:
  • The actual management of adhesions.
  • The prevention of adhesion re-formation.
The scars are removed by lysis (cutting away) vaginally or abdominally using an instrument called hysteroscope under direct vision. Hysteroscope uses energy to "burn" away the scar tissue. The energy can be laser. Laparoscopic or ultrasound guidance may be required for dense scar tissue and when the entry into the cervix is difficult. When the cervix was occluded, hysteroscopy guided by abdominal sonography had been shown to be suitable [Zapardiel et al 2008].

After the removal of scar tissue, the womb cavity must be kept open to prevent reformation of scars. A small stent or balloon is placed inside the womb for several days and you may be prescribed oestrogen therapy for several months while the lining of the womb heals.
There is little data to guide what is the best optimal approach for keeping the womb cavity open after Asherman's treatment.

The necessary use of hormones for prevention of scar formation is based on general consensus. There is no standard regimen or protocol for the dosage of hormones or starting dose or how long they should be given for. Both oestrogens and progesterones have been used at high doses for promoting regrowth of the lining of the womb.
One regimen involves the use of 2.5mg conjugated oestrogens at 4 times the standard physiologic dose to stimulate rapid endometrial proliferation after primary surgery and the regimen is limited to 1 month.
9. What are treatment outcomes of Asherman's?
  • There are no universally-acceptable defined clinical end-points for treatment success.
  • Restoring fertility as well as menses was the main interest for many women with Asherman's.
  • Intra-uterine pregnancy rates range from 22-45% and live birth rates range from 28-32% after treatment.
  • About 88.2% of the women get their normal menstrual periods back after the lysis treatment.
  • After hysteroscopic adhesiolyis, post treatment menstrual pattern and reformation of intrauterine adhesions are two important factors which determine the rates of success of conception [Yu et al 2008]. Women with normal periods after hysteroscopic adhesionlyis and those with normal uterine cavity are more likely to conceive than those with hypo/amenorrhea. Restoration of normal menses is prerequisite for pregnancy [Mackenzie et al 2008].
  • Recurrent adhesion is a major problem, which is determined by the severity of the original adhesive condition (see Table below).

    Asherman's Recurrence Rates
    Severity of the initial scar condition Rates
    Mild None
    Moderate 16.75%
    Severe 41.9%
10. What are treatment complications for Asherman's?
  • Most common complications are bleeding and perforation of the womb, rarely pelvic infection, and recurrence of adhesions.
  • Pregnancy related complications. Risks for those who manage to achieve pregnancy include significant risk for placenta acreta, subsequent blood loss & transfusion and hysterectomy.
11. What are the preventative measures for Asherman's?
  • Sadly, there is currently no universal method of adhesions prevention other than oestrogen therapy with or without balloon or IUD (non medicated) but this usage is in the realm of "expert opinion".
  • Very few gel barrier has been shown to be effective in reducing intrauterine adhesions.
  • Many gynaecologists feel that cutting (lysing) adhesions in the cavity of the uterus with mechanical scissors is associated with less subsequent adhesion formation than using electrical or laser energy to cut the adhesive tissues.
11.1. Intrauterine device (IUD)
Post operative insertion of an IUD keeps the raw dissected surface separated during the initial healing phase and thereby may reduce the chances the walls re-adhere to one another.
Up to now, there have been no randomised, controlled clinical trials to prove the usefulness of IDUs in preventing adhesion reformation. IUD insertion may also carry a small risk of perforation of the uterus.
In the case of transcervical resection of septa in infertility women, Zheng demonstrated that IUD was not helpful and advocated for the use of individualised post-operative artificial cycle treatment and GnRHa therapy.
11.2. Foley Balloon Catheter
The balloon cathether is inserted in to the uterine cavity then inflated and kept there for 7-10 days after lysis of adhesion. One study showed that Foley catheter was safer and more effective than IUD.
Also, one prospective controlled study found that intrauterine balloon application after operative hysteroscopy is of value in preventing uterine adhesions.
11.3. Hyaluronic Acid (HA)
Hyaluronic acid is a natural component of the extracellular matrix, the vitreous humour and synovial fluid of the joint.
Seprafilm, a membrane made from chemically modified HA, is cut into 2 pieces and rolled into 2 thin cylinders. The first cylinder is inserted into the endometrial cavity and the second cylinder is detained in the endocervical canal, covering the exo-orifices and endo-orifices. The Seprafilm turns into a hydrophilic gel about 24 hours after placement. The gel acts as a protective coat round the traumatised tissues up to 7 days during re-epithelisation.
In a small study involving 24 patients, the success rate in the Seprafilm group was 10% adhesion versus 50% in the control group.

Auto-crossed-linked HA has higher adhesivity and more prolonged residence time on the injured uterine surface compared with un-modified HA. A study involving 43 patients treated for Asherman's, showed the re-adhesion rate of 14% versus 31.7% in the control group.
11.4. Hormone treatment
Oestrogens are used here to stimulate the re-generation of the endometrium and promote re-epithelialisation of the scarred surface.
There is a study in 60 women undergoing D&C to show that oestrogen-progestin therapy does increase endometrial thickness and volume. However, there is no objective evidence to show the effectiveness of oestrogen treatment on the reduction of reformation of intrauterine adhesions.
Use of oestrogen therapy after lysis of intrauterine adhesions has not been standardised. Sheffield hospital [Yu el al] adopts a regimen involving estradiol valerate 4mg/day for 4 weeks plus medroxyprogesterone 10 mg/day in 3rd and 4th weeks.
12. What are the preventative measures for abdominal adhesions?
Because intra-abdominal adhesion can be a major problem after many gynaecological surgeries such as myomectomy and caesarean delivery, it is clear that putting in preventative measures is very important.
12.1. Hydroflotation
  • Generally speaking, it is an irrigation procedure where crystalloid solution or high molecular weight dextran solution is left in the pelvis at end of surgery to allow the tissue to float apart from one another, therefore reducing the risk of scar formation.
  • Sometimes, heparin is added to the crystalloid solution to prevent blood clotting and fibrin deposition. Fibrin plays a role in scar formation.
  • Adept (Innovata Plc, Surrey, UK) - a solution containing 4% icodextrin is a recently introduced product of this range.
12.2. Adhesion barriers
There are a number of adhesion barriers available but none of them are ideal. An ideal adhesion barrier should have the following characteristics:
  • Be an effective tissue separator;
  • Remain active for 7 days during the critical healing period;
  • Be absorbed or metabolised without provoking any inflammatory reaction;
  • Remain active and effective in the presence of blood;
  • Have no adverse effect on the wound healing process;
  • Do not promote bacterial growth.
Current adhesion barriers include expanded polytetrafluoroethylene membrane, oxidised regenerated cellulose and sodium hyaluronate and carboxymethylcellulose film.
12.2.1. Expanded Polytetrafluorethylene (Gore-Tex Surgical Membrane)
  • Contains a microscopic structure that prevent cellular growth
  • It is a non-inflammatory and no-absorbable membrane.
  • It needs to be stitched in place.
  • There is limited data to demonstrate how effective it is in myomectomy.
12.2.2. Oxidised Regenerated Cellulose (Interceed)
  • It is made up of oxidised regenerated cellulose and is available in 3" x 4" sheets.
  • More than 13 studies looked into how effective this product is. Summary from a meta-analysis of 10 randomised controlled studies shows 24.2% reduction in scar formation.
  • There are still concerns whether it may not work well in the presence of blood.
  • At the moment, there is no data for safety and effectiveness in scar prevention in laparoscopic surgery or any procedures other than open microsurgical procedures.
12.2.3. Sodium Hyaluronate and Carboxymethylcellulose (Seprafilm)
  • It is made of chemically modified hyaluronic acid and carboxymethylcellulose.
  • It is designed to separate planes of tissues after surgery for 3-7 days.
  • To date, there is no evidence that Seprafilm is adhesiogenic in the presence of blood.
  • Concerns about the use of Seprafilm include the learning curve required to achieve optimal placement and the fact that it cannot be applied laparoscopically.
13. What is the advice given for a woman who was previously treated for moderate-severe intrauterine adhesions to become pregnant?
Pregnant women who were previously treated for moderate or severe adhesions are considered to have high-risk pregnancies and they should be closely monitored obstetrically, particularly to look out for spontaneous rupture of the uterus and any placental insertion abnormalities, such as placenta accreta or percreta.
14. What is the option for a woman with normal uterine cavity but no normal functional endometrium after Asherman's treatment to have a successful IVF?
There is not a lot of data for this. However, recently, there is a report [Barash et al 2009] for a successful pregnancy and delivery when a woman of similar condition who received endometrial biopsy plus IVF. It appears that endometrial biopsies after restoration of uterine cavity can improve receptivity but this should be used with great caution due to pregnancy associated complications.
15. Does GnRh agonist treatment BEFORE abdominal myomectomy help to decrease incision scar formation afterwards?
A recent study [Coddington et al 2009] shows that pre-surgical GnRha for 3 months before abdominal myomectomy did not decrease scar formation. Adhesion formation in myomectomy is governed by the length of surgical cut (incision) into the womb surface. It makes sense to remove multiple fibroids from the same cut (incision) to decrease peritoneal injury and reduce scar formation.

Reference Sources
Amihai Barash, Irit Granot, Sheila Fieldust and Yuval Or,
Successful pregnancy and delivery of a healthy baby after endometrial biopsy treatment in an in vitro fertilization patient with severe Asherman syndrome.
Fertility & Sterility; 91: 1956e1-1956e3
Cyril Touboul, Herve Fernandez, Xavier Deffieux, Richard Berry, Rene Frydman, and Amelie Gervaise.
Uterine synechiae after bipolar hysteroscopic resection of submucosal myomas in patients with infertility.
Fertil Steril 2008; In Press
Dan Yu, Tin-Chiu Li, Enlan Xia, Xiaowu Huang, Yuhuan Liu, and Xuebing Peng
Factors affecting reproductive outcome of hysteroscopic adhesiolysis for Asherman’s syndrome
Fertility & Sterility; 89:715-722.
Dan Yu, Yat-May Wong, Ying Cheong, Enlan Xia and Tin-Chiu Li.
Asherman syndrome—one century later
Fertility & Sterility; 89:759-779.
Hiroyuki Takeuchi, Mari Kitade, Iwaho Kikuchi, Hiroto Shimanuki, Jun Kumakiri, Satoru Takeda
Influencing factors of adhesion development and the efficacy of adhesion-preventing agents in patients undergoing laparoscopic myomectomy as evaluated by a second-look laparoscopy.
Fertil Steril 2008;89:1247–53
James K. Robinson, Liza M. Swedarsky Colimon, and Keith B. Isaacson
Postoperative adhesiolysis therapy for intrauterine adhesions (Asherman’s syndrome).
Fertil Steril 2008;90:409–14.
Jay M Berman
Intrauterine Adhesions
Seminars in Reproductive Medicine 2008; 26: 349-355
Mackenzie RCF, Fefelova E, Nevin A, Singh SS, Leyland NA
Asherman’s Syndrome: Women at Risk and Their Post-Treatment Reproductive Outcome
Journal of Minimally Invasive Gynecology; 15: S126
Recai Pabuccu, Gogsen Onalan, Cemil Kaya, Belgin Selam
Efficiency and pregnancy outcome of serial intrauterine device–guided hysteroscopic adhesiolysis of intrauterine synechiae.
Fertil Steril 2008;90:1973–7
Sahly NN, Hassanain F, Rouzi AA
Treatment of Severe Asherman Syndrome by Hysteroscopy.
Abstracts / Journal of Minimally Invasive Gynecology; 15: S122
Zapardiel I, DelaFuente-Valero J, Salazar FJ, Bueno B, Perez-Medina T
Asherman’s Syndrome with Cervical Adhesions Treated Hysteroscopically
Journal of Minimally Invasive Gynecology; 15: S124
Zheng J.
Investigation of Prevention of Adhesion of Post-Operation of Transcervical Resection of Septa.
Journal of Minimally Invasive Gynecology; 15: S124
Author: Dr Nicki On, PhD, MRPharmS.
The information on this page has been peer-reviewed by
Associate Prof Jay M Berman, MD, FACOG. Dept of Obstetrics and Gynaecology, Wayne State University School of Medicine, Hutzel Women's Hospital, Detroit, USA.
 
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This page was last modified on Tuesday 5 January 2010 08:28 pm.

 
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