Prevention of Postoperative Adhesion Reformation by Intrauterine Balloon Therapy: a Randomized Controlled Trial
Phase: NA
Conditions: Intrauterine Adhesion
Sponsor: Fu Xing Hospital, Capital Medical University

Title: The efficacy of intrauterine balloon dilatation therapy in 
the prevention of adhesion reformation after hysteroscopic 
adhesiolysis 
 
Clinical trial identification number: NCT03131596 
 
Date of Document: 1st, March, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 

The efficacy of intrauterine balloon dilatation therapy 
in the prevention of adhesion reformation after 
hysteroscopic adhesiolysis 
 
The study was approved by Institutional review board of Capital Medical University, 
Beijing, China (reference No. 2016FXHEC-KY, Date: 20 October 2016) 
 
Investigators 
Shi xiaoyu, Sotirios Saravelos, Zhou qiaoyun, Huang xiaowu, Xia enlan 
T.C. Li* 
 
Background information 
Intrauterine adhesions, or Asherman’s syndrome, occur after trauma to the basalis 
layer of the endometrium generally after endometrial curettage. It was first described 
by Heinrich Fritsch in 1894 and subsequently studied by Israeli gynecologist Joseph 
G. Asherman. In Asherman’s description, he differentiated between traumatic 
intrauterine adhesions, which did not typically result in menstrual disturbances, and 
atretic amenorrhea, which resulted in amenorrhea and dysmenorrhea due to cervical 
adhesions (1, 2). The syndrome occurs most frequently after incomplete abortion 
(50%), postpartum hemorrhage (24%), and elective abortion (17.5%) (3). Other less 
common etiologic factors including myomectomy, hysterotomy, diagnostic curettage, 
cesarean section, tuberculosis, caustic abortifacients, and uterine packing have been 
reported(4–7). 
 
With damage to the basalis layer, granulation tissue on either side of the endometrial 
cavity can fuse to form tissue bridges. In the most severe cases, the endometrial cavity 
can be entirely obliterated without any evidence of viable endometrium. Patients with 
Asherman’s syndrome may present with amenorrhea with or without severe 
dysmenorrhea, oligo-menorrhea, infertility, or recurrent miscarriages (6). Patients 
with amenorrhea and cyclic pain associated with hematometria are likely to have 
viable endometrium above the occlusive adhesions. Sequelae of pregnancy in the 
presence of adhesions include higher incidences of ectopic pregnancy, recurrent 
miscarriage, premature labor, and abnormal placentation (8). 
 
The main challenge of hysteroscopic adhesiolysis in Asherman syndrome is the high 
rate of reformation of adhesions, especially in those with severe adhesions, in whom 
the recurrence rate may be up to 62.5% (9).We recently conducted a study and found 
that a Foley-catheter made intrauterine balloon dilatation seemed to be effective in 
preventing adhesion reformation after intrauterine adhesiolysis. However, there has 

never been any formal randomized, control trial designed to identify the efficacy of 
the intrauterine balloon dilatation in the prevention of adhesion reformation.  
 
Objectives 
In this prospective, randomized, controlled study, we wish to determine the efficacy 
of intrauterine balloon dilatation in the prevention of adhesion reformation when 
compared with the conventional management. 
 
 
Null hypothesis 
The null hypothesis is that intrauterine balloon dilatation therapy will not reduce the 
rate of adhesion reformation compared with conventional management following a 
primary hysteroscopic adhesiolysis procedure. 
 
 
Patients 
The patients will be recruited from the Hysterscopy Center of the Fuxing Hospital, 
Beijing, China. Before the surgery all patients with suspected Asherman syndrome will 
undergo preoperative evaluations, including a detailed history of the menstrual pattern, 
any previous intrauterine surgery, and reproductive history, as well as trans-vaginal 
ultrasonography. The severity and extent of intrauterine adhesions will be scored 
according to a classification system recommended by the American Fertility Society 
(AFS) (1988 version). The inclusion criteria include [1] women aged 18–40 years; [2] 
moderate to severe intrauterine adhesion (AFS score≥5); [3] no previous history of 
hysteroscopic adhesiolysis; [4] written consent obtained; and [5] agreement to have 
second-look hysteroscopy. The exclusion criteria include [1] minimal adhesion (AFS 
score <5) and [2] previous hysteroscopic adhesiolysis. 
 
 
Study Design 
After the completion of hysteroscopic adhesiolysis, recruited patients will be 
randomized to one of the two treatment groups by computer-generated numbers: [1] 
having a Foley-catheter intrauterine balloon dilatation 2 weeks and 6 weeks after 
hysteroscopic adhesiolysis; [2] the control group without any additional treatment. A 
second-look hysteroscopy will be carried out in the early proliferative phase 4 weeks 
the surgery and a third-look hysteroscopy was carried out 8 weeks after the surgery. 
 
Power Calculation 
On the basis of the results of the two published retrospective cohort studies comparing 
the balloon and hormone therapy group (control group) in the prevention of adhesion 
reformation, we estimated that the adhesion reformation rate in the balloon group to 
be 20% and in the control group to be 45%. Accepting a type 1 error of 0.05, and a 

type 2 error of 0.10, the number of subjects in each arm of the randomized, controlled 
trial would be 79. Assuming that the dropout rate to be 20%, the total number of 
subject to be recruited would be 100 in each arm. 
 
Procedure 
Surgical procedure  
The surgery will be carried out by one of three experienced hysteroscopic surgeons 
with the use of a 4.5-mm rigid hysteroscope (Olympus) with 5% normal saline infusion 
under 100 mm Hg pressure. The procedure will be performed under general anaesthesia 
in a day surgery unit. Ultrasonographic guidance will be routinely used. Once the 
extent and severity of uterine adhesion has been assessed, the adhesions will be divided 
with the use of mono-polar instrument until normal uterine anatomy is achieved.  
 
Postoperative treatments 
All subjects will be treated with oral antibiotics for 5 days. In all cases hormone therapy 
will also begin from the day of operation, consisting of estradiol valerate at a dose of 6 
mg/d for 21 days, with the addition of dydrogesterone at a dose of 10 mg/d for the last 7 
days of the estrogen therapy. After the withdrawal bleed, the hormone therapy will be 
repeated for another cycle. Second-look hysteroscopy will be carried out in the early 
proliferative phase, 4 weeks after the initial operation; a third-look hysteroscopy will 
be carried out 8 weeks after the initial operation. After assessment of the extent and 
severity of any reformed adhesion, hysteroscopic adhesiolysis will also be carried out 
at the time of the second-look procedure, if adhesion has recurred. The surgeon who 
performs the second-look and third-look hysteroscopy will be blinded to the 
randomization. 
 
IUB dilatation 
IUB dilatation therapy will be performed according to the methodology published in 
the literature (10-11). In brief, a Foley catheter (size 8-12fr) will be prepared by 
cutting the excess catheter tip protruding beyond the balloon prior to insertion into the 
uterine cavity. Once the catheter has reached the fundus, 3-5mls of saline will be 
slowly introduced into the balloon under ultrasound guidance, in order to directly 
visualise the distention of the cavity and stretching and blunt dissection of any 
intrauterine adhesions, if present. The whole process requires merely a few minutes.  
 
Statistical Analysis 
The rate of the recurrence of adhesion in the two groups will be compared using the χ2 
test. The reduction of AFS score in the two groups will be compared using the 
Mann-Whitney U test. A p value of < 0.05 will be considered statistically significant. 
All statistical analysis will be carried out with the use of SPSS 21.0. 

 
Outcome measures  
The primary outcome measure will include the degree of intrauterine adhesions and 
AFS score at follow-up. The secondary outcome measures will include the menstrual 
improvement, need for re-operation and future reproductive outcome. 
 
Data processing and analysis 
The researchers will ensure the confidentiality of sensitive data by minimizing the 
number of personnel who handle subject data. In addition, computer data will be 
encrypted as required to maximize security, while paper documents will be locked in 
filing cabinets, with only authorized personnel having access to the information. 
 
Ethical considerations  
IUB dilatation has been published as a novel technique with no untoward complications 
identified to date (14-16). The procedure will be performed according to the 
methodology available in the literature and the study has gained approval from the local 
ethical committee (Approval Notice Number: 2016FXHEC—KY). 
 
Consent  
All subjects will be given a detailed explanation of the study and sufficient time to 
consider their participation. A written consent form will be signed by the patient and 
retained in our confidential records. 
 
 

 
Participant patient flow 
 
 
 
 
 
 

References 
1. March CM. Intrauterine adhesions. Obstet Gynecol Clin North Am 1995;22:491–
505. 
2. Asherman JG. Traumatic intra-uterine adhesions. J Obstet Gynaecol Br Emp 
1950;57:892–6. 
3. Asherman JG. Amenorrhea traumatica atretica. J Obstet Gynaecol Br Emp 
1948;55:23–30. 
4. Valle RF, Sciarra JJ. Intrauterine adhesions: hysteroscopic diagnosis, classification, 
treatment, and reproductive outcome. Am J Obstet Gynecol 1988;158:1459–70. 
5. Orhue AA, Aziken ME, Igbefoh JO. A comparison of two adjunctive treatments for 
intrauterine adhesions following lysis. Int J Gynaecol Obstet 2003;82:49–56. 
6. Schenker JG. Etiology of and therapeutic approach to synechia uteri. Eur 
J Obstet Gynecol Reprod Biol 1996;65:109–13. 
7. Klein SM, Garcia CR. Asherman’s syndrome: a critique and current review. Fertil 
Steril 1973;24:722–35. 
8. Schenker JG, Margalioth EJ. Intrauterine adhesions: an updated appraisal. Fertil 
Steril 1982;37:593–610. 
9.Yu D, Wong YM, Cheong Y, Xia E, Li TC. Asherman syndrome–one century 
later. Fertil Steril 2008;89:759–79. 
10. Saravelos SH and Li TC. Ultrasound guided treatment of intrauterine adhesions in 
the outpatient setting. Ultrasound in Obstetrics & Gynecology [Epub ahead of print] 
11. Saravelos SH and Li TC. Intrauterine balloon therapy: a novel ultrasound guided 
treatment for intrauterine adhesions. Gynecological Surgery [Epub ahead of print]