TePA-study (Tertiary Prevention of morbus Asherman-study);Evaluation of placement of hyaluronic acid (hyalobarier ® Gel Endo) and placement of a intrauterine device without cu or hormones to maintain separation of the cavity and mechanically to prevent spontaneous recurrence of adhesions.

Recognition that organic intrauterine adhesions can lead to secondary
amenorrhea has been demonstrated since the end of the 19th century, although
not until 1948, when Joseph Asherman described the eponymous condition in 29
patients, did the syndrome became popularized and treatment described.
Asherman*s original description related to post pregnancy intrauterine
adhesions in all cases, and such adhesions remain the commonest cause of this
syndrome. Asherman expanded his original thoughts, and related endometrial
trauma and adhesion formation to menstrual disturbance, cyclical pelvic pain,
and sub fertility including recurrent pregnancy loss. Important in his
description was that the adhesions seemed to have an inherent effect on the
endometrium, causing it to be inactive.
Asherman syndrome is a condition of uterine distortion resulting in amenorrhea
or hypomenorrhea, infertility and recurrent pregnancy loss. The re-adhesion
rate is high after (20%) surgical intervention. The prevalence of M. Asherman
varies widely depending on the trauma caused to the uterus. The true incidence
of this condition is difficult to determine, ranging from 1.5% of patients
referred for fertility testing up to 40% of women following secondary removal
of placental tissue or repeat curettage after a missed abortion .Recurrent
miscarriage is often associated with intrauterine adhesions, with adhesions
reported in 5% to 39% of women. The risk of developing intrauterine adhesions
postpartum is high, affecting 21.5% to 40.0% of women requiring uterine
instrumentation. Postpartum hemorrhage is a risk factor for intrauterine
adhesions, with an early report noting an incidence of intrauterine adhesions
of 9%. Surgical treatment of a silent miscarriage (missed abortion) has been
reported to lead to 31% of intrauterine adhesions compared to an incomplete
miscarriage, in which only about 6.4% of women are likely to develop
intrauterine adhesions. Trauma to the non pregnant uterus can also cause
intrauterine adhesions, the risk is lower, with rates of intrauterine adhesions
estimated to be 1.6% after diagnostic curettage, 1.3% after abdominal
myomectomy, 0.5% after cervical biopsy or polypectomy, and 0.2% after insertion
of an intrauterine device (IUD).
There is almost universal support that surgical treatment is the criterion
standard in management of Asherman syndrome, and there is no role for medical
treatments. There is no consensus as to the optimal technique of division of
adhesions. The most used technique is according to the methods described by
Broome and Vancaillie in 1999 .
A number of strategies have been proposed to reduce the recurrence of adhesions
after surgery. Insertion of an IUD provides a physical barrier between the
uterine walls, separating the endometrial layers after lysis of intrauterine
adhesions . Several studies have also recently examined the application of
hyaluronic acid gel into the uterine cavity after adhesiolysis. There appears
to be some evidence that the hyaluronic acid gel may be of benefit in reducing
intra-uterine adhesions . One cohort study compared the efficacy of three
adjuvant measures (IUD, balloon and gel), the gel appeared to be the least
effective . A randomized controlled trial was never performed to study this
effect.

In this randomized controlled trial a comparison is made of the efficacy of the
placement of the intrauterine device without Cu or hormones versus hyaluronic
acid (hyalobarier ® Gel Endo) preventing adhesion reformation after
adhesiolysis.

Does the installation hyaluronic acid (hyalobarier ® Gel Endo), in patients
with M. Asherman reduces or prevents the incidence and severity (ESGE
score/classification) of spontaneous recurrence of adhesion better then the IUD
without Cu or hormones (Flexie T) Presence and extent of adhesions will be
evaluated by second look hysteroscopy between 8-10 weeks after the initial
procedure, using the ESGE classification

Singlecenter prospective single blind randomised controlled trial.

The same hysteroscopic adhesion resection will be performed on all patients,
and then they will be randomly allocated to two groups.
Intervention Group: installation of gel immediately after surgery (hyalobarier
® Gel Endo)
Control Group: fitting of Cu-IUD (Multiload or Flexi-T) and will be removed 2
week prior to the second look hysteroscopy
A second look hysteroscopy will be carried out 8-10 weeks after the initial
operation.

A hysteroscopy for identification of adhesions and their extent will be
performed 1months after the initial operation. A pregnancy test will be
performed before the examination; if positive the examination will not be
performed.

The gynaecologist who will perform the second look hysteroscopy at 8-10 will be
blinded for which group the patient was allocated to.

The severity and extent will be classified according to the European Society of
Gynecological Endoscopy classification of IUAs (1995 version). (Appendix 3).

The menstrual blood flow will be quantified with a pictorial blood loss
assessment chart (PBAC). (Appendix 4) The chart will be evaluated at the 3
months visit. Patients will be asked to fill in the chart with during the last
menstrual blood loss period they have before the 3 month visit.

After 6 months they will be asked to fill in a PBAC as well. The patients will
be addressed by telephone or email.

After 1 year patients will be addressed by phone or email. During a follow up
of 1 year the number and time to conceive will be recorded. The clinical as
well as the ongoing pregnancies (defined as intra-uterine heart activity * 12
weeks gestation) and the course of the pregnancies will be recorded.
The number of patient requiring hysteroscopic treatment for adhesions will also
be recorded.
The number of patients requiring cervical dilation in an outpatient clinic
setting will also be recorded