Postoperative Intermittent Intrauterine Balloon Dilatation Therapy.
Condition: Intrauterine Adhesion
MeSH terms: Tissue Adhesions
Study type: Interventional

Summary: 
      In this prospective, randomized, controlled study, the investigators wish to determine the
      efficacy of intrauterine balloon (IUB) dilatation in the prevention of adhesion reformation
      when compared with the conventional management.
    

Detailed description: 
      Patients

      The patients will be recruited from the Hysteroscopy 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] first episode of hysteroscopic adhesiolysis in FuXing hospital; [4]
      written consent obtained; and [5] agreement to have second-look and an optional third-look
      hysteroscopy. The exclusion criteria include [1] minimal adhesion (AFS score <5) and [2]
      previous hysteroscopic adhesiolysis in FuXing hospital.

      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 after the surgery and an optional third-look
      hysteroscopy will be 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 estimate 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 two experienced hysteroscopic surgeons with the use
      of a 8.5-mm rigid hysteroscope (Olympus) with 0.9% normal saline infusion under 120-150 mmHg
      pressure. The procedure will be performed under general anesthesia 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 bipolar instrument
      until normal uterine anatomy is achieved.

      Postoperative treatments

      All subjects will be treated with oral antibiotics(Cefaclor 0.375 mg twice daily Tianjin
      Central Pharmaceutical Co Ltd., Tianjin, China.) for 5-7 days. In all cases hormone therapy
      also began from the day of operation, consisting of estradiol valerate at a dose of 4 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 was repeated for a
      further two cycles, i.e. 3 months in total. 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 using a Foley catheter(14fr) and according to the
      methodology published in the literature. This will be prepared by cutting the catheter tip
      protruding beyond the balloon. Once the catheter has reached the fundus, 3-4.5mls of saline
      will be slowly infiltrated into the balloon under ultrasound guidance in order to distend the
      cavity, thereby separating any reformed intrauterine adhesions.

      Statistical Analysis

      Intention-to-treat analysis was conducted primarily on all outcomes for all randomized
      subjects. Numerical data with normal distribution were presented as the mean ± standard
      deviation, whereas data with skewed distribution were presented as the median (interquartile
      range). The Student t test was used to compare normally distributed data between two groups
      and paired t test was used to compare normally distributed data within two groups. The
      Mann-Whitney U test was used to compare data with skewed distribution. Contingency table
      analysis and the χ2 test were used to compare categorical data. A p value of < 0.05 was
      considered statistically significant. All statistical analysis was carried out with the use
      of SPSS 21.0.

      Outcome measures

      The primary outcome measure was defined as the AFS score at each follow-up, including the
      adhesion reformation rate, in addition to the menstrual improvement, which was evaluated
      according to Pictorial Blood Loss Assessment Chart (PBAC) score.

      Secondary outcomes included pregnancy rate, miscarriage rate and ectopic rate.

      Data processing and analysis

      The investigators 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. The procedure will be performed according to the methodology available in
      the literature and the study has gained approval from the local ethical committee.

      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 the confidential records.
    

Intervention name(s): IUB dilatation therapy
Intervention type(s): Procedure
Intervention description(s): A Foley catheter (size 14fr) 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, 3-4.5mls of saline will be slowly introduced into the balloon under ultrasound guidance, in order to directly visualize the distention of the cavity and division of any intrauterine adhesions, if present.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Prevention
Keywords: Intrauterine Adhesion; Hysteroscopy; Intrauterine balloon; Reformation; Prevention