Treatment of Severe and Moderate Intrauterine Adhesions: Results of PREG2 International RCT on the Effectiveness of Womed Leaf Barrier Film

Study Objective

Recurrence rate after hysteroscopic adhesiolysis can be as high as 60%. This RCT aimed to assess the effectiveness of a new intrauterine mechanical barrier film in the management of IUA.

Design

PREG2 is a double-blind randomized, controlled, stratified study.

Setting

16 sites in Europe and China.

Patients or Participants

Patients scheduled for hysteroscopic adhesiolysis because of symptomatic severe or moderate adhesions (AFS score ≥ 5).

Interventions

Following adhesiolysis, patients were randomized to either have a Womed Leaf film inserted or not. Womed Leaf (Womed SAS, France) is a degradable polymer film that expands to fill the entire cavity and acts as a mechanical barrier between the uterine walls. After about a week, it degrades and is discharged naturally. Hormonal treatment was authorized in both groups. Patients were scheduled for second-look hysteroscopy (SLH) after 4 to 8 weeks.

Measurements and Main Results

The effectiveness endpoints were: Change in AFS score between baseline and SLH, responder rate (i.e. patients who improved of at least two clinical categories, e.g. from severe to mild or from moderate to no IUA) and absence of IUA at SLH. The patient and the SLH evaluator were blind. 160 women were randomized. The reduction in AFS score at SLH was significantly higher in the intervention compared to the control group (5.2 ± 2.8 vs. 4.2 ± 3.2; p=0.0153). The responder rate was significantly higher in the intervention group (51% vs 29% OR 2.7 [1.4–5.5]; p=0.0052). The absence of adhesions at SLH was significantly higher in the intervention group (41% vs 24% OR 2.44 [CI 1.161 - 5.116]; p=0.0189). None of the reported adverse events were serious or considered related to the device.

Conclusion

This large RCT of patients with severe or moderate IUA demonstrated the effectiveness of Womed Leaf. It is the first adhesion barrier to show any clinically meaningful improvement in this challenging indication.