Eradicate intrauterine adhesions once and for all
About intrauterine adhesions
Intrauterine adhesions (IUA) or synechiae are fibrous strings at opposing walls of the uterus leading to partial or complete obliteration of the cavity. They may also be referred to as Asherman syndrome. They occur as the consequence of surgery in the uterine cavity and are the major long term complications of operative hysteroscopy.
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They are responsible for menstrual disorders, infertility and obstetrical complications such as abnormal placentation. They are associated with miscarriages and retained product of conception with a reported incidence as high as 20% following dilation and curettage for those conditions (1, 2) and up to 45% after myomectomy (3,4).
Removing adhesions, or adhesiolysis, is performed by hysteroscopy. The recurrence rate after intrauterine adhesiolysis is between 42% and 60% in case of severe adhesions or Asherman syndrome (5). Women with Asherman syndrome who try to conceive often need to go through multiple interventions, without any assurance of achieving pregnancy.
Surgical adhesions can be prevented by separating the adjacent injured tissues at the beginning of the scaring phase. While adhesion barrier products exist for abdominal or pelvic surgery like absorbable films or gels, none of them is adequate for intrauterine use, leaving women's uterus unprotected after an intervention.
Womed Leaf™
Intrauterine Adhesion Barrier Film
Womed Leaf is the first and only MECHANICAL BARRIER against adhesions that protects the entire uterine cavity for a week.
Principle
Insertion
At the end of the surgical procedure, Womed Leaf is inserted through the cervix like an IUD and the uterine film is released.
Self deployment
It soaks uterine fluids and grows up to become a film that shields the entire cavity.
Mechanical barrier
By keeping the walls apart, Womed Leaf acts as a mechanical barrier during 1 week.
Natural discharge
After a week, the uterine film breaks-up, dissolves and is naturally discharged without any intervention of a healthcare professional.
Intended use: Womed Leaf is intended for the prevention or reduction of new or recurrent intrauterine adhesions formation by creating a temporary mechanical barrier.
Indication: Womed Leaf is indicated for use in all transcervical procedures.
Womed Leaf is a CE marked product.
Not for sales in the US.
Why Womed Leaf?
Mechanical barrier
Womed Leaf anti adhesion film self deploys and keeps the uterine walls apart after an intrauterine procedure.
Long lasting effect
Womed Leaf acts as a mechanical barrier during a week, the critical part of the healing phase.
Full cavity protection
Thanks to its swelling ability when in contact with water, Womed Leaf grows to fill the entire uterine cavity.
Rapid insertion
At the end of the surgical procedure, Womed Leaf is inserted through the cervix with a flexible inserter, just like an IUD. The uterine film is not sticky and the insertion takes less than 1 minute.
No follow-up required
After a week, the uterine film breaks-up, dissolves and is naturally discharged through the cervix without any intervention of a healthcare professional.
Safe by design
Product composition and tolerance
Womed Leaf has been designed from well known highly biocompatible compounds: poly(D,L-lactide) acid (PLA) which is commonly used in medical devices like surgical sutures, and poly(ethylene oxide) (PEO) which is a common pharmaceutical excipient. Womed Leaf biocompatibility, tolerance and non toxicity has been thoroughly proven in preclinical and clinical studies.
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Fertility
A pre-clinical study evaluating possible effects on fertility showed that Womed Leaf had no negative impact on the implantation and development of embryos (Huberlant et al).
Efficacy
Womed Leaf significantly reduces the likelihood of complete IUA formation compared to hyaluronic acid (HA) gel and sham group, demonstrating its efficacy in an animal model (Huberlant et al).
Clinical evidence
Womed is committed to evidence-based medicine and is investing in clinical research to demonstrate the medical value of its products and establish them as new standards of care.
Womed Leaf clinical program
Womed Leaf's clinical evaluation is part of a large ongoing study program. The program aims to bring solid scientific evidence to the ObGyn community and benefit women in their fertility projects. It is designed in phases. :
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PREG1: European study to validate safety after hysteroscopic myomectomy (completed)
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PREG2: International study to evaluate efficacy after adhesiolysis ​​(on going)
PREG1 clinical study
PREG1 (NCT04381728) is a prospective, multi-center, single arm clinical study that aimed to evaluate the safety of Womed Leaf after hysteroscopic myomectomy and its efficacy in preventing intrauterine adhesions at second look hysteroscopy. This first-in-human study demonstrated the safety of Womed Leaf. None of the study participants suffered any procedure related injuries, reactions or adverse events. A first set of data on the efficacy of Womed Leaf in humans was also generated and 20 of the 23 study participants had no post hysteroscopic myomectomy IUAs on second look hysteroscopy.
The study manuscript is published in JMIG (Journal of Minimally Invasive Gynecology).
PREG2 clinical study
PREG2 (NCT04963179) is a multi-center, randomized, controlled, two-arm, double blind, superiority clinical study that aimed to evaluate the safety and effectiveness of Womed Leaf in reducing intrauterine adhesions severity after hysteroscopic adhesiolysis.
​Target population: Women with moderate or severe intrauterine adhesions (AFS score over 5)
Follow-up assessments: at 6 weeks, all subjects underwent a “second look” hysteroscopy.
Intervention group: Womed Leaf intrauterine barrier film was inserted at the end of the surgery
Control group: no IUA barrier was used at the end of the surgery
Effectiveness endpoints:
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Absence of IUA at second look
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Responder rate, measured as the percentage of patients with improved IUA status of at least two clinical categories, e.g. from severe to mild or from moderate to no IUA.
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Results
160 patients were randomized in 16 sites from 7 countries in Europe and China. Mean age was 35 years old. Baseline AFS score was 8 in both groups. 31% of the patients had severe adhesions at baseline and 48% of them already had at least one adhesiolysis.
The absence of adhesions at follow up was significantly higher in the treatment group compared to the control group (41% vs 24% OR 2.44 [CI 1.161 - 5.116]; p=0.0189). Similarly, the responder rate was significantly higher in the treatment arm compared to controls (51% vs 29% OR 2.72 [CI 1.353 - 5.447]; p=0.0052). The reduction in IUA severity at follow up was also significantly higher in the treatment (mean AFS score reduction 5.2 ± 2.8 vs. 4.2 ± 3.2; p=0.0153).
Safety: No serious adverse events and 9 non device related adverse events were reported.
No polymer remnant or endometrial abnormalities were reported at second look.
Effectiveness: The rate of absence of IUA and the responder rate at second look hysteroscopy were significantly higher in the intervention group than in the control group. Receiving a Womed Leaf increases by 2.4 the probability to avoid adhesion recurrence at second look.
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Patient reported outcomes
Womed Leaf intrauterine film does not generate additional pain or discomfort, even during its discharge.
Conclusion
This large RCT of patients with severe or moderate IUAs demonstrated the safety and effectiveness of Womed Leaf in the management of severe and moderate adhesions. It is the first adhesion barrier to show any clinically meaningful improvement in this challenging indication.
References
Womed Leaf publications
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First Use Of A Novel Barrier Film In An Infertile Woman With Severe Asherman Syndrome - Sroussi et al (2022) JMIG
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Hysteroscopic and ultrasound evaluation of a novel degradable polymer film for the prevention of intrauterine adhesion formation after hysteroscopic surgery - Zizolfi et al (2022), European Journal of Obstetrics and Gynecology
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Safety and efficacy of a novel barrier film to prevent intrauterine adhesion formation after hysteroscopic myomectomy: The PREG1 clinical trial - Weyers et al (2021). Journal of Minimally Invasive Gynecology.
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In Vivo Evaluation of the Efficacy and Safety of a Novel Degradable Polymeric Film for the Prevention of Intrauterine Adhesions. Huberlant et al., Journal of Minimally Invasive Gynecology. 2021, vol. 28, no 7, p. 1384-1390
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Preliminary design of a new degradable medical device to prevent the formation and recurrence of intrauterine adhesions - Leprince et al., Communications Biology (2019) 2:196
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A new bioabsorbable polymer film to prevent peritoneal adhesions validated in a post-surgical animal model - Allègre et al., (2018) PLoS ONE 13(11): e0202285.
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Other publications
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Salazar et al. A comprehensive review of Asherman’s syndrome: causes, symptoms and treatment options Curr Opin Obstet Gynecol 2017, 29:249–256
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Hooker et al. Systematic review and meta-analysis of intrauterine adhesions after miscarriage: prevalence, risk factors and long-term reproductive outcome Human Reproduction Update, 2014;20(2)262–278
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Taskin et al. Role of endometrial suppression on the frequency of intrauterine adhesions after resectoscopic surgery. The Journal of the American Association of Gynecologic Laparoscopists 2000;7(3):351–4
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Guida et al. Effectiveness of auto-crosslinked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic surgery: a prospective, randomized, controlled study. Human Reproduction 2004;19(6):1461-64
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Warembourg S et al. Prevention and treatment of intrauterine synechiae : Review of literature. J Gynecol Obstet Biol Reprod. 2015 Apr ; 44 :366-79.