Incidence of Intrauterine Adhesions After Myomectomy With Intrauterine Anti-Adhesion Gel

Official title

Incidence of Intrauterine Adhesions Following Myomectomies With the Use of an Intrauterine Anti-adhesion Gel

Overview

This prospective randomized study aims to evaluate whether the application of an intrauterine anti-adhesion gel reduces the incidence of intrauterine adhesions (IUAs) following robotic-assisted laparoscopic myomectomy. Intrauterine adhesions may develop after endometrial trauma during surgery and can negatively affect menstrual function, fertility, and future pregnancy outcomes. Robotic myomectomy offers a minimally invasive approach, but postoperative adhesion formation remains a concern. Sixty-two women undergoing myomectomy will be randomized to receive either intrauterine anti-adhesion gel (intervention group) or no adhesion-prevention method (control group). Adhesions will be assessed by ultrasound and hysteroscopy during follow-up. Secondary outcomes include reproductive results over a 24-month period, such as implantation rate, clinical pregnancy, miscarriage, live birth, pregnancy complications, and neonatal outcomes. The study seeks to determine whether combining a minimally invasive surgical approach with an intrauterine gel provides additional protection against adhesion formation and improves fertility-related outcomes.

Detailed description

Intrauterine adhesions (IUAs), or uterine synechiae, are fibrotic bands that develop when the endometrium is damaged and the normal healing process is disrupted. Surgical trauma-particularly involving the basal layer of the endometrium-is one of the main triggers for adhesion formation. Myomectomy is recognized as the gynecologic procedure most frequently associated with the development of adhesions, which may compromise uterine function, menstrual regularity, fertility, and obstetric outcomes. Although minimally invasive approaches such as conventional or robot-assisted laparoscopy have reduced postoperative morbidity, they cannot eliminate the risk of adhesion formation, especially when the uterine cavity is entered or extensive suturing is required.

Adhesion formation results from excessive fibrin deposition and insufficient fibrinolytic activity during tissue repair. When fibrin persists on the injured surfaces, fibroblast proliferation and neovascularization may lead to permanent fibrotic bridges between areas that should remain separated. This process is particularly relevant following myomectomy, where the endometrium may be inadvertently injured. Several studies have reported high rates of intrauterine adhesions after open myomectomy and, to a lesser extent, after minimally invasive procedures. Adhesions may occur even when the cavity is not breached, suggesting that the myometrial trauma itself can contribute to this pathological process.

Anti-adhesion gels have been proposed as an adjunctive strategy to prevent postoperative synechiae. These sterile, absorbable, highly viscous hydrophilic gels-typically composed of sodium carboxymethylcellulose (CMC), polyethylene oxide (PEO), and electrolytes-act as temporary mechanical barriers, physically separating traumatized surfaces during the healing period. Evidence from previous studies suggests that intrauterine gel application after hysteroscopic procedures may reduce adhesion formation and improve postoperative reproductive outcomes. However, few trials have evaluated the efficacy of these gels after laparoscopic or robotic myomectomy.

This study is a prospective, randomized, controlled, non-profit clinical trial designed to assess whether the application of an intrauterine anti-adhesion gel at the end of robotic-assisted laparoscopic myomectomy reduces the incidence of IUAs compared with no adhesion-prevention method. Sixty-two women undergoing myomectomy will be randomized 1:1 into an intervention group (with gel application) or a control group (without gel). All participants will undergo standardized preoperative assessment, including ultrasound and office hysteroscopy. Postoperative follow-up includes ultrasound at one month to evaluate pelvic adhesions and diagnostic hysteroscopy at two months to assess intrauterine adhesions. Reproductive outcomes will be monitored for up to 24 months through spontaneous or assisted conception attempts.

The primary endpoint is the incidence of intrauterine adhesions at follow-up hysteroscopy. Secondary endpoints include clinical pregnancy rate, implantation rate, miscarriage rate, live birth rate, pregnancy complications, mode of delivery, and neonatal outcomes.

The study aims to clarify whether combining a minimally invasive robotic approach with an intrauterine gel can synergistically reduce adhesion formation and improve fertility outcomes. Results may contribute to optimizing postoperative management in women undergoing myomectomy and refining strategies to preserve reproductive potential.

Interventions

• Device Women will receive the application of an anti-adhesion gel at the end of the myomectomy procedure
  The difference compared to other studies published in the past is that, in our trial, at the end of the robotic myomectomy-which will be performed using the same technique in both groups-an anti-adhesion gel will be applied in the intervention group to prevent the formation of intrauterine adhesions.

Primary outcome measures

• Efficacy of intrauterine gel in reducing the formation of intrauterine adhesions [Time frame: Up to two months after surgery]

Secondary outcome measures (5)

• Clinical Pregnancy Rate [Time frame: Up to 24 months after surgery]
• Live Birth Rate (LBR) [Time frame: Up to 24 months post-surgery.]
• Miscarriage Rate [Time frame: Up to 24 months after surgery]
• Pregnancy Complications [Time frame: Up to 24 months after surgery]
• Mode of delivery [Time frame: Up to 24 months after surgery]

Eligibility criteria

Inclusion criteria

• Age between 18 and 45 years;
• BMI 18-35;
• One or more fibroids diagnosed via ultrasound;
• First myomectomy or uterine surgery;
• Incomplete reproductive plans and/or infertility;
• Adequate immune, respiratory, liver, cardiac, bone marrow, and kidney function;
• Compliance and psychological ability to follow study procedures;
• Acceptance and signing of informed consent.

Exclusion criteria

• Age under 18 years;
• Age over 46 years;
• Pregnancy or breastfeeding;
• History of intrauterine adhesions;
• Diagnosis or suspicion of malignant gynecological pathologies and/or autoimmune diseases;
• Completed reproductive plans;
• Severe respiratory, bone marrow, liver, or kidney dysfunction preventing safe surgical access.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Mercorio A, Della Corte L, Boccia D, Palumbo M, Reppuccia S, Buonfantino C, Cuomo L, Borgo M, Zitiello A, De Angelis MC, Lagana AS, Bifulco G, Giampaolino P. Myomectomy in infertile women: More harm than good? Front Surg. 2023 Apr 17;10:1151901. doi: 10.3389/fsurg.2023.1151901. eCollection 2023. PMID 37139194
• Bortoletto P, Keefe KW, Unger E, Hariton E, Gargiulo AR. Incidence and risk factors of intrauterine adhesions after myomectomy. F S Rep. 2022 May 28;3(3):269-274. doi: 10.1016/j.xfre.2022.05.007. eCollection 2022 Sep. PMID 36212555
• Asgari Z, Hafizi L, Hosseini R, Javaheri A, Rastad H. Intrauterine synechiae after myomectomy; laparotomy versus laparoscopy: Non-randomized interventional trial. Iran J Reprod Med. 2015 Mar;13(3):161-8. PMID 26000007
• Lagana AS, Garzon S, Dababou S, Uccella S, Medvediev M, Pokrovenko D, Babunashvili EL, Buyanova SN, Schukina NA, Shcherbatykh Kaschchuk MG, Kosmas I, Licchelli M, Panese G, Tinelli A. Prevalence of Intrauterine Adhesions after Myomectomy: A Prospective Multicenter Observational Study. Gynecol Obstet Invest. 2022;87(1):62-69. doi: 10.1159/000522583. Epub 2022 Feb 15. PMID 35168241
• Capmas P, Pourcelot AG, Fernandez H. Are synechiae a complication of laparotomic myomectomy? Reprod Biomed Online. 2018 Apr;36(4):450-454. doi: 10.1016/j.rbmo.2018.01.010. Epub 2018 Feb 2. PMID 29454580
• Pellicano M, Guida M, Bramante S, Acunzo G, Di Spiezio Sardo A, Tommaselli GA, Nappi C. Reproductive outcome after autocrosslinked hyaluronic acid gel application in infertile patients who underwent laparoscopic myomectomy. Fertil Steril. 2005 Feb;83(2):498-500. doi: 10.1016/j.fertnstert.2004.09.019. PMID 15705404
• Acunzo G, Guida M, Pellicano M, Tommaselli GA, Di Spiezio Sardo A, Bifulco G, Cirillo D, Taylor A, Nappi C. Effectiveness of auto-cross-linked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic adhesiolysis: a prospective, randomized, controlled study. Hum Reprod. 2003 Sep;18(9):1918-21. doi: 10.1093/humrep/deg368. PMID 12923149
• Guida M, Acunzo G, Di Spiezio Sardo A, Bifulco G, Piccoli R, Pellicano M, Cerrota G, Cirillo D, Nappi C. Effectiveness of auto-crosslinked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic surgery: a prospective, randomized, controlled study. Hum Reprod. 2004 Jun;19(6):1461-4. doi: 10.1093/humrep/deh238. Epub 2004 Apr 22. PMID 15105384

Identifiers

NCT: NCT07280286 · KE5DXJL9Z1F5

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗