Crosslinked Hyaluronic Acid Gels for the Prevention of Intrauterine Adhesions after a Hysteroscopic Myomectomy in Women with Submucosal Myomas: A Prospective, Randomized, Controlled Trial

Intrauterine adhesion (IUA), fibrosis, and scarring resulting from damage to the endometrium is a rare but serious clinical disease, contributing to a significant impairment of reproductive function. Uterine instrumentation, especially that of a hysteroscopic myomectomy, has become the main cause of IUA. Therefore, a prospective randomized controlled study to assess the effectiveness and short-term safety of the use of hyaluronic acid gels in the prevention of IUA after a hysteroscopic myomectomy and an evaluation of the characteristics of IUA observed at follow-up are presented here. A total of 70 patients were analyzed at the end of 16 March 2020. The results show that the incidence of IUA in women who underwent a hysteroscopic myomectomy is 21.4% (15/70), overall. Women treated with hyaluronic acid gels have a statistically significantly lower incidence of IUAs than non-treated women (12.8% vs. 39.1%, p = 0.012). In addition, women in the anti-adhesive gel treatment group had a dramatically reduced severity of IUA than women in the no-treatment group (p = 0.002). Further analysis shows that the International Federation of Gynecology and Obstetrics (FIGO) classification type and the use of anti-adhesive gels are independent factors associated with moderate and severe degrees of IUA formation. The results here highlight the significant therapeutic benefits of the application of hyaluronic acid gels in women undergoing a hysteroscopic myomectomy, especially for those patients with a uterine myoma classified as FIGO type 2. Since the risk of IUA after a hysteroscopic myomectomy is high, especially for patients who have not received prophylactic anti-adhesive gels, the application of hyaluronic acid gels as a prevention strategy is highly recommended. More studies are encouraged to confirm our observation.

[1]  Fei Zheng,et al.  Meta-analysis on the use of hyaluronic acid gel to prevent intrauterine adhesion after intrauterine operations , 2020, Experimental and therapeutic medicine.

[2]  Dabao Xu,et al.  A novel intrauterine stent for prevention of intrauterine adhesions. , 2020, Annals of translational medicine.

[3]  Y. Hwu,et al.  Intrauterine adhesion prevention with Malecot catheter after hysteroscopic myomectomy: A novel approach. , 2020, Taiwanese journal of obstetrics & gynecology.

[4]  Zheng Fei,et al.  Meta-analysis on the use of hyaluronic acid gel to prevent recurrence of intrauterine adhesion after hysteroscopic adhesiolysis. , 2019, Taiwanese journal of obstetrics & gynecology.

[5]  Wen-Liang Liao,et al.  Combined treatment for big submucosal myoma with High Intensity Focused Ultrasound and hysteroscopic resection. , 2019, Taiwanese journal of obstetrics & gynecology.

[6]  Zheng Fei,et al.  Meta-analysis of the use of hyaluronic acid gel to prevent intrauterine adhesions after miscarriage. , 2019, European journal of obstetrics, gynecology, and reproductive biology.

[7]  Tsuyoshi Saito,et al.  Efficacy of silicone sheet as a personalized barrier for preventing adhesion reformation after hysteroscopic adhesiolysis of intrauterine adhesions , 2019, Reproductive medicine and biology.

[8]  S. Fay,et al.  Early Second-Look Hysteroscopy: Prevention and Treatment of Intrauterine Post-surgical Adhesions , 2019, Front. Surg..

[9]  A. Di Spiezio Sardo,et al.  Adhesions and Anti-Adhesion Systems Highlights , 2019, Facts, views & vision in ObGyn.

[10]  J. Kjer,et al.  Asherman’s syndrome: current perspectives on diagnosis and management , 2019, International journal of women's health.

[11]  M. Xue,et al.  New Crosslinked Hyaluronan Gel for the Prevention of Intrauterine Adhesions after Dilation and Curettage in Patients with Delayed Miscarriage: A Prospective, Multicenter, Randomized, Controlled Trial. , 2019, Journal of minimally invasive gynecology.

[12]  L. Goldsmith,et al.  The role of mesenchymal–epithelial transition in endometrial function , 2018, Human reproduction update.

[13]  H. Duan,et al.  Comparison of Intrauterine Suitable Balloon and Foley Balloon in the Prevention of Adhesion after Hysteroscopic Adhesiolysis , 2018, BioMed research international.

[14]  C. Yaşa,et al.  Efficacy of a New Crosslinked Hyaluronan Gel in the Prevention of Intrauterine Adhesions , 2018, JSLS : Journal of the Society of Laparoendoscopic Surgeons.

[15]  J. Wong,et al.  Hysteroscopic myomectomy: a comparison of techniques and review of current evidence in the management of abnormal uterine bleeding , 2018, Current opinion in obstetrics & gynecology.

[16]  G. Jakiel,et al.  Complications in modern hysteroscopic myomectomy. , 2018, Ginekologia polska.

[17]  Dongmei Xu,et al.  The Effect of Adjuvant Treatment to Prevent and Treat Intrauterine Adhesions: A Network Meta-Analysis of Randomized Controlled Trials. , 2017, Journal of minimally invasive gynecology.

[18]  H. Horng,et al.  WOUND HEALING , 1969, Journal of the Chinese Medical Association : JCMA.

[19]  H. Horng,et al.  Estrogen Effects on Wound Healing , 2017, International journal of molecular sciences.

[20]  KathleenR. Brandt,et al.  Clinical limitations of the International Federation of Gynecology and Obstetrics (FIGO) classification of uterine fibroids , 2017, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[21]  P. M. van de Ven,et al.  Prevalence of intrauterine adhesions after the application of hyaluronic acid gel after dilatation and curettage in women with at least one previous curettage: short-term outcomes of a multicenter, prospective randomized controlled trial. , 2017, Fertility and sterility.

[22]  B. Mol,et al.  Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility. , 2015, The Cochrane database of systematic reviews.

[23]  C. Gargett,et al.  Fertile ground: human endometrial programming and lessons in health and disease , 2016, Nature Reviews Endocrinology.

[24]  M. Hill,et al.  Intrauterine adhesion prevention after hysteroscopy: a systematic review and meta-analysis. , 2016, American journal of obstetrics and gynecology.

[25]  M. G. Soteras,et al.  Hysteroscopic myomectomy outcomes after 3-month treatment with either Ulipristal Acetate or GnRH analogues: a retrospective comparative study. , 2016, European journal of obstetrics, gynecology, and reproductive biology.

[26]  T. Thubert,et al.  Influence of auto-cross-linked hyaluronic acid gel on pregnancy rate and hysteroscopic outcomes following surgical removal of intra-uterine adhesions. , 2015, European journal of obstetrics, gynecology, and reproductive biology.

[27]  KrajčovičováRenáta,et al.  The Role of Hyaluronan in Asherman's Syndrome Therapy , 2015 .

[28]  S. Dias,et al.  Adhesion prevention agents for gynaecological surgery: an overview of Cochrane reviews. , 2015, The Cochrane database of systematic reviews.

[29]  S. Chudnoff,et al.  Hysteroscopic morcellation: review of the manufacturer and user facility device experience (MAUDE) database. , 2015, Journal of minimally invasive gynecology.

[30]  M. Xue,et al.  [Prevention of intrauterine adhesion with auto-crosslinked hyaluronic acid gel: a prospective, randomized, controlled clinical study]. , 2015, Zhonghua fu chan ke za zhi.

[31]  U. Salma,et al.  Efficacy of Intrauterine Device in the Treatment of Intrauterine Adhesions , 2014, BioMed research international.

[32]  F. Multinu,et al.  Monopolar versus bipolar device: safety, feasibility, limits and perioperative complications in performing hysteroscopic myomectomy. , 2014, Clinical and experimental obstetrics & gynecology.

[33]  M. Heymans,et al.  Systematic review and meta-analysis of intrauterine adhesions after miscarriage: prevalence, risk factors and long-term reproductive outcome. , 2014, Human reproduction update.

[34]  R. Halperin,et al.  Intercoat (Oxiplex/AP gel) for preventing intrauterine adhesions after operative hysteroscopy for suspected retained products of conception: double-blind, prospective, randomized pilot study. , 2014, Journal of minimally invasive gynecology.

[35]  Songying Zhang,et al.  A comparison of intrauterine balloon, intrauterine contraceptive device and hyaluronic acid gel in the prevention of adhesion reformation following hysteroscopic surgery for Asherman syndrome: a cohort study. , 2013, European journal of obstetrics, gynecology, and reproductive biology.

[36]  Liping Cai,et al.  Management of intrauterine adhesions: a novel intrauterine device. , 2013, Medical hypotheses.

[37]  H. Fernandez,et al.  Surgical techniques and outcome in the management of submucous fibroids , 2013, Current opinion in obstetrics & gynecology.

[38]  Shee-Uan Chen,et al.  Optimal waiting period for subsequent fertility treatment after various hysteroscopic surgeries. , 2013, Fertility and sterility.

[39]  J. W. Kim,et al.  A randomized, multi-center, clinical trial to assess the efficacy and safety of alginate carboxymethylcellulose hyaluronic acid compared to carboxymethylcellulose hyaluronic acid to prevent postoperative intrauterine adhesion. , 2012, Journal of minimally invasive gynecology.

[40]  L. Mettler,et al.  Complications of Uterine Fibroids and Their Management, Surgical Management of Fibroids, Laparoscopy and Hysteroscopy versus Hysterectomy, Haemorrhage, Adhesions, and Complications , 2012, Obstetrics and gynecology international.

[41]  R. Torrejón,et al.  Intrauterine Adhesions following Conservative Treatment of Uterine Fibroids , 2011, Obstetrics and gynecology international.

[42]  M. Guida,et al.  Efficacy of a polyethylene oxide-sodium carboxymethylcellulose gel in prevention of intrauterine adhesions after hysteroscopic surgery. , 2011, Journal of minimally invasive gynecology.

[43]  C. March Management of Asherman's syndrome. , 2011, Reproductive biomedicine online.

[44]  J. Abbott,et al.  Review of intrauterine adhesions. , 2010, Journal of minimally invasive gynecology.

[45]  K. Chao,et al.  Office hysteroscopic early lysis of intrauterine adhesion after transcervical resection of multiple apposing submucous myomas. , 2008, Fertility and sterility.

[46]  Y. Cheong,et al.  Asherman syndrome--one century later. , 2008, Fertility and sterility.

[47]  M. Fawzy,et al.  The nature of intrauterine adhesions following reproductive hysteroscopic surgery as determined by early and late follow-up hysteroscopy: clinical implications , 2008, Archives of Gynecology and Obstetrics.

[48]  M. Guida,et al.  Effectiveness of auto-crosslinked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic surgery: a prospective, randomized, controlled study. , 2004, Human reproduction.

[49]  M. Guida,et al.  Effectiveness of auto-cross-linked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic adhesiolysis: a prospective, randomized, controlled study. , 2003, Human reproduction.

[50]  V. Tsapanos,et al.  The role of Seprafilm bioresorbable membrane in the prevention and therapy of endometrial synechiae. , 2002, Journal of biomedical materials research.

[51]  J. Wheeler,et al.  Role of endometrial suppression on the frequency of intrauterine adhesions after resectoscopic surgery. , 2000, The Journal of the American Association of Gynecologic Laparoscopists.

[52]  J. Asherman Amenorrhoea Traumatica (Atretica) , 1948, The Journal of obstetrics and gynaecology of the British Empire.