Role of hyaluronic acid intrauterine injection in the prevention of Asherman’s syndrome in women undergoing uterine septum resection: An RCT

Abstract

Background: Adhesion due to intrauterine surgery such as septal resection associated with damaged endometrium can increase the risk of Asherman’s syndrome. The main goal of treatment in this syndrome is to repair the damaged endometrium for creating a physiological pregnancy.


Objective: To investigate the effect of intrauterine injection of hyaluronic acid on the prevention of Asherman’s syndrome in women undergoing uterine septum resection.


Materials and Methods: In this double-blind randomized clinical trial, 65 women undergoing the uterine septum resection were divided into two groups; the case group (n = 34) and the control group (n = 31). Immediately after the septal resection with a resectoscope, 1cc of hyaluronic acid gel in the case group and 1cc normal saline solution as a placebo in the control group was injected into the uterine cavity. After two months, existence of intrauterine adhesions in the both groups was examined by the hysteroscope and assessment of menstrual patterns, according to the American Society for Reproductive Medicine criteria.


Results: Our results showed that after intervention, the incidence of Asherman’s syndrome in the control group was higher than the case group (p = 0.012). In the case group, only four women had poor adhesion (Asherman’s syndrome) at the end of the study, while the rest of them were free of any adhesions in the uterine cavity. In the control group, however, only 19 were free of intrauterine adhesions and 12 had mild symptoms.


Conclusion: The results of the study exhibited the hyaluronic acid capacity to reduce the risk of Asherman’s syndrome in women with endometrial damage following a septal resection surgery.


Key words: Asherman’s syndrome, Septum, Uterine, Hyaluronic acid, Resection.

References
[1] Salazar CA, Isaacson K, Morris S. A comprehensive review of Asherman’s syndrome: Causes, symptoms and treatment options. Curr Opin Obstet Gynecol 2017; 29: 249–256.

[2] Dreisler E, Kjer JJ. Asherman’s syndrome: Current perspectives on diagnosis and management. Int J Women’s Health 2019; 11: 191–198.

[3] Cenksoy PO, Ficicioglu C, Yesiladali M, Kizilkale O. The diagnosis and management of Asherman’s syndrome developed after cesarean section and reproductive outcome. Case Rep Obstet Gynecol 2013; 2013: 450658.

[4] Aghajanova L, Cedars MI, Huddleston HG. Platelet-rich plasma in the management of Asherman syndrome: Case report. J Assist Reprod Genet 2018; 35: 771–775.

[5] March CM. Management of Asherman’s syndrome. Reprod BioMed Online 2011; 23: 63–76.

[6] Papakonstantinou E, Roth M, Karakiulakis G. Hyaluronic acid: A key molecule in skin aging. Dermatoendocrinol 2012; 4: 253–258.

[7] Bukhari SNA, Roswandi NL, Waqas M, Habib H, Hussain F, Khan Sh, et al. Hyaluronic acid, a promising skin rejuvenating biomedicine: A review of recent updates and pre-clinical and clinical investigations on cosmetic and nutricosmetic effects. Int J Biol Macromol 2018; 120: 1682–1695.

[8] Fei Zh, Xin X, Fei H, Yuechong C. Meta-analysis of the use of hyaluronic acid gel to prevent intrauterine adhesions after miscarriage. Eur J Obstet Gynecol Reprod Biol 2020; 244: 1–4.

[9] Conforti A, Alviggi C, Mollo A, De Placido G, Magos A. The management of Asherman syndrome: A review of literature. Reprod Biol Endocrinol 2013; 11: 118.

[10] Huberlant S, Fernandez H, Vieille P, Khrouf M, Ulrich D, Detayrac R, et al. Application of a hyaluronic acid gel after intrauterine surgery may improve spontaneous fertility: A randomized controlled trial in New Zealand White rabbits. PloS One 2015; 10: e0125610.

[11] Krajčovičová R, Hudečk R, Ventruba P, Surgentová K. The role of hyaluronan in Asherman’s syndrome therapy. J Gynecol Surg 2015; 31: 250–254.

[12] Liu H, Xu Y, Yi N, Yi W. Efficacy and safety of hyaluronic acid gel for the prevention of intrauterine adhesion: A meta-analysis of randomized clinical trials. Gynecol Obstet Invest 2018; 83: 227–233.

[13] Molotkov AS, Popov EN, Sudakov DS, Aivazyan TA, Alexandrova LA, Dymarskaya YR. Experience of intrauterine application of anti-adhesive gel based on hyaluronic acid in the prevention of Asherman’s syndrome in patients with the pathology of the uterine cavity and severe forms of endometriosis. J Obstet Women’s Dis 2017; 66: 12–19.

[14] Mais V, Bracco GL, Litta P, Gargiulo T, Melis GB. Reduction of postoperative adhesions with an auto-crosslinked hyaluronan gel in gynaecological laparoscopic surgery: A blinded, controlled, randomized, multicentre study. Hum Reprod 2006; 21: 1248–1254.

[15] Acunzo G, Guida M, Pellicano M, Tommaselli GA, Di Spiezio Sardo A, Bifulco G, et al. 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; 18: 1918–1921.

[16] Esmaeilzadeh S, Agajani Delavar M, Ghanbari Andarieh M. Reproductive outcome following hysteroscopic treatment of uterine septum. Mater Sociomed 2014; 26: 366–371.

[17] Practice Committee of the American Society for Reproductive Medicine. Uterine septum: A guideline. Fertil Steril 2016; 106: 530–540.

[18] Hooker AB, de Leeuw R, van de Ven PM, Bakkum EA, Thurkow AL, Vogel NEA, 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. Fertil Steril 2017; 107: 1223–1231.

[19] Guida M, Acunzo G, Di Spiezio Sardo A, Bifulco G, Piccoli R, Pellicano M, et al. Effectiveness of auto−crosslinked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic surgery: A prospective, randomized, controlled study. Hum Reprod 2004; 19: 1461–1464.

[20] Tsapanos VS, Stathopoulou LP, Papathanassopoulou VS, Tzingounis VA. The role of Seprafilm bioresorbable membrane in the prevention and therapy of endometrial synechiae. J Biomed Mater Res 2002; 63: 10–14.

[21] Salma U, Xue M, Sheikh A, Sayed A, Xu D. Efficacy of intrauterine device in the treatment of intrauterine adhesions. BioMed Res Int 2014; 2014: 589296.

[22] Lin X, Wei M, Li TC, Huang Q, Huang D, Zhou F, 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. Eur J Obstet Gynecol Reprod Biol 2013; 170: 512–516.