The Efficacy and Reproductive Outcome of Auto-Cross-Linked Hyaluronic Acid Gel for the Prevention of Recurrence of Mild to Moderate Intrauterine Adhesions

doi:10.12280/gjfckx.20230717

Abstract

Abstract:

Objective: To investigate the efficacy of auto-cross-linked hyaluronic acid (ACP) gel in preventing adhesion recurrence after transcervical resection adhesion (TCRA) in patients with mild to moderate intrauterine adhesion (IUA) and its effect on reproductive outcomes. Methods: 188 patients with mild to moderate IUA who underwent TCRA in Fuxing Hospital of Capital Medical University from May 2020 to March 2021 were collected, and the recurrence rate of postoperative IUA, American Fertility Association (AFS) score, menstrual improvement and reproductive outcomes were observed in a single-center prospective randomized controlled manner, and the efficacy of ACP gel in preventing recurrence of IUA and its effect on reproductive outcomes were analyzed. The study group (84 cases) was received intrauterine injection of ACP gel + balloon stent at the end of surgery, and the control group (87 cases) only received balloon stent at the end of surgery. Results: 171 cases underwent the second and third hysteroscopies at 4 and 8 weeks after surgery, respectively. The recurrence rate of IUA in the study group was slightly lower than that in the control group, but the difference was not statistically significant (20.2% vs. 23.0%, 9.5% vs. 11.5%, both P>0.05). There was no significant difference in AFS scores between the two groups (P>0.05). There was no significant difference in menstrual improvement between the two groups at 12 weeks after surgery (P=0.630). More than one year after TCRA operation, there was no significant difference in pregnancy rate and live birth rate between the two groups (both P>0.05). Conclusions: In patients with mild to moderate IUA, compared with balloon stent alone after TCRA, balloon stent combined with intrauterine injection of ACP gel did not reduce the recurrence rate and adhesion severity of IUA, nor could it promote the improvement of menstrual pattern and postoperative reproductive outcome.

Key words: Hysteroscopes, Hyaluronic acid, Gels, Recurrence, Menstruation disorders, Pregnancy outcome, Intrauterine adhesion

GUO Yan, XIA En-lan, XIAO Yu, HUANG Xiao-wu, LIU Yu-huan, YANG Ling-ling, LI Tian-zhao. The Efficacy and Reproductive Outcome of Auto-Cross-Linked Hyaluronic Acid Gel for the Prevention of Recurrence of Mild to Moderate Intrauterine Adhesions[J]. Journal of International Obstetrics and Gynecology, 2024, 51(1): 110-113.

Figures/Tables 4

References 21

[1]	Lee WL, Liu CH, Cheng M, et al. Focus on the Primary Prevention of Intrauterine Adhesions: Current Concept and Vision[J]. Int J Mol Sci, 2021, 22(10):5175. doi: 10.3390/ijms22105175.
[2]	Cheng M, Chang WH, Yang ST, et al. Efficacy of Applying Hyaluronic Acid Gels in the Primary Prevention of Intrauterine Adhesion after Hysteroscopic Myomectomy: A Meta-Analysis of Randomized Controlled Trials[J]. Life(Basel), 2020, 10(11):285. doi: 10.3390/life10110285.
[3]	Dou Y, Yu T, Li Z, et al. Short- and Long-term Outcomes of Postoperative Intrauterine Application of Hyaluronic Acid Gel: A Meta-analysis of Randomized Controlled Trials[J]. J Minim Invasive Gynecol, 2022, 29(8):934-942. doi: 10.1016/j.jmig.2022.05.006.
[4]	Wang YQ, Song XH, Wu SL, et al. Comparison of Autocross-Linked Hyaluronic Acid Gel and Intrauterine Device for Preventing Intrauterine Adhesions in Infertile Patients: A Randomized Clinical Trial[J]. Gynecol Minim Invasive Ther, 2020, 9(2):74-80. doi: 10.4103/GMIT.GMIT_103_19.
[5]	Zhou Q, Shi X, Saravelos S, et al. Auto-Cross-Linked Hyaluronic Acid Gel for Prevention of Intrauterine Adhesions after Hysteroscopic Adhesiolysis: A Randomized Controlled Trial[J]. J Minim Invasive Gynecol, 2021, 28(2):307-313. doi: 10.1016/j.jmig.2020.06.030.
[6]	The American Fertility Society classifications of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, müllerian anomalies and intrauterine adhesions[J]. Fertil Steril, 1988, 49(6):944-955. doi: 10.1016/s0015-0282(16)59942-7. pmid: 3371491
[7]	Fritsch H. Ein Fall von volligen Schwund der Gebaumutterhohle nach Auskratzung[J]. Zentralbl Gynaekol, 1894, 18:1337-1342.
[8]	Hooker AB, Mansvelder FJ, Elbers RG, et al. Reproductive outcomes in women with mild intrauterine adhesions; a systematic review and meta-analysis[J]. J Matern Fetal Neonatal Med, 2022, 35(25):6933-6941. doi: 10.1080/14767058.2021.1931103.
[9]	Sun D, Mao X, Zhang A, et al. Pregnancy Patterns Impact Live Birth Rate for Patients With Intrauterine Adhesions After Hysteroscopic Adhesiolysis: A Retrospective Cohort Study[J]. Front Physiol, 2022, 13:822845. doi: 10.3389/fphys.2022.822845.
[10]	Chiu CS, Hwu YM, Lee RK, et al. Intrauterine adhesion prevention with Malecot catheter after hysteroscopic myomectomy: A novel approach[J]. Taiwan J Obstet Gynecol, 2020, 59(1):56-60. doi: 10.1016/j.tjog.2019.11.008. pmid: 32039801
[11]	张庆华, 黄立苹, 陈燕美. 电刺激联合艾灸预防人工流产术后宫腔粘连的临床观察[J]. 中国中医药科技, 2022, 29(5):826-828.
[12]	Liu HD, Wang SW. Role of noncoding RNA in the pathophysiology and treatment of intrauterine adhesion[J]. Front Genet, 2022, 13:948628. doi: 10.3389/fgene.2022.948628.
[13]	霍真真. 自交联透明质酸钠凝胶预防中重度宫腔粘连宫腔镜术后再粘连效果分析[J]. 河南外科学杂志, 2023, 29(2):154-155.
[14]	蒋文军, 黄晓武. 宫腔粘连分离术后预防粘连复发的方法及研究进展[J]. 国际妇产科学杂志, 2021, 48(4):409-414. doi: 10.12280/gjfckx.20201136.
[15]	中华医学会妇产科学分会. 宫腔粘连临床诊疗中国专家共识[J]. 中华妇产科杂志, 2015, 50(12):881-887. doi: 10.3760/cma.j.issn.0529-567x.2015.12.001.
[16]	段华, 甘露. 宫腔粘连子宫腔整复手术质量控制[J]. 中国实用妇科与产科杂志, 2022, 38(1):36-40. doi: 10.19538/j.fk2022010110.
[17]	Bosteels J, Weyers S, Kasius J, et al. Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility[J]. Cochrane Database Syst Rev, 2015(11):CD011110. doi: 10.1002/14651858.CD011110.pub2.
[18]	Fei Z, Xin X, Fei H, et al. Meta-analysis of the use of hyaluronic acid gel to prevent intrauterine adhesions after miscarriage[J]. Eur J Obstet Gynecol Reprod Biol, 2020, 244:1-4. doi: 10.1016/j.ejogrb.2019.10.018. pmid: 31731019
[19]	Hooker AB, de Leeuw RA, Twisk J, et al. Reproductive performance of women with and without intrauterine adhesions following recurrent dilatation and curettage for miscarriage: long-term follow-up of a randomized controlled trial[J]. Hum Reprod, 2021, 36(1):70-81. doi: 10.1093/humrep/deaa289.
[20]	刘慧星, 宾力, 朱雪红, 等. 宫腔粘连分离术后雌激素辅助治疗的研究进展[J]. 国际妇产科学杂志, 2023, 50(6):618-622. doi:10.12280/gjfckx.20230474.
[21]	Mao X, Tao Y, Cai R, et al. Cross-linked hyaluronan gel to improve pregnancy rate of women patients with moderate to severe intrauterine adhesion treated with IVF: a randomized controlled trial[J]. Arch Gynecol Obstet, 2020, 301(1):199-205. doi: 10.1007/s00404-019-05368-6. pmid: 31883044

组别	n	年龄（岁）	BMI （kg/m²）	导致IUA的诱因			月经量			IUA程度		AFS评分（分）
组别	n	年龄（岁）	BMI （kg/m²）	终止妊娠	宫腔镜手术*	宫内节育器	正常	减少	闭经	轻度	中度	AFS评分（分）
研究组	84	32.99±3.74	22.35±3.29	81（96.4）	2（2.4）	1（1.2）	11（13.1）	69（82.1）	4（4.8）	27（32.1）	57（67.9）	6（4，7）
对照组	87	32.60±3.85	22.18±3.36	83（95.4）	3（3.4）	1（1.1）	14（16.1）	71（81.6）	2（2.3）	27（31.0）	60（69.0）	6（4，7）
t或χ²或Z		-0.672	-0.340		-			-		0.024		-0.011
P		0.503	0.734		0.808^#			0.606^#		0.876		0.991

组别	n	年龄（岁）	BMI （kg/m²）	导致IUA的诱因			月经量			IUA程度		AFS评分（分）
组别	n	年龄（岁）	BMI （kg/m²）	终止妊娠	宫腔镜手术*	宫内节育器	正常	减少	闭经	轻度	中度	AFS评分（分）
研究组	84	32.99±3.74	22.35±3.29	81（96.4）	2（2.4）	1（1.2）	11（13.1）	69（82.1）	4（4.8）	27（32.1）	57（67.9）	6（4，7）
对照组	87	32.60±3.85	22.18±3.36	83（95.4）	3（3.4）	1（1.1）	14（16.1）	71（81.6）	2（2.3）	27（31.0）	60（69.0）	6（4，7）
t或χ²或Z		-0.672	-0.340		-			-		0.024		-0.011
P		0.503	0.734		0.808^#			0.606^#		0.876		0.991

组别	n	术后4周		术后8周
组别	n	IUA复发率	AFS评分	IUA复发率	AFS评分
研究组	84	17（20.2）	0（0，2）	8（9.5）	0（0，2）
对照组	87	20（23.0）	0（0，2）	10（11.5）	0（0，2）
χ²或Z		0.191	-0.867	0.176	-0.130
P		0.662	0.386	0.675	0.897

组别	n	术后4周		术后8周
组别	n	IUA复发率	AFS评分	IUA复发率	AFS评分
研究组	84	17（20.2）	0（0，2）	8（9.5）	0（0，2）
对照组	87	20（23.0）	0（0，2）	10（11.5）	0（0，2）
χ²或Z		0.191	-0.867	0.176	-0.130
P		0.662	0.386	0.675	0.897

组别	n	所有患者		轻度IUA		中度IUA
组别	n	改善	无改善	改善	无改善	改善	无改善
研究组	84	57（67.9）	27（32.1）	44（77.2）	13（22.8）	13（48.1）	14（51.9）
对照组	87	56（64.4）	31（35.6）	44（73.3）	16（26.7）	12（44.4）	15（55.6）
χ²		0.232		0.233		0.075
P		0.630		0.629		0.785