ABSTRACT
The aim of this study was to determine whether intrauterine device (IUD) combined with Foley balloon could obtain better efficacy in preventing re-adhesion for patients with intrauterine adhesions (IUAs). The data of 89 patients with IUAs, who underwent transcervical resection of adhesion (TCRA) operation, were retrospectively collected. According to the method used for preventing re-adhesion of the uterine cavity after TCRA, the enrolled patients were divided into IUD group, Foley balloon group and the combined group. The second-look hysteroscopy was carried out at 3 months after TCRA surgery. The severity and extent of IUA were scored by American Fertility Society (AFS) scoring system. The endometrial thickness (EMT) was measured by ultrasound. Furthermore, the menstruation and pregnancy outcomes were also assessed. Our results showed that the postoperative decrease in AFS score was significantly greater in the combined group than in the IUD group or in the Foley balloon group. The increase in menstrual score among the 3 groups was not significantly different. The difference between preoperative and postoperative values of EMT was greater in the combined group than in the other 2 groups. In conclusion, the effect of a Foley balloon combined with IUD in preventing re-adhesion after TCRA might be better than that of IUD or Foley balloon alone.
Introduction
Intrauterine adhesion (IUA), also known as Asherman’s syndrome, is a uterine disorder caused by damage to the endometrial basal layer (Kou et al. Citation2020; Wang et al. Citation2020). In the healing process, the opposing walls of the uterus adhere together, resulting in minimal, marginal, or complete obliteration of the uterine cavity (Hooker et al. Citation2014). An IUA disorder is often caused by intrauterine operations, especially those involving dilation and curettage (Sun et al. Citation2020). Women with IUA will generally experience a series of clinical symptoms, including hypomenorrhea, amenorrhea, periodic abdominal pain, infertility, and recurrent pregnancy loss (Zhu et al. Citation2018). With the increased rate of induced abortion, the incidence of IUA is also increasing. In fact, it has been reported that the prevalence of IUA ranges from 6 percent to 30 percent in women undergoing various types of abortions (Conforti et al. Citation2013).
Hysteroscopy is the standard method for diagnosing and treating IUA, with most confirmed cases treated via a transcervical resection of adhesion (TCRA) procedure. However, the recurrence rate following TCRA is reported to be as high as 62.5 percent (Yu et al. Citation2008), and the high rate of postoperative reformation of adhesions remains a challenge for patients with IUA. Thus, preventing adhesion reformation is essential to the successful treatment of this disorder. Currently, various adjuvant treatments aimed at reducing the recurrence of adhesion following TCRA have been proposed, including those involving hormone treatment, an intrauterine balloon or intrauterine device (IUD), and hyaluronic acid gel (Huang et al. Citation2020; Kou et al. Citation2020; Sun et al. Citation2020). Among these treatments, those involving IUDs and intrauterine balloons are the most widely used. However, the use of these devices remains controversial, with no clear consensus on which is best.
A retrospective study found that the Foley catheter is more effective for restoring normal uterine anatomy and for menstruation restoration compared with IUDs (Orhue, Aziken, and Igbefoh Citation2003), while in their randomized controlled trial, Lin et al. found that the intrauterine balloons and IUDs demonstrated similar efficacy in the prevention of adhesion reformation following TCRA (Lin et al. Citation2015). Meanwhile, Xiao et al. found that using an IUD or intrauterine balloon was not beneficial in reducing the incidence of postoperative IUA formation (Xiao et al. Citation2016).
Recently, the combined use of an IUD and an intrauterine balloon has been applied to prevent adhesion reformation following TCRA (Zhang et al. Citation2021), an approach that has the potential to achieve more effective outcomes. The present study aims to determine whether this combined approach could indeed improve the efficacy, both in terms of preventing re-adhesion and improving the pregnancy rate among patients with IUAs, with the overall aim of providing an effective treatment strategy for the postoperative management of this disorder.
Materials and methods
Patients
A total of 89 patients with IUAs who underwent a TCRA operation at our hospital between January 2016 and December 2020 were selected as the research subjects. The inclusion criteria were as follows: (1) patients aged 18–45 years, (2) patients with a hysteroscopy diagnosis of moderate and severe IUA according to the American Fertility Society (AFS) scoring system (AFS score ≥5) (Valle and Sciarra Citation1988), and (3) patients with normal endocrines and ovulation. Meanwhile, the exclusion criteria included the following: (1) patients with a TCRA operation history, (2) patients with premature menopause, and (3) patients with significant medical disorders, including thrombophilia, cardiovascular, and respiratory disease. This retrospective study was approved by the institutional review board of our hospital. All the patients enrolled in this study signed the informed consent form after agreeing that their data could be published.
Based on the method used for preventing re-adhesion of the uterine cavity following TCRA, the enrolled patients were divided into the IUD group, the Foley balloon group, and the combined group (Foley balloon + IUD).
Procedure
The three groups of patients underwent TCRA within 3–7 days after the termination of their menstruation. The surgical procedures were carried out by the same team of surgeons at our center under general anesthesia, with all the procedures having successful outcomes. No laparotomy or laparoscopy was performed during the operation.
In the IUD group, the patients received IUD implantation (copper coil, Yandai Contraceptive Instrument Company, China) immediately following the TCRA, with the IUD removed three months after surgery. In the Foley balloon group, a 16-f Foley catheter was placed into the uterine cavity immediately following the TCRA, with the balloon then filled with 4 ml of normal saline solution. The balloon catheter was then removed seven days following surgery. In the combined group, a 16-f Foley catheter was inserted immediately after the TCRA and was then removed after seven days and replaced by an IUD. The IUD was then removed three months after surgery. All the patients across the three groups received sequential treatment of estrogen and progesterone, commenced on the day of TCRA surgery, to promote reparative proliferation of the endometrium. Dydrogesterone tablets (20 mg daily; manufacturer: Abbott Biologicals B.V.) were taken orally from the 12th day of operation for 10 days, while the oestrogen (4–6 mg daily; manufacturer: Abbott Biologicals B.V.) was administered orally from the day of surgery for 21 days.
Second-look hysteroscopy was carried out at three months following TCRA surgery to observe the condition of the uterine cavity. The severity and the extent of the IUA were scored according to the classification system recommended by the AFS (Valle and Sciarra Citation1988). Based on the nature and scope of the adhesions, as well as the menstrual mode, the following quantitative scale was devised: 1–4 indicates mild adhesion (zero patients), 5–8 indicates moderate adhesion (59 patients), and 9–12 indicates severe adhesion (30 patients). The menstruation condition was evaluated using a method similar to the visual analogue scale method, in which 0 indicated amenorrhea and 10 indicated normal menstruation (Chen et al. Citation2017a; Sun et al. Citation2020). In addition, all patients underwent transvaginal ultrasonography at the early follicular phase to assess the endometrium thickness (EMT). The median follow-up was 13 months (range = 12–20 months), with a telephone follow-up carried out to record any pregnancy details.
Statistical analysis
The data were analyzed using SPSS software (version 22.0). After applying the Kolmogorov – Smirnov test, the quantitative data were expressed in terms of mean ± standard deviation (SD). The significance of the differences among the groups was determined using the one-way analysis of variance (ANOVA) method followed by a LSD post hoc test. The categorical data were expressed in terms of numbers and percentages and compared using a chi-squared test and Fisher’s test. The AFS scores were expressed as median (range) and compared using a Kruskal – Wallis rank test. A P value of <0.05 was considered to be statistically significant.
The primary outcome of this study pertained to the AFS scores, and the sample size was calculated based on these scores. With reference to the study conducted by Zhang et al. (Zhang et al. Citation2021) and our preliminary experiment, a sample size of 75 participants (25 per group) was estimated to achieve 90 percent power. However, to allow for a 10 percent–20 percent loss rate during the follow-up, it was decided to analyze the data of 82–90 patients.
Results
A total of 89 patients with IUAs who underwent a TCRA operation at our hospital were retrospectively studied. Among the enrolled patients, 31 (34.83 percent) were included in the IUD group, 30 (33.71 percent) were included in the Foley balloon group, and 28 (31.46 percent) were included in the combined group. shows the baseline characteristics of the patients prior to therapy, with the baseline characteristics among the three groups found to be well balanced. There were no significant differences in the EMT prior to surgery (0.50 ± 0.06 vs. 0.51 ± 0.05 vs. 0.52 ± 0.05, P = .365), the AFS score prior to surgery (8 [5–12] vs. 7 [5-12] vs. 7.5 [5–12], P = .857), or the menstrual score prior to surgery (3.39 ± 1.91 vs. 3.57 ± 1.87 vs. 4.04 ± 2.12, P = .432) among the three groups.
Table 1. The clinical characteristics of each group.
summarizes the AFS and menstrual scores across the three groups. There was no difference in postoperative AFS score among the three groups, while the postoperative decrease in AFS score was significantly greater in the combined group than in the IUD group (4 [1–10] vs 4 [1-8], P = .032) and the Foley balloon group (4 [1–10] vs 4 [1–7], P = .018). In terms of the patients with moderate adhesion prior to surgery, the postoperative AFS score reduction was not significantly different among the three groups (P = .334), while in terms of the patients with severe adhesion prior to surgery, the AFS score reduction was greater in the combined group than in the other two groups (P = .044).
Table 2. Comparisons of AFS and menstrual scores in patients with intrauterine adhesions.
Meanwhile, there was no difference in postoperative menstrual scores among the three groups (P = .385), while the postoperative increase in menstrual scores among the three groups was not significantly different across the total population, i.e., patients with moderate adhesion and patients with severe adhesion (P = .180, P = .978, P = .564, respectively) ().
There was also no difference in preoperative EMT among the three groups. However, following the surgery, the EMT was significantly thicker in the combined group than in the IUD group and the Foley balloon group (P < .001) (). The difference between the preoperative and postoperative EMT values was also greater in the combined group than in the other two groups (P < .001) ().
Table 3. Comparisons of endometrial thickness in patients with intrauterine adhesions (mean ± SD).
During the follow-up period, 10 patients (32.26 percent) in the IUD group, 13 patients (43.33 percent) in the Foley balloon group, and nine patients in the combined group (32.14 percent) were pregnant. There was no statistical significance in the pregnancy rate among the three groups (P = .586).
Discussion
In the present study, the therapeutic efficacy of three methods was compared in terms of the prevention of re-adhesion following TCRA in patients with moderate and severe IUAs. The results indicated that the postoperative reduction in AFS score when using the combination of an IUD and a Foley balloon was far higher than when using an IUD or a Foley balloon alone. Furthermore, the difference between the preoperative and postoperative EMT values was also greater in the combined group. These results indicated that the combined use of an IUD and a Foley balloon could have a better therapeutic effect in terms of re-adhesion prevention among IUA patients following TCRA.
The occurrence of IUA is common among women, and its presence could interfere with normal reproductive functioning, ultimately resulting in infertility (Xiao et al. Citation2016). Currently, the standard treatment for IUAs is TCRA. However, while TCRA can improve the reproductive-related outcomes of women with IUA, the re-adhesion rate following surgery markedly limits its applicability (Chen et al. Citation2017; Sun et al. Citation2020). Various adjuvant therapies aimed at reducing adhesion reformation following TCRA have been proposed, including those involving the use of IUDs and Foley balloons (Kou et al. Citation2020; Xiao et al. Citation2014). The use of an IUD allows for keeping opposing surfaces of the uterine cavity separated, inducing physiological endometrial regeneration (Wang et al. Citation2020), while the device can be left in the uterine cavity for more than two months, thus playing its protective role for a long period of time. Furthermore, removing the IUD may also help eliminate some of the adhesions that may have reformed (Lin et al. Citation2013). However, the use of IUDs is not recommended by a number of investigators, largely because the device’s surface area is too small to prevent adhesion reformation (Xiao et al. Citation2016). An IUD may also induce an excessive inflammatory reaction, which could increase the likelihood of the reformation of adhesions (Kou et al. Citation2020).
Meanwhile, the use of a Foley catheter balloon also potentially allows for effectively keeping the damaged opposing walls of the uterine cavity apart, thereby preventing re-adhesion (Kou et al. Citation2020). Compared with IUDs, the Foley balloon has the advantage of a larger surface area. Orhue et al. found that IUA patients had better menstruation outcomes following treatment with a Foley catheter balloon than using an IUD (Orhue, Aziken, and Igbefoh Citation2003). However, the shape of the Foley balloon can render fitting the device into the uterine cavity problematic, especially when inserting it over the lateral uterine wall (Kou et al. Citation2020). Furthermore, Foley catheter balloon can stay in the uterine cavity for only a week, because it leaves a tube exteriorizing through the vagina. Leaving the balloon in the uterine cavity for more than one week may significantly increase the risk of infection (Lin et al. Citation2013).
Given the relative advantages and disadvantages of IUDs and Foley balloons, combined use of these two methods for re-adhesion protection has been proposed (Huang et al. Citation2020; Wu et al. Citation2021; Zhang et al. Citation2021). For their part, Huang et al. (Citation2020) conducted a prospective randomized study and found that the combination of an IUD and a Foley balloon had better efficacy in preventing re-adhesion than the Cook® balloon stent alone, while Zhang et al. (Zhang et al. Citation2021) found that the efficacy of a Foley balloon combined with an IUD in preventing re-adhesion was superior to that of an IUD alone. In line with these studies, the present study found that the postoperative reduction in AFS score was far higher when using the combination of an IUD and a Foley balloon than when using an IUD or Foley balloon alone.
The AFS classification assesses the IUA severity based on a combined evaluation incorporating hysteroscopic or hysterosalpingography findings and the menstrual pattern (Cao et al. Citation2021; Valle and Sciarra Citation1988), with a higher AFS score indicating a more severe adhesion. Our results indicated that the combined use of an IUD and a Foley balloon demonstrates better efficacy in preventing re-adhesion following TCRA. Specifically, while the sub-group analysis indicated that the postoperative AFS score reduction was not significantly different among the three groups for patients with moderate adhesion prior to surgery, in patients with severe adhesion, the combined method had a clear advantage over the other two methods. This indicates that patients with severe adhesion may benefit from the combined treatment in terms of re-adhesion prevention.
As noted, IUA occurs due to the disruption of the basalis layer of the endometrium (Salazar, Isaacson, and Morris Citation2017). The maximum EMT is a critical factor predicting the live birth outcomes of IUA patients, as the EMT can directly affect conception and even lead to adverse pregnancy outcomes (Bhandari et al. Citation2015; Cao et al. Citation2021). In the present study, the EMT of the IUA patients was compared preoperatively and postoperatively across the three groups, and the difference was found to be statistically significant. It was thus concluded that the combined use of an IUD and a Foley balloon could effectively improve the EMT.
Meanwhile, the post-TCRA pregnancy rate was not significantly different among the three groups. In fact, while the combined treatment improved the EMT, it did not improve the pregnancy rate. However, this may have been partly due to the small sample size and the short follow-up period. Furthermore, as previously reported, in addition to the direct effect of the EMT on pregnancy outcomes, other influencing factors, such as age, endometrial area, preoperative adhesion degree, and postoperative menstrual improvement, may also affect the outcome (Zhao et al. Citation2020). Thus, whether the combined treatment could improve the pregnancy outcome following TCRA should be investigated in further studies.
To the best of our knowledge, this study is the first to compare three different methods aimed at preventing re-adhesion following TCRA in patients with moderate and severe IUAs. However, the study also involves several limitations. First, the results were based on a retrospective analysis of 89 patients with IUAs, and the inherent bias involved in a retrospective study design could have come into play here. Second, the sample size was comparatively small, while all the patients were treated in a single center, which may have introduced some selection bias. Third, the follow-up period for the pregnancy assessment was relatively short, and the pregnancy outcomes thus could not be accurately evaluated. Finally, this study did not collect safety data related to postoperative complications, such as uterine perforation, severe bleeding, water poisoning, and intrauterine infection. Thus, further multi-centre studies with larger sample sizes are required to confirm our results and conclusions.
Conclusions
Overall, the results obtained in this study indicated that the combined use of a Foley balloon and an IUD has a superior effect compared with the use of an IUD or Foley balloon alone in terms of preventing re-adhesion following TCRA. As such, this combined treatment may have a better therapeutic effect in patients with IUAs.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Additional information
Funding
References
- Bhandari, S., P. Bhave, I. Ganguly, A. Baxi, and P. Agarwal. 2015. Reproductive outcome of patients with asherman’s syndrome: A SAIMS experience. Journal of Reproduction & Infertility 16 (4):229–35.
- Cao, M.Z., Y.Y. Pan, Q.Y. Zhang, D.M. You, S.Y. Feng, and Z. Liu. 2021. Predictive value of live birth rate based on different intrauterine adhesion evaluation systems following TCRA. Reproductive Biology and Endocrinology 19 (1):13. doi:10.1186/s12958-021-00697-1.
- Chen, Y.Q., L.X. Liu, Y.N. Luo, M.H. Chen, Y. Huan, R.L. Fang, and Z. Tu. 2017a. MET18 deficiency increases the sensitivity of yeast to oxidative stress and shortens replicative lifespan by inhibiting catalase activity. BioMed Research International 2017:8526104. doi:10.1155/2017/7587395.
- Chen, L.M., H.W. Zhang, Q. Wang, F. Xie, S.J. Gao, Y. Song, J. Dong, H. Feng, K. Xie, and L. Sui. 2017b. Reproductive outcomes in patients with intrauterine adhesions following hysteroscopic adhesiolysis: Experience from the largest women’s hospital in China. Journal of Minimally Invasive Gynecology 24 (2):299–304. doi:10.1016/j.jmig.2016.10.018.
- Conforti, A., C. Alviggi, A. Mollo, G. De Placido, and A. Magos. 2013. The management of Asherman syndrome: A review of literature. Reproductive Biology and Endocrinology 27 (11):118. doi:10.1186/1477-7827-11-118.
- Hooker, A.B., M. Lemmers, A.L. Thurkow, M.W. Heymans, B.C. Opmeer, H.A.M. Brölmann, B. W. Mol, and J. A. F. Huirne. 2014. Systematic review and meta-analysis of intrauterine adhesions after miscarriage: Prevalence, risk factors and long-term reproductive outcome. Human Reproduction Update 20 (2):262–78. doi:10.1093/humupd/dmt045.
- Huang, X.W., M.M. Lin, H.Q. Zhao, M. Powell, Y.Q. Wang, R.R. Zheng, L. B. Ellis, W.-T. Xia, and F. Lin. 2020. A prospective randomized controlled trial comparing two different treatments of intrauterine adhesions. Reproductive Biomedicine Online 40 (6):835–41. doi:10.1016/j.rbmo.2020.02.013.
- Kou, L.F., X. Jiang, S.Y. Xiao, Y.Z. Zhao, Q. Yao, and R.J. Chen. 2020. Therapeutic options and drug delivery strategies for the prevention of intrauterine adhesions. Journal of Controlled Release 318:25–37. doi:10.1016/j.jconrel.2019.12.007.
- Lin, X.N., M.L. Wei, T.C. Li, Q.X. Huang, D. Huang, F. Zhou, and S.Y. Zhang. 2013. 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. European Journal of Obstetrics & Gynecology and Reproductive Biology 170 (2):512–16. doi:10.1016/j.ejogrb.2013.07.018.
- Lin, X.N., F. Zhou, M.L. Wei, Y. Yang, Y. Li, T.C. Li, and S.Y. Zhang. 2015. Randomized, controlled trial comparing the efficacy of intrauterine balloon and intrauterine contraceptive device in the prevention of adhesion reformation after hysteroscopic adhesiolysis. Fertility and Sterility 104 (1):235–40. doi:10.1016/j.fertnstert.2015.04.008.
- Orhue, A.A.E., M.E. Aziken, and J.O. Igbefoh. 2003. A comparison of two adjunctive treatments for intrauterine adhesions following lysis. International Journal of Gynecology & Obstetrics 82 (1):49–56. doi:10.1016/S0020-7292(03)00030-4.
- Salazar, C.A., K. Isaacson, and S. Morris. 2017. A comprehensive review of Asherman’s syndrome: Causes, symptoms and treatment options. Current Opinion in Obstetrics & Gynecology 29 (4):249–56. doi:10.1097/GCO.0000000000000378.
- Sun, J.H., C. Shi, Y. Liang, J.M. Niu, S.S. Guo, and Z.X. Cheng. 2020. Effects of early second-look hysteroscopy combined with intrauterine balloon dilatation on reproductive outcomes for women with intrauterine adhesions. International Journal of Gynecology & Obstetrics 149 (2):192–96. doi:10.1002/ijgo.13108.
- Valle, R.F., and J.J. Sciarra. 1988. Intrauterine adhesions: Hysteroscopic diagnosis, classification, treatment, and reproductive outcome. American Journal of Obstetrics and Gynecology 158 (6 Pt 1):1459–70. doi:10.1016/0002-9378(88)90382-1.
- Wang, Y.Q., X.H. Song, S.L. Wu, Y.Z. Huang, L. Yan, and C.Z. Li. 2020. Comparison of autocross-linked hyaluronic acid gel and intrauterine device for preventing intrauterine adhesions in infertile patients: A randomized clinical trial. Gynecology and Minimally Invasive Therapy 9 (2):74–80. doi:10.4103/GMIT.GMIT_103_19.
- Wu, C.Y., Y.S. Dong, Y. Li, and H.F. Liu. 2021. The efficacy of amniotic membrane-mediated sequential double-barrier therapy for the treatment of postoperative intrauterine adhesions. Medicine (Baltimore) 100 (15):e25416. doi:10.1097/MD.0000000000025416.
- Xiao, S.S., Y.J. Wan, M. Xue, X.Y. Zeng, F. Xiao, D.B. Xu, X. Yang, P. Zhang, W. Sheng, J. Xu, et al. 2014. Etiology, treatment, and reproductive prognosis of women with moderate-to-severe intrauterine adhesions. International Journal of Gynecology & Obstetrics 125(2):121–24. doi:10.1016/j.ijgo.2013.10.026.
- Xiao, Y., YH. Liu, DM. Song, E. Xia, and TC. Li. 2016. The incidence of post-operative adhesion following transection of uterine septum: A cohort study comparing three different adjuvant therapies. European Journal of Obstetrics & Gynecology and Reproductive Biology 201:61–64. doi:10.1016/j.ejogrb.2016.01.039.
- Yu, D., Y.M. Wong, Y. Cheong, E. Xia, and T.C. Li. 2008. Asherman syndrome—one century later. Fertility and Sterility 89 (4):759–79. doi:10.1016/j.fertnstert.2008.02.096.
- Zhang, X.M., W. Liu, Y. Zhou, J.X. Qiu, Y.J. Sun, M. Li, Y. Ding, and Q. Xi. 2021. Comparison of therapeutic efficacy of three methods to prevent re-adhesion after hysteroscopic intrauterine adhesion separation: A parallel, randomized and single-center trial. Annals of Palliative Medicine 10 (6):6804–23. doi:10.21037/apm-21-1296.
- Zhao, X.P., Y.Z. Liu, A.Q. Zhang, B.S. Gao, Q. Feng, H. Huang, X. Zhu, X. Sun, and D. Xu. 2020. Logistic regression analyses of factors affecting fertility of intrauterine adhesions patients. Annals of Translational Medicine 8 (4):49. doi:10.21037/atm.2019.11.115.
- Zhu, R., H. Duan, L. Gan, and S. Wang. 2018. Comparison of intrauterine suitable balloon and Foley balloon in the prevention of adhesion after hysteroscopic adhesiolysis. BioMed Research International 2018:9494101. doi:10.1155/2018/9494101.