Analysis of Cases with Severe Intrauterine Adhesions Treated by Intrauterine Balloon Stent Combined with PRP Perfusion

Intrauterine Adhesions Syndrome (IUA), also known as asheman syndrome, is a common gynecological disease. It is caused by the trauma of pregnant or non pregnant uterus, resulting in the damage of endometrial basal layer, partial or total occlusion of uterine cavity, resulting in abnormal menstruation, infertility or repeated abortion. The history of uterine trauma operation is an important inducing factor. At present, the incidence of intrauterine adhesions remains high, which is an important factor affecting women's fertility. For patients with moderate to severe intrauterine adhesions with fertility needs, the traditional surgical methods and drugs can not effectively make endometrial hyperplasia. Therefore, it is particularly important to develop and try new treatment methods and give patients more systematic and individualized treatment. In this paper, the clinical data of 2 cases of intrauterine adhesions treated with drug therapy and PrP intrauterine perfusion and placement of biological stents in our hospital were analyzed, so as to provide reference for the treatment of intrauterine adhesions with reproductive needs. The case summary is as follows.

• Case 1 

A 34-year-old female patient with fertility desires reported regular menstruation since menarche at age 16, with a cycle of 3/28 days, scanty dark red menstrual flow, no dysmenorrhea, and normal vaginal discharge. Last menstrual period (LMP): January 30, 2024. The patient underwent curettage 3 years ago for retained products of conception after spontaneous abortion, after which menstrual volume significantly decreased. In January 2021, hysteroscopic cold knife adhesiolysis was performed at our hospital for severe intrauterine adhesions (IUA score: 24). Postoperative hormonal therapy (estrogen-progesterone artificial cycles) was administered for 3 cycles, resulting in improved menstrual flow. Follow-up hysteroscopic adhesiolysis and intrauterine balloon stent placement were performed in March, May, and July 2021, with gradual improvement. Two years ago, menstrual volume decreased again, and in 2022, she underwent hysteroscopic adhesiolysis at another hospital (severity unspecified) without follow-up. In February 2023, she returned to our hospital for adhesiolysis (moderate IUA, score: 16) and one cycle of hormonal therapy, with improved menstruation. Three months prior to admission, menstrual volume decreased to spotting. Ultrasound (February 6, 2024) revealed thin, heterogenous endometrium with irregular margins, suggesting adhesions. Hysteroscopic adhesiolysis and stent placement (IUA score: 16, moderate; thin endometrium) were performed, followed by hormonal therapy and 5-day platelet-rich plasma (PRP) intrauterine perfusion. Menses resumed 5 days post-treatment with moderate flow. Follow-up hysteroscopy showed reduced IUA (score: 9) and moderate endometrial thickness. After another hormonal cycle, normal menses resumed, and repeat hysteroscopy confirmed further improvement (IUA score: 6, moderate endometrium). 

• Case 2 

A 29-year-old female with fertility desires reported regular menstruation since menarche at age 14 (4-5/28-30 days, scanty flow, no dysmenorrhea). Two years prior, she underwent curettage for missed abortion, followed by markedly reduced menstrual duration (2 days). Despite herbal therapy for infertility, symptoms persisted. Ultrasound at our hospital suggested thin endometrium and mid-cavity hypoechoic band, indicating IUA. Hysteroscopy confirmed severe IUA (score: 24), treated with hysteroscopic adhesiolysis, balloon stent placement, and hormonal therapy (Estradiol Valerate + Progesterone). Post-treatment menses remained scanty. Repeat hysteroscopy (score: 18) led to repeat adhesiolysis, stent placement, hormonal therapy, and PRP perfusion. Subsequent menses normalized (moderate flow), with hysteroscopy showing significant improvement (IUA score: 6, moderate endometrium). Normal pregnancy occurred 6 months later. After 3 months, the morphology of uterine cavity was normal again, and the pregnancy was normal half a year later.

Etiology of IUA

Intrauterine adhension or synechiae (IUA) is a gynecological disease that causes endometrial basal layer damage and endometrial fibrosis after intrauterine operation, infection or radiation, resulting in adhesion of cervical canal or uterine cavity, which can lead to menstruation reduction, amenorrhea, recurrent abortion and even infertility. It is a gynecological disease that seriously endangers the reproductive health of women of childbearing age, and is an important reason to affect the pregnancy rate of assisted reproductive technology [1,2]. 94.3% of patients with endometrial injury had a history of intrauterine operation, and 90% of them were in pregnancy [3]. It mainly includes termination of pregnancy related vacuum aspiration, curettage, and curettage of embryo and placental tissue residues [4,5]. The outcome of endometrial damage is severe damage to the morphology of the uterine cavity, and the most common disease in clinic is called intrauterine adhesion [6]. According to literature reports [7], the incidence of IUA caused by multiple induced abortion and curettage is as high as 25% -30%, which has become the main reason for menstrual volume reduction and secondary infertility. Studies have found that the artificial use of gonadotropin releasing hormone (GnRH) agonists may also induce endometrial atrophy and increase the risk of IUA formation [8]. A study of 1287 women found that [8], 87 had periodic and painless menstruation, and IUA was detected in infertile patients. Therefore, IUA could not be excluded in women with normal menstruation. 

Diagnostic Criteria

At present, there are many diagnostic methods for IUA. Hysteroscopy is the gold standard for IUA diagnosis [1]. With its direct viewing characteristics, it can comprehensively understand the morphological changes of uterine cavity, the tissue type, location and scope of intrauterine adhesion, and the area distribution of retained endometrium, but hysteroscopy as a diagnostic tool has certain limitations. In clinical practice, when the patient's medical history is highly suspicious of IUA, transvaginal three-dimensional ultrasound is recommended to initially diagnose or exclude iua [9]. For patients with intrauterine adhesions diagnosed by three-dimensional ultrasound, hysteroscopy is generally recommended to determine the degree of adhesions, so as to make a better treatment plan. The severity grading of IUA in this study refers to the Chinese IUA scoring standard [10]. 

Treatment of intrauterine adhesions 

The treatment methods of IUA are various, but the effect is not good. Transcervical Resection of Adhesion (TCRA) is currently the most commonly used method for the treatment of IUA, but the recurrence rate is high. If the operation is improper, TCRA may even cause further damage to the residual normal endometrial tissue. The recurrence rate of patients with severe IUA after TCRA can reach 62.5% [11]. Secondly, drug therapy for IUA, including oral estrogen, tamoxifen, aspirin, subcutaneous injection of GnRH agonist, intrauterine injection of low-dose human chorionic gonadotropin, has little effect [12]. It is reported that these drugs can not provide stable curative effect. Therefore, it is particularly important to develop and try new treatment methods and give patients more systematic and individualized treatment [13]. The effect of intrauterine balloon stent implantation combined with PRP in the treatment of patients with severe intrauterine adhesion is obvious.
Platelet rich plasma therapy 

Platelet Rich Plasma (PRP) is a high concentration platelet rich plasma [higher than (150.0-350.0) × 106 L-1] obtained from the centrifugation of animal or human whole blood, which was initially used as a blood transfusion product for the treatment of patients with thrombocytopenia [14]. Because platelets secrete Vascular Endothelial Growth Factor (VEGF), Platelet Derived Growth Factor (PDGF), transforming growth factor β, epidermal growth factor, fibroblast growth factor, insulin-like growth factor and epidermal growth factor after activation, and the concentration is 3-5 times that of normal growth factor [15]. These factors induce and regulate the proliferation of cells involved in tissue repair, promote the formation of endometrial glands and blood vessels, reduce the expression of fibrosis related molecules after endometrial injury, inhibit the formation of endometrial fibrosis, and thus accelerate the process of tissue repair [16,17]. At the same time, PRP is rich in white blood cells, which can participate in the immune defense process of the body. Moderate inflammatory reaction plays an important role in the process of endometrial damage repair, and excessive inflammatory reaction may lead to endometrial pathological repair [18]. Studies have found that [19], PrP intrauterine therapy has the clinical effect of improving the severity of IUA, pregnancy rate and menstrual mode, and is a safe and effective treatment for IUA patients. Studies have found that [20], the clinical pregnancy rate in the PrP group was significantly higher than that in the control group, the difference was statistically significant (35.82% vs. 20.22, P=0.003), and the persistent pregnancy rate (23.88% vs. 12.36%, P=0.006) tended to increase. In recent years, Platelet Rich Plasma (PRP) intrauterine perfusion can significantly improve the implantation rate and clinical pregnancy rate of patients with intrauterine adhesions [21,22]. PRP intrauterine perfusion may improve pregnancy outcomes by improving endometrial receptivity in patients with intrauterine adhesions. Platelet rich plasma is being explored as a means of endometrial regeneration therapy, but the data are still limited [23]. 

Intrauterine balloon stent treatment 

Intrauterine balloon stent: cook balloon is a triangle shaped by silica gel, which can effectively block the uterine cavity muscle wall and wound, and then play the effects of drainage, compression hemostasis and so on, so as to reduce the infection rate as much as possible [24]. Through mechanical expansion, the uterine cavity is separated to avoid the adhesion of the front and rear walls and effectively prevent the re formation of postoperative adhesion [25]. Its design is suitable for the shape of uterine cavity, can evenly support the walls of uterine cavity and bilateral uterine angles, and reduce the necrosis of intima caused by excessive compression [26]. After operation, by injecting liquid into the balloon and using its mechanical compression effect, uterine bleeding can be significantly reduced and wound healing can be promoted [26]. Research shows that [26], the amount of bleeding at 2 hours and 12 hours after operation in patients using balloon stents is significantly lower than that in patients using traditional methods. For patients with abnormal uterine cavity morphology caused by intrauterine adhesions, the balloon uterine stent can help restore the normal morphology and function of the uterine cavity through expansion and separation, and create good conditions for embryo implantation and growth [26]. Balloon uterine stent can also relieve gynecological symptoms such as dysmenorrhea and irregular menstruation, and improve the quality of life of patients [26]. It is relatively safe to place the balloon stent in the uterine cavity for 1 week, and the patients have good tolerance [26]. More than 85% of patients expressed their willingness to use the balloon again and were willing to recommend it to others [26]. In addition, balloon stents do not increase the risk of postoperative infection [25,26]. 

A study showed that the postoperative effective rate and cure rate of patients using balloon stents were 95.2% and 59.5%, which were higher than those in the control group using contraceptives [25]. The amount of bleeding in 48 hours after operation in patients using balloon stents was significantly less than that in the control group [25]. There was no significant difference in the infection rate between the balloon stent group and the contraceptive device group, and there was no obvious postoperative infection symptoms [25]. Intrauterine balloon stent has excellent performance in preventing recurrence of intrauterine adhesions, reducing postoperative bleeding, and restoring intrauterine morphology, with high safety and patient acceptance. Its application prospect in the treatment of intrauterine adhesions is broad, and it is worthy of further promotion in clinical practice [25]. 

Treatment of intrauterine adhesion by intrauterine balloon stent combined with PRP perfusion 

Based on the above two treatment methods for severe intrauterine adhesions have good therapeutic effect, but at present, little is known about the effect of the combination of the two on severe intrauterine adhesions. In this study, the effect of intrauterine balloon stent combined with PRP in the treatment of severe IUA patients is obvious, and two patients are pregnant. The intrauterine balloon stents were placed in the uterine cavity after the decomposition of intrauterine adhesions. PrP perfusion was performed on the 3rd/5th/7th day after the operation. Regular review showed that the intrauterine adhesions were significantly reduced, indicating that the treatment was effective. In conclusion, intrauterine balloon stent implantation combined with PRP after IUA release surgery can effectively reduce IUA classification, improve pregnancy rate, and improve menstrual duration and menstrual volume. It is a safe and effective treatment for IUA patients.

The authors are grateful for the support from the Science.

There was no funding support for this work.

Wang Jianfen: Writing–original draft, Data curation, Conceptualization.

Shu Chengzhao: Writing–original draft, Data curation.

Dong Yan: Writing–review & editing, Supervision.

The authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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