1.Effect of growth hormone on endometrium growth of intrauterine adhesion and the underlying mechanism.
Qing FENG ; Aiqian ZHANG ; Dabao XU ; Fei ZENG
Journal of Central South University(Medical Sciences) 2022;47(11):1522-1531
OBJECTIVES:
The main treatment for intrauterine adhesion (IUA) is hysteroscopic adhesiolysis (HA), which most of treatment frequently employs estrogen and progesterone cycle therapy. The growth and coverage of endometrium after operation is a difficult problem, and several hospitals in China have performed growth hormone (GH) in empirically treating IUA, which has achieved excellent curative effects. Unfortunately, the mechanism of action has not yet been clearly elucidated. In previous study, an IUA animal model after surgical abortion and curettage in pregnant rats has been successfully established. In this experiment, the IUA animal model after surgical abortion and curettage in pregnant rats, which is more in line with the mechanism of human intrauterine adhesion, was used for the first time to investigate the therapeutic effect of GH on IUA in the pregnant rat curettage model. The expression of signal transducers and activators of transcription 3(STAT3), phosphorylated STAT3 (p-STAT3), STAT5 and p-STAT5 content were detected by immunohistochemistry to preliminarily explore the possible mechanism of GH involving in promoting endometrial growth of IUA, and to provide a theoretical basis for clinical medication and treatment.
METHODS:
Pregnant rats were anesthetized, and the bilateral embryos were removed completely. Then the rat endometrium was scraped with a curette in 4 different directions (front, back, left, and right). After the IUA animal model was established, the rats were randomly divided into 3 groups (n=5): a control group, a GH group, and a GH + AG490 group. Normal saline (0.4 mL/100 g) was injected subcutaneously at the 7th day after curettage in the control group;0.15 U/100 g of GH was injected subcutaneously at the 7th day after curettage in the GH group; 0.15 U/100 g of GH was injected subcutaneously and 1 mg/100 g AG490 was injected intraperitoneally at the 7th day after curettage in the GH+ AG490 group. All the rats were injected continuously for 5 days. The rats in each group were sacrificed at the 14th day. The uterus of rats in each group was stained with HE staining to explore the endometrial morphology and the number of endometrial glands in each group, and Masson staining was utilized to observe the degree of endometrial fibrosis. The levels of STAT3, p-STAT3, STAT5 and p-STAT5 were detected by immunohistochemistry.
RESULTS:
1) The number of glands in the GH group was more than that in the control group on the 14th day, with statistical difference (P<0.05). However, the number of endometrial glands in the AG490+GH group was decreased compared with the GH group on the 14th day (P<0.05). 2) The fibrosis ratio in the GH group was less than that in the control group at the 14th day after operation (P<0.05). However, the area of endometrial interstitial fibrosis in the AG490+GH group was much higher than that in the GH group 14 days after operation (P<0.05). 3) Compared with the control group, there was not significant difference in the levels of STAT3 and STAT5 in GH group (both P>0.05), while the levels of protein p-STAT3 and p-STAT5 were increased in the GH group (both P<0.05). Compared with the GH group, there was not significant difference in the levels of STAT3 and STAT5 in the AG490+GH group (both P>0.05), while the levels of p-STAT3 and p-STAT5 were decreased in the AG490+GH group (both P<0.05).
CONCLUSIONS
GH can not only promote the growth of endometrial glands in the IUA model, but also reduce the degree of fibrosis and play a role in the treatment of IUA, which may be related to the activation of the Janus kinase (JAK), JAK/STAT3 and STAT5 signaling pathways.
Animals
;
Rats
;
China
;
Growth Hormone
;
Endometrium/pathology*
;
Tissue Adhesions/drug therapy*
2.Chinese medicine Yangmo decoction ameliorates intrauterine adhesion prognosis following hysteroscopic adhesiolysis.
Xingping ZHAO ; Shuhan HE ; Zhaoling YOU ; Hua WANG ; Dabao XU ; Aiqian ZHANG
Journal of Central South University(Medical Sciences) 2022;47(11):1540-1549
OBJECTIVES:
Hysteroscopic adhesiolysis (HA) remains the mainstay on treatment for intrauterine adhesions (IUA). The fertility outcome of patients with moderate and severe intrauterine adhesions after HA is still far from satisfactory. Estrogen combined with progesterone is the most common treatment; however, they do not help in improving the fertility rate to the maximum because of the limitations. This retrospective, non-randomized controlled study will assess the effects of traditional Chinese medicine Yangmo decoction after HA in restoration of the endometrium and improvement of the fertility rate.
METHODS:
A total of 427 patients, who met the inclusion criteria, aged between 20 and 45 years and diagnosed with moderate or severe IUA underwent HA at the Third Xiangya Hospital from January to August 2021, were enrolled for this study. Participants were assigned into 2 groups: A Yangmo decoction group (n=213, patients were given Yangmo decoction consisting of Ginseng flower, Sanchi flower, Daidai flower, Snow lotus, Licorice and so on after HA), and an estrogen and progesterone group (n=214, patients were given estrogen and progesterone after HA). The following basic information was collected retrospectively for both groups, including age, parity, history of abortion, menstrual status, and times of hysteroscopic interventions. American Fertility Society (AFS) score was used by a senior surgeon and the density of opening of endometrial glands was evaluated during HA. The parameters were obtained from three-dimensional transvaginal ultrasound (3D-TVUS) preoperatively and postoperatively, to evaluate the efficacy of Yangmo decoction, estrogen, and progesterone. All patients were followed up on telephone to determine the fertility rate until 6 months from the last HA.
RESULTS:
Based on the basic information collected preoperatively, there were no significant differences between the groups (all P>0.05). Postoperatively, patients in the Yangmo decoction group had a better surgical success rate with a more significant AFS reduction (P<0.001), better density of opening of endometrial glands in the uterine cavity (P<0.000 1) after HA, and a better fertility rate (40.4%) in the time of 6 months after the last HA than those of the estrogen and progesterone group.
CONCLUSIONS
Yangmo decoction has better therapeutic efficacy in the treatment of intrauterine adhesion after HA than the combined effect of estrogen and progesterone. Yangmo decoction helps restore the endometrium and improve the fertility rate, therefore, it can be adopted as a routine practice for IUA patients who have fertility requirements.
Humans
;
Young Adult
;
Adult
;
Middle Aged
;
Retrospective Studies
;
Progesterone/therapeutic use*
;
East Asian People
;
Medicine, Chinese Traditional
;
Estrogens/therapeutic use*
3.Value of transvaginal three-dimensional ultrasound in evaluating the curative effect of Yangmo decoction in the treatment of uterine adhesion.
Xingping ZHAO ; Jingrong DENG ; Zhaoling YOU ; Xiaoli GAN ; Dabao XU ; Aiqian ZHANG
Journal of Central South University(Medical Sciences) 2022;47(11):1550-1558
OBJECTIVES:
Intrauterine adhesions (IUA) is the damage of the basal layer of the endometrium caused by various reasons, resulting in adhesion of the uterine muscle walls to each other, which is manifested as clinical symptoms such as spanomenorrhea, amenorrhea, and infertility. Hysteroscopic adhesiolysis (HA) is the main treatment, for patients with moderate or severe adhesion or angular adhesion, the incidence of postoperative adhesion is high. Traditional Chinese medicine "Yangmo decoction" can promote endometrial growth. Three-dimensional transvaginal ultrasonography (3D-TVUS) can judge IUA and evaluate uterine receptivity through three-dimensional imaging. This study aims to investigate the value of 3D-TVUS in judging the efficacy of Yangmo decoction in the treatment of intrauterine adhesions.
METHODS:
The clinical data of patients who underwent HA at two different centers in department of Gynecology of Third Xiangya Hospital of Central South University and Changsha Jiangwan Hospital from January 2021 to August 2021 were retrospectively collected. A total of 275 eligible patients were included. According to the postoperative management measures, the selected patients were divided into two groups. Yangmo decoction group (n=138): the use of Yangmo decoction and uterine-shaped silicon stent post HA; Hormone group (n=137): the use of estrogen, progesterone and uterine-shaped silicon stent post HA. The preoperative general data, preoperative and postoperative 3D-TVUS parameters of the two groups were analyzed.
RESULTS:
The endometrial thickness of Yangmo decoction group was thicker than that of hormone group (P<0.001), the intercornual distance was wider (P=0.016), the endometrial echo was more homogeneous (P=0.018), the percentage of bilaterally visible tubal opening was higher (P<0.001), the endometrial morphology was better (P=0.012), and endometrial blood flow, endometrial motility and uterine motion were better in Yangmo decoction group than that in the hormone group (all P<0.001).
CONCLUSIONS
The endometrial thickness, echo, blood flow, and peristalsis, the number of visible tubal opening, uterine motion, and the intercornual distance obtained by 3D-TVUS examination are important factors to evaluate the prognosis of postoperative drug treatment for IUA. 3D-TVUS is of great significance in evaluating the efficacy of Yangmo decoction in the treatment of IUA.
Humans
;
Retrospective Studies
;
Hormones
4.In vitro fertilization and embryo transfer may improve live birth rate for patients with intrauterine adhesions after hysteroscopic adhesiolysis.
Dan SUN ; Xingping ZHAO ; Huan HUANG ; Aiqian ZHANG ; Wenwei CHENG ; Yimin YANG ; Dabao XU
Journal of Central South University(Medical Sciences) 2022;47(11):1559-1567
OBJECTIVES:
The prevalence of intrauterine adhesion (IUA) increased gradually, which seriously affected female reproductive health and fertility. This study aims to analyze the clinical features of pre-, intra-, and post hysteroscopic adhesiolysis (HA) and to identify the main risk factors for non-live birth and other factors affecting pregnancy outcome in patients with IUA.
METHODS:
A total of 486 IUA patients with reproductive needs, who underwent HA in the third Xiangya Hospital of Central South University from January 2017 to May 2018, were retrospectively included. The follow-up period was 2-3 years after operation. Univariate analysis and multivariate logistic regression analysis were used to explore the relationship between clinical features and live birth rate in patients with IUA. Pre-operative clinical indicators included age, gravidity, parity, abortion, IUA recurrence, menstrual patterns, and disease course. Intraoperative clinical features assessed in the last operation were uterine cavity length, IUA appearance, IUA area, number of visible uterine cornua, number of visible tubal ostia, and American Fertility Society (AFS) scores. The relationship between clinical indicators and postoperative live birth rate was investigated by univariate analysis and multivariate logistic regression analysis. Pregnancy pattern was the main variable.
RESULTS:
Among the 486 IUA patients included in this study, there were 256 (52.67%) live births and 230 (47.33%) non-live births. Univariate analysis and multivariate logistic regression showed that the live birth rate of in vitro fertilization and embryo transfer (IVF-ET) after HA was higher than that of spontaneous pregnancy (OR=0.557, 95% CI 0.361 to 0.861, P=0.008). When the bilaterally fallopian tube ostia were invisible in the last operation (OR=0.322, 95% CI 0.104 to 0.997, P=0.049), patients were more likely to have live birth. The older the patient was, the lower the live birth rate was (OR=1.081, 95% CI 1.034 to 1.131, P<0.001). The live birth rate would be low when the last AFS score was moderate (OR=2.973, 95% CI to 1.541 to 5.738, P<0.010).
CONCLUSIONS
Based on the outcome of the first pregnancy after HA, IUA patients' pregnancy patterns, age, number of visible tubal ostia, and AFS scores noted by a second-look hysteroscopy, are the factors influencing the prognosis for the live birth rate in IUA patients. IVF-ET may improve live birth rate for patients with IUA after HA.
Humans
;
Female
;
Pregnancy
;
Birth Rate
;
Retrospective Studies
;
Embryo Transfer
5.Clinical study on 2 types of intrauterine stents with different thickness and hardness in the treatment of moderate-to-severe intrauterine adhesions.
Huan HUANG ; Xuetao MAO ; Yang YU ; Bingxin XIAO ; Xingping ZHAO ; Aiqian ZHANG ; Dabao XU
Journal of Central South University(Medical Sciences) 2022;47(11):1575-1585
OBJECTIVES:
Although hysteroscopic adhesiolysis (HA) is the main treatment for intrauterine adhesion (IUA), postoperative management of IUA remains challenging because there is no consensus on how to mitigate the high rate of postoperative adhesions reformation. This study aims to compare the effectiveness and safety of 2 types of intrauterine stents with different thickness and hardness in treating moderate-to-severe IUA.
METHODS:
A retrospective clinical study was conducted in the Third Xiangya Hospital of Central South University from November 2020 to July 2021. A total of 191 patients with moderate-to-severe IUA who received surgical treatment and placed intrauterine stents after HA to prevent recurrence of postoperative adhesions were included. According to the hardness and thickness of the intrauterine stents, the participants were divided into a case group (placed the novel thin intrauterine stent, n=62) and a control group (placed the conventional stent, n=129). After 2-3 menstrual cycles, a second-look hysteroscopy was performed, and the intrauterine stents were removed. The postoperative efficacy [the reduction of American Fertility Society (AFS) scores, the adhesions reformation rate, the changes in menstrual pattern, and the pregnancy rate during the follow-up], safety (the adverse events), and applicability (the difficulty of stent removal) were compared between the 2 groups.
RESULTS:
No significant differences in preoperative clinical characteristics were observed between the 2 groups (all P>0.05). The menstrual volume of all patients was increased after the treatment. The reduction of AFS scores and the menstruation recovery rate were not significantly different between the 2 groups (P=0.519 and P=0.272, respectively). Notably, there was no case of displacement in the case group, while the displacement rate of the control group was 2.3% (P=0.552). Moreover, there was no significant difference in abdominal pain or postoperative abnormal vaginal bleeding between the 2 groups (P=0.823 and P=0.851, respectively). However, the difficulty rate of removing the thinner stents was significantly lower than that of removing the traditional stent (21.0% vs 38.8%, P=0.014). During the follow-up for half a year of the postoperative period, the pregnancy rate did not differ significantly in the case and control groups (45.0% vs 34.6%, P=0.173).
CONCLUSIONS
The novel intrauterine stent shows noninferior efficacy and had a good safety profile compared with conventional stents in treating moderate-to-severe IUA. Importantly, it was more convenient to be removed without increasing the rate of displacement and detachment. Therefore, it could reduce the amount of damage to the endometrium and has higher applicability than conventional stents.
Humans
;
Retrospective Studies
;
Tissue Adhesions
;
Uterus/pathology*
6.Preliminary study on the advantages of hysteroscopic myomectomy with cold knife.
Waixing LI ; Lingxiao ZOU ; Pan GU ; Yang YU ; Aiqian ZHANG ; Dabao XU
Journal of Central South University(Medical Sciences) 2022;47(11):1593-1599
OBJECTIVES:
At present, hysteroscopic submucosal fibroids resection is mostly performed by hysteroscopic electric resection (hereinafter referred to as electric knife). During the operation, the electrothermal effect could not only damage the endometrial tissues covered by the surface of the fibroid, but also easily damage the endometrial tissues around the fibroid, which is very unfavorable for patients with fertility requirements. In addition, for some special fibroids (located at horn and fundus) or Type II and multiple submucosal fibroids, the traditional electric resection is still very difficult. With the opening of the second-child policy and the urgent desire of patients for fertility, more and more attention is paid to the concept of fertility protection in China. Therefore, hysteroscopic cold knife technology (hereinafter referred to as cold knife) has gradually entered the vision. The cold knife has the advantages of simple operation, such as little trauma and quick postoperative recovery. In this study, the advantages of cold knife in the surgical resection of submucosal fibroids are discussed by comparing the safety and effectiveness between the hysteroscopic cold knife resection (hereinafter referred to as cold knife) and the electric knife resection in the submucosal fibroids.
METHODS:
The clinical data of 112 patients with submucosal fibroids diagnosed and treated by hysteroscopic surgery at the Third Xiangya Hospital of Central South University from January 2017 to October 2021 were retrospectively analyzed, including preoperative general information (such as age, gravidity, abortion times, the size, location, type and number of submucosal fibroids, preoperative hemoglobin value) and intraoperative conditions [such as intraoperative bleeding, the operation time, residual rates and intraoperative complications (massive bleeding, perforation, water poisoning)]. The patients were divided into a cold knife group and an electric knife group, and there were 40 cases in the cold knife group and 72 cases in the electric knife group. The postoperative complications and the pregnancy outcomes in the 2 groups were followed up by telephone, the follow-up data included postoperative recurrence rate, pregnancy rate, pregnancy mode, and pregnancy outcome.
RESULTS:
Compared with the electric knife group, the cold knife group had more submucous myomas located in the horn or fundus of the uterus (9.7% vs 25.0%), and more Type II myomas or combined with Type II myomas (26.4% vs 70.0%). However, there were no significant difference in intraoperative bleeding, the operation time, intraoperative complications and the residual rates between the 2 groups (all P>0.05). A total of 98 patients were followed up, including 32 patients in the cold knife group and 66 patients in the electric knife group. Compared with the electric knife group, there were lower postoperative complications in the cold knife group (12.5% vs 37.9%) (P<0.05). Among the 7 patients with multiple submucosal fibroids (the number of fibroids ≥5), there were 4 patients in the electric knife group and 3 patients in the cold knife group. In the electric knife group, the postoperative menstrual volume in the 4 patients was significantly reduced and 3 patients had postoperative fertility requirements, which were all diagnosed as intrauterine adhesion by hysteroscopy and performed further surgery. Later, 2 patients had successful pregnancy, 1 had miscarriage, and 1 had full-term spontaneous labor. However, the menstrual volume of the 3 patients in the cold knife group was not significantly reduced compared with normal menstrual volume, and 2 of them had fertility requirements, and they had natural pregnancy and full term vaginal delivery. There were no significant differences in postoperative recurrence rate, pregnancy rate, pregnancy mode and pregnancy outcome between the 2 groups (all P>0.05).
CONCLUSIONS
Both the electric knife and cold knife resection are safe and effective methods for the treatment of submucosal fibroids. Compared with electric knife resection, the cold knife resection has fewer postoperative complications and perhaps more advantages in endometrial protection, especially for the patients with fertility requirements, submucosal fibroids located at the fundus or horn of the uterus, Type II submucosal fibroids, and multiple submucosal fibroids.
Humans
;
Pregnancy
;
Female
;
Retrospective Studies
;
Postoperative Complications
;
China/epidemiology*