| Background and Objective:Intrauterine adhesion(IUA)results from injury of endometrial basal layer caused by surgical operation,inflammation and infection,injury of endometrial repair,and formation of fibrous scar tissue leading to partial or complete adhesion of the uterine cavity.The transcervical resection of adhesions(TCRA)was the preferred treatment for IUA,with a postoperative re-adhesion rate of 62.5%.Currently,many methods have been used to prevent adhesion recurrence after TCRA surgery,including the use of estrogen,intrauterine placement of intrauterine device(IUD),intrauterine injection of hyaluronic acid,intrauterine stem cell transplantation,etc.,but the efficacy is not good,so it is necessary to explore a safe and effective method to prevent adhesion recurrence after TCRA surgery.Vaginal microbiota plays an important role in maintaining the health of female reproductive system.Our previous study found differences in the vaginal microflora between healthy women and IUA patients,with Lactobacillus predominant in the vagina in healthy women(97%)and less than 50%in IUA patients,with significant increases in pathogenic bacteria such as Gardnerella and Prevotella.Other research teams have also shown that IUA formation is associated with vaginal microflora disruption due to decreased vaginal Lactobacillus.Therefore,we speculate that vaginal probiotics supplementation may be beneficial for the prevention and treatment of IUA recurrence after TCRAEstrogen can promote endometrial hyperplasia and repair,help wound healing,and reduce the occurrence of adhesions.Currently,estrogen is routinely used after TCRA surgery to prevent the recurrence of adhesions.This study intends to conduct a randomized controlled study to compare the efficacy difference between intra vaginal supplementation with Lactobacillus crispatus(L.crispatus)and oral estrogen in preventing recurrence after IUA isolation after TCRA surgery,and to explore the feasibility of probiotics as the postoperative management of TCRA.In order to provide a new effective measure to prevent the recurrence of IUA after TCRA surgery.Research methods:1.A total of 125 patients diagnosed with IUA by hysteroscopy were enrolled in Jiujiang Maternal and Child Health Hospital of Jiangxi Province from January 1,2019 to June 30,2020.Preoperative examination was improved,and the IUA group(Group I)was determined according to the exclusion criteria.After TCRA operation,group I was randomly divided into estrogen therapy group(group E)and L.crispatus intervention group(group L).Group E:Estradiol valerate was taken orally for 21days,a daily dose of 4mg,and progesterone was added to 10mg for the last 10 days.Group L:One L.crispatus freeze-dried powder capsule(1×10~8CFU/capsule)was placed in the vagina every night after surgery for 14 days.Patients in group E and Group L were re-examined 3-7 days after the next menstrual cycle to evaluate the endometrium and adhesion after TCRA by vaginal color ultrasound and hysteroscopy.Meanwhile,50 healthy women were selected from the physical examination Center of the Second Affiliated Hospital of Nanchang University as the healthy control group(Group C).2.Basic information and clinical data of the patients were collected:name,age,menstrual status,reproductive history,endometrial thickness,uterine adhesion degree,endometrial pathology report after TCRA surgery,and improvement of postoperative menstruation and adhesion.3.The vaginal secretions of groups I,E,L and C were collected,and the differences in the composition of vaginal flora among groups were analyzed by high-throughput sequencing technology.Results:1.The preoperative clinical data of group E and group L showed no significant differences in age,pregnancy time,delivery time,menstruation,adhesion degree and other aspects(P>0.05).2.There was no statistical significance in endometrial thickness between group E and group L before and after surgery(P>0.05).However,there were statistically significant differences in endometrial thickness before and after operation between the two groups(P<0.05 in group L and P<0.001 in group E).3.After TCRA,the improvement rate of menstruation in group E was higher than that in group L,both of which were above 80%,without statistical significance(P>0.05).4.The hysteroscopic review after TCRA showed that the cure rate of group E was 65.31%(32/49)and the recurrence rate was 34.69%(17/49),in the group L the cure rate of was 82.98%(39/47)and the recurrence rate was 17.02%(8/47),which was statistically significant by X~2test(P<0.05).5.Alpha diversity:Shannon index(P<0.01)and Simpson index(P<0.005)increased in group I compared with group C.After TCRA surgery,the diversity of vaginal microbial community was decreased in both group E and group L.6.Beta diversity:PCA results showed that the vaginal microbial community in group I was significantly changed compared with group C.After TCRA operation,the difference between group L and group C was significantly reduced,almost close to group C.However,the difference between group E and group C is still obvious,while the difference between group I and group E is not obvious.7.At the phylum level:compared with group C,the relative abundance of Firmicutes was decreased(93.52%vs.76.88%,P<0.05)and the relative abundance of Bacteroidetes was increased(0.09%vs.4.37%,P>0.05)in IUA patients.After treatment,the relative abundance of Firmicutes increased(76.88%vs.85.99%,P>0.05)and the relative abundance of Bacteroidetes decreased(4.37%vs.2.05%,P>0.05)in group E.In group L,the increasing trend was more obvious(76.88%vs.89.35%,P>0.05;4.37%vs.0.31%,P>0.05).At the genus level:compared with group C,the relative abundance of Lactobacillus in group I was significantly decreased(93.14%vs.62.19%,P<0.01),and the relative abundance of Gardnerella was significantly increased(0.24%vs.2.27%,P>0.05).After treatment,the relative abundance of Lactobacillus in group E(62.19%vs.83.18%,P<0.05)and group L(62.19%vs.88.11%,P<0.01)were increased.The relative abundance of Gardnerella in E and L groups showed an opposite trend(2.27%vs.5.83%,P>0.05;2.27%vs.0.19%,P>0.058.8.Species composition heat map:The relative abundance of beneficial bacteria Lactobacillus was the highest in group C and the lowest in group I.In addition,in group I,the content of the following bacteria is relatively high,such as Prevotella,Anaerococcus,Megasphaera,etc.In group E,Gardnerella and Finegoldia were relatively abundant.The relative content of Pseudomonas,Methylobacterium,Enterococcus and other bacteria in the L group was relatively high.Conclusion:1.Both estrogen therapy and L.crispatus intervention can promote endometrial growth after TCRA surgery,and estrogen therapy has a better effect.2.Estrogen therapy and L.crispatus intervention are both effective in improving menstruation.3.Vaginal supplement L.crispatus can restore the vaginal microbiota of IUA patients to nearly healthy women,which is more advantageous than estrogen therapy in preventing adhesion recurrence after TCRA surgery. |
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