| ?Objective?1.Hysteroscopic surgery has been widely used in clinic due to its advantages of less trauma,less bleeding and direct vision.However,there is no study to strictly evaluate its effectiveness and safety as a treatment for intrauterine adhesions.At the same time,the conclusions of randomized controlled trials(RCT)based on a small sample size are sometimes contradictory.In view of this,this study conducts systematic evaluation and meta-analysis on all these RCTs in an objective and quantitative manner,with a view to providing more effective and credible evidence for hysteroscopic surgery to treat intrauterine adhesions.2.Platelet-rich plasma(PRP)is known to have tissue regeneration effect and has positive effects on wound healing,re-epithelialization and scar prevention.Based on this animal mechanical injury model,this study is expected to investigate the effect of PRP injection into damaged endometrium on endometrial repair and adhesion formation.Whether PRP administration can promote endometrial regeneration,restore endometrial function and prevent intrauterine adhesions can provide theoretical basis for clinical application,so as to provide a new method for preventing IUA.?Research Methods?1.A randomized controlled study on hysteroscopic surgery and other traditional methods for the treatment of intrauterine adhesions was systematically retrieved from7 electronic databases in Chinese and foreign languages.The duration of the study was until October 1,2019.The Cochrane Collaboration Network Offset Risk Assessment Tool(Version5.3.5)was used for literature quality assessment and Rev Man5.3 software was used for Meta-analysis.2.With the approval of IRB,human PRP with a platelet count of 688x103 /?L extracted platelet-rich plasma from apheresis platelets(a platelet-plasma mixture with a concentration of 12.5x1011/L)obtained from the blood transfusion department of Sun Yat-en Hospital.3.Fifty female Sprang-Dawley rats were randomly divided into two groups:experimental group and control group,with 25 rats in each group.Experimental rats were treated with misoprostol tablet solution to soften cervix and mini self-made curettage spoon to simulate curettage.The left side of uterus was treated with vaginal curettage under open abdomen and the right side was not treated.After mechanical scratch injury,the experimental group was treated with PRP after injury,while the control group was treated with corresponding amount of normal saline.4.Five rats corresponding to the two groups were killed 1,4,8,12 and 24 days after operation,and samples were taken from the middle of uterus.Histopathological changes were observed under microscope by hematoxylin-eosin(HE)and Masson trichrome(MT)staining.IPP image analysis was used to count the number of endometrial glands,endometrial thickness and collagen fiber area ratio between groups,and to evaluate the regeneration after endometrial injury and the degree of uterine adhesion fibrosis to analyze the functional and structural recovery of endometrium.Immunohistochemistry(IHC): Expression of transforming growth factor-?1(TGF-?1),uterine keratin-18(CK-18),matrix metalloproteinase(MMP-9),etc.in uterus.?Results?1.Twenty randomized controlled trials(RCT)including 2239 patients met the inclusion criteria.Meta-analysis results show that compared with traditional treatment methods,hysteroscopic surgery has clinical effective rate(OR=5.4,95%CI=3.80~7.67,P<0.00001),menstrual recovery rate(OR=3.73,95%CI=2.62~5.32,P<0.00001),pregnancy rate(OR=2.57,95%CI=1.75~3.76,P<0.00001),lower abdominal pain relief rate(OR=4.12,95%CI=2.13~7.94,P=0.0001),uterine cavity shape improvement rate(OR=4.39,95%CI=1.98~9.75,P=0.0003),complication incidence rate(OR=0.25,95%CI=0.13~0.46,P=0.00001),recurrence rate(OR=0.25,95%CI=0.13~0.46,P=0.003),intraoperative blood loss(SMD=-2.22,95%CI=-2.52~-1.92,P=0.00001),postoperative hospital stay(SMD=-1.51,95%=-2.09~-0.93).2.Morphological observation after HE staining: In the control group,the uterine surface epithelium is atrophic,the endometrium is damaged and thinned,the glands are obviously reduced,the uterine cavity disappears,accompanied by a certain degree of stenosis.In contrast,the uterine histology using PRP immediately after the endometrial injury shows that the uterine cavity morphology has recovered to varying degrees,the epithelial cells of the uterine cavity and endometrial glands are increased,and the endometrial stromal cells are increased.3.The number of endometrial glands on the 1st day,4th day,8th day,12 th day and 24 th day after operation was counted by HE staining.The number of glands in PRP group and control group increased with the prolongation of postoperative time,but the growth rate and degree of PRP experimental group were significantly higher than that of control group,and were similar to the number of normal uterine glands.Measurement of endometrial thickness showed that there was no significant difference in endometrial thickness between normal group,PRP group and control group on the 1st,4th,8th,12 th and 24 th days after operation.4.HE staining and counting the number of endometrial glands on the 1st,4th,8th,12 th and 24 th days after operation showed that the number of glands in PRP group and control group increased with the prolongation of postoperative time,but the growth rate and degree of PRP experimental group were significantly higher than that of control group,and were similar to the number of normal uterine glands.Measurement of endometrial thickness showed that there was no significant difference in endometrial thickness between normal group,PRP group and control group on the 1st,4th,8th,12 th and 24 th days after operation.5.Manson staining was used to evaluate the degree of fibrosis.On the 1st day,4th day,8th day,12 th day and 24 th day after operation,the ratio of endometrial interstitial fibrosis area to the total endometrial area was calculated.it was found that the degree of fibrosis in the control group was significantly worse than that in the normal endometrium and PRP treatment group(p < 0.05).the average percentage of fibrosis in the PRP experimental group was higher than that of the normal uterine fiber,but the difference was not statistically significant(P>0.05).The staining showed that PRP experimental group showed inhibition of excessive collagen deposition to near normal level.6.Immunohistochemical staining showed that the average optical density of CK-18 in the uterus of PRP treated rats in the experimental group was significantly higher than that in the control group(P < 0.05),the expression of TGF-?1 decreased,while the expression of MMP-9 increased(P < 0.05).Immunohistochemical staining showed that intrauterine infusion of PRP can effectively restore the injured endometrium.PRP can prevent the development of intrauterine adhesion by inhibiting TGF-?1 and increasing MMP-9 production..?Conclusion?1.Hysteroscopic surgery can effectively treat intrauterine adhesions and reduce the incidence of complications and recurrence rate compared with traditional treatment methods.2.The experimental results show for the first time that local application of PRP in uterus stimulates and accelerates the regeneration of endometrium,and also reduces fibrosis in the rat model of damaged endometrium,which can effectively prevent adhesion formation after uterine curettage and has positive effect on reducing intrauterine adhesion stenosis.These results can guide further clinical research on prevention of adhesion formation after any intrauterine operation by using autologous PRP.PRP may be an alternative to clinical treatment,because it can be used to prevent adhesion after any intrauterine operation in clinical practice and protect female fertility. |
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