| Part one The value of repeating hysteroscopic adhesiolysis at short time interval in Asherman syndrome treatment:a cohort studyObjectives:To improve the pregnancy and live birth rate after operation, it is the core in the treatment of Asherman syndrome that choosing appropriate surgical intervention to reduce the uterine adhesion reformation. In this retrospective cohort study, we discuss the factors related to the uterine shape rebuilding and the pregnancy result, especially timing of second look.Methods:The patients suffered moderate to severe degree uterine adhesion were recruited during Jan.2010to Jul.2013. The including criteria are:(1) first time adhesiolysis in Sir Run Run Shaw Hospital;(2) AFS score≥5;(3)age≤40;(4) received second hysteroscopic examination some time after first surgery;(5)with completed record, including menstrual pattern, previous pregnancy history and intrauterine manipulation history, etc.All of the operation were done by sharp hysteroscopic scissors under general anesthesia. Ultrasonographic guidance were used when difficult cases were met with. Surgery ended when the normal uterine anatomy was gained or the perforation risk remarkably increased. Sometimes one of the following modalities were inserted after surgery to prevent readhesion:Cook intrauterine balloon, intrauterine contraceptive device(IUD), hyalouronic acid gel, or Foley catheter balloon.Broad spectrum antibiotics and cyclic hormone treatment were given routinely after operation. Second look hysteroscopy were conducted in certain time phase. Follow up was done in clinic and also by telephone. The following information was recorded: operation complication, the time interval between two hysteroscopic operation, AFS score in every time examination, the times of adhesiolysis, final uterine shape recovery, pregnancy time, delivery time, abnormal pregnancy procedure and pregnancy complication.Results:1. General results205cases completed primary and secondary hysteroscopic operations. The average age of the patients was29.7±4.3, average pregnancy times was2.4±1.6, and average delivery times was0.2±0.4.The main surgical complication was3cases uterine perforation,2cases repaired by laparoscopy and1by conservative therapy.Follow up time phase was between11-55months, median was27months.32cases(17.8%)dropped out;17cases had not planned to conceive;156cases reported willing to conceive.114cases(73.1%) got pregnancy after operation,79cases spontaneously,3by ovulation induction,3by artificial insemination, and the other29cases by in vitro fertilization and embryo transfer(IVF-ET). Among114pregnant women,13cases(11.4%) suffered first trimester miscarriage,8(7.0%) second trimester miscarriage and3(2.6%) ectopic pregnancy, general pregnancy lost rate21.0%.87cases had elivered until now except3woman’s pregnancy was going, live birth rate was56.9%.2. The factors related to uterine cavity shape recovery 2.1The influence of second look hysteroscopy in short time interval to the uterine shape recoveryThe patients were separated into2groups according to the different time interval between primary and secondary hysteroscopic operation, group A≤2months,155cases; group B>2months,50cases. There were no difference between2groups in age, previous uterine operation history, pregnancy related history and severity of adhesion. Group A had more oligomenorrhea patients whereas group B had more amenorrhea patients.The median AFS score reduction is7in group A at the second look, comparing to6in group B with significant difference(P=0.015).136patients (66.3%) achieved normal uterine shape at the time of second look,45improved (23.9%) and20not improved (9.8%). The ratio of normal uterine shape in group A was higher than that in group B (76.8%vs52.0%, P<0.05).186cases of205gained normal shape in the end through adhesiolysis for1-7times,93.3%in group A and94.0%in group B. The time related accumulate ratio of normal uterine shape was better in group A (50%recovery ratio group A1month vs group B3months, P<0.001).2.2The influence of adhesion degree to the uterine shape recoveryThe ratio of normalized uterine cavity was71.8%in moderate adhesion group, and54.0%in severe group (P<0.05).Comparing the recovery ratio in different second look time based on both moderate and severe group, the time related accumulate recovery ratios are both better in short time second look group(P<0.001).3. analysis of factors relating to pregnancy rateThere were no difference between pregnant or not pregnant women in age, menstrual pattern, previous pregnancy history and previous uterine manipulation history. The pregnancy rate was lower in severe group (moderate79.3%vs severe 57.8%,P<0.05). Comparing in different time second look groups, pregnancy rate in earlier second look group was77.9%, higher than later group (63.4%)(P<0.05). there were no difference between2groups in using different adhesion prevention modalities and different adhesion relaxing times.Age, second look time and adhesion degree were selected as significant effective factors for pregnancy rate by logistic regression analysis. The OR was0.893,0.413and0.283.In Kaplan-Meier model, the time related accumulate pregnancy rate was higher in earlier second look group with8months of50%PR, and19months of50%PR in the other group(P<0.01). The difference was still significant (P<0.01) in moderate adhesion subgroup, but not represent in severe subgroup.In40cases received IVF-ET treatment, the thickness of endometrium was thicker in pregnant group(7.5±0.9mm vs5.8±1.5mm in not pregnant group, P<0.05).4. analysis of factors relating to live birth rateThere was no difference between live birth or no live birth women in age, menstrual pattern, previous pregnancy history and previous uterine manipulation history. The difference of general live birth rate was not significant in different severe degree and different second look time.In logistic regression analysis, age and adhesion degree were selected as significant effective factors, OR was0.850and0.463.In Kaplan-Meier model, the time related accumulate live birth rate was higher in earlier second look group(10month vs27month of50%live birth rate, P<0.05). Comparing separately, the difference was still exist in moderate adhesion subgroup(P<0.05), but not represent in severe subgroup.As to IVF-ET patients, total live birth rate was48.7%, the thickness of endometrium was thicker in live birth group(7.5±0.9mm vs6.6±1.5mm in not pregnant group, P<0.05). Conclusion:Hysteroscopic adhesiolysis was effective intervention to treat Asherman syndrome. The age and adhesion degree affect pregnancy rate and live birth rate after operation. Performing second hysteroscopic examination in2month may speed the recovery of uterine shape, increase the accumulate pregnancy rate and live birth rate. Comprehensive treatment could improve the fertility condition after surgery. The thickness of endometrium affects the pregnancy rate and live birth rate of IVF. Part Two Research of mechanical barrier preventing adhesion reformationChapter1A comparison of intrauterine balloon stent, intrauterine contraceptive device and hyalouronic acid gel in the prevention of adhesion reformation following hysteroscopic surgery for Asherman syndrome:a cohort studyObjective:To compare the efficacy of intrauterine balloon, intrauterine contraceptive device and hyalouronic acid gel in the prevention of the adhesion reformation after hysteroscopic adhesiolysis for Asherman’s syndromeStudy design:107women with Asherman’s syndrome who were treated with hysteroscopic division of intrauterine adhesion were enrolled in this retrospective cohort study. After hysteroscopic adhesiolysis,20patients had intrauterine balloon inserted,28patients had intrauterine contraceptive device (IUD) fitted,18patients had hyaluronic acid gel instilled into the uterine cavity, and41control subjects did not have any of the three additional treatment measures. A second-look hysteroscopy was performed in all cases. The effect of hysteroscopic adhesiolysis was scored by AFS. The main results were compared by Wilcoxon test and Kruskal-Wallis test. A p value of<0.05was considered as statistically significant.Results:The preoperative AFS scores among4groups are not significantly differed. The median dropping of scores after surgery were as following:balloon group8(0-10), IUD group6(0-10), gel group4.5(0-12) and control group3(2-12). Both the intrauterine balloon group and IUD group achieved significantly (P<0.001) greater amount of reductions in the adhesion score than that of the hyaluronic acid gel group and control group; the efficacy of the balloon is greater than that of the IUD(P<0.001). There was no significant difference in results between the hyaluronic acid gel group and the control groups.We defined the second-look hysteroscopic finding as normal, improved and no change, and named normal and improved as effective. The effective rates in4groups are:balloon group95%, IUD group93%, gel group67%and control group71%. Comparing the recovery rates of uterine shape, the balloon group was greater than all of the other groups(P<0.001),and the IUD was following (comparing to the gel and control group,P<0.001)。Conclusion:The insertion of intrauterine balloon and intrauterine device are more effective than the use of hyaluronic acid gel in the prevention of intra-uterine adhesion reformation, and the intrauterine balloon performed better. Chapter2A prospective randomized controlled trial comparing the efficacy of intrauterine balloon and intrauterine contraceptive device in the prevention of adhesion reformation following hysteroscopicadhesiolysisObjective:To compare the efficacy of heart-shaped intrauterine balloon and intrauterine contraceptive device(IUD) in the prevention of adhesion reformation after hysteroscopic adhesiolysis.Design:Prospective, randomized controlled trial.Setting:University hospitalPatients:201women with moderate to severe degree of Asherman syndromeIntervention:Women were randomised to having either a heart-shaped intrauterine balloon or an IUD fitted after hysteroscopic adhesiolysis. The devices were removed after7days. A second look hysteroscopy was carried out1to2months after the surgery.Main outcome measure:The incidence of adhesion reformation and the reduction of adhesion score before and after surgery.Results:201cases were recruited initially,39cases dropped out, resulting in82cases in the balloon group and80cases in IUD group. The age, menstrual characteristics, pregnancy history and AFS score before surgery were comparable between the two groups. The median adhesion score reduction (balloon group,7; IUD group,7) and the adhesion reformation rate (balloon group30%, IUD group35%) were not significantly different between the two groups. There are also not different between2groups in median adhesion score reduction and adhesion reformation rate when the subjects were divided into moderate and severe subgroups.Conclusion:The heart-shaped intrauterine balloon and intrauterine contraceptive device are of similar efficacy in the prevention of adhesion reformation following hysteroscopic surgery for Asherman syndrome.Clinical Trial Registration Number:ISRCTN69690272, Chapter3The infection risk of keeping intraterine balloon stent in the uterine cavity for7days Objective:To compare the bacteria flora in the cervical canal between the COOK intrauterine balloon stent and IUD being kept in uterine cavity for one week after the hysteroscopic adhesiolysis.Method:Women with moderate-sever Asherman syndrome were enrolled in this study from June2012to December2013. as were removed the devices one week after hysteroscopic adhesion relaxing in the infertility clinic of Sir Run Run Shaw Hospital. The patients were divided into two groups:intrauterine balloon stent subgroup, tailed intrauterine contraceptive device subgroup. Any complain was recorded and checked by physical examination and laboratory test when necessary. The sterile swabs were taken from the cervical canals for bacteria culture.Results:93subjects were enrolled into the observation,59cases in balloon group and34in IUD group. Positive microorganism in culture media were seen in20patients (34%) in the balloon group and12patients (35%) in the IUD group, and the positive rate was no different between these two groups. The positive flora include:Escherichia coli, Staphylococcus faecalis, Gardnerella vaginalis, Acinetobacter, Streptococcus agalactiae, Streptococcus viridans, and Candida albicans.The constituent ratio of bacterial culture has no difference in these two groups. No obvious pelvic infection was found in these patients.Conclusion:The sake of infection is not different between intrauterine balloon stent and IUD groups by keeping in the uterine cavity for one week after hysterocopic adhesiolysis, when the prophylactic antibiotics were given. Part3The experiment of eMSC repairing injured mouseendometriumObjective:Investigate the grafting of eMSC to heat injured mouse endometrium and positive effect in endometrial repair.Methods:Establish the mouse endometrial heat injured model, inject Dil marked eMSC through tail vein3days after injury. The control group was injected0.9%Nacl. Obeserve the homing of eMSC3,7,14days after injection. Compare the thickness of endometrium, numbers of endometrial glands between2groups in7and14days, as well as the microvessel density in endomtrium.Results:1. Dil marked eMSC presented obvious homing effect to the injured uterus comparing to the control side and control group.2. The thickness of endometrium was remarkably thicker in the eMSC injection group than the control, but the numbers of endometrial glands were not different in7and14days.3. The MVD after7days injection elevated in eMSC injection group,which has statistic significancy comparing with NaCl injection group. There is no difference of MVD between2groups after14days injection.Conclusion:The injection of eMSC could home to injured side of uterus, might help the injured endometrium repair due to increase the endometrial thickness and accelerate angiogenesis. |
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