Efficacy Of Vaginal Estradiol In The Prevention Of Moderate To Severe Intrauterine Adhesions From Recurrence After Adhesiolysis

BackgroundIntrauterine adhesions(IUA)or Asherman’s syndrome is a common disease in which pathological repair occurs in the uterine after the trauma of the basalis layer of the endometrium, causing adhesions within the uterine cavity and/or cervical canal,and finally resulting in the dysfunction of menstruation and fertility.Primary causes include uterine surgeries and infection,such as genital tuberculosis.IUA is characterized by hypomenorrhea,amenorrhea,dysmenorrhea,infertility and recurrent pregnancy losses.Hysteroscopy is the gold standard to diagnose IUA, while ultrasound and hysterosalpingography are auxiliary diagnosis methods.According to American Fertility Society classification made in 1988, combining the menstrual history and hysteroscopic findings,IUA can be classified into mild,moderate and severe grades,which may indicate the prognosis and guide the management.Transcervical resection of adhesions is the primary treatment for IUA,with the difficulty lying in reducing recurrence rate and improving prognosis.Currently,frequently-used adjuvant protocols include insertion of mechanical barriers and biocolloids,high-dose estrogen therapy and biological graft.With a recurrent rate as high as 20.0%~78.9%, the outcomes of moderate and severe adhesions are far from satisfaction.Vaginal estrogen has showed a better effect in improving endometrial proliferation in the studies of assisted reproductive technique,compared to oral estrogen.In this study,by giving moderate and severe IUA patients either oral or vaginal 17β-estradiol supplement after TCRA followed by the insertion of a uterine balloon stent,and comparing their effects and side-effects,we try to assess the value of vaginal 17 β-estradiolin preventing IUA patients from recurrence.ObjectivesThe primary aim is to assess the efficacy and safety of vaginal estradiol(E2)supplement as an ancillary therapy to reduce recurrence rate of moderate to severe IUA patients after TCRA in comparison to oral estradiol supplement.The secondary aim is to evaluate the corresponding serous E2 levels and endometrial thickness of the patients receiving the two therapies.The last but no the least aim is to explore the relationship between the serous E2 levels,endometrial thickness and the outcomes of IUA patients undergoing treatment.Materials and Methods50 patients diagnosed with moderate to severe IUA by hysteroscope in our hospital from 1st March,2014 to 31 st December,2014,were enrolled in this study.They were randomly assigned to two groups, the study group and the controlled one.To reform the cavity,all subjects underwent the ultrasound guided TCRA along with an instillation of biocolloid.Whereafter,in combination with prophylactic oral antibiotic,a balloon stent was inserted into the cavity and removed one week later.After the surgery,the study group was treated with vaginal 17β-estradiol(1mg daily)and the controlled group with oral 17β-estradiol(4mg twice a day).Estradiol therapy both lasted for 3 weeks and oral dydrogesterone(10mg twice a day) was added in the last week,followed by one week hormone-freeinterval.The protocols lasted for three cycles and patients had periodical follow-ups to assess their menses,serous E2leve1 s,endometrial thickness and side-effects. Reassess the indexes concerning functions of liver, renal and coagulation profile of all the patients,and address them with medical interference if necessary.A second-look hysteroscope was done to evaluate the restoration of the normal cavity,and blunt dissection should be resolved to in case of re-adhesion.A second hospitalized surgery was needed once the adhesions were too dense to dissection. All the medical history were collected and statistically analyzed..Results1. There was no statistical difference between the study and controlled groups concerning period flow improvement rates(68.0%VS80.0%),cavity restoration rates(64.0%VS72.0%),cavity improvement rates(100.0%VS96.0%),second surgery rates(12.0%VS8.0%), pregnancy rates(26.7%VS26.7%) or the AFS grading differences(median:8.0VS8.0) after the treatments(P>0.05).2. The serous E2 levels of the study group and controlled group was(742.30±435.58)pg/ml and(253.28±131.31)pg/ml,respectively,and the former is significantly higher than the latter(P < 0.001). During every cycles,the endometrial thickness of the study group was more than that of the controlled group,but with no statistical difference(P>0.05).3. There were no statistical relations between the serous E2 level and the growing endometrial thickness, or between the serous E2 level and the AFS grading difference after the treatments(P>0.05).Further more, patients were divided into three groups according to the different serous E2 levels( < 500pg/ml,between500~999pg/ml and ≥1000pg/ml),there was still no statistical difference of the endometrial thickness of the third cycle,growing endometrial thickness and the AFS grading difference between the three groups, respectively(P>0.05).4. The side-effect rates of the study and controlled groups were 32.0% and28.0%,respectively,with no statistical difference( P > 0.05),and the common symptoms included vulvovaginal candidiasis(12.0%VS20.0%),gastrointestinal discomfort(8.0% VS0.0%) and swelling pain of the breasts(0.0%VS4.0%).All the symptoms remitted spontaneously except for vulvovaginal candidiasis.There were no statistical differences of the serous indexes of the liver,kidneys and coagulation either prior to or after the treatment,as well as the changes of them after the treatment( P > 0.05).Vaginal estradiol therapy had no obvious side-effects on the coagulation,lipids and the functions of the liver and kidneys.Conclusions1. The vaginal and oral estradiol treatments act similarly in their effect or side-effects of preventing moderate to severe IUA from re-adhesions after the surgery.The vaginal estradiol is more economical and convenient.2. In comparison with oral estradiol,vaginal estradiol can achieve a higher serous E2 level and a faster growth of endometrial thickness during the early stage.But after treating for 3 cycles,two groups can achieve a comparatively endometrial thickness.3. Once the serous E2 level is higher than 500pg/ml,increasing it dose not result in the further improvement of endometrial thickness and outcomes.