| Part One The optimal waiting period for fresh ET after hysteroscopic adhesiolysis:a retrospective cohort studyBackgroudIntrauterine adhesions(IUA)are composed of fibrotic tissue,which may result in the adherence of opposing surfaces,producing dense or firmy adhesion bands,which can lead to partial or complete obliteration of the uterine cavity.There are several clinical features of IUA:menstrual abnormalities,infertility,recurrent spontaneous abortion,and repeated failure of embryo implantation.Implantation remains the rate-limiting step for the success of in vitro fertilization(IVF)treatment,with approximately two-thirds of implantation failures resulting from inadequate uterine receptivity.For patients with IUA,lack of a sufficient amount of normal endometrial tissue to support implantation,and defective vascularization of the residual endometrial tissue consequent on fibrosis of the endometrium,will reduce uterine receptivity.Therefore,the treatment of IUA is of great significance to endometrial receptivity.A previous study has shown that the endometrial recovery time of different hysteroscopic surgeries is different,and the wounds from adhesiolysis healed within 2 months.Therefore,we believe that the recovery time after surgery is too long to result in IUA recurring,or the time is too short to affect the embryo transfer.In 2016,the relation between the time of the start of fresh IVF-ET cycles after hysteroscopic polypectomy and the outcome of pregnancy was studied by Pereira N et al,and the data from this study suggest that the time elapsed between hysteroscopic polypectomy and the start of fresh IVF-ET cycles does not affect cycle outcomes.Thus far,there are almost no data regarding the optimal time interval between hysteroscopic adhesiolysis and the ET day.In addition,this time may be related to the severity and extent of IUA.To study this issue might be very instructive for assistant reproduction technology(ART).In this context,we attempt to investigate whether the interval between hysteroscopic adhesiolysis and the ET day affect IVF cycle outcomes.ObjectiveTo investigate the appropriate time window between hysteroscopic adhesiolysis and the embryo transfer(ET)during in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI).MethodsThe study is a retrospective cohort study.was studied in the productive hospital affiliated to Shandong University.Women diagnosed with IUAs undergoing hysteroscopic adhesiolysis before fresh IVF-ET or ICSI cycles between January 2014 and September 2017 in the productive hospital affiliated to Shandong University was screened according to the inclusion criteria and exclusion criteria.Patients were classified into three groups according to the interval between hysteroscopic adhesiolysis and the ET day:within 90 days(group 1),90 to 180 days(group 2),and greater than 180 days(group 3).To give patients of different degrees of IUA a more precise recommendation and identify the relation between severity and outcomes,patients were classified into several subgroups according to the AFS scores and were further analyzed.ResultsThree hundred twelve patients were grouped as follows:112 in group 1,137 in group 2,and 63 in group 3.There were no differences in the baseline characteristics and COS characteristics within the three groups.The live birth rate in group 2(40.1%)was significantly higher than that in Group 1(17.9%).Group 2 had a higher frequency of ongoing pregnancies(45.3%)than group 3(25.4%).There were no significant differences in the rates of biochemical pregnancy,clinical pregnancy,clinical pregnancy abortion,biochemical pregnancy abortion,and stillbirth among the groups.Among the mild and moderate groups according to AFS scores,the patients which underwent fresh embryo transplantation at three different time intervals,had different live birth rates in the transplant outcomes.In the mild AFS group,the live birth rate(42.6%)in the 90-180 day transplant group was significantly higher than that in the 0-90 day transplant group(22%),which was statistically significant(p=0.004).In the moderate group,the live birth rate(35.7%)was significantly higher than that of the group(6.7%)within 90 days after surgery(p=0.004).ConclusionThe time interval between hysteroscopic adhesion separation and fresh embryo transplantation day had an impact on the outcome of IVF/ICSI fresh embryo transplantation cycle.The optimal time interval for embryo transplantation after hysteroscopic adhesion separation is 3-6 months.Part Two Comparison of auto-cross-linked hyaluronic acid gel and an intrauterine device for preventing intrauterine adhesions in infertile patients:a randomized clinical trialBackgroudIntrauterine adhesion(IUA)is a disease caused by injury of the endometrial basal layer.IUA may cause a poor reproductive outcome,especially recurrent miscarriage.Over the last four decades,hysteroscopy has become the standard method used to diagnose and treat this condition.A number of approaches have been proposed to reduce adhesion reformation after hysteroscopic adhesiolysis,such as hormone treatment and intrauterine barriers,including mechanical barriers and absorbable barriers.However,until now,there has been a lack of definitive evidence to conclude that any treatment is effective in preventing post hysteroscopy IUA formation.The auto-cross-linked hyaluronic acid gel has been suggested as an effective method to reduce the presence and extent of intrauterine adhesions.More research is needed to assess the comparative safety and(cost-)effectiveness of different anti-adhesion treatments for improving key reproductive outcomes in subfertile women and there is some low-quality evidence on the effectiveness of gels to decrease IUA formation.trials that compare the auto-cross-linked HA gel and an intrauterine device(IUD)are rare.In 2015,a new classification system of IUA was promoted by Chinese experts.We registered and conducted a randomized clinical trial(ChiCTR-IOR-16007746)to examine whether auto-cross-linked HA could be a better barrier than an IUD after operative hysteroscopy for IUA based on both this new score system and the American Fertility Society(AFS)scoring system.ObjectiveTo evaluate the efficacy of auto-cross-linked hyaluronic acid(auto-cross-linked HA)compared with an intrauterine device(IUD)for preventing intrauterine adhesions(IUA)after hysteroscopic adhesiolysis.MethodsPatients with IUA diagnosed by hysteroscopy in the Shandong Provincial Hospital Affiliated to Shandong University were invited to participate in the study.The enrolment time was from December 2015 to March 2016.The first follow up stage represented the second hysteroscopy and other records.The second stage of follow-up was closed by May 2018 and focused on fertility outcomes.89 patients were randomly distributed into the 3 groups for the intention to treat analysis:patients in Group A(n=32)were treated with hysteroscopic adhesiolysis plus the auto-cross-linked HA(3 ml);patients in Group B(n=23)were treated with hysteroscopic adhesiolysis plus auto-cross-linked HA(3 ml)and an IUD;and patients in Group C(n=34)were treated with hysteroscopic adhesiolysis plus an IUD.Following randomization,two patients from group A and one patient from group C chose to cross over to group B due to their husband’s refusal and preference.Upon completion of adhesiolysis,3 ml of auto-cross-linked HA gel was placed into the uterine cavity in Group A;3 ml of auto-cross-linked HA gel and an IUD were placed in Group B;only an IUD was placed in Group C.A second hysteroscopic examination was performed in all patients at approximately 1 month postoperatively for evaluation of IUA.The first follow up stage represented the second hysteroscopy and other records.The second stage of follow-up was closed by May 2018 and focused on fertility outcomes.The primary outcome measure was the effective rate of IUA prevention based on the American Fertility Society(AFS)scoring system.ResultsThe statistical analysis was according to both the intention-to-treat principle(ITT)and the per-protocol principle(PP).Eighty-nine women were randomly distributed into 3 groups for intention to treat.The effective rate of IUA prevention,the AFS score after therapy and the PIs of the Chinese score and AFS score before and after surgery were significantly different between Groups A and C.The clinical pregnancy rate in Group A was higher than those in Groups B and C,but the difference was not statistically significant.ConclusionsThe auto-cross-linked hyaluronic acid gel had an advantage over IUD in reducing IUA and decreasing adhesion severity and is proposed as a good barrier for preventing IUA after intrauterine procedures.Existing research also suggests a potential benefit for pregnancy rates.Part Three Fertility preservation of PSTT by interventional therapyBackgroundPlacental site trophoblastic tumor(PSTT)is a rare form of gestational trophoblastic disease.The current cause is not completely clear,and the clinical manifestations are not typical.It is mainly manifested as irregular vaginal bleeding,menopause or metastasis.The diagnosis of this disease is difficult,and the diagnosis depends on histological examination.Total hysterectomy is the first and more effective treatment for PSTT,but for patients with PSTT who require fertility preservation,they can also be cured by some fertility-sparing techniques,but there is no standard treatment.ObjectiveTo analyze the medical history,clinical manifestations,diagnosis and treatment methods of placental trophoblastic tumor(PSTT)patients with fertility preservation at home and abroad,and to explore the most suitable treatment methods for patients who require fertility preservation.Based on that we can provides suitable medical advice to patients with PSTT who require fertility preservation.MethodsA case of trophoblastic tumors in the placenta that preserves fertility is reported,including information on this patient’s medical history,clinical manifestations,auxiliary examinations,and treatment.Retrieving database through Pubmed,Web of science,Wan-fang database,China’s national knowledge infrastructure project(CNKI),and VIP database,we collect domestic and foreign cases of placental trophoblastic tumors who accepted fertility preservation treatment,and analyze their age,medical history,clinical manifestations,disease course,auxiliary examination and treatment.ResultsThe patient is a 24-year-old female,gravida 2,para 1,with intermittent vaginal bleeding episodes for 10 days following her latest pregnancy of 50 days ago.Pelvic utrasonography results showed a 4 x5 x5cm mass in hypo-hyperechogenic areas of the uterine wall and the initial serum β Human Chorionic Gonadotropin(β-hCG)level was 6359mIU/ml.Immunohistochemical analysis revealed the Ki-67 proliferative index was about 10%;the tumor cells showed strong diffuse staining with Pan Cytokeratin,human placental lactogen,placental alkaline phosphatase,and epidermal growth factor receptor(EGFR).Meanwhile,the tumor cells also showed focal positive with HCG.The histological and immunohistochemical findings led to the diagnosis of PSTT.At first,the patient took three courses of chemotherapy and three times of curettages,but the condition was not in remission.In order to preserve the patient’s fertility,the patient accepted two times of uterine artery drug pouring and embolism treatment.The drugs included Adriamycin,Cisplatin and Methotrexate.This therapy had gained a satisfactory effect.In order to further study the characteristics of patients of PSTT who accepted fertility preservation treatment,we collected 23 cases of patients with PSTT reported in China,and 35 cases of patients with PSTT reported abroad.The earliest case was reported in 1996.The age of 58 patients was counted.The age of 23 patients in China was between 21 and 46 years old.The median age at diagnosis was 30 years old and the upper and lower quartiles was 24,34 years old.The age of 35 patients abroad was between 21 and 37 years old.The median age at diagnosis was about 28 years old,and the upper and lower quartiles was 26 and 31 years old.The median age of patients in total was 29 years old,with the upper and lower quartiles was 26,32 years old.The type of the previous pregnancy was studed in 58 patients.Among the 23 patients in China,there was only 1 patient’s previous pregnancy type was ectopic pregnancy,accounting for 4%;9 cases of abortion,accounting for 39%;3 cases of moles,accounting for 13%;10 cases of full-term delivery,accounting for 44%.Among the 35 foreign patients,1 case was following the ectopic pregnancy,accounting for 3%;10 cases of abortion,accounting for 29%;4 cases of hydatidiform mole,accounting for 11%;17 cases of full-term delivery,accounting for 49%;There were 3 cases without previous pregnancy information,accounting for 8%.The full-term delivery pre-pregnancy cases accounted for 46.5%in the total number of patients,cases of abortion accounted for 33%,and cases of the moles accounted for 12%.The shortest interval time between the onset of the disease and the previous pregnancy is 0 months,and the longest is 108 months.Except for 15 cases without information of it,only 2 patients’s time interval were longer than 25 months.There were 16 patients had insufficient clinical manifestations.Among the remaining 42 patients,27 cases(64%)had vaginal bleeding,4(10%)of them had vaginal bleeding after menopause,and 7 patients had simple menopause(16%),there are 4 more special patients,which were characterized by uterine cavity occupying,the amount of menstruation decreased;pulmonary metastasis symptoms(2 years after delivery);vaginal swelling.The last patient was diagnosed occasionally by pathological examination of the curettage tissue after giving premature birth to a boy.Total hysterectomy is the first and more effective treatment for PSTT,but for patients with PSTT who require fertility preservation,they can also be cured by some fertility-sparing techniques,but there is no standard treatment.The methods for the preservation of fertility reported in the literature mainly include local lesion resection,curettage,interventional uterine arterial infusion chemotherapy,systemic chemotherapy or adopting several methods mentioned above.The methods for the preservation of fertility reported in the literature mainly include local lesion resection,curettage,interventional uterine arterial infusion chemotherapy,systemic chemotherapy or adopting several methods mentioned above.The resection of the lesion can be performed by abdominal,laparoscopic or hysteroscopy.The chemotherapy regimen mainly includes EMA-CO,MAC,VCR+FUDR+KSM+VP16,EMA/EP,TP/EP and so on.In 58 patients,the sixth patient died of forgoing treatment,the 7th and 11th patients were lost to follow-up.There werel3 patients who cured by surgery alone,without following relevant chemotherapy(24%).37 patients were cured by combining of surgery,chemotherapy or intervention,etc.(67%).Two patients were cured by uterine artery interventional chemotherapy alone(4%),and three patients were cured by systemic chemotherapy alone(5%).ConclusionThrough case review,we found that patients with PSTT who retained fertility were mainly aged 20-35 years old,with atypical clinical manifestations,mainly vaginal bleeding,followed by menopause,or corresponding symptoms in metastatic sites.It is mainly metastasis to the lung.Most of them were following full-term delivery.Due to the heterogeneity of the clinical manifestations,the diagnosis for PSTT is usually difficult and requires a combination of clinical manifestation,including blood β-hCG test,the imaging examinations,histology examinations,and immunohistochemical staining.For women who require fertility preservation,they mainly use lesion resection,curettage,interventional uterine arterial infusion chemotherapy,systemic chemotherapy,etc.Most of them were cured by combine several methods,only a small number of cases were cured only by simple surgery,simple whole body Chemotherapy or simple intervention.Our patient was treated with uterine artery drug pouring and embolism treatment,and she succeeded to giving birth again.This may be a better option for patients with PSTT who strongly request to conserve fertility.but interventional chemotherapy has corresponding side effects and need to further verificate the safety and efficacy. |
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