| Part I Analysis of Influencing Factors Related to Embryo Implantation FailureObjectiveEmbryo implantation failure is the key factor restricting the development of assisted reproductive technology,and it is also the key research issue in the field of assisted reproductive technology.However,the etiology and influencing factors of embryo implantation failure are complex,and the failure of embryo implantation may be related to many factors.Suppose the influencing factors of embryo Implantation failure are identified early.In that case,it will be of great reference significance for finding potential patients with embryo implantation failure,finding the cause of embryo implantation failure and targeted clinical treatment.This paper discusses the clinical data and revelant factors of 592 infertile patients to provide a reference for the clinical management of patients with embryo implantation failure.MethodA total of 296 patients who received in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI)at the Reproductive Medicine Center of Qilu Hospital of Shandong University from September 2018 to April 2022 and failed to implant embryos more than 2 times were selected as the case group,and the first embryo transfer(including fresh cycle and resuscitation cycle)in our hospital at the same time was randomly chosen to obtain the clinic.The information of patients in the two groups was collected,including age,BMI,infertility time.endometrial thickness,the level of TSH.abortion times,past medical history(including the history of embryo termination,intrauterine adhesions,endometrial polyps,submucosal myoma,chronic endometritis,hydrosalpinx,endometriosis),the number of intrauterine operations,chromosome polymorphism,infertility type,semen routine results,insemination methods,and anti-cardiolipin antibody and anti-β2-glycoprotein 1 antibody.The relevant factors of embryo implantation failure were analyzed by single factor analysis,and the elements with statistical differences in single factor analysis were included in multivariate logistic regression analysis to explore the risk factors of embryo implantation failure.Result1.The results of the univariate analysis showed that the age,infertility time,the proportion of hydrosalpinx and ICSI insemination methods in the case group were higher than those in the control group,and the endometrial thickness in the case group was lower than that in the control group on the day of embryo transfer,with statistical differences(P<0.05).There was no statistical difference in BMI,the level of TSH,number of abortions,past medical history(including the history of embryo abortion,intrauterine adhesions,endometrial polyps,submucous myoma,chronic endometritis and endometriosis),number of intrauterine operations,chromosome polymorphism,infertility type,semen results,anticardiolipin antibody positive rate and anti-β2-glycoprotein 1 antibody positive rate between the two groups(P>0.05).2.Multivariate logistic regression analysis showed that age,infertility time,history of hydrosalpinx and ICSI were positively correlated with embryo implantation failure(P<0.05),while endometrial thickness on embryo transfer day was negatively correlated with embryo implantation failure(P<0.05).ConclusionOld age,prolonged time of infertility,history of hydrosalpinx,ICSI fertilization method,and thin endometrium(≤8mm)on embryo transfer day are related to the increased risk of embryo implantation failure.Part II Effect of Cyclosporine on Pregnancy Outcome and Neonatal Outcome of Patients with Embryo Implantation Failure≥2 TimesObjectiveWith the continuous development of assisted reproductive technology(ART),the success rate of ART in assisted pregnancy is increasing,but repeated planting failure is still an unsolved problem in the field of ART.In recent years,some studies have found that cyclosporine,an immunosuppressant,has the potential to improve pregnancy outcomes by inducing maternal and fetal immune tolerance and enhancing the invasion of embryonic trophoblast cells,which suggests that the clinical application of cyclosporine may bring good news to patients with repeated implantation failure.However,there are few studies on the clinical application of cyclosporine in the field of ART,and the relationship between cyclosporine and the neonatal outcome is rarely reported.In clinical work,there are more patients when embryo implantation fails more than two times.Therefore,it is of important reference significance to explore the therapeutic effect of cyclosporine on such people.This study aimed to investigate cyclosporine’s effect on pregnancy and neonatal outcomes in patients with embryo implantation failure≥2 times.MethodA total of 296 patients who received in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI)at the Reproductive Medicine Center of Qilu Hospital of Shandong University from September 2018 to April 2022 were selected and were divided into cyclosporine group(101 cases)and control group(195 patients)according to whether cyclosporine was added to the second embryo transfer.Using the method of Propensity Score Matching(PSM),the matching ratio was 1:1,and 101 pairs of patients were matched,including 101 cases in the cyclosporine group and 101 patients in the control group.There were 85 newborns,45 in the cyclosporine group and 40 in the control group.After matching,the data were analyzed as a whole,and then the patients were divided into two subgroups according to the number of embryo implantation failures.One subgroup had embryo implantation failure twice,and the other subset had embryo implantation failure≥3 times.The pregnancy outcomes of the cyclosporine and the control groups were compared,including embryo implantation rate,biochemical pregnancy rate,clinical pregnancy rate,live birth rate,ectopic pregnancy rate,abortion rate,early abortion rate and late abortion rate.Neonatal outcomes were compared between the two groups,including birth mode,type(single child,twins),sex,gestational age,weight and birth defects.Result1.There was no statistical difference in basic data such as age,implantation failure times,BMI,pregnancy times,abortion times and the level of TSH between the cyclosporine and the control groups(P>0.05).2.Generally speaking,there was no ectopic pregnancy in the cyclosporine and control groups.Compared with the control group,the biochemical pregnancy rate in the cyclosporine group decreased(5.9%vsl4.9%),and the difference was statistically significant(P<0.05).Compared with the control group,the embryo implantation rate(44.6%vs38.8%),clinical pregnancy rate(54.5%vs48.5%)and live birth rate(42.6%vs34.7%)in the cyclosporine group were all improved,and the abortion rate(21.8%vs28.6%),the early abortion rate(16.4%vs20.4%)and the late abortion rate(5.5%vs8.2%)were all decreased,but there was no statistical difference(P>0.05).There were no birth defects in the newborns in the cyclosporine group and the control group,but the birth mode,type(single child,twins),sex,gestational age and weight of the newborns in the two groups were similar,and there was no statistical difference(P>0.05).3.When embryo implantation failed twice,there was no ectopic pregnancy in the cyclosporine and control groups.Compared with the control group,the biochemical pregnancy rate in the cyclosporine group decreased(5.7%vs16.1%),and the difference was statistically significant(P<0.05).Compared with the control group,the embryo implantation rate(45.8%vs39.2%),clinical pregnancy(54.0%vs48.3%)and live birth rate(42.5%vs35.6%)in the cyclosporine group were all improved,the abortion rate(21.3%vs26.2%),the early abortion rate(14.9%vs16.7%)and the late abortion rate(6.4%vs9.5%)were all decreased,but there was no statistical difference(P>0.05).When the embryo implantation failed twice,there were no birth defects in the newborns in the cyclosporine group and the control group,and there was no statistical difference in the birth mode,newborn type(single child,twins),sex,gestational age and weight between the two groups(P>0.05).4.When the embryo implantation failed more than 3 times,there were no ectopic pregnancies and late abortions in the cyclosporine and the control groups.The biochemical pregnancy rate(7.1%vs7.1%)was the same.Compared with the control group,the cyclosporine group had a higher embryo implantation rate(38.1%vs36.8%),clinical pregnancy rate(57.1%vs50.0%),live birth rate(42.9%vs28.6%),and lower miscarriage rate(25.0%vs42.9%)and early abortion rate(25.0%vs42.9%).However,there was no statistically significant difference(P>0.05).When embryo implantation failed more than 3 times,there were no birth defects,twins,overdue babies,low birth weight babies and macrosomia in the newborns in the cyclosporine group and the control group,and there was no statistical difference in the birth mode,sex,gestational age and weight between the two groups(P>0.05).ConclusionThis study is a retrospective analysis.The results show that cyclosporine can improve the implantation rate,clinical pregnancy rate and live birth rate and reduce the abortion rate(including early abortion rate and late abortion rate)of retransplantation patients with embryo implantation failure,but the statistical difference is not significant.In the future,it is necessary to increase the sample size and carry out multi-center randomized controlled research to clarify further.2.Cyclosporine has no apparent effect on the way of birth,type(single child,twins),sex,gestational age,weight and birth defects of newborns,and further study is needed to increase the sample size in the future. |
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