The Predictive Value Of The New Ultrasound Model For Adverse Pregnancy Outcomes And The Correlation Between FMR1 Gene Amplification And Abortion

Part 1 Construction and prediction value of ultrasonic prediction model for adverse pregnancy outcomeBackgroundSpontaneous abortion(SAB)refers to the loss of pregnancy that occurs when the pregnancy is less than 28 weeks and the weight is less than 1000 g,of which more than 80%are early abortions.Research shows that 15%-30%of pregnancies have spontaneous abortion at the early stage.At a time when reproductive health is being paid more and more attention,early spontaneous abortion has brought great harm to patients and families,especially the intrauterine infection and intrauterine adhesion caused by missed abortion,which has seriously affected patients’ physical and mental health and the outcome of next pregnancy.Therefore,in order to alleviate patients’anxiety,avoid waste of medical resources and improve the outcome of next pregnancy,it is of great clinical significance to timely predict the outcome of pregnancy.With the development of ultrasound imaging,transvaginal ultrasound has gradually become an important means for evaluating the potential of embryos,such as regular detection of gestational sac size,yolk sac size,embryo and fetal heart rate,which is of great significance to the prediction of the potential of embryos in early pregnancy.Some studies have suggested that the ratio of embryo to gestational sac is too large to indicate placental damage,but no exact ratio has been proposed.Various research conclusions on other research indicators are also different,even controversial and uncertain,and most of them are single index or combined prediction of the two indexes.At present,there is a lack of a unified and highly sensitive ultrasound prediction model for reference at home and abroad,and it is not possible to predict early pregnancy outcomes timely.Based on the study of pregnancy sac size,yolk sac size,fetal heart and embryo to gestational sac ratio,this study attempts to synthesize the four ultrasound indexes,establish a prediction model based on scores,unify the measurement of gestational age and methods,clarify the time point of examination,improve the accuracy of prediction,and avoid repeated examinations.Its significance lies in that patients can accurately predict the early outcome of pregnancy,timely identify embryo abortion,terminate pregnancy in time,prevent physical and mental injury caused by missed abortion in later period,and reduce the waste of medical resources when they perform routine ultrasound examination for the first time after pregnancy.Objective1.To evaluate the predictive value of each ultrasound index for early pregnancy outcomes by measuring and evaluating individual ultrasound indicators.2.Integrate the ultrasound indicators into an ultrasound prediction model,and establish a predictive model with high sensitivity and operability,so that embryos can be identified in time for the first routine ultrasound examination after pregnancy.Predict the potential of early pregnancy embryos,thereby achieving the goal of saving medical resources,reducing or avoiding late complications caused by adverse pregnancy outcomes,thereby improving reproductive health and improving the outcome of the next pregnancy.Methods1.Research object208 cases of IVF/ICSI(in vitro fertilization/intracytoplasmic sperm injection)were randomly selected from the Department of Reproductive Medicine,Affiliated Hospital of Binzhou Medical College.The first vaginal ultrasonography is performed at the time point 33-35 days after transplantation(48-50 days of pregnancy),and then the ultrasound is reviewed regularly.The follow-up of the ongoing pregnancy is 14 weeks after pregnancy.2.Method The following ultrasound parameters were measured:gestational sac size,the proportion of the embryo and gestational sac(embryo/gestational sac),yolk sac size,and fetal cardiac activity.3.Establishment of ultrasound prediction modelThe above data were assigned according to the ongoing pregnancy rate(up to 14 weeks),and the score grew in parallel to the pregnancy rate.Then,all patients were grouped by their different scores.Results1.Predictive value of ultrasound single index for early pregnancy outcomewhen gestational sac size was found to be>21 mm,the ongoing pregnancy rate was 94.74%,When gestational sac size was found to be 16-21 mm,ongoing pregnancy rate was 90.48%.If gestational sac size was found to be<16 mm,ongoing pregnancy rate was 33.3%;and this was statistically significant when compared with the other two groups(P<0.05).However,there was no significant difference between the>21 mm and 16-21 mm groups(P>0.05).When embryo/gestational sac was found to be>0.25,the ongoing pregnancy rate was 100%,When the embryo/gestational sac was found to be 0.10-0.25,ongoing pregnancy rate was 90.63%.When embryo/gestational sac was found to be<0.10,ongoing pregnancy rate was 60%.If the embryo could not be seen at this time,no patient had ongoing pregnancy.There was no significant difference between the>0.25 group and 0.10-0.25 group(P>0.05),but the difference between the other groups was statistically significant(P<0.05).When yolk sac size was found to be 2-6 mm,ongoing pregnancy rate was 85.42%.Surprisingly,when yolk sac size was found to be<2 mm or no yolk sac,no patient had ongoing pregnancy.Among patients with fetal cardiac activity on days 33-35 after ET,ongoing pregnancy rate was 90.91%(160/176).Conversely,if no fetal cardiac activity was observed,ongoing pregnancy rate(12.50%,4/32)was extremely low.Furthermore,in eight of 32 patients who had no fetal cardiac activity,the embryo had an ongoing pregnancy rate(50%,4/8).Moreover,24 of 32 patients had either embryo nor fetal cardiac activity,these patients had a miscarriage.2.Establishment of ultrasound prediction model and its predictive value for adverse outcomes in early pregnancyPatients with 5 scores had a low ongoing pregnancy rate of 33.33%(4/12),and patients with 6 scores had an ongoing pregnancy rate of 50.00%(8/16),patients with 7 scores had an ongoing pregnancy rate of 60.00%(12/20).Surprisingly,patients with 8 scores had an ongoing pregnancy rate of 96.3%(104/108).In addition,we found that the ongoing pregnancy rate was 100%(36/36)in patients with nine scores.Conversely,there was no ongoing pregnancy in patients with four scores.Patients with a history of recurrent spontaneous abortion(n=32)also had a surprising ongoing pregnancy rate of 100%,when they gained 8-9 scores,and if patients could gain 8-9 scores,success rate was also 100%in the 35-40 years age range,which was still at a high success rate(66.67%)in patients older than age 40 years.The ROC curve analysis showed that the AUC(area under the curve)of the prediction model was 0.925,and the optimal threshold for normal and abnormality was 7.5.The optimal threshold for ongoing pregnancy and spontaneous abortion in this model was 7.5.The ongoing pregnancy rate of<7.5 points(4-7 points)was 37.50%(24/64),>7.5 points(8-9 points)was 97.22%(140/144).The square test showed that the two groups were statistically significant(P<0.05).Conclusions1.Every ultrasound parameter plays an important role in evaluating Embryo potential.2.This scoring system is strongly associated with ongoing pregnancy over 14 weeks.With the decrease of the score,the abortion rate was higher and higher between 4 and 7 points.A score of 8 and 9 indicates a good pregnancy outcome,which can give the patient a more positive answer.3.For patients with a history of recurrent abortion or advanced age,the predictive model also has a certain predictive value.Part 2 Relationship between FMR1 gene sequence amplification and abortion in early pregnancyBackgroundThe prevention and treatment of spontaneous abortion are mostly related to the diagnosis of the cause.This study attempts to further explore the etiology of spontaneous abortion in early pregnancy while predicting pregnancy outcomes.The causes of spontaneous abortion in early pregnancy are complicated,including genetic,anatomical,infectious,immunological,hematological and endocrine-related factors.However,some patients with spontaneous abortion still cannot find the exact cause.Embryo chromosomal abnormalities can lead to spontaneous abortion in early pregnancy,but the mechanism of embryonic chromosomal abnormalities is not very clear.In recent years,many studies have linked molecular-level events to pathological manifestations and the etiological interpretation of spontaneous abortion at the molecular level.For example,studies have shown that MAD2,MAD1,BUB3,NOG,STOT4 and other genes promote the occurrence of spontaneous abortion through different molecular mechanisms.But research is still in its infancy,and molecular studies on the etiology of spontaneous abortion require a long and complex process.Studies have confirmed that human embryonic development is a process of regulation of multi-gene expression.The disorder of gene expression regulation leads to incompatibility of life,which leads to abortion.The Hanzlik study found that FMR1(fragile-X mental retardation 1)gene is widely present in human embryonic tissue at 11 weeks,and is also expressed in some tissues of embryos in 20 weeks,the expression of FMR1 gene and its homologous genes during embryonic development,with tissue specificity and time specificity,indicating that these genes are involved in the regulation of embryonic development,possibly it plays an important role in the process of embryonic development,so the amplification and mutation of this gene may cause disease during the development of the body.Studies have confirmed that fragile X syndrome,POF(premature ovarian failure),FXTAS(fragile X trembling ataxia syndrome)is a different disease associated with FMR1 gene CGG sequence amplification.The different characteristics of each disease are the degree of amplification.The regulation of FMR1 gene during life development and the correlation between FMR1 gene mutation and POF suggest whether our FMR1 gene amplification or even mutation is related to spontaneous abortion?Hence,the objective of the current study was to determine if CGG repeat expansion is related to the risk of miscarriage.ObjectiveStudy the relationship between the expansion of FMR1 gene CGG sequence and spontaneous abortion,and determine if CGG repeat expansion is related to the risk of miscarriage.MethodsBlood samples were obtained and checked for the presence of expanded alleles of the FMR1 gene using polymerase chain reaction.Patients harboring the expanded allele,with a threshold set to 40 repeats,were further evaluated by sequencing.ResultsThe number of abortions each woman had,was not associated with her respective CGG repeat number(P=0.255).All the positive cases involved intermediate zone carriers.Statistical analysis found no difference in the incidence of intermediate zone carriers between the two groups(Chi-square,P=0.364).The number of CGG sequence repeats in the case group was higher than that in the control group,and it was significantly different in the two groups(P=0.027).ConclusionsThe CGG expanded allele of the FMR1 gene might be related to spontaneous abortion in early pregnancy.