Discussion For Clinical Outcomes Of Singletons With Vanishing Twin Syndrome Following In Vitro Fertilization-double Embryo Transfer

Vanishing twin syndrome(VTS)refers to the disappearance of one of the gestational sacs or the cessation of embryo development in early twin pregnancy(1).Although the etiology of VTS is currently unknown,studies have shown that this phenomenon may be related to the impaired developmental potential of embryos and the chromosomal abnormalities of embryos(2).In addition,the early embryo implantation is crowded,resulting in insufficient exchange area between uterine and placental,which adversely affects the site of surviving embryo implantation and causes adverse outcomes in surviving newborns.The results of placental pathology studies have confirmed this conclusion(3).In vitro fertilization/intracytoplasmic sperm injection-embryo transfer(IVF/ICSI-ET)and its derived assisted reproduction technology have been born for more than 40 years,bringing the gospel to many infertile patients.As the number of ART offspring increases,researchers are paying more attention to the safety of ART.Although most of the.babies born through ART are healthy,recent studies have found that ART increases many postpartum complications,such as pregnancy hypertension,gestational diabetes,premature delivery,placenta previa,placental abruption,premature rupture of membranes,low birth weight,etc.Twin pregnancy is also one of the common pregnancy complications following IVF/ICSI-ET.Recent studies on the perinatal outcome of twin pregnancy following IVF/ICSI-ET have found that the incidence of adverse pregnancy outcomes in VTS in twin pregnancy is higher than in those with initial single pregnancy.Therefore,this study intends to compare the outcomes of singleton live births from the initial twin pregnancies with VTS and the initial single pregnancy following IVF/ICSI with double embryos transfer(DET),and further explores the influencing factors that lead to adverse neonatal outcomes in single-birth live births,and provides evidence for new concepts of embryo transfer strategies related to IVF/ICSI and FET cycles.Objective(1)To investigate the neonatal outcomes of singleton live births following double embryo transfer with vanishing twin syndrome(VTS)in fresh and frozen cycles respectively(2)To analyze the relevant influencing factors leading to the above-mentioned adverse neonatal outcomes in singleton live births.Materials and Methods1.Groups1.1 Retrospective cohort study:From January 1st,2008 to October 1st,2018,anonymized data on all cycles performed in China were obtained from the Reproductive Medicine Department at the Third Affiliated Hospital of Zhengzhou University,which had involved 2772 fresh embryo transfer(ET)cycles and 3448 frozen embryo transfer(FET)cycles.VTS group refers to those who have twin pregnancy with VTS during 9-12 weeks of pregnancy;Non-VTS(Non-vanishing twin syndrome)group refers to those who had single embryo implantation during pregnancy and did not occur VTS.1.2 Case-control study:Adverse neonatal outcomes were grouped as composite endpoints again,that is,those with adverse neonatal outcomes were group A(Adverse neonatal outcomes),and those of group B(Non-adverse neonatal outcomes),and further analysis of the correlations factor.According to statistics,in the fresh ET cycles,there were 985 cases in group A and 1787 cases in group B;in the FET cycles,there were 728 cases in group A and 2720 in group B.2.Observation indicators2.1 Baseline data:Age,BMI,infertile year,cause of infertility(tubal factor,male factor),current cycle,bFSH,bE2,bLH,PRL,AMH,AFC,number of retrieved oocytes,number of available embryos,number of high-quality embryo,embryo stage(cleavage stage embryo,blastocyst),endometrial thickness at the day of transplantation,mode of delivery(cesarean section,vaginal delivery).2.2 Neonatal outcomes:Gestational age,PTB,BW,LBW,SGA,birth defects,pediatric admission rate,and NICU admission rate.3.Statistical methodsData were analyzed using the SPSS 21.0 statistical software.3.1 Retrospective cohort study:Cohort characteristics were described using the chi-square test for categorical variables,while continuous variables were expressed as means±SD.Logistic regression analysis was performed to adjust the confounders,including maternal age,BMI,value of AMH,infertile years,current cycle,AFC,cause of infertility,number of oocytes retrieved,endometrial thickness at the date of transplantation,umber of high-quality embryos,and embryo stage.3.2 Case-control study:The statistical method is the same as above.Univariate and multivariate analysis of adverse neonatal outcomes,including variables:age,BMI,value of AMH,infertile years,current cycle,AFC,cause of infertility,number of oocytes retrieved,endometrial thickness at the date of transplantation,umber of high-quality embryos,and embryo stage.The univariate and multivariate Logistic regression analysis results were expressed by OR/aORand 95%CI;p<0.05 was considered statistically significant.Results1.Fresh ET cycles1.1 Retrospective cohort study1.1.1 Baseline characteristics Firstly,for the fresh ET cycles,the maternal age in control group was higher than that in study group(29.8±4.2 vs.29.5±3.9,p=0.031).At the same time,the value of AMH was also higher in study group compared with that in control group(5.4±0.60 vs.5.3±0.67,p=0.029).Moreover,more high quality embryos obtained from the fresh cycles and more cleavage-stage embryos were included in study group than those in control group,which were(5.1 ± 2.6 vs.4.8 ± 2.4,p=0.003)and(84.9%vs.66.0%,p=0.000),respectively.But the endometrial thickness at the date of transplantationin control group was greater than that in study group(11.7±1.1 vs.11.6 ± 1.3,p=0.002),More women received cesarean section in control group than in study group(78.2 vs.64%,p=0.000)(Tablel.1.1).1.1.2 Neonatal outcomes of singleton live births in the fresh ET cycles In the fresh ET cycles,the BW and gestational age in study group were lower than those in control group,which were(2962.4 ± 563.1 vs.3104.9±498.5,p=0.000)and(262.8± 8.4 vs.268.9 ±13.9,p=0.000),respectively.Relative to control group,the study group was linked with increased risks of PTB(aOR=2.45,95%CI:1.98,3.03,ap=0.000),LBW(aOR=2.11,95%CI(1.67,2.65),ap=0.000),pediatric admission(aOR=2.55,95%CI(2.07,3.13),ap=0.000),and NICU admission(aOR=1.98,95%CI(1.32,2.96),ap=0.001),but there were no statistically significant differences in the risks of SGA(aOR=1.09,95%CI(0.82,1.45),ap=0.960)and congenital malformation(aOR=0.94,95%CI(0.53,1.68),ap=0.640)between the two groups(Table 1.1.2).1.2 Case-control study1.2.1 Comparison of baseline data There were statistically significant differences in general baseline characteristics such as infertility factors,bE2,AMH,embryo stage,and whether or not VTS occurred in groups A and B(p<0.05);however,age,infertile year,current cycle,BMI,bFSH,PRL,bLH,AFC,endometrial thickness on the day of transplantation,number of retrieved oocytes,number of high-quality embryos,and number of available embryos were not different among the baseline data groups(p>0.05)(Table 1.2.1).1.2.2 Univariate and multivariate analysis of groups A and B The results showed that univariate analysis suggested that age,infertile factors,bE2,AMH,embryo stage,and VTS had significant effects on neonatal outcomes;multivariate analysis showed BMI and VTS are influencing factors for adverse neonatal outcomes.BMI>25(aOR=1.90,95%CI(1.53,2.06),ap=0.044)is risk factor for adverse neonatal outcomes.So was VTS(aOR=2.73,95%CI(2.31,3.23),ap=0.000)for adverse neonatal outcomes(Table1.2.2)2.FET cycles2.1 Retrospective cohort study2.1.1 Baseline characteristics For the FET cycles,the maternal age and BMI werehigher in study group than in control group,which were(30.7±4.9 vs.30.2±4.8,p=0.001)and(23.0 ±2.5 vs.22.8 ± 2.3,p=0.0016),respectively.In addition,the infertile year was lower in study group compared with that in control group(2.5±1.5 vs.2.7 ± 1.5,p=0.001).Besides,there were more cleavage-stage embryos included in study group than those in control group(68.5%vs.64.2%,p=0.01),and more infants are delivered through cesarean section in control group than in study group(87.4%vs.66.7%,p=0.000)(Table 2.1.1).2.1.2 Neonatal outcomes of singleton live births in the FET cycles In the FET cycles,the gestational age and BW in study group were lower than those in control group,which were(263.0 ± 15.7 vs.273.0±10.5,p=0.000)and(3099±662.1vs.3352 ± 671.5,p=0.000),respectively.The study group was associated with increased risks of PTB(aOR=2.45,95%CI(2.23,3.43),ap=0.000),LBW(aOR=2.67,95%CI(2.13,3.34),ap=0.000),pediatric admission(aOR=2.62,95%CI(2.14,3.21),ap=0.000),and NICU admission(aOR=2.22,95%CI1.43,3.46,ap=0.001)compared with those in control group,but differences in the risks of SGA(aOR=0.98,95%CI(0.71,1.36),ap=0.730)and birth defect(aOR=0.99,95%CI(0.60,1.63),ap=0.940)were not statistically significant between the two groups(Table 2.1.2).2.2 Case-control study2.2.1 Analysis of related factors of adverse neonatal outcomes The general baseline data of groups A and group B:the current cycle,infertile cause,BMI,AMH,endometrial thickness on the day of transplantation,and VTS were significantly different between groups A and B(p<0.05);There was no significant difference between the other two groups when compared with other indicators(p>0.05)(Table 2.2.1).2.2.2 Univariate and multivariate analysis of groups A and B Univariate analysis showed that endometrial thickness at the day of transplantation,embryo stage,and VTS had significant effects on adverse neonatal outcomes on the day of transplantation.Endometrial thickness less than 10 mm at the day of transplantation increased the risk of adverse neonatal outcomes(aOR=1.70,95%CI(1.56,1.88),ap=0.002);patients with VTS were more likely to have adverse neonatal outcomes(aOR=3.24,95%CI(2.70,3.88),ap=0.000),no statistically significant effects were found in the remaining variables(Table2.2.2).Conclusions1.Our study finds that in IVF/ICSI cycles and frozen embryo cycles,neonatal outcomes of singleton live births with VTS are worse than those without VTS following double embryos transfer.2.BMI≥25 and VTS are risk factors for adverse neonatal outcomes in singleton live births in IVF/ICSI cycles.3.Endometrial thickness<10mm at the day of transplantation and VTS are risk factors for adverse neonatal outcomes in singleton live births in FET cycles.