Study On The Obstetric Outcome And Birth Defects Of The Children Born From Infertile Couples Treated By In Vitro Fertilization And Embryo Transfer

PartⅠStudy on the obstetric outcome and birth defect of the children up to 5 years conceived by IVF/ICSI-ETOBJECTIVETo evaluate the safety of ICSI technology,the neonatal outcome and congenital malformation of the children up to 5 years born after ICSI compared with the children born after IVF.MATERIALS AND METHODSA retrospective cohort study was performed on the neonatal outcome and congenital malformation of the children up to 5 years born after ICSI and IVF. Infertile women were recruited at Reproductive Medicine center of Southern Hospital during January 1,2003 and December 30,2007,meanwhile all the infertile couples were healthy,understood and consented this study.Only children born after a replacement of fresh embryo was considered in this study.Children born after mixed IVF-ICSI procedure were not take into account as well as the children born after oocyte or sperm donation,we divided these patients into two groups:those patient whose implantated embryo was came from IVF procedure was considered as IVF group;and those patient whose implantated embryo was came from ICSI procedure was considered as ICSI group.ICSI was carried out using ejaculated,epididymal or testicular sperm.To compared the data such as clinical pregnancy rate,live birth rate, perinatal death,neonatal death,congenital malformations at birth between the two groups.For the children age 1-5 years old,we follow up them mainly through telephone to collect the data of congenital malformation.Total malformation rate taking into account malformations in stillborns,in terminations,in live born and found up to 5 years.SPSS 13.0 software was applied for statistical analyze.Data was expressed by mean±standard deviation,and independent samples test and crosstabsχ~2 test.P＜0.05 was accepted as indication of statistical significance.Comparisons of the two groups for the theoretical frequency lower than 5 were performed using Fisher’s exact test.RESULTSThere are 869 infertility couples included in our study.ICSI and IVF maternal characteristics were comparable for age and infertility duration except for the higher primary infertility rate in the ICSI couples(P=0.000).There were no significance in differences of the COH protocol,the total dose of gonadotropin and the oocyte retrieval rate between two groups.In two cohorts,similar rates of live birth,premature birth,multiple pregnancy, cesarean section,perinatal mortality,neonatal death,birth weight,low birth weight rate and gender ratio were observed.We found significantly higher rate for premature birth,cesarean section,low birth weigh in twins than in singletons,both in IVF and ICSI group.Among singleton,also among twins,there were no significance difference in all of the above rates between two groups.378 ICSI children and 905 IVF children were live born after replacement of fresh embryo.Congenital malformations were observed at birth in 4.5%of the ICSI and in 2.5%of the IVF(OR=1.99,95%CI=1.04～3.81).Major malformations(defined as those causing functional impairment or requiring surgical correction),were observed at birth in 4.0%of the ICSI children and in 1.8%of the IVF children. (P=0.019).We found significantly increased risks after ICSI for heart defects (P=0.026) of the neonate.The follow up rate was 60.3%and 60.6%of the total number of children aged 1～5years old,39.7%and 39.4%of children were lost follow up even after several attempts for IVFand ICSI children respectively.We found no significance in differences of the total malformation rate,major malformation rate between the IVF and ICSI.When analyzing the different organ system of the abnormal conditions,we still found significantly increased risks after ICSI for heart defects(P=0.026).There was no difference in the total malformation and major malformation between singleton and twins both in IVF and in ICSI group.Stratifying by plurality and gender showed that the high risk of heart defects was only increased for the singleton boys(P=0.020).But limited to the singletons at term, we didn’t find any differency in heart defects between two groups(P=0.079).And the skeleton malformation and Glucose-6-phosphatase deficiency was significantly higher in ICSI twins(p=0.027).But we found no difference in twins at term between two groups.We found the similar malformation rate,major malformation rate between IVF children and ICSI children of the infertility couples aged lower than 35 years old.We also found the similar malformation,major malformation between two groups for the femal-factor infertility couples except for higher rates for the skeleton malformation. But we didn’t found any difference in skeleton malformation in sigletons at term between two group.CONCLUSIONSOur analysis does not indicate that the ICSI-procedure represents significant risk of birth defects in addition to the high risk involved in prematurity and in multiple. The data was limited,particularly on risks of specific categories of defects.PartⅡRetrospective case-control study on the neonatal outcome and birth defect between the children born after IVF/ICSI-ET and the children conceived spontaneously OBJECTIVETo evaluate the safety of the IVF/ICSI technology,the neonatal outcome and congenital malformation at birth were investigated in children conceived by IVF/ICSI-ET compared with the case-control group,the children conceived spontaneously.MATERIALS AND METHODSA retrospective matched case-controlled study was performed on the neonatal outcome and congenital malformation at birth between the children born after IVF/ICSI-ET and the children conceived naturally.The ART group consisted of 967 infertility couples and their children born after a replacement of fresh embryo,using IVF or ICSI at reproductive medicine center of Southern Hospital during January 1, 2003 to December 30,2007.IVF/ICSI children were eligible if they are born at least 28 weeks of gestation.Children born after mixed IVF-ICSI procedure were not take into account as well as the children born after oocyte or sperm donation.All the infertile couples understood and consented to this study.The comparison group consisted of 1934 fertility women and their children conceived spontaneously.They were recruited from Obstetrics department of Southern Hospital.The included comparison group was matched according to matanal age(equal to the infertility women or no more than 5 years range),the last menstruation period(in the same year with ART group) and the gestational duration (≥28 weeks of gestation),with the proportion of matching was 2:1 to the infertility women.Those women who terminated the pregnancy because of non-iatrogenic reason were excluded in our study.To compared the data such as live birth rate,perinatal death,neonatal death, congenital malformations at birth between the two groups.Total malformation rate taking into account malformations in stillborns,in terminations,and in live bornSPSS 13.0 software was applied for statistical analysis.Data was expressed by mean±standard deviation,and independent samples test and crosstabsχ~2 test.P＜0.05 was accepted as indication of statistical significance.Comparisons of the two groups for the theoretical frequency lower than 5 were performed using Fisher’s exact test.RESULTSPerinatal outcomes of ART were worse than the control group,including twins birth,premature delivery,mean birth weight,low birth weight,cesarean section. There was no significant difference in the perinatal mortality between ART and conrtoll group.Among singletons,no difference was found in the above index between the two groups,except for the higher cesareab delivery rates after ART,as well as among twins.Compared with both spontaneously conceived children and all ART children, there were no significance in difference of the neonatal total congenital malformation, major malformation,except for the slightly higher birth defects of ear,face and neck. (P=0.040).We found no significantly increased risks after IVF for birth defects compared with the control group.Whereas in the analysis by different organ system, the ear,face and neck malformation was higher in IVF children compare to the SC children(P=0.013).Stratifying by plurality and gender,there was no difference in ear,face and neck malformation both in sigletons and in twins between IVF children and SC children.But the figures shows us that the increased risk for the defects of ear, face and neck was mainly focused on IVF twins.Compared ICSI children with the SC children,we found no significantly increased risks for birth defects and major malformations.Whereas in the analysis by different organ system,the vascular malformation and Glucose-6-phosphatase deficiency was higher in ICSI children (P=0.015).Stratifying by plurality and gender showed that the risk for vascular malformation was only increased for the singleton boys(P=0.013) and the risk for Glucose-6-phosphatase deficiency was only increased for girls(P=0.006).But we didn’t found any difference in vascular malformation in sigletons at term between ICSI children and SC children.We also found no difference in Glucose-6-phosphatase deficiency in singleton girls.And the figures shows us that the increased risk for the Glucose-6-phosphatase deficiency was mainly focused on ICSI premature twins.CONCLUSIONS The outcome of singletons born at term following ART is generally reassuring. The adverse outcomes of ART,including the neonatal mortality,high vascular malformation for the ICSI children,mainly due to the multiple pregnancy and premature.Follow-up of these children is necessary in order to evaluate the risks of infertility treatment upon subsequently conceived offspring.