Study On In Vitro Fertilization Outcome Of HBV Carriers And The Health Of Mother And Offspring

BackgroundChronic infection of Hepatitis B virus(HBV)is one of the public health problems drawing worldwide attention.There are approximately 350 million HBV carriers throughout the entire world;China is a high endemic area of Hepatitis B and asymptomatic hepatitis B surface antigen(HBsAg)carriers.The carrying rate of the hepatitis B virus is up to 10%～15%.Development of Hepatitis B shows both familial and sporadic characters.About 80%HBV cariers got it through familial vertical transmission,other 20%got it through horizontal transmission by body fluids or medicine channel.In our country,about 1.5 millions HBV cariers give birth to childs every year,and up to 1million newborn babys would be infected if without intervention,of which 800 thousand are infected through mother-to-child vertical transmission.Since immune tolerance is easy to set up during infancy,infected infants often not only become persistent or even lifelong hepatitis B surface antigen(HBsAg) positive carriers,but also result in hepatic cirrhosis or even hepatic carcinoma easily.With the development and popularity of assisted reproductive technologies(ART), more and more infertile and sterile couples carring HBV are receiving ART treatment. Parts of these couples can have own offspring by in vitro fertilization-embryo transfer(IVF-ET).However,as solving the procreation problem,whether HBV carring would influence the implementation of IVF-ET,whether process of vitro fertilization and different fertilization methods would raise the infection rate of offspring and influence the health condition of both mother and offspring,all of these questions are drawing people's attention.Around the world,there were few systemic studies on in vitro fertilization outcome of HBV carriers and the health of mother and offspring.To address this gap,the collection of information has carried out,hoping the results can provide references for the future of IVF technology for HBV carriers.ObjectiveAnalysis of IVF-ET performance of infertile HBV carriers,pregnancy complications of IVF mothers earring HBV,neonatal outcomes,infection rate of offspring and their influential factors.Then compared it with nature cyophoric data of HBV suffers in our country and IVF-ET data of general population.We hope the paper can provide reference for ARTs.MethodsInfertile HBV couples with at least one partner being HBV seropositive(positive for hepatitis B surface antigen(HBsAg))and their IVF children of year 2004-2005 of Women's Hospital Zhejiang University School of Medicine were studied.There are totally 195 couples of infertile HBV carriers cases,of which 61 couples complying with the above conditions.And"Table of IVF-ET implementation and health condition of mother and offspring"is established.Through the record information,this information such as telephone number,HBV serostatus,fertilization methods,semen source, embryo transfer date,hospitalization number,have been registered.Trough the telephone survey,we register the following five categories of information:1,whether embryo transfer of this time lead to successful conception and successful delivery;number of births;2.Pregnancy information:pregnancy complications of IVF mothers earring HBV,such as:ovarian hyper-stimulation syndrome(OHSS),anemia, gestational diabetes mellitus(GDM),hypenensive disorders in pregnancy,impaired liver function(liver damage,),intrahepatic cholestasis of pregnancy(ICP),placenta previa, placental abruption,premature rupture of membrane,oligohydramnios, polyhydramnios,etc.whether inject HBIG during lategestation;3,Delivery and postnatal information:delivery manner,gestational age,postpartum hemorrhage, etc;4,Offpring outcomes:birth weight,APGAR score,neonatal history,congenital malfomlations,serological testing of HBV;5,After birth and preschool offrspring health:feeding manner,whether or not inject HBIG after birth,serological testing of HBV during preschool age.Statistical methods were used in calculating the above infomlation.These statistics are compared with nature cyophoric data of HBV suffers in our country and IVF data of general population.Use SPSS 10.0 software to analysis the data.Results1,Basic informationwe stared 195 IVF cycles of HBV carrying couples from year 2004 to 2005,of which 61 cases successfully delivered(31.28%)(higher than IVF data of general population).A total of 59 cases were successfully followed-up(96.72%).46 cases were single births(77.97%),11 cases were twin births(18.64%),2 case were three births(3.3 %).The ratio of multiple births is lower than IVF data of general population.There are totally 74 fetal offspring,with which 37 are boys(50.68%),36 are girls(49.31%),1 case is dead fetus(1.35%).The male to female ratio is lower than nature cyophoric data.2,Delivery rate of IVF-ET and infection rate of offspringDelivery rate of"three small positive"(HBsAg,HBeAb,HBcAb are all positive) and"three large positive"(HBsAg,HBeAg,HBcAb are all positive)mothers are 31.40%,21.9%and infection rate of their offspring are 12.90%,22.22%,both of which are lower than the nature cyophoric data of 21.9%,37.0%.Delivery rate of"three small positive"and"three large positive"fathers are 32.30%,25%and infection rate of their offspring are 0,50%,the former is lower than the nature cyophoric data of 20%,but the latter is higher than the nature cyophoric data of 37.0%.Totally 23 cases use the way of IVF fertilization(38.98%),36 cases ICSI(61.02 %).For HBV carriers there is no statistical difference of high-order birth rate,dead baby rate,premature rate,birth weight,congenital malfonnation rate and infected baby rate between IVF and ICSI fenilization.However,in numerical high-order birth rate,dead baby rate,congenital malfomation rate,HBV infection rate of baby born to"three small positive"parents are higher in IVF than ICSI,premature rate,birth weight and HBV infection rate of baby born to"three large positive"(HBsAg,HBeAg,HBcAb are all positive)parents of IVF is less than ICSI.The source of semen is to a lager proportion of husband spem injection(89.83%),testicular puncture(TESA)has only 3 cases(5.08%),semen donation 3 cases(5.08%).3,Pregnancy informationThe mother during pregnancy may occur one or more complications:OHSS in 3 cases(6.52%)(lower than IVF data of general population),anemia in 7 cases(15.22 %)(lower than nature cyophoric data),2 case of GDM(4.35%)(consistent with nature cyophoric data),hypertensive disorders in pregnancy in 1cases(2.17%)(lower than nature cyophoric data),7 cases of liver damage(15.22%)(lower than nature cyophoric data),ICP in 1 cases(2.17%)(consistent with nature cyophoric data),1 case of placenta previa(2.17%)(higher than nature cyophoric data),placental abruption in 0 case(0 %)(lower than nature cyophoric data),premature rupture of membrane in 6cases(13.04 %)(lower than nature cyophoric data),1 cases of oligohydramnios(2.17 %)(consistent with nature cyophoric data),1cases of polyhydramnios(2.17%)(higher than nature cyophoric data),0 case of separation pubic symphysis(0%),fetal umbilical cord around the neck 9 cases(16.07%)(lower than nature cyophoric data).There is statistical difference between the different severity degree of HBV carrying and the incidence of liver damage during pregnancy(OR 0.0857,95%CI 0.0139-0.5288),There is no statistical difference between degree of HBV carrying and premature rupture of membrane.Among mothers of different severity degree of HBVcarrying,there is no statistical difference in their HBIG injection rate during late pregnancy.And there is no statistical difference between HBIG injection rate and HBV infection rate of offspring.4,Delivery and postpartum informationCesarean section is of higher proportion in 54 cases(91.53%)(higher than nature cyophoric data).The proportion of full-term delivery(84.75%)is higher than premature delivery(15.25%)(consistent with nature cyophoric data),with an average of 38.00(34.90—39.50)weeks gestation.1 case suffered postpartum hemorrhage (1.69%)(lower than nature cyophoric data).1 case restored the natural function of pregnancy after IVF(1.69%).Cesarean section rate of HBVcarrying mothers is lower than of the total cases,and advance in order of the severity level of their HBV carring.But there is no statistical difference between cesarean section rate and HBV infection rate of offspring.5,Neonatal informationAtotal of 74 fetal offspring were successfully followed-up,including live births of 73 births(98.65%),dead fetus of 1 cases(1.35%).5 were over weight at birth(6.76%), normal birth infants has 51 cases(68.92%),low birth weight infants of 13(17.57%) very low birth weight infants of 3(4.05%).Rate of low and very low birth weight infants is higher than nature cyophoric data.There is statistical difference between the different number of births and the incidence of low birth weight(p＜0.0001).The incidence of low birth weight in single birth is lower than that of multiple birth (OR=0.0364,95 CI:0.0073-0.1815).The average birth weight is 2926.986±728.1897g (lower than nature cyophoric data).There is no statistical difference between low birth weigh and HBV infection rate.Nor doseHBV infectionraise the incidence of both low birth weight and congenital malformation.One minute of normal APGAR score(8-l0 point)has 64 births(87.67%),mild asphyxia(4—7 point)9 children(12.33%),severe asphyxia(0-3 point)0 cnildren(0 %).There is statistical difference between premature infant and the incidence of neonatal asphyxia(p＜0.0001).The incidence of neonatal asphyxia in premature infant is higher than that in term infant(OR=12.2222,95%CI:2.5817-57.8617).But there is no statistical difference between neonatal asphyxia and HBV infection rate of offspring.Neonatal disease is various:with a higher proportion of jaundice 6 infants(8.22 %)(higher than nature cyophoric data),neonatal respiratory distress syndrome(NRDS) 2 children(2.74%)(lower than nature cyophoric data),hypocalcemia 4 infants(5.48%), infectious diseases 1 child(1.37%)(lower than nature cyophoric data).Cogenital malfornlation rate was 2.74%(lower than nature cyophoric data).There is no statistical difference of congenital malformations rate between IVF and ICSI fertilization.And so does it between infected and taintless infants by HBV.However,in numerical congenital malfomation rate are higher in IVF than ICSI,and higher in infected infants by HBV than taintless infants.6,Postnatal informationAmong parents of different severity degree of HBVcarrying,there is no statistical difference in postnatal HBIG injection rate of their offspring,which in numerical advance in order of the severity level of parents' HBV earring.But no statistical difference exists between postnatal HBIG injection rate and HBV infection rate of offspring.Only in numerical,postnatal HBIG injection can decrease HBV infection rate of offspring born to"three small positive"parents,but raise that of offspring born to"three large positive"parents on the contrary.For chidren of"three small positive"parents,The positive turning rate of HBsAb in infant who have received postnatal HBIG injection is higher than that of nonimmune infant.Among mothers of different degree of HBVcarrying,there is no statistical difference in breast—feeding rates of their offspring,all of which are far lower than the Breast-Feeding-Standard recommended by World Health Organization.There is no statistical difference between feeding method and HBV infection rate of offspring.Conclusion1,HBV carring dose not influence delivery rate of IVF-ET.During 2004-2005,for HBV carriers receiving IVF-ET,The ratio of multiple births is lower than IVF data of general population.The male to female ratio is lower than nature cyophoric data.2,Implementation of in vitro fertilization for HBV carriers dose not increase HBV infection rate of offspring,instead cut down it.Among couples of different HBVcarrying number and different severity level,there is no difference in delivery rate and HBV infection rate of offspring.3,For HBV carriers,There is no statistical difference of neonatal outcome between IVF and ICSI fertilization,including HBV infection rate of offspring.4,The incidence of macrosomia is close to nature cyophoric data.The proponion of low birth weight infant is higher than nature cyophoric data.The average birth weigh and was below the average nature cyophoric data.The elevation of low birth weigh infant is related to the high rate of multiple births(OR 0.0364,95%CI 0.0073-0.1815).Low birth weigh and HBV infection of offspring do not influence each other.5,Neonatal asphyxia rate is consistent with nature cyophoric data.Premature birth raise the rate of neonatal asphyxia,which didn't raise HBV infection rate of offspring. We need increasing the sample size and further follow—up investigations to explain the reason of its elevation.6,In vitro fertilization does not increase the incidence of pregnancy complications of HBV carring mothers.Only placenta previa and polyhydramnios are higher than nature cyophoric data due to sample size.The elevation of liver damage rate in pregnancy is related to HBVcarrying and the severity level(OR 0.0857,95%CI: 0.0139-0.5288)。7,For HBV carrying mothers,HBIG injection during late pregnancy dose not notably cut down the HBV infection rate of offspring.8,Cesarean section rate of HBV carrying mothers is higher than nature cyophoric data and advance in order of the severity level of their HBV carring.But cesarean section dose not notably cut down HBV infection rate of offspring.9,Postnatal HBIG injection rate of offspring advance in order of the severity level of parents' HBV earring.It raised the positive turning rate of HBsAb in infants born to"three small positive"parents(OR=7.7345 95%CI:1.4553-38.0099),but did not strikingly cut down HBV vertical transmission rate.10,For HBV carrying mothers,breast-feeding rate of their offspring is far lower than the Breast-Feeding-Standard recommended by World Health Organization.Reast-feeding didn't increase mother-to-child transmission rate of HBV.