Live Birth After Fresh Embryo Transfer Versus Frozen Embryo Transfer At Cleavage Stage: A Randomized Clinical Trial

Objective1.Compare the pregnancy rate,the live birth rate,the rate of low birth weight,the rate of small for gestational age,the incidence of neonatal complications,the incidence of pregnancy complications and the incidence of delivery complications with fresh embryo transfer and frozen embryo transfer at cleavage stage in in vitro fertilization /intracytoplasmic sperm injection-embryo transfer(IVF/ICSI-ET)cycle.2.Effect of gonadotropin releasing hormone antagonist(Gn RH-ant)protocol and gonadotropin releasing hormone agonist(Gn RH-a)long protocol on embryo quality and comparison of IVF/ICSI-ET outcomes.Methods The first part is a prospective randomized clinical trial.According to the inclusion criteria and the exclusion criteria,we selected 244 participants.The inclusion criteria:1.Infertility duration longer than 1 year;2.Female age between 20 and 35;3.Menstrual cycle length between 21 and 35;4.The first cycle of IVF/ICSI-ET;5.Have tubal factors or male factors as causes of infertility;6.Sign the informed consent.The exclusion criteria:1.Have only one ovary;2.Diagnosed as polycystic ovary syndrome(PCOS)in Chinese criteria;3.Uterine malformations(uterus unicornis,uterus septum,uterus didelphys,uterus bicornis),adenomyosis,submucous uterine myoma,intrauterine adhesion,scar uterus;4.Either one of the couple have chromosome abnormality(except chromosomal polymorphism);5.Spontaneous abortion(including biochemical pregnancy abortion)more than one time;6.Have the contraindication of assisted reproductive technology(ART)or pregnancy,including hypertension,heart disease with clinical symptoms,diabetes,hepatic disease,kidney disease,severe anemia,the medical history of phlebothrombosis,cerebrovascular disease and malignant tumor;7.Total number of oocytes retrieval less than 5.All the participants use Gn RH-ant protocol and random allocation into two groups at the day of oocytes retrieved.Group A use the fresh embryo transfer policy(total 124persons),group B use the frozen embryo transfer policy(total 120 persons).Follow upafter the embryo transfer at the time of biochemical pregnancy,clinical pregnancy,the12 gestational weeks,the 28 gestational weeks,the 37 gestational weeks,delivery and puerperium.If they don't have live birth at the first embryo transfer cycle,then we'll follow up subsequent embryos transfer state.Compare the data between the two groups.The data including age,infertility duration,body mass index(BMI),waist-hip ratio,basic hormone level,the duration of gonadotropin(Gn),the total dose of Gn,endometrium thickness,the number of follicles and mature follicles and hormone level on the day of human chorionic gonadotropin(HCG),the number of retrieved oocytes,oocytes retrieval rate,the number of 2PN fertilization,the fertilization rate of 2PN,the number of 2PN cleavage,the cleavage rate of 2PN,the number of available transferred embryos on Day3,the number of available embryos,the available embryos rate,biochemical pregnancy rate,clinical pregnancy rate,ongoing pregnancy rate,embryo implantation rate,ectopic pregnancy rate,abortion rate,live birth rate,preterm birth rate,full-term delivery rate,single birth delivery rate,cesarean section rate,the number of live-born infant,baby boy ratio,low birth weight(LBW)ratio,small for gestational age(SGA)ratio,the incidence of neonatal complications,the incidence of delivery complications and the incidence of pregnancy complications.The second part enrolled 1929 patients who started IVF/ICSI-ET treatment during 2015 to 2016 in Reproductive Medicine Center,Tianjin Central Hospital of Obstetrics and Gynecology.Besides the inclusion criteria and the exclusion criteria in part one,these patients accepted Gn RH-a long protocol and transfer 2 embryos at the first time.The fresh embryo transfer patients are group C(total 954 persons),the frozen embryo transfer patients are group D(tatal 975 persons).Referring to relevant medical records,the embryo quality,pregnancy rate,live birth rate,LBW ratio and SGA ratio after fresh versus frozen embryo transfer were retrospectively analyzed.As well as the effect of different protocols on embryo quality and the IVF/ICSI-ET outcomes.Results1.Gn RH-ant protocol:The biochemical pregnancy rate,clinical pregnancy rate,ongoing pregnancy rate and embryo implantation rate are higher in frozenembryo transfer group(P<0.05).The live birth rate,ectopic pregnancy rate,abortion rate,preterm birth rate,the incidence of neonatal complications,the incidence of delivery complications and the incidence of pregnancy complications between the two groups did not reach statistical difference(P>0.05).What's more,the LBW ratio and SGA ratio are significant lower in frozen embryo transfer group(P<0.05).2.Gn RH-a long protocol:Fresh embryo transfer group has higher available embryos rate(P < 0.05).The biochemical pregnancy rate,clinical pregnancy rate,ongoing pregnancy rate and embryo implantation rate are higher in frozen embryo transfer group(P < 0.05).The ectopic pregnancy rate,abortion rate and preterm birth rate between two groups have no statistical difference(P>0.05).Crucially,the LBW ratio and SGA ratio are significant lower in frozen embryo transfer group(P<0.05).3.Fresh embryo transfer:Gn RH-ant protocol owns higher oocytes retrieval rate(P<0.05).But there is no difference in the available embryos rate,as well as the pregnancy rate.However,the duration of Gn and the total dose of Gn are significant lower in Gn RH-ant protocol(P<0.05).4.Frozen embryo transfer:Gn RH-ant protocol has lower oocytes retrieval rate(P<0.05),but higher available embryos rate(P < 0.05).what's more,the biochemical pregnancy rate,clinical pregnancy rate,ongoing pregnancy rate and embryo implantation rate are higher in Gn RH-ant protocol(P<0.05).And the duration of Gn and the total dose of Gn are significant lower in Gn RH-ant protocol(P<0.05).Conclusions1.Compared with fresh embryo transfer,the biochemical pregnancy rate,clinical pregnancy rate,ongoing pregnancy rate and embryo implantation rate are higher in frozen embryo transfer.2.There is no significant difference in live birth rate,ectopic pregnancy rate,abortion rate,preterm birth rate,the incidence of neonatal complications,the incidence of delivery complications and the incidence of pregnancy complications between fresh and frozen embryo transfer.3.The LBW ratio and SGA ratio are significant lower in frozen embryo transfer than fresh embryo transfer.4.Compared with Gn RH-a long protocol,the duration of Gn and the total dose of Gn are significant lower in Gn RH-ant protocol.5.The Gn RH-ant protocol may don't have effect on embryo quality.6.Compared with Gn RH-a long protocol,Gn RH-ant protocol has the better pregnancy outcomes.