Neonatal Birth Weight After Transferred Delayed Blastocysts Frozen

Background:Embryo transfer(ET)at the blastocyst stage is now widely recommended in assisted reproductive technology(ART).Theoretically,the prolonged process of embryos makes the embryos selected by time,thereby the pregnancy rate improved after transferred.In addition,in the early stage of the development of assisted reproductive technology,the number of transferred embryos was used to increase the pregnancy rate,which was accompanied by an increase in the multiple pregnancy rate.With the advancement of laboratory culture technology,single blastocyst transfer is gaining more attention,and have been widely adopted.Moreover,single ET reduces the incidence of multiple pregnancy rates,which is associated with a higher risk of maternal and neonatal complications.The rate of blastocyst development in vitro is not consistent with the development of human embryos in vivo.Blastocysts are usually formed on the fifth day(D5)of in-vitro culture,while blastulation of some embryos can be delayed to the sixth day(D6)or even later.The embryonic development rate is suggested as an essential indicator of reproductive outcomes.Evidence from a meta-analysis of clinical studies revealed that the transfer of D5 blastocyst present higher rates of clinical pregnancy and live birth than D6 in both fresh and frozen transfers,respectively.It has been reported that D6 blastocysts generally have a higher rate of aneuploidy than D5 blastocysts.In recent years,it has been observed that the transfer of D5 euploid blastocysts results in higher rates of clinical pregnancy and live birth compared with those at D6 in preimplantation genetic testing(PGT)cycles.A proposed explanation is that the superior implantation potential of D5 blastocysts can be attributed to metabolic or epigenetic factors that may differ in the embryos at different development stages.The birth weight of neonates has long been regarded as an indicator of offspring’s health.It has been reported that infants born with small-for-gestational-age(SGA)or large-for-gestational-age(LGA)show adverse cardio-metabolic profiles during childhood and adolescence,leading to an increased risk of cardiovascular diseases later in life.In addition,LGA is associated with a high risk of offspring obesity and depression.Previous findings have indicated that frozen embryo transfer(FET)is associated with a higher birthweight and an increased risk of delivering LGA babies as compared to fresh embryo transfer,implying that the process of cryopreservation can adversely affect the embryo quality and developmental potential.Moreover,FET at the blastocyst stage is associated with higher birthweight and an increased risk of LGA compared with the cleavage stage.As far as we know,the effects of the day of blastocyst expansion during frozen blastocyst transfer on neonatal outcomes are unclear.However,limited studies have compared the perinatal outcomes after the transfer of frozen-thawed blastocysts formed on D5 and D6,and the results remain controversial.ObjectiveIn the present study,we aimed to explore the effect of frozen-thawed blastocyst formed at different developmental stage on perinatal outcomes.MethodWe performed a retrospective cohort study including 17,127 singleton live births after the transfer of frozen-thawed blastocysts,from January 2011 to January 2020.Live birth was defined as a birth exhibiting life signs with ≥24 gestational weeks.This study was approved by the institutional review board in the Centre for Reproductive Medicine affiliated to Shandong University.Inclusion criteria were as follows:(1)age ≤40 years;(2)body mass index(BMI)≤35 kg/m2;and(3)the transfer of frozen-thawed blastocysts formed on D5 or D6.The exclusion criteria were as follows:(1)women with uterine malformations or intrauterine adhesions;(2)women diagnosed hypertensive disorders,chronic diabetes and gestational diabetes mellitus(GDM).Hypertensive disorders included gestational hypertension(HDP,blood pressure ≥140/90 mm Hg after 20 weeks of gestation),preeclampsia,and eclampsia;and(3)frozen embryos that had undergone the re-cryopreservation process or preimplantation genetic testing.The primary outcomes included birth weight,including absolute birth weight,SGA,LGA,low birth weight(LBW)and macrosomia.Baseline characteristics and neonatal outcomes were compared between the study groups by t-test(for continuous variables)or chi-square test(for categoric variables).A multiple linear regression analysis was performed to assess the relationship between blastocyst development rate and birth weight with adjustment for potential confounding factors.ResultsThe mean neonatal birth weight in the D5 group(3.47±0.49 kg)was significantly higher compared with the D6 group(3.45±0.50 kg),although the discrepancy was only 0.02 kg.Multiple linear regression analysis for birth weight between the two groups showed no statistically significant difference(β=-0.01 t=-1.218;P>0.05).Logistic regression analysis revealed that the risks of SGA(OR 1.166;95%CI,0.911-1.491;P>0.05),LGA(OR 0.917;95%CI,0.831-1.012;P>0.05),LBW(OR 1.192;95%CI,0.926-1.533;P>0.05),and macrosomia(OR 0.975;95%CI,0.864-1.100;P>0.05)were similar in the two groups after adjusting for confounders.ConclusionIn the FET cycle,delayed blastocyst transfer would not affect the neonatal birth weight.However,it is noteworthy that the cesarean delivery rate was significantly increased after D6 blastocyst transfer,which needs to be further explored in a large sample randomized controlled study.