The Effect Of Endometrial Preparation Protocols On Maternal And Neonatal Complications In Frozen Embryo Transfer

BackgroundThe proportion of frozen embryo transfer(FET)has been increasing along with the development of laboratory techniques for cryopreservation.FET can avoid the effect of high estrogen environment on endometrium in the process of hyperstimulation,reduce the rate of multiple pregnancies,increase the cumulative pregnancy rate.So it is a more secure and effective transplanting strategy.At present,FET is suitable for patients with ovarian hyperstimulation syndrome(OHSS)and increased progesterone level after controlled ovarian hyperstimulation,preimplantation genetic testing(PGT)and uterine factors that are not suitable for pregnancy.Endometrial condition is one of the important factors that affect the pregnancy rate and pregnancy complications.The common endometrium preparation protocols include natural cycles(NC),artificial cycle with hormone replacement therapy(HRT),and cycle with ovulation induction(OI).Previous studies have suggested that there were no significant differences in pregnancy rates,miscarriage rates,or live birth rates among different endometrial preparation protocols for FET.However,the effect of different protocols on maternal and neonatal outcomes is still uncertain.ObjectiveTo compare the maternal and neonatal outcomes in women with different endometrial preparation protocols during frozen embryo transfer(FET),i.e.natural cycle(NC),hormone replacement therapy(HRT)and cycle with ovulation induction(OI).MethodsThe study included 6886 women aged 20-40,who received FET treatment after IVF/ICSI cycles in Center for Reproductive Medicine,Shandong University from January,2015 to July,2018 and delivered singleton live birth baby after 28 weeks of pregnancy.Women were divided into three groups according to the protocols used for endometrial preparation during FET:NC group(N=4727),HRT group(N=1642)and OI group(N=517).Results1.BMI(23.2±3.4 vs.22.8±3.3 vs.22.5±3.2 kg/m2,p<0.001),AFC(15.6±6.6 vs.15.3±6.0 vs.14.9±5.9,P<0.001),levels of testosterone(26.0±11.9 vs.25.6±12.5 vs,24.4± 11.7 ng/dL,p<0.001)and AMH(5.3±3.6 vs.5.0±3.5 vs.4.7±3.7 ng/mL,p<0.001)were higher in HRT group compared to OI and NC group.As expected,HRT group and OI group had higher rates of irregular menstruation(21.9%vs.21.7%vs.5.6%,p<0.001)compared with NC group.2.Women using HRT protocol had higher rates of HDP(7.9%in HRT vs.4.6%in OI vs.3.5%in NC,p<0.001)than women in OI and NC group.HRT and OI groups had higher risk of PTB compared to NC group(7.9%in HRT vs.4,6%in NC,p<0.001 and 7.7%in OI vs.4.6%in NC,p=0.001),but no significant difference was found between HRT and OI groups(7.9%vs.7.7%,p=0.773).The HRT group had increased risk of LBW compared with the NC group(4.5%vs.2.8%,p=0.001);however,no significant difference was observed between the OI group and the NC group(3.7%vs.2.8%,p-0.289).3.After adjusting for the effect of age,body mass index(BMI),irregular menstruation,antral follicle count(AFC),endometrial thickness,the levels of testosterone,anti-Mullerian hormone(AMH),preconceptional fasting glucose(PFG),systolic and diastolic pressure et al,the HRT group still had higher risk of hypertensive disorders of pregnancy(HDP)compared with the NC group(adjusted odds ratio(aOR)2.00,95%confidence interval(CI)1.54-2.60).Singletons born after HRT FET were at increased risk of low birth weight(LBW)compared to NC group(aOR 1.49,95%CI 1.09-2.06).The risks of preterm birth(PTB)in the HRT and OI group were elevated compared with the NC group(aOR 1.78,95%CI 1.39-2.28 and aOR 1.51,95%CI 1.02-2.23,respectively).ConclusionsThe HRT protocol for endometrial preparation during frozen embryo transfer may be associated with increased risk of maternal and neonatal complications,compared to the NC and OI protocol.