Risk Factors Of Monozygotic Twins In Assisted Reproductive Technology

Research Background:With the rapid development of assisted reproductive techniques(ART)since the 1970s,the incidence of multiple pregnancy has increased significantly,and the maternal and infant complications during pregnancy and postpartum caused by multiple pregnancy have received extensive public attention.Relevant investigations found that the rate of monozygotic twins(MZT)after ART was higher than that of natural pregnancy,which not only increased the risk of neonatal related adverse outcomes,but also had a far-reaching impact on the long-term health of offspring.Researches have shown that characteristics of infertile population,such as maternal age,hereditary,manipulation related to ART,included ovulation induction,gamete and embryo manipulation,in vitro culture,and embryo factors all might affect the rate of MZT.However,the results were not very clear,they were inconsistent in different studies.Research Objective:The purpose of this study is to explore the incidence of MZT after ART,and clarify the risk factors associated with it.Research Design:Nested case-control study.Material and Method:A total of 255 MZT were enrolled(experimental group),and then matched singletons in a ratio of 1:4 randomly(1020 in control group).All cases in this study were recruited in Reproductive Hospital Affiliated to Shandong University from July 2014 to December 2017.And all offspring were conceived by in vitro fertilization and single embryo transfer.The users of donated oocytes or sperms,opposite sex twins,triplets and more than triplets and after reduction or stillbirth were excluded.By analyzing the relationship between characteristics of infertile population,manipulation related to ART and embryo factors and the risk of MZT,to clarity the incidence of MZT after ART and related risk factors.Results:The incidence of MZT is 1.81%(282 out of 15567 single embryo transfer,contain 23 donated oocytes or sperms users and 4 after reduction or stillbirth).Compared with singleton,MZT had significant lower rate of frozen embryo transfer(FET)(78.0%VS 86.1%P=0.002).multivariate logistic regression analysis also showed that FET would decrease the risk of MZT(OR=0.487,95%CI:0.335-0.707,P<0.001),on the contrary,blastocyst transfer might increase the rate of MZT(OR=4.196,95%CI:1.413-12.460,P=0.010).We also analyzed the grading of blastocyst and found that the grading of trophectoderm(TE),inner cell mass(ICM)and TE,and the classification of top-quality embryos were associated with the incidence of MZT(P=0.025,P=0.012,P=0.020,respectively).In multivariate logistic regression analysis,the results demonstrated that the high grade of TE(A/B)was a risk factor of MZT(B:OR=1.960,95%CI:1.202-3.196,P=0.007;A:OR=2.018,95%CI:1.105-3.682,P=0.022).And compared with BC/CB/AC,the grade of ICM+TE was BB or AB/BA might increase the risk of MZT(OR=1.952,95%CI:1.195-3.187,P=0.008;OR=2.032,95%CI:1.165-3.546,P=0.013),and the classification of top-quality embryos were 4BA also have a higher risk of MZT than other non top-quality blastocysts(OR=2.573,95%CI:1.169-5.663,P=0.019).In addition,except multiplicative interaction between the cultivation time of embryo(cleavage embryo/long culture)and gamete and embryo manipulation(p=0.039),maternal age,paternal age,the cultivation time of embryo,gamete and embryo manipulation and the types of embryo transfer had no interaction.Conclusion:The results showed that fresh embryo transfer,blastocyst transfer and transfer embryo with high-grade of TE would increase the incidence of MZT,which provided clinical guidance for reducing the rate of MZT.