Analysis Of Pregnancy Outcomes In Unexplained Recurrent Spontaneous Abortion Couples With Chromosome Polymorphism After Preimplantation Genetic Testing For Aneuploidy

Background:Recurrent spontaneous abortion(RSA)is a common complication during pregnancy with a complex etiology.Approximately 50%of RSA cases are unexplained recurrent spontaneous abortion(URSA).Chromosome polymorphism is generally considered non-pathological variation,but studies shown that it may lead to adverse pregnancy outcomes such as embryo aneuploidy and miscarriage.Currently,whether chromosome polymorphism affect the pregnancy outcomes after preimplantation genetic testing for aneuploidy(PGT-A)in URSA couples remains unclear.Objective:To explore whether chromosome polymorphism affects embryo quality and pregnancy outcomes in URSA couples.Methods:A retrospective cohort study analyzed the clinical data of 871 URSA couples who underwent PGT-A at Hospital for Reproductive Medicine Affiliated to Shandong University from January 2016 to May 2022.According to chromosomal karyotype,the couples were divided into the normal karyotype group(n=646)and the chromosome polymorphism group(n=225).The chromosome polymorphism group was further divided into male group(male with chromosome polymorphism and female with normal karyotype,n=151),and female group(female with chromosome polymorphism and male with normal karyotype,n=74).According to chromosome polymorphism types,it can be further divided into "qh+/-" group(n=62),"ACR" group(n=63),"inv(9)" group(n=48)and Y polymorphism group(n=42).The baseline characteristic,embryo quality and pregnancy outcomes after the first euploid embryo transfer were statistically analyzed for each group.Results:(1)The detection rate of male chromosome polymorphism was higher than that of female;There was still no significant difference in the composition of chromosome polymorphism types between different gender after excluding Y chromosome variation.(2)There was a statistical difference in blastocyst rate between the normal karyotype group and chromosome polymorphism group(55.5%vs 52.1%,P<0.05).The blastocyst rate in male polymorphism group was significantly lower than that in normal karyotype group(51.3%vs 55.5%,P=0.010),and the aneuploidy rate in male polymorphism group was higher than that in female polymorphism group(39.0%vs 31.8%,P=0.041).However,there were no significant differences in pregnancy outcomes among the three groups after PGT-A assisted(all P>0.05).(3)Subgroup analysis based on polymorphic type found that the blastocyst rate in Y polymorphism group was significantly lower than that in normal karyotype group(49.3%vs 55.5%,P<0.0125),while other indicators of embryo quality and pregnancy outcomes showed no statistical difference(P>0.05).Conclusion:Male polymorphism carriers have lower blastocyst rate and higher aneuploidy rate than female carriers,but the carrier’s gender and polymorphic type do not affect pregnancy outcomes of the transfer cycle of euploidy in URSA couples.This study can provide more detailed genetic counseling and clinical guidance for URSA couples with polymorphism on whether to use PGT-A assisted.