Analysis Of Assisted Reproduction Outcomes In Seven Ring Chromosome Carriers And Literature Review

Background:Ring chromosomes,which is defined as the result of breakage and fusion at the distal regions of both chromosome arms,belong to a rare type of intra-chromosome structural abnormality with an estimated pregnancy incidence of 1 in 25,000,following the loss of genetic materials or not.Ring chromosome carriers are at a significantly increased risk of fertility difficulties such as infertility,spontaneous abortion,and neonatal growth retardation,which has been repeatedly presented in the case reports in the previous literatures.Due to the effects of multiple factors such as the low incidence of ring chromosomes and the limited level of genetic testing technology,the specific mechanism of adverse pregnancies in carriers remains unclear.With the advancement of assisted reproduction,especially the development of preimplantation genetic testing(PGT),ring chromosome carriers can receive euploid embryos through genetic analysis,thus significantly reduced the incidence of adverse pregnancies caused by chromosomal abnormalities.However,owing to the low incidence of ring chromosomes,the high mortality rate of severe phenotypic carriers and the potential low marriage rate,the reproduction situation of ring chromosome carriers are reported sporadically in the previous literature,and no clinical consensus on the pre-pregnancy and prenatal diagnosis of them are formed,which increase the limitations of reproductive genetic counseling for carriers.Objective:To investigate the meiosis behavior and genetic pattern of ring chromosome,the proportion of abnormal embryos and pregnancy outcomes of ring chromosome carriers,so as to provide more information for genetic counseling and assisted reproduction of carriers.Methods:Collecting and analyzing the blastocyst testing results and assisted reproductive outcomes of ring chromosome carriers during March 2014 to April 2022.The chromosomal composition of trophectoderm cells was defined by next generation sequencing and arraybased comparative genomic hybridization.The genetic pattern of ring chromosomes and the significance of PGT were synthetically analyzed according to the basic information of carriers,embryo karyotypes and pregnancy outcomes.Results:A total of 7 carriers were included and 2 female carriers showed decreased ovarian reserve in varying degrees and 5 male carriers showed oligospermia or azoospermia.Three carriers received oocyte/sperm donation.The carrier P2 received oocyte donation but did not obtain cleavage or blastocyst embryos.The carrier P4 intended to receive PGT but did not obtain blastocyst and received donor sperm later but failed to be pregnant.The carrier P6 underwent sperm donation but developed to ectopic pregnancy,which was treated with transabdominal surgery.Four carriers received PGT-A.For female carrier P1,only 1 euploid embryo was obtained in the second cycle,while transplantation was failed.For carrier P3,one euploid embryo was obtained in the first cycle but transplantation was failed,and in the second cycle,3 euploid embryos were obtained and a balanced embryo was implanted successfully,which had resulted a healthy boy.For carrier P5,2 euploid embryos were obtained and a balanced embryo was implanted successfully,which resulted in a healthy girl.For carrier P7,one euploid embryo was obtained but transplantation failed.A total of 33 embryos were detected,including 8 euploid embryos(24.24%)and 8 aneuploid/mosaic embryos with ring chromosome related abnormality(32.00%).Conclusions:Ring chromosome carrier,especially female carriers,have a low rate of embryo euploidy.Screening of euploid embryos by PGT can reduce the risk of adverse pregnancy caused by embryonic factors.