SNP-based Preimplantation Genetic Diagnosis For Aneuploidy Screening Significantly Improves Clinical Outcomes For Chromosomal Balanced Translocation Carriers

ObjectiveBalanced chromosomal translocation is the most commonchromosomal aberrations, and the carriers are usually have normalphenotype. However, they usually present infertility, repeated miscarriages,delivery aneuploidy fetal and so on. Preimplantation genetic diagnosis(PGD) is the earliest prenatal diagnostic techniques, since the first case ofPGD, the method has been greatly improved. In recent years, singlenucleotide polymorphism microarray (SNP array) based PGD can detect23pairs of chromosomes and select chromosomal euploid and balancedembryos for transfer.This article was aim to establish the single nucleotide polymorphismarray (SNP array) technology, evaluate the effects of SNP array-based PGDfor aneuploidy screening in infertile couples of whom one was a reciprocalor Robertsonian translocation carrier, and to observe the effect of PGD combined with different biopsy stage on clinical outcomes of chromosomalbalanced translocation carriers.Subjects and groupsWe collected and prespectively analyzed the clinical outcomes of allreciprocal or Robertsonian translocation carriers at our center between Jun2012and December2013. According to the reported proportion of normalembryo after PGD in balanced translocation carriers[1-2], This PGD groupinclusion criteria specified that the available biopsy embryos must bemore than four on day3after insemenation for the translocation carriers. Ifnot, they would be suggested to cancel it. The chromosomal translocationcarriers were divided into three groups, PGD group, refused PGD andcancelled PGD group.Methods1. Patients were down-regulated with GnRH agonist using longprotocols and stimulated with FSH and hMG. The written informed consentwere obtained from all couples before the ovum pick-up (OPU).2. The mature oocytes of metaphase II (MII) were fertilized byintracytoplasmic sperm injection (ICSI) in the PGD group and the cancelledPGD group. However, in the refused PGD group,10cycles were fertilizedby ICSI because of male factors, and others were fertilized by in vitrofertilization (IVF).3. In the PGD group, only those embryos with euploid and balanced complement could be transferred into uterus of the patient. In the non-PGDgroup, embryo transferred was based on morphologic criteria.4. Compared the difference of implantation rate, clinical pregnancy rateand delivery rate among the groups.Results1.83infertile couples with reciprocal or Robertsonian translocationobtained fresh IVF cycles at our center during this period were included inthis study,21couples refused PGD before IVF cycles.62couples hadchosen PGD initially, but24couples were suggested to cancel the PGDtreatment because of the available diagnose D3embryos <4.2. In the PGD group,38couples generated4152PN embryos,231ofthem were biopsied,208embryos were amplified successfully, thediagnosed efficiency is90.0%(208/231). Of the diagnosed embryos, theproportion of euploid and balanced embryos, euploid and unbalancedembryos, aneuploidy and balanced embryos, aneuploidy and unbalancedembryos is32.7%(68/208),19.2%(40/208),27.0%(56/208) and21.1%(44/208), respectively.3. PGD group was divided into blastocyst biopsy stage and cleavagebiopsy stage. In the blastocyst biopsy group, the diagnosed efficiency andthe proportion of euploid and balanced embryos is97.7%(42/43) and47.6%(20/42), respectively, and in the cleavage biopsy group is88.3%(166/188) and29.4%(48/166), respectively. 4. In the PGD group, embryos were not transferred in26.3%(10/38) ofcycles due to lack of euploid and balanced embryos available for transfer.Embryo transfer was performed in the25PGD cycles where euploidy andbalanced embryos were available. Embryo transferred based onmorphological was performed in the21and20cycles in the refused andcancelled PGD-AS group, respectively.5. In the PGD group, the implantation rate and (delivery plus ongoingpregnancy) rate is61.4%(27/44) and60%(15/25), respectively, and in thecancelled group is18.4%(7/38) and25%(5/20), respectively, and in therefused group is27.3%(12/44) and33.3%(7/21), respectively.Conclusion1. SNP analysis can achieved a higher diagnosed efficiency, and it candetect aneuploidy of any of the24chromosomes found in humans.2. The SNP analysis following blastocyst biopsy can achieved a higherdiagnosed efficiency and proportion of euploid and balanced embryos thancleavage biopsy.3. the implantation rate in the PGD group is higher than cancelled andrefused group, and the (delivery plus ongoing pregnancy) rate is higherthan cancelled group. For the balanced translocation carriers, the availablediagnose embryos more than four may predict a better clinical outcome.4. This study was restricted by the number of available diagnoseembryos on day3, and one third of couples cancelled PGD because of have no euploid and balanced embryos available for transfer after SNP analysis.So we are considering that repeating several controlled ovarian stimulationcycles to collect enough available diagnose embryos, it may be help todecrease the chance of cycles with no euploid and balanced embryo fortransfer.