Possible impact of interchromosomal effect at the blastocyst stage in cases undergoing PGT-A for translocations

Abstract

Introduction PGT-A for translocations has been a valid approach in order to detect chromosomally normal/balanced embryos. While earlier studies utilized PGT-A for only rearranged chromosomes, comprehensive chromosomal analysis by array comparative genomic hybridization (aCGH) is nowadays the gold standard in PGT-A for translocation cases, allowing detection of a wide range of chromosomal abnormalities other than the ones involved in rearrangement -known as interchromosomal effect. Estimating the impact of interchromosomal effect based on the type of rearrangement can therefore greatly help the clinical management and may lead to the development of individual clinical strategies to maximize the outcome involving PGT-A approach at the blastocyst stage. This study is performed in order to analyze the presence as well as possible impact of interchromosomal effect in embryos of reciprocal and Robertsonian translocation carriers undergoing PGT-A for translocations. Material & Methods This retrospective study was conducted in Bahceci Fulya IVF Centre, between January 2014 and December 2017. It included a total of 128 PGT-A for translocations cycles performed for female and male reciprocal (n=87) and Robertsonian (n=41) translocation carriers. For all suitable embryos, a trophectoderm (TE) biopsy was performed on either on day 5 or day 6 and aCGH was used for comprehensive chromosomal screening (CCS) analysis. Patients and their embryos were grouped according to the nature of translocation as Group I (Reciprocal translocation carriers) and Group II (Robertsonian translocation carriers). Major laboratory as well as clinical parameters were compared between groups. Results Main patient & cycle parameters such as mean female age, number of previous ART trials, number of oocytes retrieved, fertilized, biopsied etc. were found to be similar in both groups (p>0.05). Results regarding embryo analysis and clinical outcome are shown in Table 1. Percent of embryos containing chromosomal abnormalities not involving rearranged chromosomes was significantly lover in embryos of reciprocal translocation carriers (Group I) whereas in the same group, the contribution of translocated chromosomes in overall aneuploidy was found to be significantly higher. Table 1: Embryo analysis and clinical outcome between groups. Group I Group II p Num. of cycles (n) 87 41 Embryos biopsied (n) 315 145 Embryos processed for analysis (n) 307 137 Embryos diagnosed (n, %) 304 (99.0) 135 (98.5) NS Normal embryos (n, %) 77 (25.3) 50 (37.0) NS Abnormal embryos (n, %) 227(74.7) 85 (63.0) NS Aneuploid/balanced embryos (n, %) 73 (24.0) 58 (43.0) p=0.0061 Euploid/unbalanced embryos (n, %) 100 (32.9) 14 (10.4) P Num. of cycles cancelled prior to ET (n) 39 (44.8) 13 (31.7) NS Num. of ET cycles (n) 40 31 Pregnancy rate (b-hCG+, n, %) 31 (77.5) 20 (64.5) NS Clinical pregnancy rate (Sac+, n, %) 29 (72.5) 17 (54.8) NS Live birth/Ongoing (%) 22 (55.0) 13 (41.9) NS Missed abortus (%) 6 (15.0) 4 (12.9) NS Conclusions Our data and results have shown that, although they generate acceptable clinical pregnancies, embryos of Robertsonian translocation carriers have increased aneuploidies for chromosomes not involved in the translocation. This result indicates that besides cleavage stage, interchromosomal effect can significantly contribute the genetic status of human embryos at the blastocyst stage, leading to poorer clinical outcome.