Retrospective analysis of meiotic segregation pattern and interchromosomal effects in blastocysts from inversion preimplantation genetic testing cycles

Abstract

Objective: To determine factors affecting unbalanced chromosomal rearrangement originating from parental inversion and interchromosomal effect occurrence in blastocysts from inversion carriers. Design: Retrospective study. Setting: University-affiliated center. Patient(s): Couples with one partner carrying inversion underwent preimplantation genetic testing for chromosomal structural rearrangement cycles. Intervention(s): Not applicable. Main Outcome Measure(s): Unbalanced rearrangement embryo rate, normal embryo rate, interchromosomal effect. Result(s): Preimplantation genetic testing was performed for 576 blastocysts from 57 paracentric (PAI) and 94 pericentric (PEI) inversion carriers. The percentage of normal/balanced blastocysts was significantly higher in PAI than PEI carriers (70.4% vs. 57.5%). Logistic regression indicated the inverted segment size ratio was a statistically significant risk factor for abnormality from parental inversion in both PEI and PAI. The optimal cutoff values to predict unbalanced rearrangement risk were 35.7% and 57%. In PAI, rates of abnormality from parental inversion were 0% and 12.1% in the <35.7% and R35.7% groups, respectively, with no gender difference. For PEI, the rates of abnormality from parental inversion were 7.9% and 33.1% in the <57% and R57% groups, respectively. In the R57% group, the rate of unbalanced rearrangement was significantly higher from paternal than maternal inversion (43.3% vs. 23.6%). In inversion carriers, 21,208 chromosomes were examined, and 187 (0.88%) malsegregations were identified from structurally normal chromosomes. In controls, 56,488 chromosomes were assessed, and 497 (0.88%) aneuploidies were identified, indicating no significant difference. Conclusion(s):The risk of unbalanced rearrangement is affected by the ratio of inverted segment size in both PAI and PEI carriers and is associated with gender. (Fertil Steril Ò 2019;112:336-42. Ó2019 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

Clinical outcomes of Preimplantation genetic testing (PGT) application in couples with chromosomal inversion, a study in the Chinese Han population

“…Researchers used to reckon that it is less likely for paracentric inversion carriers to produce recombinant gametes than for pericentric inversion carriers and that most paracentric inversions were innocuous [4]. For example, a recent retrospective study with 57 paracentric and 94 pericentric inversion carriers showed that the percentage of normal/balanced blastocysts was significantly higher in paracentric carriers than pericentric carriers [21]. In this study, inconsistent with previous research, the aneuploid rates of pericentric inversion carriers were not higher than those of paracentric inversions with similar pregnancy outcomes.…”

“…Our observations showed that there were no statistically significantly differences in de novo aneuploid rates between pericentric and paracentric inversion carriers. As is well-known, the production of de novo aneuploids is closely related to maternal advanced age, and the interchromosomal effect is inconspicuous just as many studies indicated [7,21]. Therefore, paracentric inversion cannot be considered less pernicious than pericentric inversion in genetic counseling.…”

“…Since there have been several studies assessing reciprocal translocation samples whose meiotic segregation might be affected by the carrier's gender, we wonder if it would be similar for inversion carriers [23,24]. A recent retrospective study found that for pericentric inversion carriers with an inverted segment accounting for more than 57% of the whole chromosome, the rate of unbalanced rearrangement was significantly higher for paternal than maternal inversion [21]. In our study, however, the result of both aneuploids rate and pregnancy outcome showed no significant differences between female carrier subgroup and male carrier subgroup.…”

Clinical Outcomes of Preimplantation Genetic Testing (PGT) Application in Couples with Chromosomal Inversion, a Study in the Chinese Han Population

“…Researchers used to reckon that it is less likely for paracentric inversion carriers to produce recombinant gametes than for pericentric inversion carriers and that most paracentric inversions were innocuous [4]. For example, a recent retrospective study with 57 paracentric and 94 pericentric inversion carriers showed that the percentage of normal/balanced blastocysts was significantly higher in paracentric carriers than pericentric carriers [20]. In this study, inconsistent with previous research, the aneuploid rates of pericentric inversion carriers were not higher than those of paracentric inversions with similar pregnancy outcomes.…”

Clinical Outcomes of Preimplantation Genetic Testing (PGT) Application in Couples with Chromosomal Inversion, a Study in the Chinese Han Population

“…Therefore, paracentric inversion cannot be considered less pernicious than pericentric inversion in genetic counseling. Just like a large review of 446 cases of paracentric inversions found, paracentric inversion carriers do not appear to be free of risks of abnormalities or abnormal progeny and caution is recommended when counseling [21]. More samples and data are needed to verify the difference of gametes and pregnancy outcome originated from these two inversion types.…”