Chromosomal Analysis of Blastocysts Derived From 0Pn and 1Pn Zygotes
Abstract
Introduction: Current guidelines recommend against the use of abnormally fertilized oocytes due to concerns that these embryos have abnormal chromosome content [1]. Therefore, most clinics default to culture of 2PN embryos and discard of embryos with other pronuclear configurations. Prior studies have shown that a portion of 0, 1, 2.1, and 3PN zygotes can result in good quality euploid blastocysts, however, parental origin of ploidy (diploid vs. haploid or triploid) remains a concern and cannot be detected with conventional pre-implantation genetic testing for aneuploidy (PGT-A) [2,3]. The objective of this study is to determine whether PGT-A with short tandem repeat (STR) analysis can identify which abnormally fertilized embryos (0PN and 1PN, respectively), ultimately develop into usable, euploid-diploid blastocysts.
Methods: : All 0PN and 1PN embryos that developed to the blastocyst stage between September 1, 2021 to February 24, 2023 at 61 embryology labs in the United States were included. Blastocyst trophectoderm biopsies were performed on day 5 and day 6 for PGT-A. Embryos classified as euploid then underwent STR analysis to determine ploidy status in the same genetics laboratory.
Results: A total of 279 0PN and 153 1PN embryos that developed to the blastocyst stage were collected. The mean maternal age of the 0PN group was 38.3 6.2 years, compared to 36.3 5.4 years in the 1PN group (p = 0.001). Of the 0PN embryos, 177 (63.4%) resulted as euploid and of those 171 (96.1%) were true diploid. Of the 1PN embryos, 85 (62.7%) resulted as euploid and of those 54 (56.8%) were true diploid. Forty-two percent of the embryos categorized as 1PN and euploid were chromosomally haploid.
Conclusion: In this study the majority of embryos that appeared to be abnormally fertilized were found to be euploid-diploid after PGT and STR analysis. Two-thirds of the embryos initially classified as 0PN by morphologic assessment were found to be euploid and of those almost all were found to be diploid. Similarly, two-thirds of the embryos initially classified as 1PN were found to be euploid and of those less than half of the embryos were found to be truly chromosomally haploid. While current guidelines recommend against the use of abnormally fertilized embryos, for some patients the ability to use these embryos would mean a substantial increase in their chance of success. In addition to standard morphologic assessment, extended culture with PGT and STR should be considered.