Introduction of Expanded Carrier Screening (Ecs) Has Increased Referrals for Preimplantation Genetic Testing for Monogenic Conditions (Pgt-M)

Abstract

OBJECTIVE: To determine the prognostic utility of day of biopsy on mosaic embryo (ME) transfer outcomes.MATERIALS AND METHODS: Sub-analysis was performed of data collected in the 2021 study by Viotti et al 1 . Descriptive statistics (mean AE standard deviation for continuous variables; frequencies and percentages for categorical variables) were calculated separately by biopsy day (5, 6, or 7). The three groups were compared using the chi-square test or Fisher's exact test, as deemed appropriate, for categorical variables, and analysis of variance (ANOVA) for continuous data. A result was considered statistically significant at p<0.05. All analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC).RESULTS: Of the 1000 ME transfers documented, 825 specified day of biopsy (day 5, 6, or 7). There was a significant difference in mosaic type by biopsy day (p<0.0001); day 7 MEs resulted in significantly more complex and single monosomy/trisomy types. Day 6 MEs resulted in significantly more double monosomy/trisomy type. Day 5 MEs resulted in significantly more segmental types overall, including single, double, and complex segmental. There were also significant differences in outcomes; day 7 MEs were significantly less likely to result in pregnancy (p¼0.0015), while day 5 MEs were significantly more likely to result in implantation (p¼ 0.0005) and ongoing pregnancy/live birth (p <0.0001). There was no significant difference in biochemical pregnancy (p¼ 0.717) or spontaneous abortion (p¼0.757) based on biopsy day. There was no significant difference in maternal age (p¼ 0.455) or percent mosaicism (p¼0.319) based on biopsy day. Day 5 MEs had significantly better morphology (p< 0.0001).The difference in ongoing pregnancy rate among the three biopsy days remained statistically significant after adjusting for mosaic type (p<0.0005). However, there was no significant difference in ongoing pregnancy rate between mosaic types after adjusting for biopsy day (p¼0.1369).CONCLUSIONS: MEs biopsied on day 5 are more likely to have segmental type mosaicism, better morphology, and better transfer outcomes. The mechanism for these differences are unclear; however, a hypothesis is that embryos with mosaicism associated with poorer outcomes may be slower to develop into blastocysts. These data can be incorporated into ME prioritization decisions. Further studies are needed to determine whether larger sample sizes would show similar findings, and how biopsy day can be combined with embryo morphology and mosaic type to continue improving ME selection and better inform patient counseling.IMPACT STATEMENT: Day of embryo biopsy is an important predictor of ME transfer success.References: 1. Viotti M, Victor AR, Barnes FL, et al. Using outcome data from one thousand mosaic embryo transfers to formulate an embryo ranking system for clinical use [published online ahead of print, 2021 Mar 6]. Fertil Steril. 2021;S0015-0282(20)32716-3.