Larger size of the oocyte cohort does not affect risk of embryo aneuploidy when using next generation sequencing (NGS)

Abstract

Recent advances in comprehensive chromosomal screening technology with NGS, have enhanced our ability to identify euploid embryos with high implantation potential 1,2. Embryos with lower potential for live birth containing aneuploidy or mosaicism, are discarded or reserved. Given this improved ability of NGS to detect the number of normal embryos developing from a single cohort of oocytes, we sought to evaluate whether oocyte retrieval yield, number of mature oocytes, or number of blastocyts biopsied, correlates with euploidy rate. Retrospective cohort study. 477 in vitro fertilization (IVF) cycles performed at a large university-based center during a three-year period were evaluated. IVF cycles with planned preimplantation genetic testing (PGT) performed using NGS were included for analysis. PGT results were reported as euploid, aneuploid or mosaic. Patients were divided into approximately equal groups based on number of oocytes retrieved, number of mature oocytes, and number of blastocysts biopsied. Patients were further stratified by age according to SART criteria. The primary outcome was rate of euploid embryos per cohort. Continuous variables were evaluated using Student’s t-test and ANOVA with Tukey’s multiple comparison test. Chi-square was used to assess categorical variables. Multivariate logistical regression was performed to control for potential confounding variables. Euploidy rates differed based on number of oocytes retrieved (1-5: 23.9%, 6-10: 26.2%, 11-15: 29.5%, >16: 35.4%; p=0.03), number of mature oocytes (1-5: 19.1%, 6-10: 30.4%, 11-15: 32.6%, >16: 36.1%; p<0.01), and number of embryos biopsied (1-2: 24.3%, 3-4: 29.7%, 5-8: 35.8%, >9: 35.0%; p<0.01). After performing multivariate linear regression to control for potential confounding factors, no association between increasing oocyte yield and euploidy was appreciated (p=0.59). Similar findings were noted when analyzing euploidy rates by the number of mature oocytes (p=0.07) and embryos biopsied (p=0.43). After stratifying by age, only patients in the 38-41yo cohort were found to have higher rates of euploidy when more than 10 oocytes were retrieved, with a trend towards higher rates in the younger groups (Table). Euploidy rate is not adversely affected when more oocytes are retrieved when measured within age strata. With the advent of Leuprolide trigger, reliable cryopreservation, and FET, this finding will likely lead us to more aggressive ovarian stimulation protocols, increase the odds of a euploid blastocyst, and maximize the chance of live birth with a single ovarian stimulation.TableAge & Euploidy Rates by Number of Oocytes RetrievedAge Groups (yrs)<3535-3738-41>41Oocytes Retrieved≤10 ≥11≤10 ≥11≤10 ≥11≤10 ≥11% Euploidy36.1 47.841.2 46.219.2 28.915.9 10.9Bold: p<0.05 Open table in a new tab