IS DAY OF BIOPSY A PREDICTOR OF OUTCOMES FOLLOWING MOSAIC EMBRYO TRANSFER?

Abstract Study question Should we consider embryo quality as one of the most important criteria to follow when transferring a mosaic embryo? Summary answer Embryo quality is an implantation biomarker both for euploid and mosaic embryos, and also a determinant for selecting the most eligible mosaic for transfer. What is known already Several studies show the benefit of transferring mosaic embryos when there are no euploid embryos to transfer, and they still result in ongoing pregnancies and what is more important is that they result in healthy babies. Studies and guidelines suggest prioritizing mosaic embryos based on maternal age, chromosomes impacted, percentage of aneuploidy, number of chromosomes involved, type of mosaic (simple vs complex, segmental vs complete, monosomy vs trisomy) but embryo quality is never part of these criteria. Studies claim that mosaic implantation rate is lower than euploid embryos, but they never show if both populations are comparable in terms of quality. Study design, size, duration This is a retrospective observational study performed in a private centre between February 2018 and January 2020. The study includes the data analysis of 96 euploid blastocysts and 14 low risk mosaic blastocysts (defining low risk regarding chromosome syndromes and less than 50% level mosaicism). All transferred in single embryo transfer (SET) to 105 patients after PGT-A (mean maternal age 38,9 years). The SET factor enables us to track the implantation outcome of all embryos. Participants/materials, setting, methods PGT-A with NGS technology was offered to patients of advanced maternal age and/or with repeated IVF failures. Trophectoderm biopsies were performed on day 5 and/or day 6 embryos, with laser assistance. Blastocyst morphology was scored in 3 groups: A: excellent (AA, AB, BA), B: good (BB), C: average and poor-quality embryos (BC, CB, CC). (Gardner-Schoolcraft classification) Low risk mosaic embryo transfer was offered to patients with no euploid embryos to transfer. Main results and the role of chance We found no significant differences between both populations (euploid and mosaic embryos) in terms of embryo quality (Chi^2 p-value =0,0975) so we were able to compare the overall implantation of similar quality populations. Despite euploid implantation being higher as described in most studies, no statistical differences (Chi^2 p-value = 0,4344) were found in terms of implantation rates between mosaic (57,0%) and euploid (67,6%) blastocysts during the same period. There are no differences between the mean age of both groups (39,7 vs 38,8 years, respectively). The implantation rates for euploid blastocysts were 79,5% (n = 39), 62,7% (n = 51) and 33,3% (n = 6) in the A, B and C blastocyst quality groups, respectively, showing significative differences among the three groups. The implantation rates of low-risk mosaic blastocysts were 100% (n = 3), 62,5% (n = 8) and 0,0% (n = 3) in the A, B and C blastocyst morphology groups, respectively, showing also still significant differences among the three groups despite the small population. (Chi^2 p-values according to implantation: Euploid =0,0434; Mosaic=0,0419) We have also compared the three quality categories between both populations showing no significative differences (Chi^2 p-values according to quality: A = 0,4344; B = 0,9894; C = 0,2568), concluding that same quality embryos behave the same way despite being euploid or mosaic. Limitations, reasons for caution The study is limited by its retrospective nature and the low number of mosaic embryos transferred as they are the last option for transfer. Additionally, it is common to transfer more than one mosaic embryo to increase the chances of pregnancy, therefore losing implantation track. Wider implications of the findings: Embryo quality has always been a strong biomarker predictable for implantation and this is also true for mosaic embryos as well. It is a simple concept, but we cannot compare implantation potential of euploid embryos with mosaic embryos without describing both populations in terms of quality. Trial registration number Not applicable

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P–564 Analysis of efficiency and outcomes of assisted reproductive technology (ART) programs after embryo transfer with a low-level of mosaicism

Human Reproduction ◽

10.1093/humrep/deab130.563 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

M Shishimorova ◽

S Tevkin ◽

T Jussubaliyeva

Keyword(s):

Embryo Transfer ◽

Live Birth ◽

Live Birth Rate ◽

Control Group ◽

Art Programs ◽

Low Level ◽

Mosaic Embryo ◽

Group A ◽

Group B ◽

High Level

Abstract Study question How does embryo transfer with a low-level of mosaicism affect the success of ART programs, pregnancy, and live birth in comparison with euploid embryo transfer? Summary answer The transfer of mosaic embryos results in the delivery of a healthy baby however significantly decreases the outcome of ART programs and live birth rate. What is known already Present methods of preimplantation genetic testing of aneuploidy (PGT-A) allow detecting a mixture of euploid and aneuploid cells at the blastocyst stage with high accuracy. Such embryos are classified as mosaics with varying levels according to the guidelines of the International Society for Preimplantation Genetic Diagnosis (PGDIS). Numerous sources describe that number of mosaic embryos can vary from 4 to 22%. Several publications report that mosaic embryos can lead to successful pregnancies and healthy childbirth, but with a lower frequency and higher rates of pregnancy loss compared to euploid embryos. Nevertheless, the effect of mosaicism on ART outcomes remains controversial. Study design, size, duration It has been analyzed 2506 embryos from 648 patients undergoing the ART program with PGT-A at the Institute of Reproductive Medicine for 2018 - 2019. Embryos after PGT-A were classified as euploid, aneuploid, and having mosaicism of less than 40% as low level and more than 40% as high level following PGDIS guidelines. Patients of (group A) were transferred 467 single euploid embryos, and 43 patients (group B) underwent single low-level mosaic embryo transfer. Participants/materials, setting, methods The embryos on day 5 or 6 were graded by Gardner Scoring System. Approximately 5–10 TE cells were biopsied from good quality blastocysts and subsequently vitrified. PGT-A was performed utilizing an array comparative genomic hybridization (aCGH) (Agilent). The transfer of mosaic embryos was performed in the absence of an alternative, only after medical genetic counseling with a risk explanation and the subsequent signing of an informed agreement. Statistical tests processed by Pearson’s chi-squared test. Main results and the role of chance Of all analyzed embryos, the proportion of euploid embryos was 48.6% (n = 1002), the total number of mosaics was 18.6% (n = 384) and aneuploid ones were 32.8% (n = 676). Depending on the level of mosaicism, the ratio between embryos with low-level mosaicism (≤40%) / high-level (≥40%) was 38.3% / 61.7%, respectively. According to the study, there was a significant decrease in the indicator of clinical pregnancy rate after embryo transfer with a low-level of mosaicism of 44.1% versus 63.2% transferred euploid embryo (р<0,01), however, despite an increase losses pregnancy in the group B (26.3%) there was no significant difference (p = 0.16) in comparison with the control group (15.4%). The live birth rate (LBR) significantly decreased (p < 0.001) after the transfer of the mosaic embryo by 32.5%, while in the control group the indicator was 53.9%. In all cases, after the transfer of the mosaic embryo, healthy babies were born. There were 2 cases of high-level mosaic embryo transfer as a result of which pregnancy did not occur. According to the survey, about 70% of patients agree to replant mosaic embryos, 20% are ready to go to the new program, and 10% cannot make a decision. Limitations, reasons for caution The number of patients in group B was significantly lower than in group A. Not enough cases of embryo transfer with a high-level of mosaicism. Wider implications of the findings: The current study might help to develop and to select a more appropriate strategy for transfer mosaic embryos. The next series of studies should focus on obstetric and neonatal outcome data from mosaic embryo transfer to gain a better understanding of the chromosomal and physiological health of children. Trial registration number Not applicable

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