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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