Abstract

Abstract Study question Does the transfer of a poor-quality blastocyst along with a good-quality blastocyst improve clinical outcomes compared to single good-quality blastocyst transfer in euploid-only transfer cycles? Summary answer Transferring a poor-quality with a good-quality blastocyst improved clinical pregnancy rates but live birth rates were not significantly increased compared to single good-quality blastocyst transfer. What is known already Single embryo transfers (SET) are often preferred when using euploid blastocysts with good morphological characteristics. However, co-transfer of a euploid blastocyst with poor morphological characteristics along with a good-quality euploid blastocyst is still practiced. Studies on embryos with unknown ploidy status suggested that poor-quality blastocysts may hinder the outcomes of good-quality blastocysts when transferred together. Controversial results imply that co-transfer of a poor-quality along with a good-quality blastocyst is associated with similar clinical pregnancy rates and significantly increases multiple pregnancy rates. Outcomes of such double embryo transfers (DET) compared to SETs are yet to be determined in euploid-only blastocyst transfers. Study design, size, duration Retrospective cohort of two centers including 500 SETs and 718 DETs using only euploid blastocysts in FET autologous cycles between March 2017 to January 2021. Transferred blastocysts were graded ≥BL3CC (Gardner criteria) and underwent trophectoderm biopsy on days 5-7 for aneuploidy testing with Next Generation Sequencing. Classification of blastocyst quality (good vs poor) was based on inner cell mass, trophectoderm grades, and the day of blastocyst biopsy. Participants/materials, setting, methods Patients underwent SET of good-quality or DET of good and poor-quality euploid-blastocysts. Endometrial preparation of frozen embryo transfer cycles was achieved with hormonal replacement or within a natural cycle. Reported outcomes included clinical pregnancy (CP), live birth (LB), and high-order pregnancy rates. For comparison of expected and observed LB rates, theoretical rates were estimated with Monte-Carlo simulations using binomial density function and SET data, under the assumption of independency for success rates of individual embryos. Main results and the role of chance After adjusting for Age, AMH, BMI, and cycle preparation method (artificial vs natural), DET of good-quality and poor-quality blastocysts was associated with higher CP rates compared to SET of a good-quality blastocyst (73.1% vs 63.8%, OR: 1.67, 95% CI: 1.12-2.55, P = 0.014). After adjusting for confounders, DET of good-quality and poor-quality blastocysts was not associated with significantly higher LB rates compared to SET of a good-quality blastocyst (56.8% vs 52.8%, OR: 1.25, 95% CI: 0.87-1.83, P = 0.234). Moreover, high-order pregnancy rates were significantly higher in the DET group compared to SET (40.4% vs 1.1%, P < 0.001). Using a model based on SET data, we estimated theoretical LB rates that should be achieved if the LB chance of co-transferred embryos were independent. The model showed that the observed LB rates of DET good and poor-quality blastocysts were significantly lower than the expected average (observed 56.8% vs expected 66.4% [95% CI: 59.0 to 73.8%], P = 0.0154). Limitations, reasons for caution This study has a retrospective design, and estimates are susceptible to residual confounding from unobserved or unaccounted variables. Theoretical rates were estimated under the assumption of independency of transferred embryos. Wider implications of the findings Despite higher CP, DET of poor and good-quality blastocysts did not increase LB compared to SET of good-quality blastocyst and was associated with higher multiple-pregnancy rates. Lower than expected LB rates imply DET to be detrimental to cumulative-LB, and sequential-SET may be preferable, regardless of morphological quality of euploid blastocysts. Trial registration number Not applicable

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