Abstract

Abstract Study question Are there correlations among male-female sex ratio, human blastocyst ploidy status and artificial intelligence (AI)-based morphokinetics embryo selection? Summary answer Embryo selection based on morphological evaluation by time-lapse system (TLS) with AI technology could lead to a female-biased sex ratio of resulting newborns. What is known already As of now, there have been only limited attempts to evaluate how AI-based TLS embryo selection for priority transfer could affect male-to-female sex ratio in human population, and the results of different publications were contradicting. However, the morphokinetic assessment was made without calculating the embryos KID Score (Embryos with Known Implantation Data), which significantly improves and make faster the decision-making process. Study design, size, duration This is a monocentric, retrospective study from October 2019 to December 2021 including 251 blastocysts with PGT-A results. Embryos were cultured in time-lapse incubator (EmbryoScope, Vitrolife) up to the time of trophectoderm biopsy. All embryos were evaluated based on the KIDscoreTM D5 algorithm (Vitrolife) under routine supervision by experienced embryologists. The PGT-A results were obtained by using next-generation sequencing (NGS) platform from Medical Genomics LLC laboratory (Illumina MiSeq, Illumina). Participants/materials, setting, methods Sample size was 251 embryos from 101 women (mean female age was 36.0 ± 5.6 years). All embryos were divided in four groups in accordance with their final KID score: <2.5 ( n = 7), 2.6-5.0 ( n = 33), 5.1-7.5 ( n = 123) and >7.5 ( n = 88). The embryos with sex chromosome abnormalities were also included in research to assess the frequency of occurrence in embryos with low and high KID score. Main results and the role of chance As expected, the percentage of aneuploid blastocysts, as well as the rate of sex chromosome abnormalities, decreased with increasing the embryo KID score. The highest male-female sex ratio among all embryos was observed for the group with KID score <2.5 (1.33), and gradually decreased to values of 0.92 and 0.74 in groups with KID score 5.1-7.5 and >7.5, respectively. At the same time, the highest male-female sex ratio among euploid blastocysts was maximal in the group with KID score 2.6-5.0. The obtained data contradict results of some other studies, which reported faster development of male embryos (which should mean their higher KID score). However, the KID score was not evaluated in them, and thus these results cannot be directly compared to ours. Limitations, reasons for caution Most patients in this study had complicated reproductive history, with repeated failures in IVF programs, often with a stop in embryo development. Also, the present investigation is retrospective. A following multicenter researches with larger sample size and cross-centered validation of embryologist-performed annotation is considered in our future approach. Wider implications of the findings Obtained data doesn’t allow to establish the female-gender prevalence among embryos. Nevertheless, further accumulation of knowledge about relation between KID Embryo Score and embryo gender can be used for presumptive sex determination in special cases with sex-linked diseases, where poor embryo morphology doesn’t allow to perform biopsy for genetic analysis. Trial registration number -

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