Abstract
Purpose: This study aimed to establish a non-invasive predicting model via Raman spectroscopy for evaluating the blastocyst development potential of day 3 high-quality cleavage stage embryos.Methods: Raman spectroscopy was used to detect the metabolic spectrum of spent day 3 (D3) embryo culture medium, and a classification model based on deep learning was established to differentiate between embryos that could develop into blastocysts (blastula) and that could not (non-blastula). The full-spectrum data for 80 blastula and 48 non-blastula samples with known blastocyst development potential from 34 patients were collected for this study.Results: The accuracy of the predicting method was 73.53% and the main different Raman shifts between blastula and non-blastula groups were 863.5, 959.5, 1,008, 1,104, 1,200, 1,360, 1,408, and 1,632 cm–1 from 80 blastula and 48 non-blastula samples by the linear discriminant method.Conclusion: This study demonstrated that the developing potential of D3 cleavage stage embryos to the blastocyst stage could be predicted with spent D3 embryo culture medium using Raman spectroscopy with deep learning classification models, and the overall accuracy reached at 73.53%. In the Raman spectroscopy, ribose vibration specific to RNA were found, indicating that the difference between the blastula and non-blastula samples could be due to materials that have similar structure with RNA. This result could be used as a guide for biomarker development of embryo quality assessment in the future.
Highlights
Infertility has become the third-most disease, after cancer and cardiovascular diseases
High quality cleavage embryos, which contained seven or eight blastomeres on day 3 (D3) were included in this study. 80 of 128 embryos mentioned above formed blastocysts during subsequent blastocyst culture, which defined as group “blastula,” the others were as group “non-blastula.”
During the 34 patients, 10 of which were totally categorized to group “non-blastula,” and seven of which to group “blastula” (Figure 1A and Supplementary Table 1), we further analyzed the essential characteristics of patients to above two tendencies of embryonic development, and found only the young maternal age and more antral follicle count contributed to higher embryonic development potential (Supplementary Table 2)
Summary
Infertility has become the third-most disease, after cancer and cardiovascular diseases. Since first human to have been born after in vitro fertilization (IVF) in July 25, 1978, assisted reproduction technology (ART) has gradually become the mainstream for treating infertility (Kamel, 2013). Patients who do not have a sufficient number of high-quality embryos for extended culture to the blastocyst stage still persist to have their embryos transplanted on day 3 (D3) (Scott et al, 2008). In this scenario, a fast, reliable, and non-invasive evaluation method for differentiating viable and non-viable D3 embryos could largely improve the success rate of current IVF pregnancy
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