Prediction of the cumulative live birth rate of IVF using a human embryonic stem cells-derived trophoblastic spheroid implantation model

Abstract Study question Can the attachment rate of a human embryonic stem cell-derived trophoblastic spheroids (BAP-EB) onto endometrial epithelial cells predict the cumulative live birth rate of an IVF cycle? Summary answer The BAP-EB attachment rate offers modest prediction of the cumulative live birth rate of women aged ≥35 years undergoing IVF. What is known already Implantation failure is one of the major causes leading to a low IVF success. There is no reliable tool for assessing endometrial receptivity in IVF. Study design, size, duration Prospective observational study of 240 infertile women from 2017 to 2021. Participants/materials, setting, methods Infertile women with regular cycles attending IVF centres were recruited. Endometrial aspirates were collected from a natural cycle one month before IVF for the BAP-EB attachment rate. The cumulative live birth rate of a stimulated cycle and its derived frozen embryo transfer cycles within 6 months of ovarian stimulation were obtained. Main results and the role of chance The BAP-EB attachment rate in women with a cumulative live birth was similar to those who failed to have a live birth. When women were stratified by age into <35 years and ³35 years, the BAP-EB attachment rate was significantly higher only in women aged ³35 years who had a live birth when compared to those without a live birth. The receiver operating characteristic (ROC) curve analysis of BAP-EB attachment rate in predicting cumulative live birth showed the area under the curve (AUC) of 0.559 (95% CI 0.479 – 0.639, p = 0.151), 0.448 (95% CI 0.310 – 0.585, p = 0.461) and 0.613 (95% CI 0.517 – 0.710, p = 0.026) for all ages, age <35 and ≥35 respectively. Limitations, reasons for caution BAP-EB and the isolated endometrial epithelial cells may not fully represent the in vivo developed human blastocysts and endometrial cells, respectively. The in vitro nature of the experiments and the limited sample size in this study may also limit the interpretation of the data. Wider implications of the findings Implantation failure is one of the major reasons contributing to the low success rate of IVF. The BAP-EB-endometrium attachment assay could potentially be used by reproductive medicine specialists to better counsel the couples who fail in IVF treatment. Trial registration number NCT02713854