PREDICTING WHICH BLASTOCYSTS WILL DEVELOP INTO FETUSES: TIME INTERVAL FROM MORULAE TO BLASTOCYSTS IS A NOVEL AND USEFUL INDICATOR FOR SUCCESSFUL PREGNANCY

Abstract

The increased use of blastocyst transfer has emphasized the importance of selecting high-quality embryos. Analyses of embryos in a time-lapse incubator system showed that zygotes with the shortest intervals between the first and second or the second and third mitotic divisions were higher blastocyst rate. Additionally, embryos that developed relatively faster to the morulae and blastocysts had higher implantation rates. However, the useful indicators that predict which embryos will develop into fetuses without pregnancy loss have not yet been identified. Do time to morulae and interval between morulae and blastocysts predict which blastocysts will develop into fetuses? We analyzed 208 blastocysts derived from ICSI in 177 patients from September 2019 to September 2020. All embryos were monitored by a time-lapse system. The outcome of vitrified-thawed single blastocyst transfers was classified into pregnancy and non-pregnancy groups. The pregnancy group was divided into ongoing pregnancy and pregnancy loss. Data were analyzed using multiple logistics regressions. According to the logistic analysis of women age, the data were classified as less than or more than 39 years old. Time-lapse analyses provided data on time from pronuclear fading to morulae (tM), time to expanded blastocysts (tEB), interval between morulae and blastocysts (tB-tM), the number of equatorial trophectoderm cells (eTE), and the KIDScore D5 v3 (KS5). Data from pregnancy (hCG > 50 mIU/ml at 4 weeks) versus non-pregnancy were compared, as well those from ongoing pregnancy (a gestational sac at 12 weeks) versus pregnancy loss groups. In this study, 51.4% of total blastocyst transfers resulted in pregnancy. Significant differences were found between pregnancy and non-pregnancy groups: tM, 63.0 vs. 65.8 h; tEB, 92.4 vs. 95.5 h; tM-t8, 29.5 vs. 32.2 h; eTE, 6.5 vs. 5.5; and KS5, 6.7 vs. 5.8. The pregnancy rate in women less than 39 years old was significantly higher than in women over 39 years old (67.4% vs. 38.1%). Under 39-years-old, ongoing pregnancy rate was 79.7%, and pregnancy loss rate was 20.3%. A faster tM, a longer tB-tM, and a more eTE was found in the ongoing pregnancy group compared to the pregnancy loss group. The potential of tM, tB-tM and eTE as indicators for pregnancy was predicted with an AUC of 0.79. Over 39-years-old, ongoing pregnancy rate was 72.1%, and pregnancy loss rate was 27.9%. In ongoing pregnancy group, t2, t4 and tM were significantly different to the pregnancy loss group, which suggested delay of early embryonic development increases pregnancy loss risk. Under 39 years old, tM, tB-tM and eTE are effective predictors for selection of high-quality blastocysts that will be successful pregnant. The time interval tB-tM is a new indicator for identifying high-quality blastocysts. Over 39 years old, faster embryo development is a critical indicator for pregnancy.