trophectoderm grade is associated with the risk of placenta previa in frozen-thawed single blastocyst transfer cycles

Abstract Study question Dose obstetric and perinatal complications differ among different blastocyst developmental parameters after frozen-thawed single blastocyst transfer (SBT) cycles? Summary answer Blastocysts with grade C trophectoderm (TE) were associated with an increased risk of placenta previa compared to those with grade A TE. What is known already Existing studies investigating the effect of blastocyst morphology grades on birth outcomes have mostly focused on fetal growth and have produced conflicting results, while the risk of obstetric complications has rarely been reported. Additionally, growing evidence have suggested that the appearance of TE cells could serve as the most important parameter for predicting implantation and live birth. Given that the TE ultimately develops into the placenta, it is plausible that this independent predictor may also impact placentation. Study design, size, duration This was a retrospective cohort study conducted at a single tertiary-care academic reproductive center. A total of 6168 patients who underwent frozen-thawed SBT and resulted in singleton delivery beyond 20 weeks of gestation between January 2017 and December 2021 were analyzed. Participants/materials, setting, methods Main outcomes included placenta previa, placental abruption, placenta accreta, pregnancy-induced hypertension (PIH), preeclampsia, preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA). Multivariate logistic regressions were performed to evaluate the effect of blastocyst developmental stage (day 5 and 6), embryo expansion stage (stages 3, 4, 5 and 6), inner cell mass (ICM) grade (A, B and C), and TE grade (A, B and C) on measured outcomes adjusting for potential confounders. Main results and the role of chance The overall rates of placenta previa, placental abruption, placenta accreta, PIH, preeclampsia, PTB, LBW and SGA was 2.8% (n = 173), 0.4% (n = 26), 1.3% (n = 83), 5.3% (n = 328), 4.3% (n = 267), 6.8% (n = 417), 3.7% (n = 230), and 2.8% (n = 172), respectively. Specifically, the incidence of placenta previa derived from blastocyst with TE of grade C was higher compared with those derived from blastocyst with TE of grade A (1.8%, 2.5% and 3.9% for A, B and C, respectively, P = 0.003 for all comparisons). No such differences were observed for any other outcomes. After adjusting for potential covariates (maternal age, maternal BMI, maternal education, duration of infertility, gravidity, parity, previous caesarean section, infertility diagnosis, IVF or ICSI, previous embryo transfer, and type of endometrial preparation), TE grade C blastocyst had 2.58 times the likelihood of resulting in the risk of placenta previa compared to TE grade A blastocysts (adjusted odds ratio [AOR] 2.58, 95% confidence interval [CI] 1.05-6.31). No statistically significant associations were detected between any other measured outcomes and blastocyst developmental parameters. Furthermore, when restricted to pregnancies above 28 gestational weeks, the risk of placenta previa remained significantly higher with TE of grade C (AOR 2.56, 95% CI 1.05-6.27) than with TE of grade A. Limitations, reasons for caution The retrospective design, lack of controlling for residual confounding factors, and inter-observer variability limited this study. Wider implications of the findings The study extends our knowledge of the potential downstream effect of TE grade on placental abnormalities. Trial registration number not applicable