Embryo selection by non-invasive preimplantation genetic testing for aneuploidy in women of advanced maternal age: a randomized, clinical trial.

Non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) can detect embryo chromosomal aneuploidy by analyzing the cell-free DNA in embryo culture media. However, evidence for its clinical efficacy is insufficient. In this investigator-initiated, multicenter, double-blind, randomised controlled trial, women aged 35-42 who agreed to single frozen-thawed blastocyst transfer with at least two blastocysts were enrolled from 13 fertility centers in China. Eligible participants were randomly assigned (1:1) to the niPGT-A(n = 594) or morphology group(n = 595) using a computer-generated block randomization list, stratified by participating center. In the niPGT-A group, embryos were selected for the first transfer cycle based on niPGT-A results, whereas in the morphology group, embryos were selected according to standard morphological criteria. The primary outcome was the ongoing pregnancy rate (OPR) (pregnancy beyond 12 weeks). Secondary outcomes included clinical pregnancy, miscarriage (pregnancy loss before the 28th week, with those before the 12th week as early miscarriages), and live birth rates. The trial has been completed. The modified intention-to-treat population(mITT) contained 581 couples in the morphology group and 571 in the niPGT-A group. Among 1152 randomised patients, OPR was 38.7% (221/571) in the niPGT-A group and 36.8% (214/581) in the morphology group (adjusted p = 0.49). There were no statistically significant between group differences in the rates of clinical pregnancy (47.6% vs 49.9%, adjusted p = 0.49), miscarriage (21.0% vs 27.6%, adjusted p = 0.06) and live birth (37.0% vs 35.5%, adjusted p = 0.59). Early miscarriage was significantly lower in the niPGT-A group compared with that of the morphology group (18.0% vs 25.2%, adjusted p = 0.03). Maternal and neonatal outcomes did not differ significantly between groups. No serious adverse events were reported in either group. The results indicated that there was insufficient evidence to establish a statistically significant difference in OPR between the two treatment arms. The results of this trial do not provide a basis for recommending routine use of niPGT-A in this good-prognosis population (NCT04339166).