P-733 A non-selection study to evaluate non-invasive preimplantation genetic testing for aneuploidy
Authors: Li T , Chan C , Greenblatt E 
Published: June 2023

Abstract

Study question
How does non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) perform to predict sustained implantation or live birth (SI/LB)?

Summary answer
Though not comparable to conventional PGT-A, niPGT-A can still be considered an appealing tool for clinical embryo prioritizing given its high negative predictive value (NPV).

What is known already
To omit the need for the invasive trophectoderm biopsy, niPGT-A which screens embryonic ploidy using embryonic cell free DNA released into the spent embryo culture medium (SEM) or blastocoel fluid (BF) was developed. Although the feasibility of niPGT-A has been shown and healthy live births have been reported from embryos screened by niPGT-A, the predictive value of niPGT-A for embryo transfer outcome has not been established yet and evidence is still lacking as to whether embryo selection by niPGT-A is associated with improved pregnancy outcomes. The answers to these are of vital importance to justify niPGT-A for clinical care.

Study design, size, duration
This is a single center, blinded, non-selection study consisting of single frozen embryo transfer cycles with a duration of two years, of which 117 cycles (Arm-1) were completed for 83 patients by transferring an embryo that was only morphologically assessed, and 90 cycles (Arm-2) were completed for 67 patients by transferring an euploid embryo that was screened by conventional biopsy-based PGT-A.

Participants/materials, setting, methods
Embryos were cultured in 25 μL continuous culture medium until blastocyst stage. The “SEM+BF” samples were ongoingly collected and archived at the end of culture. In Arm-1, after pregnancy outcomes were determined, the corresponding “SEM+BF” samples were pulled out for niPGT-A. In Arm-2, niPGT-A was also performed for some cases that did not end up in an SI/LB. NiPGT-A was completed by NICS and the incorporated ChromGo platform (Yikon Genomics).

Main results and the role of chance
Out of the 117 “SEM+BF” samples in Arm-1, 110 (94%) yielded an informative niPGT-A result. Among these, 46 transferred embryos were determined as “euploid” by niPGT-A and 15 resulted in SI/LB; 32 were determined as “aneuploid” and 27 did not resulted in SI/LB. Therefore, the positive and negative predictive values (PPV and NPV) of niPGT-A were 32.6% (15/46) and 84.4% (27/32), respectively. Another 32 transferred embryos in Arm-1 were determined as “suspected mosaic” and they showed a similar rate of SI/LB per embryo transfer to those “euploid” ones (37.5% vs. 32.6%, P = 0. 8092). Compared to Arm-1 overall, the “transferrable” embryos (“euploid” + “suspected mosaic”) determined by niPGT-A resulted in a much higher rate of SI/LB (34.6% vs. 27.6%, P = 0.3399). In Arm-2, 39 out of the 90 transferred euploid embryos resulted in SI/LB. “Euploid” embryos determined by PGT-A resulted in significantly better rate of SI/LB than “euploid” embryos determined by niPGT-A in Arm-1 (43.3% vs. 32.6%, P = 0.0243). Out of the 51 PGT-A “euploid” embryos that did not end up in SI/LB, 25 were also tested by niPGT-A with 6 being “suspected mosaic” and 3 being “abnormal/aneuploid”, raising the concern of possible false negative of conventional PGT-A.

Limitations, reasons for caution
The study enrolled a non-selected patient population which resulted in the inclusion of a few patients with a history of repeated implantation failure. Therefore, the PPV of niPGT-A might be underestimated as implantation failure could be attributed to defects in endometrial receptivity rather than in embryo quality.

Wider implications of the findings
This is the first non-selection study to validate niPGT-A in the setting of continuous culture medium. The high informative rate indicates its feasibility for clinics using a similar culture system. It also forms the foundation of a prospective, randomized controlled trial to further assess the benefit of niPGT-A.

Trial registration number
Not applicable