Pregnancy outcomes of embryos diagnosed as putative mosaic (pm) using preimplantation genetic testing for aneuploidy (pgt-a): a multi-site blinded non-selection study

Toevaluate pregnancy outcomes of mosaicism masked, whole chromosome aneuploid (WCA) negative embryo transfers (ET) that after unmasking of the raw data were PM, in comparison to transfers of WCA-negative embryos without PM. An interim analysis was performed on a multi-site, blinded, non-selection retrospective cohort study completed from Feb 2020 to Oct 2022. Patients underwent ICSI and blastocyst trophectoderm biopsy, followed by PGT-A using PGTseq, a validated NGS platform. Patients were given the option to receive PM findings after genetic counseling. Patients who opted to only report WCA, the PM status of the WCA-negative embryos was unblinded after single ET and outcomes were compared. The PM status of embryos analyzed included PM negative (control), segmental mosaic (SM) and whole chromosome mosaic (WCM). Sustained implantation rate (SIR; pregnancy > 8 weeks gestational age (GA)) and clinical miscarriage rate (loss of heartbeat < 20 weeks GA) was reported for all transfers. At time of analysis, pregnancy outcomes were available for 82.6% of cases. 9,828 mosaicism masked, WCA-negative frozen single ETs were included. Among these, 947 (9.6%) were SM and 636 (6.5%) were WCM. The SIR in the control, SM and WCM groups was 62%, 58% and 50.3%, respectively. While the SIR was lower in the WCM group (p <0.01), a multivariate SIR prediction (AUC) was 0.580 without WCM and 0.585 with mosaicism included. The clinical miscarriage rate was not different between groups (control, SM, WCM): 384 (4.7%), 53 (5.9%) and 24 (4.0%), respectively (p = 0.28). The rate of preterm delivery was similar (control, SM, WCM): 455 (11.1%), 40 (10.1%), 18 (7.6%), respectively (p = 0.21). There were no differences in adverse pregnancy outcomes between the groups. Multivariate analysis confirmed a lack of association between SM, WCM and adverse pregnancy outcomes, while female age and BMI were identified as risk factors (OR=1.02;95%CI: 1.01 to 1.04 and OR=1.06; 95%CI:1.005 to 1.07, respectively). Transfer of PM embryos had no impact on clinical miscarriage rate, preterm delivery rate and frequency of adverse pregnancy outcomes compared to the PM negative control group.