P-726 The impact of reporting low-grade mosaicism in PGT cycles according to the number of cycles with at least one embryo for transfer
Authors: Lorenzi D , Dizon Bautista A , Munkherdene B , Muro A , Nguyen V , Akinwole A , Kayali R , Riboldi M 
Published: June 2023

Study question

How did the unmasking of low-grade mosaic embryos affect the number of cycles with an embryo for transfer for patients undergoing preimplantation genetic testing?

Summary answer

5.4% of PGT-A cycles that would have resulted in no embryos for transfer, had one low-grade mosaic embryo that could be considered for transfer.

What is known already

Before the publication of the last practice recommendations for managing mosaic embryos (2022), many fertility clinics requested masking mosaic results in PGT-A reports (mosaic embryos were reported as aneuploid). Recent publications revealed that low-range mosaic embryos had pregnancy rates, live birth rates and miscarriage rates comparable to euploid embryos (Capalbo et al, 2022). New recommendations suggested that it is not appropriate to discard low mosaic embryos, as they had a high chance of resulting in a healthy baby. Therefore, fertility clinics are now asking for the report of mosaic embryos and are developing their own procedures for mosaic embryo transfer.

Study design, size, duration

A cohort of 1696 blastocysts from 553 PGT-A cycles were retrospectively included. The data was collected from PGT-A cases analyzed in the same genetic laboratory between July and December 2022. PGT-A cycles were performed in 17 different fertility clinics from Argentina and all of them, since July 2022, began to request the report of mosaic embryos.

Participants/materials, setting, methods

Trophectoderm biopsies from 1696 day 5, 6 or 7 blastocysts were analyzed by NGS using Ion ReproSeq PGS kit, Ion Cheftm, and Ion-S5 System (ThermoFisher Scientific). A customized algorithm was applied for the interpretation of PGT-A results. Mosaic embryos were reported as low mosaic (one or two chromosomes between 30-50% of copy number variation) or high mosaic (one or two chromosomes between 50-70%). Maternal age ranges from 22-44 years. Egg donor cycles were also included.

Main results and the role of chance

From the 1696 blastocysts analyzed, 1630 were informative (96.1%). 49.4% (805/1630) of embryos were euploid. This corresponded to 366 PGT-A cycles (66.2%) for which at least one euploid embryo was available for transfer. From the cycles with no euploid embryos (187/553, 33.8%), 30 patients (5.4%) have at least one low-mosaic embryo for transfer.

The new recommendations for mosaic embryo management made it possible to increase the number of PGT-A cycles with at least one embryo for transfer by 5.4% during this period of time. According to maternal age, these 30 cycles correspond to: 33.3% (10/30) women &lt; 38 y/o and egg donation cycles, 46.7% (14/30) for women between 38-40, and 20% (6/30) for &gt; 40 y/o. The impact was observed mainly in advanced maternal age. For this group of patients, where it could be more difficult to repeat an IVF cycle and obtain euploid embryos, the possibility of transferring a low mosaic embryo could be their only chance. These 30 PGT-A cycles would have resulted in no embryos for transfer if previous policies for masking mosaic embryos (requested by the clinic) would be applied. The possibility for low-mosaic embryo transfer must be then reviewed by the patient and the physician.

Limitations, reasons for caution

Molecular laboratories performing PGT must execute an in-house validation. Our validated algorithm reports low-grade mosaic embryos between 30-50%. However, other platforms could have been validated for different ranges and these results may not be comparable. Five affected pregnancies were reported after transferring mosaic embryos (Viotti, 2021), so caution is required.

Wider implications of the findings

Results from a short period of time (six months) were considered for this analysis and clinical data was not possible to assess. Further analysis is required to evaluate clinical benefits in patients that proceed to mosaic embryo transfers.

Trial registration number

Not applicable