Why looks matter: morphology predicts success in embryo banking (EB) with preimplantation genetic testing for aneuploidy (PGT-A)

Abstract

EB is increasingly common as more couples delay childbearing. Moreover, performing PGT-A before EB provides confidence that stored embryos are genetically competent and have a high chance of live birth (LB). We aimed to assess the specifics of blastocyst (BL) morphology in determining LB after euploid embryo (EE) transfer and develop counseling tools for patients electing EB+PGT-A. Retrospective cohort at a large university-based program. We reviewed all IVF cycles from 1/2014 - 2/2018 where fresh oocytes served as the female gamete and a single cryopreserved EE was transferred. We assessed age at retrieval, BL expansion (BE), inner cell mass (ICM) and trophectoderm (TE). BE, ICM and TE grades were based on Gardner’s criteria. Outcomes were ongoing pregnancy (>12 wks gestation) / live birth rate (LBR), implantation rate (IR) and spontaneous abortion rate (SABR). Fischer’s exact test was used. See Table. We reviewed 1641 transfers (142 donor+1499 autologous; median age at retrieval 37y, IQR 33-40y, range 21-46y). Overall IR was 66%, SABR was 12%, and LBR was 57%. There were 12 pregnancy terminations (TOP) and 7 ectopics. When stratified by BE, no differences in IR, SABR, or LBR were noted. When stratified by ICM grade, EE with ICM-C had a lower IR than with ICM-A and B (35% vs. 71% and 68%, p<0.01) and EE with ICM-A had a lower SABR than with ICM-B (6% vs. 13%, p=0.02); notably, EE with ICM-A had a higher LBR than with ICM-B and C (66% vs. 58% and 34%, p<0.03) and EE with ICM-B had a higher LBR than with ICM-C (58% vs. 34%, p<0.01). When stratified by TE grade, EE with TE-C had a lower IR than with TE-A and B (51% vs. 80% and 69%, p<0.01) and EE with TE-A had a lower SABR than with TE-C (3% vs. 18%, p=0.03); notably, EE with TE-C had a lower LBR than with TE-A and B (41% vs. 73% and 60%, p<0.01). Outcome differences re: ICM and TE were maternal-age independent. When comparing LBRs re: ICM+TE grade combinations, ICM-A+TE-A= 19/26 (73%), ICM-A+TE-B= 125/195 (64%), ICM-B+TE-A= 13/19 (68%), ICM-B+TE-B= 658/1101 (60%), ICM-B+TE-C= 91/205 (44%), ICM-C+TE-B= 23/57 (40%), and ICM-C+TE-C= 8/36 (22%). Only one EE had ICM-A+TE-C and one ICM-C+TE-A (both LBs). Euploidy is not the sole determinant when selecting embryos. Our data suggest that ICM and TE each play individual and critical roles related to IR, SABR and LBR - even with EE. In our study, EE with the best morphology had a LBR of 73% while EE with the worst had a LBR of 22%. These data add to realistic counseling for patients using EB+PGT-A for future pregnancy. Further, they help elucidate the biology of implantation and pregnancy, suggesting TE (placenta precursor) is as important as ICM (future fetus).Tabled 1Embryo morphologic parameters and outcome dataEmbryo ParameterIRSABRLBRTOP + Ectopic PregnanciesBE: <2 (n=110)73/110 (66%)14/73 (19%)58/110 (53%)1+0/110 (1%)BE: 3 (n=1389)928/1389 (67%)104/928 (11%)808/1389 (58%)9+7/1389 (1%)BE:4 (n=63)40/63 (63%)6/40 (15%)32/63 (51%)2+0/63 (3%)BE: >5 (n=79)47/79 (59%)6/47 (13%)41/79 (52%)0+0/79 (0%)ICM: A (n=221)157/221(71%)10/157 (6%)145/221 (66%)1+1/221(1%)ICM: B (n=1325)898/1325 (68%)119/898 (13%)762/1325 (58%)11+6/1325 (1%)ICM: C (n=95)33/95 (35%)1/33 (3%)32/95 (34%)0+0/95 (0%)TE: A (n=45)36/45 (80%)1/36 (3%)33/45 (73%)0+2/45 (4%)TE: B (n=1353)928/1353 (69%)107/928 (12%)806/1353 (60%)10+5/1353 (1%)TE: C (n=243)124/243 (51%)22/124(18%)100/243 (41%)2+0/243 (1%) Open table in a new tab