Rate of development of euploid blastocyst affects clinical outcomes of frozen embryo transfer

Abstract

Preimplantation genetic testing for aneuploidy (PGT-A) has been increasingly used to identify euploid embryos. The present study evaluates clinical outcomes of euploid frozen embryo transfers (FET) in 2016-2017, following trophectoderm (TE) biopsy (BX) on day 5 (D5), day 6 (D6), or day 7 (D7). Retrospective study. Trophectoderm biopsy was performed on embryos once they reached blastocyst (BL) stage on D5, D6, or D7, where the day of biopsy indicates the rate of development. We analyzed a total of 1889 FETs following D5, D6, or D7 TE BX. Comparative genomic hybridization array, SNP microarray, or Next-generation sequencing was used for PGT-A. Transfer was performed following vitrification and warming. Clinical outcomes of implantation rate (IR), ongoing pregnancy/delivered (OGD), and spontaneous abortion (SAb) were compared among different BX days per patient age groups, using Kruskal-Wallis testing for IR and Chi-squared analysis for OGD and SAb. Statistical significance was defined as P <0.05. For patients of all ages, all clinical outcomes (IR, OGD, and SAb) showed statistical significance correlated to the rate of embryo development. In patients under 35 years of age, OGD was significantly higher in D5 euploid embryos compared to D6 or D7. For patients 38 years of age and older, IR and OGD were statistically higher in D5 euploid embryos.Tabled 1Clinical Outcomes Post TE BX/FETD5 BX/FET#FETAll Ages: 684<35: 21535-37: 17538-40: 167>40: 127IR72.5%∗∗68.2%74.4%77.0%∗∗71.2%∗OGD+429 (63%)∗128 (60%)∗113 (65%)113 (68%)∗75 (59%)∗SAb (losses/CP;%)65 (10%)∗20 (9%)13 (7%)17 (10%)15 (12%)D6 BX/FET#FETAll Ages: 1113<35: 31635-37: 24838-40: 318>40: 231IR60.9%∗∗60.8%64.1%61.1%∗∗57.5%∗OGD+540 (49%)∗155 (49%)∗131 (53%)149 (47%)∗105 (45%)∗SAb (losses/CP;%)129 (12%)∗38 (12%)25 (10%)38 (12%)28 (12%)D7 BX/FET#FETAll Ages: 92<35: 2035-37: 1538-40: 41>40: 16IR43.2%∗∗45.5%68.8%31.7%∗∗43.8%∗OGD+32 (35%)∗8 (40%)∗8 (53%)11 (27%)∗5 (31%)∗SAb (losses/CP;%)8 (9%)∗2 (10%)2 (13%)2 (5%)2 (13%)*: P < 0.05 ; **: P < 0.01 ; + :Ongoing pregnancies were defined as those with fetal cardiac activity at or beyond 8 weeks of gestational age. Open table in a new tab *: P < 0.05 ; **: P < 0.01 ; + :Ongoing pregnancies were defined as those with fetal cardiac activity at or beyond 8 weeks of gestational age. Overall, D5 euploid BL showed improved clinical outcomes compared to D6 or D7, suggesting that delayed embryo development may have an adverse effect on clinical outcomes, despite the proven euploid status. Interestingly, for younger patients (<35), D5 euploid BL improved continuation of pregnancy (OGD), while other clinical outcomes were not significantly different among D5, D6, or D7. However, for older patients (≥38), implantation rates as well as ongoing pregnancy rates were improved for D5 embryos compared to D6 or D7. Even though D7 euploid BL result in much lower IR and OGD compared to D5 or D6, they still result in 35% OGD, suggesting that slow developing embryos can still be beneficial for the patients, and therefore should not be overlooked.