Dados do Trabalho

Title

Day 6 Euploid Embryos vs. Day 5 Euploid Embryos: How important is morphology in selecting the embryo to transfer?

Objective

Several studies have shown that live birth rates (LBR) of day 5 (D5) blastocyst transfers are significantly higher when compared with day six (D6) embryos in both fresh and vitrified-warmed embryo transfer cycles. Despite the slower development of D6 blastocyst and lower pregnancy rates, they still have a reasonable implantation potential and, therefore, they are regularly transferred. Most studies evaluating results of D5 and D6 blastocyst transfer did not considered Preimplantation Genetic Testing for Aneuploidy (PGT-A) and differences between transfer of euploid blastocysts on D5 versus D6 remains unclear. The objective of this study was to compare ongoing pregnancy rates (OPR) in in-vitro fertilization (IVF) cycles between euploid embryos that reached expanded blastocyst stage and were biopsied at the 5th day of development with those reaching that stage at the 6th day.

Methods

The retrospective study included single center real-world data from IVF cycles performed between 2019 and 2022, in which embryo biopsy for PGT-A was performed and euploid embryos were available for transfer. All embryos were cultured in a time-lapse incubator and were biopsied when they reached the expanded blastocyst stage, on D5 or D6 of development. Blastocysts were vitrified after biopsy and single euploid blastocyst transfers were placed in subsequent hormone replacement cycles.

Results

A total of 265 single blastocysts transfers were included, comprising 210 D5-embryos and 55 D6-embryos. Groups have similar mean women age (37.6±3.2 versus 38.4±3.4; p=0.122), and most transfers were from first IVF cycles (D5: 75% and D6: 62%; p=0.055). Pregnancy rates were similar between groups (D5: 56% and D6: 49%; p=0.346), but OPR was higher on D5 group (37%) compared to D6 group (24%; p=0.065) with borderline statistical significance. Nevertheless, the incidence of top-quality (TQ) blastocysts transferred on D5 (81.4%) was significantly higher than those in D6 (49.1%; p<0.001). Then, a multivariate logistic regression model was performed, the OPR was associated to TQ-blastocysts transferred (OR: 2.66; p=0.005) independently from the day of blastocyst development (OR: 0.66; p=0.258) or women age (OR: 1.04; p=0.339). To assess the interaction between TQ and day of development on OPR, a generalized linear model with a binomial distribution was conducted. The model showed a significant association of TQ and OPR (p=0.024), but not for day of development (p=0.190) or interaction of them (p=0.598). To confirm those findings, transfers were divided in four groups by quality of blastocyst transferred (TQ or noTQ) and day of development (D5 or D6). OPR rates were: TQ-D5 40.4%, noTQ-D5 25.6%, TQ-D6 33.3% and noTQ-D6 14.3%. There was a statistically significant difference between TQ-D5 vs. noTQ-D6: p=0.008, and borderline statistical difference between TQ-D5 vs. noTQ-D5: p=0.087 and TQ-D6 vs. noTQ-D6: p=0.096.

Conclusion

Our study indicates a remarkable disparity on OPR between euploid D5 and D6 embryos when morphology is not considered. However, the complete analysis showed a stronger relationship to the quality of the blastocyst transferred, thus morphology may be a better predictor of OPR than the day of development of euploid blastocysts. Limitations are the small number of euploid D6 blastocysts available for inclusion and its retrospective nature, but these findings bring an important discussion about the choice of euploid blastocysts of different morphology and development day. The doubt about transfer an euploid TQ-D6 embryo or a noTQ-D5 require further investigation to be completely elucidated, so does the underlying causes for this differences. Conduct more comprehensive investigations to thoroughly examine the factors contributing to the observed variations in success rates between euploid blastocysts transferred at the same development stage but with distinct developmental times and morphological classifications.

Keywords

Euploid blastocysts transfer, preimplantation genetic testing for aneuploidy (PGT-A), embryo transfer day, embryo morphology