Blastocyst telomere length predicts successful implantation after frozen-thawed embryo transfer: Study

The lifetime TL is established in the early cleavage cycles following fertilization through a recombination-based lengthening mechanism and starts erosion beyond the blastocyst stage. In addition, a telomerase-mediated slow erosion of TL in human fetuses has been observed from a gestational age of 6–11 weeks. Finally, an abnormal shortening of telomeres is likely involved in embryo loss during early development.

Blastocyst samples were obtained from patients who underwent PGT-A and FET in an IVF center from March 2015 to May 2018. Digitally estimated mitochondrial copy number (mtCN) and TL were used to study associations with the implantation potential of each embryo. In total, 965 blastocysts from 232 cycles (164 patients) were available to investigate the biological and clinical relevance of TL. A WGS-based workflow was applied to determine the ploidy of each embryo. Data from low-pass WGS-PGT-A were used to estimate the mtCN and TL for each embryo.

Of the 965 blastocysts originally available, only 216 underwent FET. While mtCN from the transferred embryos is significantly associated with the ploidy call of each embryo, mtCN has no role in impacting IVF outcomes after an embryo transfer in these women. The results indicate that mtCN is a marker of embryo aneuploidy. On the other hand, digitally estimated TL is the most prominent univariant factor and showed a significant positive association with pregnancy outcomes (P < 0.01, odds ratio 79.1).

Study combined several maternal and embryo parameters to study the joint effects on successful implantation. The machine learning models, namely decision tree and random forest, were trained and yielded classification accuracy of 0.82 and 0.91, respectively. Taken together, these results support the vital role of TL in governing implantation potential, perhaps through the ability to control embryo survival after transfer.

In this study, authors directly estimated TL in embryos using sequencing data from preimplantation genetic testing. The study aimed to determine if embryos with longer TL have a higher chance of successful implantation after transfer. These findings highlight that blastocyst TL is a critical factor influencing implantation potential, likely because of its role in controlling embryo survival after transfer. In an attempt to reduce to time to pregnancy in the in vitro fertilization (IVF) processes, authors studied various maternal and embryo parameters, including TL, that have a high impact on successful implantation into an artificial intelligence model suitable for routine use in IVF clinics. Prioritizing embryos based on implantation potential is vital in clinical infertility treatment, aiming to reduce twin pregnancies and shorten waiting times during IVF. The predictive model developed in this study offers a valuable tool to enhance clinical practice, providing an optimized approach for individuals facing fertility challenges to increase their chances of achieving parenthood.

Source: Chien et al.; Human Reproduction Open, 2024, 2024(2), hoae012