Blastocyst telomere length predicts successful implantation after frozen-thawed embryo transfer: Study
Infertility affects millions of people of reproductive age and has become the third most common disease globally. With help from in vitro fertilization (IVF) technology, it is now estimated that more than 6 million babies have been born through the IVF procedure. However, many factors, including maternal dysfunction and embryonic chromosomal abnormalities, can cause the failure of IVF treatment resulting in an overall live birth rate. Previously, studies have reported that chromosome integrity (i.e. euploidy) is the primary determinant of IVF success; thus, with the additional support of preimplantation genetic testing for aneuploidy (PGT-A), the IVF success rates have been improved in women with advanced maternal age and those who experience recurrent miscarriage (RM). Nevertheless, the success rate only rises to 50%. Thus, developing methods which will increase the implantation rate is the top priority of the current move towards personalized maternal–fetal medicine in an IVF center. Furthermore, the results also indicate that, in addition to chromosomal integrity of the embryo, other factors related to embryo viability may need to be considered to maximize the efficacy of IVF treatment.
Telomeres are stretches of DNA found at the ends of the chromosomes. They cap and protect the end of a chromosome like the end of a shoelace. Telomeres are crucial for the survival of all living cells and telomere length (TL) is the key to controlling lifespan and aging of a cell. Previous research hinted at the importance of TL in early human development, suggesting that abnormal shortening may lead to embryo loss and implantation failure. 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.
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
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