Embryos in Vitro: Advancements and Future Directions
Embryos in vitro are those that develop outside of the body in controlled laboratory conditions. The most common application of the technology is in vitro fertilization (IVF), the process by which embryos are created outside the womb, implanted, and carried to term as in a typical pregnancy. The first child conceived through IVF was born in 1978,1 which brought the concept into the public’s awareness. However, embryos in vitro are useful for a wide range of research applications, and recent advancements have done much to further what researchers can do with and learn from them.
One of the key advancements in the field of in vitro embryo research is, ironically, to find ways to avoid using actual embryos. In addition to being difficult to obtain, human embryos in vitro cannot be used for research past 14 days of development, according to law first passed in the United Kingdom that has been adopted elsewhere.2 Instead, researchers have developed models from human embryonic stem cells—found in an early-stage embryo, known as a blastocyst—that behave like and resemble embryos in many ways but bypass the ethical concerns of research on embryos.
This research has led to the emergence of blastoids, blastocyst-like structures that self-organize from human pluripotent stem cells. The term was coined in a 2021 publication that described the model,3 which resembles an embryo in many important ways. Like embryos, blastoids develop into the three main cell types that form in the very early stages of human development, known as the founding lineages: the epiblast, trophectoderm, and primitive endoderm. Blastoids also recapitulate the sequence of lineage specification and certain aspects of implantation into the uterus in vitro that occur in embryos.
Another such embryo model is the gastruloid, which mimics gastrulation, the process in which the embryo’s three germ layers—ectoderm, mesoderm, and endoderm—are formed. Because they are used for studying post-implantation development, gastruloids tend to be simpler and more reproducible compared with blastoids. A recent publication described a new method for developing and maintaining a gastruloid model for up to 10 days, a major advance beyond the 2 days that these models typically last.4
The field of embryo selection for IVF has also seen advancements. About 10 to 20 eggs are retrieved during a typical IVF cycle, and the embryo deemed to have the best chance of leading to a successful pregnancy is selected for implantation. This is an area where artificial intelligence (AI) may prove useful. A 2024 trial found that a deep-learning system for embryo ranking performed similarly to experienced embryologists.5
Furthermore, in assessing embryos for implantation, there has been a recent trend towards non-invasive genetic testing. Instead of taking a biopsy of cells, laboratories can analyze cell-free DNA shed by embryos into culture media, known as niPGT-A, to determine the status of the embryo’s chromosomes.6 While promising for its safety and simplicity, there are some concerns when it comes to the method’s ability to detect embryonic mosaicism, a condition where an embryo has two or more genetically distinct cell lines. More research is needed on niPGT-A, and the other advances described here, to ensure that their safety and effectiveness is maximized.
References
1. Louise Brown | Biography & Facts | Britannica. https://www.britannica.com/biography/Louise-Brown.
2. Pera, M. F. Human embryo research and the 14-day rule. Development 144, 1923–1925 (2017), DOI: 10.1242/dev.151191
3. Kagawa, H. et al. Human blastoids model blastocyst development and implantation. Nature 601, 600–605 (2022), https://doi.org/10.1038/s41586-021-04267-8
4. Chen, B. et al. Extended culture of 2D gastruloids to model human mesoderm development. Nat Methods 22, 1355–1365 (2025), DOI: 10.1038/s41592-025-02669-4
5. Illingworth, P. J. et al. Deep learning versus manual morphology-based embryo selection in IVF: a randomized, double-blind noninferiority trial. Nat Med 30, 3114–3120 (2024), DOI: 10.1038/s41591-024-03166-5
6. Sakkas, D. et al. The impact of implementing a non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) embryo culture protocol on embryo viability and clinical outcomes. Hum Reprod 39, 1952–1959 (2024), DOI: 10.1093/humrep/deae156