Human embryo implantation filmed for the first time

The real time process of a human embryo implanting has been recorded for the first time in 3D, offering a glimpse into a critical yet previously hidden process.

Implantation failure is a major cause of infertility, responsible for around 60 percent of miscarriages. Until now, this stage of early development, typically five to six days after fertilisation, when the embryo consists of just 100-200 cells, could only be studied through still images, as it is too small to be seen via ultrasound. However, new footage, published in Science Advances, could offer insights into the mechanisms underlying the implantation, improve fertility outcomes and optimise assisted reproduction techniques.

'We have observed that human embryos burrow into the uterus, exerting considerable force during the process. These forces are necessary because the embryos must be able to invade the uterine tissue, becoming completely integrated with it. It is a surprisingly invasive process. Although it is known that many women experience abdominal pain and slight bleeding during implantation, the process itself had never been observed before,' said Dr Samuel Ojosnegros, principal investigator at the Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain, and leader of the study.

To simulate implantation outside the body, the IBEC team built an artificial model of the uterus lining in the laboratory from a gel rich in collagen, a fibrous protein found in uterine tissue, along with other proteins necessary for embryo development. In collaboration with Dexeus Fertility, part of the Hospital Universitari Dexeus, Barcelona, which was responsible for the selection of human embryos donated for research, the team placed embryos near the gel and used a microscope to capture an image every 20 minutes for 16-24 hours.

It was previously known that the human embryo releases enzymes to break down uterine tissue during implantation. However, the new footage revealed that embryos also exert mechanical force, not only adhering to the uterus surface but actively remodelling their environment as they penetrate deeper layers of the uterus to connect with maternal blood vessels.

'We observe that the embryo pulls on the uterine matrix, moving and reorganising it. It also reacts to external force cues. We hypothesise that contractions occurring in vivo may influence embryo implantation,' explained Dr Amélie Godeau, co-first author of the study.

A further comparison between species showed that mouse embryos only invaded the gel superficially, adhering to the surface while the uterus adapts and folds around them. In contrast, human embryos fully embedded themselves into the gel, penetrating the uterine tissue completely before growing from the inside out. This highlights the limitations of relying on mouse models to study human implantation.

While the current platform cannot yet simulate the uterine tissue's response to these forces, its composition can be adjusted, such as by adding certain compounds, to study how human embryos respond to different environments. In future experiments, the team hopes to explore why some healthy embryos fail to attach to the uterus, or to track the implantation process over longer time periods.