Selecting the healthiest embryo is a critical, yet uncertain, step in in-vitro fertilization (IVF). Approximately 15 percent of couples globally experience infertility, and IVF success rates often fall below 33 percent. A significant challenge lies in the embryologist’s need to choose a single embryo for implantation based on microscopic observation, where even subtle visual cues regarding cell division and internal structure can indicate the potential for a successful pregnancy.
Traditionally, embryologists have faced a trade-off when choosing culture dishes for embryo development. Newer “well-of-the-well” (WOW) dishes, featuring small 3D microwells, offer a more natural environment for embryo growth. However, the materials commonly used to construct these wells – plastics and silicone – interfere with microscopic imaging. These materials bend light differently than the surrounding culture medium, creating blurred regions, warped edges, and visible ridges that obscure crucial details. This forces a compromise between optimal growth conditions and clear visibility, a particularly problematic situation given the importance of detailed observation in IVF.
Researchers at Vanderbilt University have recently addressed this challenge with a novel approach: fabricating WOW dishes from agarose, a hydrogel composed primarily of water. Published in Biophotonics Discovery, their work demonstrates that because agarose shares a nearly identical optical refractive index with the culture medium, light passes through the dish with minimal bending or scattering. This effectively renders the 3D structure “invisible” to the microscope, enabling the capture of sharp, undistorted images.
The team rigorously tested their agarose dishes against traditional polydimethylsiloxane (PDMS) versions. Initial optical assessments utilized tiny microspheres to evaluate resolution and geometric accuracy. The PDMS dishes exhibited visible warping of the image due to manufacturing ridges, while these ridges were nearly imperceptible in the agarose dishes. Previously blurred or interrupted details became sharply defined.
To quantify the optical improvements, the researchers employed a Shack–Hartmann wavefront sensor, a tool that measures how light waves change shape as they pass through a material. The sensor revealed that PDMS dishes introduced significant and complex distortions, known as high-order aberrations. In contrast, the agarose dishes produced wavefront patterns almost identical to those observed when imaging through a standard flat petri dish, confirming the hydrogel’s minimal optical interference.
Crucially, the researchers confirmed that the improved imaging didn’t come at the expense of embryo development. Mouse embryos cultured in the agarose dishes exhibited normal growth patterns, comparable to those seen in established culture systems. Microscopic images revealed sharply resolved internal structures, highlighting fine details essential for accurate embryo grading.
The development of these “invisible” culture dishes removes a significant barrier to the wider adoption of 3D microwell culture. By allowing embryologists to utilize dishes that both promote healthier embryo growth and maintain clear visibility, this innovation has the potential to improve the accuracy of embryo selection and, increase pregnancy rates for patients undergoing IVF. The agarose-based design offers a solution to a long-standing problem in assisted reproductive technology, potentially leading to more successful outcomes for couples struggling with infertility.
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