Non-invasive molecular assessment of human embryo development and implantation potential

Biosens Bioelectron. 2020 Jun 1:157:112144. doi: 10.1016/j.bios.2020.112144. Epub 2020 Mar 14.

Abstract

In vitro fertilization (IVF) is the most common assisted reproductive technology used to treat infertility. Embryo selection for transfer in IVF cycles relies on the morphological evaluation by embryologists, either by conventional microscopic assessment or more recently by time-lapse imaging systems. Despite the introduction of time-lapse imaging improvements in IVF success rates have failed to materialize, therefore alternative approaches are needed. Recent studies have shown that embryos resulting in successful pregnancy differ in their secretome and metabolism compared to embryos that fail to implant, suggesting that molecular analysis of embryo culture medium could assist in non-invasive single embryo selection. However, this approach has yet to be adopted clinically due to the lack of appropriate highly sensitive screening technologies needed to assess volume-limited samples. Here we report the detection of hCGβ, IL-8 and TNFα from conditioned culture media of single human embryos using electrochemical impedance spectroscopy. The impedimetric immunosensors revealed that morphologically non-viable embryos produce higher levels of IL-8 and TNFα, associated with abnormal cell division and cell death, respectively. More importantly, hCGβ detection was able to discriminate apparently morphologically identical viable embryos. This work brings an objective dimension to embryo selection, which could overcome the major limitations of morphology-based embryo selection for implantation. Future work should include the validation of these biomarkers in a large patient cohort.

Keywords: Electrochemical impedance spectroscopy; Human embryo; Immunosensors; In vitro fertilization.

MeSH terms

  • Biosensing Techniques / methods
  • Cell Line
  • Chorionic Gonadotropin, beta Subunit, Human / analysis*
  • Chorionic Gonadotropin, beta Subunit, Human / metabolism
  • Culture Media, Conditioned / analysis
  • Culture Media, Conditioned / metabolism*
  • Embryo Culture Techniques
  • Embryo Implantation
  • Embryo, Mammalian / metabolism*
  • Embryonic Development
  • Female
  • Fertilization in Vitro
  • Humans
  • Immunoassay / methods
  • Interleukin-8 / analysis*
  • Interleukin-8 / metabolism
  • Pregnancy
  • Tumor Necrosis Factor-alpha / analysis*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Chorionic Gonadotropin, beta Subunit, Human
  • Culture Media, Conditioned
  • Interleukin-8
  • Tumor Necrosis Factor-alpha