Ongoing research of in-vitro fertilization (IVF) is raising the success rate of the procedure every day but one aspect of the technique has remained mysterious. The inability of an embryo to implant in the uterine wall is a frequent reason for IVF failure but the reason why the embryo won’t implant has remained elusive. New research, however, reveals a secret to embryo implantation that may eventually result in a higher rate of success.

Professor John Aplin, leader of the study from The University of Manchester’s Institute of Human Development in England, says there is only a small window of opportunity for implantation: “This window is open for no more than four days.”

Aplin’s research team knew that a specific fragment of non-coding RNA — microRNA-145 (miR-145) — is active during implantation but its role wasn’t clearly understood. Non-coding RNA is functional RNA, vital for cellular processes, but it does not contain two matched sets of chromosomes like DNA does so it does not affect genetic heritability.

Previous research indicates an abnormal level of microRNA in the endometrium (uterine lining) of women who experience implantation failure. Aplin’s latest study indicates that, for implantation to succeed, miR-145 must work in sync with a protein known as insulin-like growth factor 1 receptor (IGF1R) in the endometrium.

Aplin’s research revealed that when there is too much miR-145 in the endometrial tissue, the IGF1R levels are too low for the necessary intracellular crosstalk required for implantation. His research team used mice to experiment on the effects that occur when both miR-145 and IGF1R levels are altered:

  • When the research team encouraged overexpression of miR-145, implantation was not successful.
  • When they masked the ability of IGF1R to act as the targeted receptor, even for correct levels of miR-145, implantation, again, was impossible.
  • When a target protector was applied to the IGF1R, implantation did successfully occur, even when miR-145 levels were at levels otherwise demonstrated to be too high for successful implantation.

Aplin’s research team concluded that miR-145 influences attachment of the embryo by lowering the level of IGF1R in the uterine lining. The level of both elements — miR-145 and IGF1R — must be in agreement during that four-day window of opportunity for successful implantation.

Considerable research is still needed before this knowledge can be applied in a clinical setting but the research team believes it could be possible someday to develop treatments that suppress production of miR-145 in women who experience repeated failures to implant.

“This is one of the hardest groups of women to treat in fertility science,” according to Aplin, but he feels “greater understanding of the mechanisms which control success or failure can lead directly to treatments to make IVF cycles more efficient so that infertile couples can start their families.”

Sources:

  1. Aplin, John D., et al. "miR-145 suppresses embryo–epithelial juxtacrine communication at implantation by modulating maternal IGF1R." Journal of Cell Science. The Company of Biologists Ltd., 20 Jan. 2015. Web. 10 Mar. 2015.
  2. "Prenatal Form and Function – The Making of an Earth Suit / Unit 1: The First Week." EHD: The Endowment for Human Development. The Endowment for Human Development, n.d. Web. 10 Mar. 2015.