Implantation is the last essential step on the road to pregnancy, and the embryo that’s successfully grown and travelled along a fallopian tube must now bury into the lining of the womb to get access to a blood supply or it will die. IVF has made extraordinary advances in fertility treatment, but the process of implantation still remains beyond our control, and around 70% of unsuccessful IVF cycles are attributed to apparently healthy embryos failing to implant for some reason.
There are three stages to implantation, with increasing levels of communication between the cells of the embryo and endometrium:
- Apposition is when the embryo and the lining of the endometrium “line-up” rather loosely
- Adhesion is when proteins create bonds between the two sets of cells and cells of the embryo penetrate into the womb lining
- Invasion is when the cells of the embryo bury further into the womb lining, until they reach the basal membrane and then invade the uterine muscle. This continues until the whole embryo is embedded in the endometrium, and the placenta continues to form until it makes contact with the maternal blood supply
The embryo needs to form a placenta (it means ‘flat cake’ in Greek!) and this starts when the developing embryo breaks out of the protective zona pellucida (this prevents the embryo implanting as it travels down the fallopian tube and creating an ectopic pregnancy) and enters the ‘blastocyst’ stage when it differentiates into two types of cells. The outer cells of the blastocyst are the ones that form the placenta and these must multiply rapidly during implantation to reach the mother’s blood supply. There are times when this cell type performs perfectly, but the other cells of the embryo don’t, and this leads to a ‘blighted ovum’.
The other side of the story is that the endometrial lining of the uterus needs to be able to support implantation (the structure of womb is explained in the uterus and fallopian tubes), and in the luteal phase the ‘functional layer‘ changes dramatically to offer a ‘perfect’ environment for implantation by becoming thicker, spongy, sticky and much richer in its blood supply. The changes are complex and subtle, and the womb surface changes for about two days in what’s called the ‘window of implantation’ when different proteins alter the bonding properties of the lining and increase the likelihood of pregnancy.ii, iii
Research into the make-up of the uterine ‘microbiome’ has recently raised the possibility that differences in the microbes in the womb also play an important role in the implantation process. The womb environment is quite different during the ‘window of implantation’ to the rest of the menstrual cycle, and a shift in hormones triggers the uterus to fill with a secretion that’s produced by glands in the womb wall, from the blood vessels of the endometrium and also with dead cells, and this creates an optimum fluid for the embryo to implant.
The early nourishment of the embryo is essential not just for the start of a pregnancy, but also for the longer term health of the baby, and we’ve recently learnt there are stores of glycogen (a sugar) and glycoproteins in glands in the womb, and these provide energy directly to the fetus during the first trimester when the blood supply is restricted. The glycogen and glycoproteins stored in the walls of the womb doesn’t just come from the diet eaten during the pregnancy, but is mainly stored before conception, which strongly reinforces the importance of pre-conception nutrition and care, especially for
i ‘Endometrial receptivity markers, the journey to successful embryo implantation’ Hum. Reprod. Update (November/December 2006) 12 (6): 731-746.
ii ‘Molecular and cellular aspects of endometrial receptivity’ HM Beier 0 and K Beier-Hellwig Hum. Reprod. Update (1998) 4 (5): 448-458.
iii ‘Human Endometrium Ultrastructure During the Implantation Window – A New Perspective of the Epithelium Cell Types’
Carla Bartosch et al. Reproductive Sciences June 2011 vol. 18 no. 6 525-539
iv ‘Tracking nutrient transfer at the human maternofetal interface from 4 weeks to term’ C.J.P. Jones, R.H. Choudhury, J.D. Aplin. Placenta April 2015 Vol 36, Issue 4, Pages 372–380