We're on round four, so when I sat down with my RE to plan out this last and hopefully final round of IVF I wasn't expecting anything new. I asked anyway: was there anything we could do to improve the quality of our blastocysts that we weren't already doing?
I was pretty shocked when she came back with GM-CSF Media. How had I not heard about it before? (That's always my response - if it helps, why didn't we do it in the first round?) Still, I checked it out and was easily convinced - it should help our embryos make it to blastocyst stage. We're definitely incorporating it this next round.
I couldn't find a lot of information online that was easily digestible, so I wrote up my notes in the hope it helps someone else.
What is GM-CSF Media?
GM-CSF stands for Granulocyte Macrophage Colony-stimulating factor. Check out that mouthful. As I understand it (and remember, I'm not a doctor or a scientist in anyway shape or form) the GM part - granulocyte macrophage - is a protein that contains a type of white blood cell that protects your body by eating any foreign cells. The last bit, colony-stimulating factor is because this protein is important in cell signalling - it's released by cells and affects the behaviour of other cells. I think, anyway. The literature is all written in extreme scientist.
Typically it's secreted into the fallopian tubes and the uterus a few days after ovulation - when fertilisation is due to take place. The level of GM-CSF will fluctuate throughout your cycle, but is typically at it's highest in the mid-luteal phase (a few days after ovulation).
GM-CSF is key in early pregnancy, particularly in embryo development and implantation. It's thought that GM-CSF inhibits the stress response of the embryo cells, stopping cells from dying due to stress (Source). This helps embryo growth and survival as it cleaves, all ready for implantation.
Why use it with IVF?
Typically, an embryo is naturally exposed to a large number of hormones, proteins and growth factors that are present in a woman's reproductive system. We know that with IVF, a petri dish is not as good as a uterus. Part of that is because the nutrients in the body can't always be replicated in vitro. Without the right nutrients there is an effect on the development (Source) and quality of embryos. The lack of these nutrients in the culture medium contribute to the high rates of implantation failure and miscarriage with IVF.
In some clinics, proteins like GM-CSF are considered just fine-tuning agents which can be omitted in the lab. But, the research shows the lack of growth factors like GM-CSF in the culture embryos are incubated in is a major cause of environmental stress. We know that embryos are highly sensitive to their environment - any stress is bad. If the cells are severely stressed, it will alter the rate of cell division or kill the cell, causing the blastocyst to arrest.
As GM-CSF prevents cell stress, by adding GM-CSF to the culture which the embryos are stored in, it's thought that the embryos have a better chance of survival.
What does the research say?
First things first - adding GM-CSF to the culture does no harm to the embryos. This multicentre, prospective placebo-controlled and double-blinded study (Source) found that embryos incubated in a solution of GM-CSF, they had the same chromosomal composition and similar number of top quality embryos and development on day three than embryos incubated in a solution without GM-CSF. That's good to know - essentially, there was no increase in chromosomal abnormality in embryos cultured with GM-CSF.
Several studies have found that by adding GM-CSF to the culture, you're likely to get a two fold increase in the number of embryos that develop into blastomeres (Source). Embryos cultured in the with GM-CSF reached blastocyst stage on average 14 hours quicker and contained approximately 35% more cells (Source).
In one study (Source), they took a sample of cells from the uterus lining and added it to the culture with the embryos. The tissue secreted GM-CSF and this was measured post transfer. They found the more GM-CSF that was secreted the more likely a successful pregnancy was after embryo transfer.
This large scale study (1332 patients across 14 fertility clinics in Sweden and Denmark - Source) found that there was a significant increase in the number of embryos that implanted and survived to week 12 (23% for GM-CSF vs 18.7% for control). It also found that of a subgroup of 327 women who had previously miscarried, the women who had GM-CSF media had a much higher ongoing implantation rate (24.5% for GM-CSF and 17.0% for control).
In a nutshell?
Adding GM-CSF to the medium embryos are cultured in:
- Doesn't hurt your embryos in anyway.
- Has been shown to protect embryos from cell stress.
- The research suggests it helps embryo development and implantation.
- May improve the chances of implantation in women who have miscarried in the past.
Overall, adding GM-CSF to the medium embryos are cultured in may help establish a successful pregnancy and increase the chances of a healthy infant.
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) acts independently of the beta common subunit of the GM-CSF receptor to prevent inner cell mass apoptosis in human embryos. (link)
- Granulocyte-macrophage colony-stimulating factor promotes human blastocyst development in vitro. (link)
- Culture of human oocytes with granulocyte-macrophage colony-stimulating factor has no effect on embryonic chromosomal constitution. (link)
- Granulocyte macrophage-colony stimulating factor production by autologous endometrial co-culture is associated with outcome for in vitro fertilisation patients with a history of multiple implantation failures. (link)
- A randomized clinical trial to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium for in vitro fertilization. (link)