Patients who have been unsuccessful want to know why it didn’t work. A definite explanation as to why it failed is impossible to provide in most cases. However, we think the most common cause of IVF not working a problem with the embryo.
Human reproduction has an element of natural selection and we see this in the lab with IVF. On average, 12 eggs are collected from a cycle of IVF treatment, but only about ten will be mature of which perhaps only three or four will become blastocysts by day five. The other eggs either don’t fertilise or develop into good quality embryos. The same process continues after embryo transfer. Not all blastocysts, even the top quality ones, will go on to develop into a pregnancy.
We think that a significant number of embryos have the wrong number of chromosomes–this is called aneuploidy. Chromosomes are the packages which contain our DNA. We have 46 in total, half from each parent. As the embryo develops, the cells must copy themselves. A common mistake happens when the copy and paste mechanism goes wrong, either duplicating a chromosome, or missing one out.
Down’s syndrome occurs when an extra copy of chromosome 21 is present. However, it’s possible to get extra copies of any of the other chromosomes, many of which are not compatible with life. This leads to an embryo not developing, no implantation and is the commonest cause of miscarriage.
What if we could test all of the embryos to see if they are genetically normal? Surely this would improve pregnancy rates.
Pre-implantation genetic testing for aneuploidy (PGT-A), is a technique that can be used to assess the chromosomes in a single cell. A scientist takes a biopsy of cells from the trophectoderm cells around the outside of the blastocyst. The cells are then sent to the lab for genetic testing. The embryos are then frozen while waiting for the results.
Initially, this strategy seemed promising. After all, it make complete sense as a method to determine which embryo is the best.
Nonetheless, taking a biopsy from the trophectoderm cells that is destined to form the placenta doesn’t tell you about the inner cell mass that would go on to form a baby.
A mosaic embryo contains a mixture of cells. Some normal and others aneuploid. Therefore, a normal trophectoderm biopsy cannot provide reliable information about the inner cell mass.
Furthermore, mosaic embryos also have a potential to go on and form a healthy baby. The theory is that some embryos can fix themselves as they develop. A case series of 18 mosaic embryos showed six that went on to make a health baby at birth.
PGT-A is common practice in the US, but a recent study showed that PGT-A did not improve overall pregnancy outcomes. This is not surprising as PGT-A doesn’t produce more embryos, if anything it is more likely to discard ‘abnormal’ embryos which may still have the potential to go on and form a healthy baby.
The main way to improve IVF success is to attempt more cycles. This provides more eggs, more embryos and more opportunities for a successful outcome.
Authors
Matt is an NHS Consultant in Newcastle with over ten years of experience. His PhD research into subfertility and miscarriage involved developing a clinical trial and patient engagement.
