One of the biggest factors determining the success ofis the quality of the eggs. Women are born with a fixed number of eggs which rapidly decline in quantity and quality from around their mid 30’s until menopause. It has even been reported that after the age of 40, a woman's chance of success decreases by 1% every month.
It seems so unfair that men can continue producing sperm for their whole lives with little change in the quality yet women are under continuous pressure from a ticking clock. So why is female age such an important factor in IVF and why does egg quality change so rapidly?
As the eggs stay in a woman’s ovaries her whole life, by the time the menopause comes around, some eggs will have been in there for over 50 years. The longer the eggs wait in the ovary, the more they will deteriorate and this can affect both the egg’s DNA and the cellular components inside the egg which drive all of its functions. These factors play a huge part in fertilisation, embryo development and ongoing pregnancies which is why we know that the success rates ofrapidly decline in women over 35 and the rate of miscarriage rapidly increases.
As well as the quality of eggs decreasing with age, the number of follicles also declines. This means that older women going throughare likely to have fewer follicles on their baseline scan and fewer eggs collected for treatment. This is simply due to the fact that there are fewer eggs available in the ovaries. It is not uncommon for women over 40 to have only 1 or 2 eggs collected which reduces the success rates significantly.
While there are many factors which contribute to egg quality, there are three major reasons egg quality declines as women get older:
1. Chromosome errors
This is the main problem for older eggs.
The crucial point to remember is that while eggs wait in the ovaries for decades, they are delicately suspended in a process known as 'crossing over'. This means that the chromosomes are midway through dividing and must stay that way until they get the signal to finish the process, which either comes from the trigger injection in IVF or the LH hormone surge for natural ovulation.
When these dormant eggs are eventually selected for use, the chromosomes must resume the process they started many, many years ago and continue dividing to complete egg maturation and fertilisation. The longer the egg's chromosomes stayed suspended in this position, the more 'sticky' they become. This means that when they are pulled apart they are much more likely to leave whole chromosomes behind or fragments of chromosomes where they have broken apart. Unfortunately, this is not something the egg can fix. If it does not have the correct number of chromosomes during fertilisation, the embryo will be abnormal further down the line.
Around 50% of all embryos made in IVF are chromosomally abnormal and this figure can reach as high as 95% in embryos created from older eggs when a women is close to menopause, purely because of the errors in chromosome separation during egg development. These abnormal embryos are referred to as 'aneuploid', meaning that they have the incorrect number of chromosomes in the cells. Missing chromosomes are known as monosomy and extra chromosomes are known as triploidy. Most times the embryo has an extra chromosome it will fail to develop or lead to a pregnancy that ends in miscarriage, however there are a small number of cases where an extra chromosome leads to a live birth. One example is when the embryo has an extra copy of chromosome 21 which causes Down Syndrome. Often genetic testing is recommended before having an embryo transfer to rule out abnormal embryos.
2. Older eggs cannot repair DNA errors that are brought into the embryo from the sperm.
As well as contributing more DNA errors themselves, older eggs are also less able to repair any DNA abnormalities that the sperm introduces into the embryo, whereas younger eggs are much more likely to succeed in repair.
Sperm DNA is packed so tightly that it is vulnerable to damage and doesn't have the equipment to repair errors like other cells do. Healthy eggs are able to identify errors brought in by the sperm at fertilisation and repair them using a process called 'base excision'. Eggs gradually lose this ability as they get older meaning that the embryos are more likely to be unhealthy.
3. Problems with mitochondria.
Mitochondria are the powerhouses of the cell and they are responsible for driving many essential processes during egg maturation and embryo development.
As eggs get older the mitochondria become dysfunctional and are not able to generate as much energy as the embryo needs. It also means that there may not be enough energy to correctly organise the chromosomes, contributing to the high number of abnormal embryos created from older eggs.
Some clinics have even tried inserting donor mitochondria from younger eggs into the eggs of older patients to try to boost the quality, however this is a controversial technique which comes with many ethical considerations and is not used routinely.
It's not all bad
For women over 35, every year that treatment is delayed can have huge consequences on the quality and quantity of eggs, so it is important to act quickly for the best chance of success. The main concerns associated with older eggs are lower fertilisation rates, poorer embryo development, a higher chance of miscarriage, and an increased chance of genetic abnormalities in the baby. This however, does not mean that older women cannot have success intreatment – after all it only takes one healthy egg to make an embryo and one healthy embryo to make a baby.