The Patient's Guide to Embryology

How old is too old for IVF?

At 35 years old it is thought that around 50% of eggs are abnormal and this increases to around 95% by 42 years old.

The demand for IVF has grown significantly in the last few decades largely because people are choosing to delay having babies until later in life. This is less of a problem for men who keep making new sperm every second of every day for their whole lives compared to women who have a very rigid biological clock which begins ticking at puberty and stops at menopause.

Why does age matter in IVF?

Female age is the biggest factor determining the success of IVF because it has such a big impact on the quality of the eggs and hence the quality of the embryos. Women are born with all the eggs they will ever have and they start to be released from the ovary every month from the start of puberty until there are none left at menopause. Not only that, but as the pool of eggs gets smaller, the quality of the eggs decreases rapidly too. 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 its functions. These factors play a huge part in fertilisation, embryo development and ongoing pregnancy which is why we know that the success rates of IVF rapidly decline in women over 35 and the rate of miscarriage increases.

Egg number declines with age

At birth, a female has a finite number of eggs in her ovaries and these eggs are stored in structures called follicles. Almost all of the eggs a woman is born with are wasted – out of the millions of eggs in the ovaries at birth, only around 400 are ovulated over her fertile years. During childhood, the ovaries remain relatively inactive and the number of follicles gradually decreases due to a natural process called atresia, where the follicles die off. At the onset of puberty, the brain starts to release hormones that stimulate the growth and maturation of follicles in the ovaries. Each menstrual cycle, many follicles begin maturing but only one mature follicle releases an egg and the others are wasted. The reason for so much wastage is not fully understood but one theory is that the process of atresia helps to eliminate abnormal or damaged eggs, ensuring that only healthy eggs are available for fertilization.

As women get older the pool of egg-containing follicles reduces which means that the ovaries can only produce a limited number of eggs for IVF. Fewer eggs usually results in fewer embryos being created which gives fewer chances to get pregnant. It is not uncommon for women over 40 to have only 1 or 2 eggs collected for IVF treatment which reduces the chance of success significantly.

Egg quality declines with age

The quality of the egg has a huge impact on the likelihood of getting pregnant. There are many factors which contribute to egg quality but there are three major reasons egg quality declines as women get older:

1. DNA problems

The decline in egg quality is largely due to problems with the chromosomes. This is because the eggs wait in the ovary at a delicate stage of growth where the chromosomes are vulnerable to damage. By 40 years old, those eggs which are still waiting to be ovulated have been held in this vulnerable state for decades. When they eventually start to mature, the chromosomes easily break apart leaving the egg with missing or extra chromosomes. The vast majority of chromosome abnormalities result in unhealthy embryos so it becomes very difficult to create a healthy pregnancy. At 35 years old it is thought that around 50% of eggs are abnormal and by 42 years old this increases to around 95%. Unfortunately, this is not something the egg can fix. If it does not have the correct number of chromosomes during fertilisation, the embryo will likely be abnormal further down the line.

2. Older eggs cannot repair problems in the embryo

In the early stages of development, embryos have an amazing ability to repair minor DNA errors which are usually introduced by the sperm. Embryos that are made from older eggs are less able to repair these DNA abnormalities compared to younger eggs. This means that embryos made from older eggs are more likely to be unhealthy and often show signs of being poorer quality such as more fragmentation, slower development, or stopping development before they reach the blastocyst stage.

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.

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