Biological clock studied

Several newspapers have reported that women will lose around 90% of their eggs by the age of 30. The Daily Telegraph says that by 40 their reservoir of potential eggs will have shrunk to “almost nothing”.

These findings come from a complex mathematical model used to examine age-related changes in women’s ovarian follicles cells, which have the potential to develop into eggs. The research predicts that before birth, women have roughly 600,000 follicles present in her ovaries, but at age 30 typically 12% of these will remain.

While these results may sound worrying, it should be noted that this type of study is used to make estimates and cannot provide definite figures. Equally, even the predicted 90% reduction in follicle cells numbers would still leave 72,000 cells at the age of 30, a time when many women have perfectly healthy pregnancies. Difficulty conceiving can be due to a number of reasons, but a range of medical help and support is available.

Where did the story come from?

This research was conducted by W Hamish B Wallace and Thomas W Kelsey, and published in the peer-reviewed open-access journal, PloS One . Funding was provided by grants from the UK's Engineering and Physical Sciences Research Council.

The media has mostly reflected the findings of this mathematical model accurately. But it has generally not made it clear how these results were obtained, nor has it discussed the limitations of the research. Most newspaper reports have failed to put the findings into context for concerned women who may be reading these articles. See The Daily Telegraph 's story on women losing 90 per cent of 'eggs' by 30.

What kind of research was this?

This was a modelling study researching the age-related decline in the number of undeveloped ovarian follicles that women have. An ovarian follicle is a group of cells that can potentially develop into a mature egg. All of the follicles that a girl will ever have are present prior to her birth. Not all of her follicles will develop into egg cells – only some are selected for maturation. This study looked at ovarian follicle counts from before birth until the onset of menopause.

To carry out their analysis, the authors used data from previous studies, which had examined the number of follicles in the ovaries of women at different ages. The authors then tried to apply this data to a number of different mathematical models.

All modelling studies must be interpreted in the correct context - models use mathematical formulas to create only estimates of situations, and cannot provide definite figures. The accuracy of such models depends on the accuracy of the data fed into them and the assumptions that are used in their development.

What did the research involve?

The authors gathered data from eight separate histological studies, which had looked at the number of undeveloped follicles counted in tissue samples from 325 girls and women. These ranged in age from only seven weeks post-conception to around the time of menopause at approximately 51 years.

The data obtained was fitted to 20 different mathematical models. The models were ranked according to how well they fitted the data obtained from the different studies. The researchers then chose the model that gave the closest fit to the data when the number of follicles was plotted against age.

What were the basic results?

The researchers’ chosen model predicts that the average maximum follicle population that any female would have is about 300,000 per ovary. This maximum level of follicles would occur while still in the uterus at only 18-22 weeks after conception. After this peak, follicle population would be in constant decline.

The researchers predicted the rate at which these undeveloped follicles would be ‘recruited’ for later maturation into egg cells. This recruitment would be at its greatest between birth and about 14 years of age. After 14, there would be less recruitment of undeveloped follicle cells, i.e. most of the follicles that were going to develop into egg cells in future menstrual cycles would already have been selected by the age of 14.

The authors also estimated that 95% of women will have only 12% of their maximum pre-birth follicle population left by the time they reach 30 years of age. By the age of 40, only 3% would remain. Taking a definition of menopause as being a follicle population of less than 1,000, their graphical model predicted that, on average, menopause would occur at around the age of 49. Menopause would occur between the ages of 38.7 and 60.0 years for 95% of women.

According to the model, the maximum number of follicles that a woman had before she was born would determine whether she had an earlier or later menopause. For example, while the typical peak number of follicles was 300,000, women who experienced menopause at a younger age would be expected to have had fewer follicles at the time of their peak. Equally, women who went through menopause later in life would have had a greater-than-average peak number of follicles.

How did the researchers interpret the results?

The researchers conclude that their model allows estimation of the number of undeveloped follicles present in the ovary at any given age. The model shows that the variance in remaining follicle population is mostly determined by age. The say that most follicles have already been selected for future development by the age of 14 years, after which the rate of new follicle recruitment declines with age until menopause.

Conclusion

As the authors say, their study's strength is that it is possibly the first-ever model to examine the egg reserve in the ovaries of a typical female from development in the foetus until the onset of her menopause.

As women have all of the egg follicles that they will ever possess from the time of their birth, it stands to reason that a woman will have substantially fewer follicles by the time she is 30 than she had when her periods started as a young teenager. This model has also predicted that most of the follicles that eventually mature into egg cells in later menstrual cycles will already have been selected by the age of 14 years, with less recruitment after this age.

Further findings suggest that women who reach menopause at a younger age will have had smaller-than-average number of follicles to start with, while those who experience menopause at an older age will have had an above-average number of follicles. These seem to be reasonable predictions. Unfortunately, based on current knowledge, there is very little that a woman can do to change either of these things.

However, there are a couple of important points to bear in mind regarding this research:

• All mathematical modelling studies must be interpreted in their correct context - they are designed to provide estimates only, and not definite figures.
• The data used for this model was collated from eight different studies. This assumes that each study used reliable and comparable methods to measure follicle population in the ovary. However, this may not necessarily be the case.
• The ovaries in these tissue studies would have come from women who had died or had their ovaries removed for some reason. These may not be representative of the female population as a whole.
• The model predicts that a woman with fewer follicles to start with will go through earlier menopause. But this cannot be confirmed because the number of follicles in a tissue sample would only represent the situation at the time it was extracted and not how it would change in the future. These studies did not follow the women who provided these samples to see when they went through the menopause.
• The findings of this research may give doctors and scientists a better understanding of how ovaries and egg cells develop, which may be of help in fertility counselling. However, the model’s findings have no obvious new treatment implications, and it cannot predict how many follicles an individual woman will definitely have at any one point in time.
• Based on the results of this model, the average woman starts with 300,000 follicles per ovary. This would mean that the average number at age 30 would be expected to be 72,000 (12% of maximum pre-birth levels). At age 40, it would be expected to be 18,000 (3% of maximum pre-birth levels). Although these reduced numbers may make conception less likely, they do not make it impossible.

Taken as a whole, these findings are interesting but not altogether unexpected. These findings should not cause alarm to the many women hoping to still enter parenthood above the age of 30. The optimal time for conception, in terms of the chance of conceiving, is likely to be at a younger age, but life and work circumstances mean that this is not always possible or practical. People should be assured that many women continue to have perfectly healthy pregnancies and babies well into their 30s and older, and that medical help and support is readily available to those who have trouble conceiving.