How mum's menopause can affect your fertility

"Fertility predicted by mother's age at menopause," proclaims BBC News.

This headline is based on a study in which 527 women aged 20-40 were asked how old their mothers were when they went through the menopause.

They were then given an ultrasound to measure how many follicles (the 'cellular packages' that surround an immature egg cell while it’s in the ovary) they had in their ovaries. The women also had a blood test to measure the level of a hormone released by the follicles.

These tests can give an indication of how many eggs a woman has left – her so-called 'ovarian reserve'. Women are born with all the eggs they will ever have – once they are gone, no more eggs can be produced and a woman becomes infertile.

The researchers found that women born to mothers who had an early menopause (before the age of 45) had smaller ovarian reserves compared with the daughters of women who experienced later menopause.

The main assumption of the media reporting was that having fewer eggs means that women will go on to have fewer babies, or may experience more problems conceiving. However, the study did not test this assumption.

Overall, an expert from the British Fertility Society quoted by the BBC gives perhaps the simplest advice: "The younger you start trying for a baby, the more likely you are to be successful."

Read more about fertility and conception.

Where did the story come from?

The study was carried out by researchers from the University of Copenhagen, Denmark and was funded by the Danish Agency for Science, Technology and Innovation, Copenhagen Graduate School of Health Science (CGSHS), and the Fertility Clinic at Copenhagen University Hospital.

The study was published in the peer-reviewed journal Human Reproduction.

The BBC and the Daily Mail’s coverage of the story was accurate and contained a number of useful quotes from fertility experts.

What kind of research was this?

This was a cross-sectional study looking at whether a woman's 'ovarian reserve' at a given age is associated with their mother’s age at menopause.

Women are born with all the eggs they will ever have, which are then released every month after puberty until they reach menopause. The ovarian reserve is the number of eggs in the ovaries at any one point in time that are yet to be released.

Previous research has already established that a mum's genetics are linked to her daughter's age at menopause (for example, if the mother goes through menopause early, the daughter may be likely to as well).

What did the research involve?

This study recruited a sub-group of women who were taking part in an existing prospective cohort study. The sub-group included 863 healthy women aged 20-40 years employed as healthcare workers at Copenhagen University Hospital, Rigshospitalet, Denmark.

The researchers assessed ovarian and hormone parameters said to be related to reproductive ageing. One of these measures was antral follicle count (AFC), which is assessed by ultrasound. Follicles are the 'cellular packages' that surround an immature egg cell (an egg that may or may not mature and be released in any given menstrual cycle) while it's in the ovary. The second measure was blood levels of reproductive hormones, including anti-Müllerian hormone (AMH), a hormone released by the follicles that is sometimes measured in specialist fertility clinics to determine ovarian reserve.

Together, the AFC and AMH readings give doctors an idea of how many eggs are still in the ovary waiting to be released.

As well as these physiological measures, information on reproductive history, including the age of the mother's natural menopause, was obtained through an internet-based questionnaire.

The analysis was appropriate, and looked for associations between the two biological ageing measures (AMH and AFC) and age of maternal menopause. Age of maternal menopause was split into three groups for comparison:

early (<45 years old)
normal (46 to 54 years old)
late (≥55 years old)

The statistical analysis adjusted for differences in body mass index (BMI), use of oral contraceptives, participants' smoking habits and prenatal smoking exposure.

What were the basic results?

The group analysed included 527 women with an average age of 32.7 years. The average age reported for maternal menopause was 50.2 years.

The researchers found both AMH and AFC reduced significantly faster in women whose mothers had an early menopause (before the age of 45) compared with women whose mothers had a late menopause (after the age of 55).

Median AMH declined by:

8.6% per year (95% confidence interval (CI) 6.4 to 10.8%) in the group with early maternal menopausal age
6.8% per year (95% CI 5.0 to 8.6%) in the group with normal maternal menopausal age
4.2% per year (95% CI 2.0 to 6.4%) in the group with late maternal menopausal age

Median AFC declined by:

5.8% per year (95% CI 4.0 to 7.5%) in the group with early maternal menopausal age
4.7% per year (95% CI 3.3 to 6.1%) in the group with normal maternal menopausal age
3.2% per year (95% CI 1.4 to 4.9%) in the group with late maternal menopausal age

The researchers also found that women who reported prenatal exposure to maternal smoking had, on average, 11.1% (95% CI 0.1 to 21.1%) lower AFC scores than those reporting no prenatal exposure to smoking. No smoking association was found for AMH measures.

How did the researchers interpret the results?

The researchers state that, "To our knowledge, this was the ﬁrst study to demonstrate a signiﬁcant association between age at maternal menopause and serum AMH levels in daughters". In their summary, the authors write that their research "shows that early maternal menopause is related to an advanced depletion of the ovarian reserve and that late maternal menopause is related to a delayed depletion".

Conclusion

This cross-sectional study highlighted a relationship between early maternal age of menopause (before 45 years of age) and lower levels of ovarian reserve in their daughters.

The strengths of this study include its moderately large sample size and its dual methods of estimating ovarian reserve. However, the study also has significant limitations.

Information on age at maternal menopause was obtained retrospectively, and may be prone to recall bias and a tendency to round to simple, easy-to-remember numbers. For example, a woman may have experienced her menopause at the age of 47, but her daughter may remember it and report it rounded up to 50 or rounded down to 45.

To combat this, prior to answering the question online the researchers asked women to contact their mothers for information about the specific age they were when they had at least one whole year without having a period. It was not clear how many women did this or whether this improved the quality of this measure.

Only 527 of the 863 eligible women (61%) took part in the study – the rest were excluded for reasons such as missing data on maternal age at menopause and being pregnant. It is possible that the women who chose not to take part or who were excluded from the study were different to those who were involved in an important way, and that if they had been included the results could have been different.

The women in the study were all health workers who may be more likely to lead healthier lifestyles than the wider population. This partially limits how applicable these findings are to women of other professions. Studies of more diverse groups of women would be able to confirm this study's findings.

The main assumption of the media reporting is that having fewer eggs means that women will go on to have fewer babies, or may experience more problems conceiving. This study did not test this assumption.

Nevertheless, as Dr Nick Panay, the chairman of the British Menopause Society, puts it in the Daily Mail, "one of the most important questions we can ask a woman seeking information about her ovarian reserve is, at what age did your mother go through the menopause?"

He went to on to say that, "Tests are being developed which look increasingly promising, but these will only be a guide. If a woman wants to have a baby and is in a position to start trying, then it is better to do it earlier rather than later."