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Mom’s age at menopause linked to daughter’s fertility

Thursday November 8, 2012
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A mother’s age at menopause may predict her daughter’s fertility in terms of the numbers of eggs remaining in her ovaries, according to a study.

By assessing ovarian reserve with two accepted methods — levels of anti-Müllerian hormone and antral follicle count — in daughters and comparing them with the age of menopause in their mothers, researchers found that both AMH and AFC declined faster in women whose mothers had an early menopause compared with women whose mothers had a late menopause.

"Our findings support the idea that the ovarian reserve is influenced by hereditary factors," Janne Bentzen, MD, PhD, the study’s lead investigator out of the Copenhagen (Denmark) University Hospital, said in a news release. "However, long-term follow-up studies are required."

Previous research has suggested that there is about 20 years between when a woman’s fertility starts to decline and the onset of menopause. A woman who enters menopause at 45 therefore might have experienced a decline in her fertility at age 25.

"Epidemiological studies have established a link between the age at menopause among mothers and daughters," Bentzen said. "In line with the suggested 20-year interval between the first decline in fertility and menopause, we hypothesized that maternal factors may also have an impact on a woman’s fertility potential in terms of ovarian reserve."

The researchers recruited 527 women working in healthcare at the Copenhagen University Hospital. The women were ages 20 to 40, and their mothers’ ages at natural menopause were known.

After adjusting for various factors that could affect the results (such as smoking, contraceptive use, age and body mass index), the researchers found that average AMH levels declined by 8.6%, 6.8% and 4.2% a year in the groups of women with mothers who had early, normal and late menopauses, respectively. A similar pattern was seen for AFC, with annual declines of 5.8%, 4.7% and 3.2% in the same groups.

Oral contraceptive effect

The study also found that AMH levels and AFC were significantly lower (27.3% and 26.8% lower respectively) in oral contraceptive users compared with non-users. AFC in women whose mothers smoked while they were pregnant was an average of 11% lower, but there was no significant effect on AMH levels.

Bentzen said the effect of oral contraceptive use was likely to be temporary and unlikely to influence the long-term decline in ovarian follicles. However, she said clinicians and women should be aware of it when considering women’s reproductive life spans or any fertility treatments.

"We believe there is a need for longitudinal, large studies in which ovarian reserve parameters are measured repeatedly in the same individual before, during and after the use of oral contraceptives," Bentzen said. "Additionally, we need to explore the impact of dose-response and duration of hormonal contraception on markers of ovarian reserve."

The authors concluded: "Clearly our data do not elucidate whether maternal age at menopause is a direct predictor of age at menopause of the offspring, or the chance of pregnancy. Nevertheless, from a biological point of view, it may be reasonable to assume that a low ovarian reserve may have a long-term effect that will shorten the reproductive lifespan.

"We therefore assume that markers such as 'maternal age at menopause,’ in combination with AMH or AFC, and chronological age may represent a more complete picture when evaluating the ovarian reserve of the individual. This assumption awaits longitudinal studies before it can be put to test."

The study appeared Nov. 6 on the website of the journal Human Reproduction and is available at http://humrep.oxfordjournals.org/content/early/2012/11/02/humrep.des356.full.


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