BRCA1 mutation linked to reduced egg reserves

Women with a mutation in the breast-cancer susceptibility gene BRCA1 may have reduced numbers of eggs left in their ovaries, according to a study led by Australian scientists.

The research found that women with a faulty BRCA1 gene had decreased levels of anti-Mullerian hormone (AMH), which is an indicator of egg reserves. On average, AMH concentrations were 25 percent lower in women with BRCA1 mutations than those carrying healthy copies.

Professor Kelly-Anne Phillips, consultant medical oncologist at the Peter MacCallum Cancer Centre in East Melbourne and study lead author, said: 'This means that women in their mid-30s who carry the BRCA1 mutation have, on average, ovarian reserves similar to those of non-carriers who are two years older.'

On the other hand, the researchers did not find a link between BRCA2 mutations and ovarian reserves. Professor Phillips also stressed that AMH level was only one marker of fertility; other factors such as egg quality and fallopian-tube defects can also affect a woman's chance of conceiving, she said.

The study, which was published in the journal Human Reproduction, analysed AMH levels from 693 women: 319 with BRCA mutations and 374 non-carriers. The women in the study were all aged between 25 and 45 and had never been diagnosed with cancer.

The researchers hypothesise that a possible mechanism linking BRCA mutations and ovarian reserves could hinge on the role played by the BRCA genes in repairing double-strand breaks in DNA. Inefficient DNA repair has previously been shown to contribute to the premature ageing of a woman's eggs.

'BRCA2 has a more limited role in double-strand DNA break repair compared with BRCA1, and BRCA2 mutation carriers tend to develop fewer cancers and at a later age compared with BRCA1 mutation carriers,' explained Professor Phillips. 'So it is credible that [the effect on] ovarian reserve would be more pronounced in BRCA1 mutation carriers.'

Since women are born with a finite supply of eggs that is not replenished, ovarian reserves decrease naturally with age. Professor Phillips said that the findings of the study 'suggest that women carrying the BRCA1 mutation should try to avoid delaying pregnancy until their late 30s or 40s when fertility is reduced anyway because of their age'.

She added: 'For women trying to conceive in their 20s, any difference in ovarian reserve between BRCA1 mutation carriers and non-carriers is unlikely to be of clinical significance.'