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Ageing ovaries - not eggs - may lead to IVF failure

17 August 2015
Appeared in BioNews 815

Changes to the activity of cells in the ovary may contribute to poorer IVF success rates among women in their 40s.

Researchers found that in women aged over 43, granulosa cells that support the developing egg had a hormone receptor profile that makes them more prone to premature luteinisation, a phenomenon known to reduce IVF success rates.

But by collecting eggs earlier in the IVF cycle, to try to avoid premature luteinisation, they were able to increase the numbers of high quality embryos and the pregnancy rate.

'We used to think that ageing eggs were responsible for poor IVF success rates in older women, but here we show that it is more due to the ageing of the egg's environment,' said study author Dr Yanguang Wu from the Center for Human Reproduction in New York.

'The chances of reversing damage to an egg are practically zero, and so these findings are exciting because it's much more hopeful to therapeutically target the egg's supporting environment.'

The team, who reported their findings in the Journal of Endocrinology, collected granulosa cells from 64 women aged 28-38 and 41 women aged 43-47 who were undergoing IVF for infertility. They compared the gene expression of these cells to those from 31 healthy egg donors aged 21-29.

They found that in women aged over 43, the expression of the follicular stimulating hormone (FSH) receptor in these cells drops, while expression of luteinising hormone (LH) and progesterone receptors increase. This means that the ovaries are less sensitive to FSH, which stimulates the release of an egg, and more sensitive to LH and progesterone, which are associated with luteinisation.

Luteinisation normally takes place after ovulation when progesterone and LH levels rise to prepare the uterus for pregnancy and to prevent further eggs maturing. Thus, when this process takes place prematurely, it can inhibit the release of a mature egg.

The researchers have begun exploring how these findings could be put into clinical use by collecting eggs earlier in the IVF cycle to attempt to circumvent premature luteinisation.

In a group of 71 women aged an average of 45 years, they tested administering human chorionic gonadotropin to 'ripen' the egg earlier in the cycle. Their preliminary data show that while this method produced more immature eggs, the rate of good quality embryos per cycle significantly increased to 3.6 compared with 2.7 among women who underwent normal egg retrieval. 

The percentage of cycles resulting in pregnancy was 15.5 compared with 7.7, although the authors note their sample size is too small to detect the statistical significance of this finding.

'While larger studies with more patients are needed to confirm our results, we have a new insight into ovarian ageing and we hope this will help produce new strategies for improving pregnancy outcomes in older women,' commented Dr Wu.

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