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Genetic link to fertility drug response found

5 July 2010
Appeared in BioNews 565

Scientists have discovered a genetic mutation that may make some women less likely to respond to the ovarian stimulating hormones used in fertility treatment. Dr Maria Lalioti and her colleagues from Yale University Medical School, US, reported their findings at the 26th annual meeting of the European Society of Human Reproduction and Embryology in Rome last week.

The genetic variation results in an abnormal receptor that sits on the surface of cells surrounding the developing egg in a woman's ovary. Follicle stimulating hormone (FSH) activates these receptors and promotes the maturation of an egg so it is ready for fertilisation. The hormone is given to woman during fertility treatment to stimulate the production of multiple eggs before undergoing IVF. However, some women fail to adequately respond to the hormone treatment and prior to this study an underlying reason for this was unknown. The mutation identified by the scientists could explain at least some cases and indeed, it was found in two out of five women who had poor responses to treatment.

At the meeting, the question was raised of how such a mutation had been maintained in our genome when it paradoxically hinders reproduction, to which Dr Lalioti responded: 'Our Grandmothers' generation used to reproduce earlier, so in general their fertility was better and that's how a lot of these variants are kept in the population. They may be rare. We are looking at IVF populations, selected because they can't get pregnant, so it is possible to be present in the general population but in a smaller amount. It may not have such a big influence once people try to reproduce earlier, when their ovaries are functioning better'.

This work has important implications for future research and treatment. 'The importance of this finding is that it creates a link between genetic variation and sub-fertility. These women have a normal menstrual cycle and they may present to the fertility centre as patients with unexplained infertility, before their first IVF cycle that would reveal an ovarian stimulation defect,' explained Dr Lalioti.

'Our finding explains why these women have a lower response to FSH. Currently, FSH is the only medication used to stimulate ovarian response, but once other medications are available that can bypass the receptor for FSH, they can be tested on these women. Also, at present we cannot predict if the women would profit from having higher doses of medication, and, in fact, some preliminary data from other groups show the opposite: that lower FSH may be more beneficial'.

Dr Lalioti went on to explain that the next steps were to recruit more patients to more accurately assess the prevalence of the mutation and investigate alternative drugs to FSH, which could promote egg development more effectively in these women. 'In the future, this could lead to personalised treatments for a sub-group of patients', she said.

SOURCES & REFERENCES
Researchers discover why some women are sub-fertile and have a poor response to ovarian stimulating hormones
ESHRE |  29 June 2010
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