Strong ovarian stimulation linked to egg abnormalities and poor pregnancy rates in older women

by Dr. Lux Fatimathas

BioNews.org.uk
July 4, 2010

European researchers have linked strong ovarian stimulation in women aged over 35 to increased chromosomal abnormalities.

Genetic screening shows that the production of good quality oocytes in older women is disrupted during fertility treatment involving conventional ovarian stimulation. This process uses hormones to promote the release of a greater number of oocytes than normal and, in general, larger doses are given to women over 35, who need more help producing eggs.

This research shows that strong ovarian stimulation can lead to abnormal chromosomal copy numbers, a condition known as aneuploidy. Therefore milder stimulation, or ‘mini-IVF‘ produces better quality eggs in older women. Stronger ovarian stimulation is therefore detrimental to both conception and fetal development, and can result in the failure of IVF, miscarriage and disorders such Down’s syndrome (where there are three copies of chromosome 21).

Immediately prior to ovulation and subsequently following fertilisation, healthy oocytes go through two phases of a special kind of cell division called meiosis. Successful meiosis requires chromosomes to separate from each other at the correct time. During each phase small cells called polar bodies are produced, which when analysed can provide an insight into the chromosomal make-up of the eggs.

Researchers from nine countries, including the UK, screened the polar bodies of 34 women aged between 33 and 40, who were undergoing IVF with ovarian stimulation.

‘Our evidence demonstrates that, following IVF, there are multiple chromosome errors in both meiotic divisions, suggesting more extensive premature separation of single chromosomes resulting in… multiple chromosome copy number changes in individual oocytes’, said Professor Handyside, director of the London Bridge Fertility, Gynaecology and Genetics Centre, who led the research.

He told the Times that the errors seen in these women were ‘opposite from what we see in pregnancies following natural conceptions. It raises the question of whether over stimulation of the ovaries in these women is causing those errors’.

These findings may in the future prove helpful to couples undergoing IVF and leads strong support to ‘mini-IVF’ or minimal stimulation protocols. ‘This… is already a big step forward that will aid couples hoping for a healthy pregnancy and birth to be able to achieve one’, said Professor Joep Geraedts, co-ordinator of the European Society of Human Reproduction and Embryology (ESHRE) Task Force on PGS (preimplantation genetic screening), who was involved in the study.

Professor Handyside added: ‘We need to look further into the incidence and pattern of meiotic errors following different stimulation regimes including mild stimulation such as in mini-IVF. The results of such research should enable us to identify better clinical strategies to reduce the incidence of chromosome errors in older women undergoing IVF’.

These findings were announced on 4 July at the 27th annual meeting of ESHRE in Stockholm, Sweden.