Stimulating Ovaries in Older Women

Clomid, Parlodel may increase chromosome abnormalities in older women

(RxWiki News) In vitro fertilization (IVF) techniques involve using Clomid and Parlodel -- drugs that stimulate the ovaries to release a large number of eggs for fertilization.

Ovarian stimulation may be disruptive in older women because the chromosomes are detaching prematurely, raising the risk for giving birth to a baby with Down syndrome, according to genetics experts.

"Ask your fertility specialist if ovarian stimulation is safe for you."

Professor Alan Handyside, Ph.D., Director of the London Bridge Fertility, Gynecology and Genetics Centre in London, U.K., conducted an early study of a novel method of screening polar bodies -- one of two small cells that are the by-product of oocyte development. An oocyte is the cell from which the egg develops. Handyside and his colleagues were able to gather this data by using new technology of microarray comparative genomic hybridization (array CGH) to develop a reliable method for analyzing the chromosomal status of an oocyte. Interestingly, many more chromosome copy errors arise in the pre-egg cell than in sperm.

Professor Joep Geraedts, Ph.D. and coordinator of the European Society of Human Reproduction and Embryology Task Force on preimplantation genetic screening reports that being able to retrieve pre-egg development data, they were able to observe chromosomes at the chromatid level, which is one of two identical copies of DNA that make up the copied chromosome. He explains that they opted to analyze this stage of egg development to establish better infertility treatments.

Handyside explains that in this unique study, researchers were able to use CGH to examine the copy number of all 23 pairs of chromosomes, in all three stages of female cell division in more than 100 oocytes with an abnormal numbers of chromosomes. In female cell division, the 23 pairs of chromosomes duplicate and each pair come together. The four single chromatids attach to one another along the whole length of each chromosome. This process actually occurs before a female is born and is the stage DNA is exchanged between the grandparents' chromosomes.

Decades later, right before ovulation, this attachment can dissolve; firstly, between the two duplicated chromosomes and secondly, after fertilization between the two individual chromosomes. This enables pairs of chromosomes to segregate in the first cell division, producing the first polar body, which is the small cell usually released just before ovulation. In the next cell division, the second polar body is produced, which is released after the ovum has been discharged from the ovary and is penetrated by sperm. This results in a single set of chromosomes in the fertilized egg, which, when combined with the single set in the fertilizing sperm, restores the 23 pairs.

Following natural conception in older mothers, pregnancies resulting in a child with Down syndrome are predominantly caused by errors in the first female cell division. Handyside reports that this study gives credence that, following IVF,  multiple chromosome errors occur in both cell divisions.

Further research is needed to examine the pattern of these cell division errors and which type of ovary stimulation was used when these errors occurred. It may be beneficial to only use a natural cycle and only retrieve one egg or a milder stimulation where only a small number of eggs can be removed for IVF. This may cut out the cell division errors that appear to be happening when older women are receiving drugs to stimulate their ovaries prior to IVF. The results of such proposed research should help researchers clarify which is a better clinical strategy for at-risk groups undergoing IVF.

Handyside also believes this research will help point out which women should really use a donor egg for IVF since there is almost no chance that they will have a healthy pregnancy and successful birth outcome.

Results of this study will be presented to the European Society of Human Reproduction and Embryology on July 2011. Research that is not published in a peer-reviewed journal is considered preliminary.

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Review Date: 
July 4, 2011