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March 30th, 2007, 11:54 AM
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miraceti miraceti is offline
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Some details about genetic causes - aneuplody - trisomy - advanced maternal age:

For basic knowledge about aneuplody, trisomy and non-disjunction go to : http://en.wikipedia.org/wiki/Aneuploidy and http://en.wikipedia.org/wiki/Nondisjunction

Recurrent aneuploidy happens to some couples who produce chromosomally abnormal eggs or sperm not as a result of translocation but because they have a tendency toward non-disjunction. Non-disjunction means that wrong number of chromosomes is present in the embryo: Trisomy is the most common - 3 copies of chromosome, most known Down syndrome-3 copies of number 21 chromosome instead of 2 (in recurrent aneuplody this does not mean that the chromosome involved in the trisomy is always the same, that can vary), Monosomy: X with only one X chromosome (Turner syndrome). Polyploidity – too many extra sets of 23 chromosomes. (1)

Statistics:
* as many as 50% of early miscarriages are caused by chromosomal abnormalities in the fetus, nearly all of the chromosomal defects seen in sporadic miscarriages arise out of the blue (1)
* Study in Italy performed on 3000 women showed that calculated miscarriage rate was 15%, (6% for women less than 35y and 25% for women with more than 40y) With genetically analyze of all of the miscarriages they found that in the 40y incidence of chromosomal abnormalities was over 80%. (1)
*As older women reproduce, the frequency of aneuploidy goes up. This can be best appreciated by comparing the data from two studies of human miscarriages conducted 20 years apart; the proportion of miscarriages with trisomy has doubled (from 23% to 46%), almost certainly because of the change in the maternal age distribution(from average 28y to 34,7y). (5)

Reasons:
*Tendency to non-disjunction may be inherited or induced because environmental factors. At the present time we do not understand all the mechanisms that cause this problem, although we do know that the risk of trisomies increases with maternal age (1)
* It is also possible that some couples are at increased risk of abnormalities as a result of gonadal mosaicism, increased sperm aneuploidy in the male partner ... Recently, reduced total follicular number in the ovaries has been associated with increased risk for trisomy. An altered risk for trisomy in some individuals may also be the consequence of variants in proteins affecting DNA methylation or chromosome segregation during meiosis. For example, polymorphisms in genes involved in folic acid metabolism, as well as differences in folic acid intake, are possible maternal risk factors associated with Down syndrome (trisomy 21), although they were not found to be increased among women who had M/Cs involving trisomy. Mutations in hMSH2, a mismatch repair gene, have been associated with a significant increase in chromosomally abnormal sperm. Environmental factors, such as caffeine intake, have also been implicated as modifying risk for trisomy 21. (2)
* There are some reports that if our mothers were exposed to some chemicals we can have problems with chromosomally abnormal eggs: “exposure to low doses of BPA -bisphenol A during the final stages of oocyte growth [in female fetuses] disrupts meiotic chromosome behavior, resulting in the production of chromosomally abnormal eggs. Humans are exposed to BPA on a daily basis; it is a component of polycarbonate plastics, resins lining food/beverage containers, and additives in a variety of consumer products... BPA is only one of many chemicals with hormone-like actions, and our results suggest that low-dose exposure during fetal development has the potential to impact the entire cohort of oocytes produced by a female. Further, because this is a ‘grandmaternal’ effect (i.e. exposure of a pregnant female influences the genetic quality of the offspring of her female fetuses), documenting an effect of this type in humans would require studies spanning several generations.” (4)

Prognoses for future pregnancies:
The risk of you having another miscarriage after miscarrying a chromosomally abnormal pregnancy is very low, lower than risk of miscarrying again after you have suffered a chromosomally normal miscarriage, as chromosomally normal miscarriages are less random than abnormal ones (some other cause was responsible if the baby was chromosomally normal). (1) For example, one recent study has reported 29% of abnormal karyotypes in 167 patients with 3±16 M/C before 20 weeks. These authors found that after an aneuploid miscarriage, there was a 68% live birth rate for a subsequent pregnancy compared with 41% after an miscarriage with chromosomaly normal karyotype . (3)

Some natural ways to improve egg quality:(suggestions from different sources)
- a high protein/high fat diet, less sugar and carbs, no alcohol and coffeine helps with good egg development
- supplement with Co-Enzyme Q-10, which helps to support and improve mitochondrial functioning, the powerhouse of the cell. One of the hallmarks of aging is damage to mitochondrial DNA caused by oxygen metabolism and the presence of free radicals in the system.
- supplement with the antioxidants vitamins C, E, A, zinc, and selenium, B vitamins, and pycnogenol or OPC (oligomeric proanthocyanidins) to limit oxidative damage,
- supplement with powerfoods like supergreens (wheatgrass, chlorella, spirulina)
- suplements with L-Arginine helps increase blood flow to the ovaries (can be taken in food - for example fresh cooked turkey breast and whole almonds)
- Royal jelly

Sources:
(1)Miscarriage – What Every Woman Needs to Know – A Positive New Approach Prof. Lesley Regan, 1997, 2001, second impression 2004
(2)The Origin of Abnormalities in Recurrent Aneuploidy/PolyploidyW. P. Robinson, D. E. McFadden, and M. D. Stephenson, Departments of Medical Genetics, Pathology, and Obstetrics and Gynaecology, University of British Columbia, Vancouver, Am. J. Hum. Genet. 69:1245–1254, 2001
(3) Chromosomal abnormalities and embryo development in recurrent miscarriage couples C.Rubio, C.SimoÂn , F.Vidal, L.Rodrigo, T.Pehlivan, J.Remohõ and A.Pellicer, Instituto Valenciano de Infertilidad, Valencia, Spain. Human Reproduction Vol.18, No.1 pp. 182±188, 2003
(4) Biochem. Soc. Trans. (2006) 34, (574–577)
(5) Scrambling Eggs in Plastic Bottles, R. Scott Hawley, Dorothy Warburton , PLOS Genetics Jurnal 2007
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