Premature ovarian failure (POF) is the occurrence of menopause before the age of 40 and affects 1% of the female population. Whereas the etiology of POF is largely unexplained, FMR1 premutation carriers are known to be at increased risk of POF compared with the general population. The FMR1 premutation alleles have 55-200 copies of a CGG repeat in the 5' untranslated region of the FMR1 gene. However, functional effects on gene expression may occur even for repeat sizes in what has been considered the "normal" range. To evaluate the role of the FMR1 repeat in POF, repeat sizes were examined in 53 women with idiopathic POF, 161 control women from the general population, and 21 women with proven fertility at an advanced maternal age. A significant increase in the number of FMR1 alleles between and including 35 and 54 CGG repeats was found in the POF patient population; 15 of 106 (14.2%) POF alleles were between and including 35 and 54 repeats, whereas only 21 of 322 (6.5%) alleles in the general population (P=0.02) and 2 of 42 (4.8%) alleles from women with proven late fertility (P=0.09) were of this size (P=0.01 versus combined controls). The effect was also significant for comparisons of genotype repeat size (repeat size weighted by the relative activity of the two FMR1 alleles) and biallelic mean (average size of the two alleles). These results are clinically relevant and suggest that the FMR1 gene plays a more significant role in the incidence of POF than has previously been thought.
Treatment with ganirelix effectively prevents premature LH rises, luteinization in subjects undergoing stimulated IUI. Low-dose rFSH regimen combined with a GnRH antagonist may be an alternative treatment option for subjects with previous proven luteinization or in subjects who would otherwise require insemination when staff are not working.
BACKGROUNDRate of reproductive aging may be related to rate of biological aging. Thus, indicators of aging, such as short telomere length, may be more frequent in women with a history suggestive of premature reproductive senescence.METHODSTelomere-specific quantitative PCR was used to assess telomere length in two groups of women with evidence of reproductive aging: (i) patients with idiopathic premature ovarian failure (POF, N = 34) and (ii) women with a history of recurrent miscarriage (RM, N = 95); and two control groups: (1) women from the general population (C1, N = 108) and (2) women who had a healthy pregnancy after 37 years of age (C2, N = 46).RESULTSThe RM group had shorter age-adjusted mean telomere length than controls (8.46 versus 8.92 kb in C1 and 9.11 kb in C2, P = 0.0004 and P = 0.02 for C1 and C2, respectively), although short telomeres were not confined to subsets of this group known to have experienced single or multiple trisomic pregnancies. Although sample size is limited, mean telomere length in the POF group was significantly longer than that in C1 (9.58 versus 8.92 kb, P = 0.01).CONCLUSIONSWomen experiencing RM may have shorter telomeres as a consequence of a more rapid rate of aging, or as a reflection of an increased level of cellular stress. Longer telomere length in the POF group may be explained by abnormal hormone exposure, slow cell division rates or autoimmunity in these women. Despite small sample sizes, these results suggest that different manifestations of reproductive aging are likely influenced by distinct physiological factors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.