Increased frequency of occult fragile X-associated primary ovarian insufficiency in infertile women with evidence of impaired ovarian function

Abstract

The data suggest that FMR1 premutations and intermediate alleles are increased in women with occult POI. Thus, FMR1 testing should be performed in these women as some will have fragileX-associated POI. Although the FMR1 repeat lengths were longer in women with occult POI, the data do not support the use of a repeat length cutoff to predict occult POI.

Similar prevalence of expanded CGG repeat lengths in the fragile X mental retardation I gene among infertile women and among women with proven fertility: a prospective study

“…29 In this study, in which the cohorts were selected based on (in) fertility issues entirely unrelated to the fragile X syndrome, the prevalence rates of expanded FMR1 CGG repeats among fertile women were comparable with known population-based incidence rates, whereas those of infertile women were comparable with the incidence rates found in another large scale survey among infertile women. 28 The number of women with expanded FMR1 CGG repeat numbers in this cohort among the women with overt POI was comparable to the incidence rates reported previously. 4,26 The review of all published controlled studies on the prevalence rates of expanded FMR1 CGG repeat numbers revealed that in the absence of a familial risk, the relative risk of carrying the premutation among infertile women with reduced ovarian reserve and/or POI was marginally increased 13,27 or similar 4,28,29 in all but one study.…”

“…28 The number of women with expanded FMR1 CGG repeat numbers in this cohort among the women with overt POI was comparable to the incidence rates reported previously. 4,26 The review of all published controlled studies on the prevalence rates of expanded FMR1 CGG repeat numbers revealed that in the absence of a familial risk, the relative risk of carrying the premutation among infertile women with reduced ovarian reserve and/or POI was marginally increased 13,27 or similar 4,28,29 in all but one study. 30 The prevalence rates of CGG repeat lengths of the intermediate range were similar among infertile women with reduced ovarian reserve and/or POI in all reviewed studies.…”

“…30 The prevalence rates of CGG repeat lengths of the intermediate range were similar among infertile women with reduced ovarian reserve and/or POI in all reviewed studies. 4,[27][28][29][30] Recently, no association with FMR1 CGG repeat length with the onset of natural menopause could be demonstrated. 31 Some of the discordant conclusions given by earlier studies may be explained by the characteristics of the control groups.…”

Evidence of an age-related correlation of ovarian reserve and FMR1 repeat number among women with “normal” CGG repeat status

“…Karimov et al analyzed 1056 patients (535 cases with low ovarian reserve and 521 infertile controls [unrelated to ovarian reserve] and oocyte donors) and reported that in addition to PM carriers, women who carried an intermediate ranged mutation (45-54 repeats) exhibited a higher prevalence of DOR [7]. Thereafter, four studies examined repeat lengths ranging from 35 to 54 and ovarian reserve or age at menopause [9,[23][24][25].…”

“…Emerging data suggest that not only the PM but also the intermediate repeat length are associated with both overt and occult POI [3,[7][8][9]. One group of investigators has suggested that low repeat number (<26) may also contribute to diminished ovarian reserve (DOR); however, these data have not been replicated [10].…”