Obstetrical and gynecological complications in fragile X carriers: A multicenter study

Abstract

We have conducted a multicenter obstetrical and gynecological survey of women in fragile X families. Included in the study were 131 gene carriers (39 with a full mutation and 92 with a premutation) and 109 noncarriers. Analysis indicated that higher numbers of fragile X gene carriers reported having irregular menses and other gynecological complications. As a group they also experienced cessation of menses prior to age 40 years at a significantly higher rate. The data appear to indicate that the FMR1 gene may play a role in the development and proliferation of oogonia.

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

“…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.…”

“…31 Some of the discordant conclusions given by earlier studies may be explained by the characteristics of the control groups. Three studies compared the incidence of expanded FMR1 CGG repeat lengths among women with POI with that of infertile controls, 13 of healthy family members of fragile X relatives, 4 and of postmenopausal women with timely onset of menopause. 30 Two other studies 28,29 compared the incidence of expanded CGG repeat lengths in women with reduced ovarian reserve with that of infertile women with normal ovarian reserve.…”

“…Because of the high incidence rates of POI among relatives suffering from fragile X syndrome 13,14 and as POI may be preceded by reduced ovarian reserve, 15 an increasing number of women presenting with infertility with or without POI are now being offered a FMR1 gene diagnostic test. Several medical organizations dealing with reproduction and obstetrics including the American College of Obstetricians and Gynecologists and the European Society of Human Reproduction and Embryology have decided to recommend FMR1 carrier testing in infertile women with signs of early onset of ovarian insufficiency 16 or to counsel women diagnosed with POI about their risk of carrying the premutation.…”

Reproductive and menstrual history of females with fragile X expansions

“…4 However, there is evidence that female premutation carriers are at increased risk of premature ovarian failure (POF) or menopause before the age of 40. 5,6 An international collaboration involving over 700 women from fragile X families concluded that premutation carriers over the age of 40 had approximately a 24% chance of having POF compared with < 1% of normal relatives and full mutation carriers. 6 Also studies of women ascertained because of POF have shown that they have about a 2% chance of being a premutation carrier, which can rise to 16% for familial cases.…”

Premature ovarian failure (POF) in Brazilian fragile X carriers

“…A possible association of the fragile X premutation with premature ovarian failure was first reported by Cronister et al (1991), who found eight women with POF among 61 normal fra(X) heterozygotes. In a multicenter study of obstetrical and gynecological complications in fra(X) carriers, Schwartz et al (1994) observed that premutated carriers had POF (25%) more frequently than noncarriers (6%). Vianna-Morgante et al (1996) described a threegeneration family in which POF segregated with the premutation.…”