Cytogenetic analyses of premature ovarian failure using karyotyping and interphase fluorescence in situ hybridization (FISH) in a group of 1000 patients

Abstract

To evaluate the implication of chromosome abnormalities in the etiology of premature ovarian failure (POF), 1000 patients with POF recruited at the Department of Cytogenetics of Farhat Hached Hospital (Sousse, Tunisia) between January 1996 and December 2008. Chromosome analyses were performed by using karyotyping and interphase fluorescent in situ hybridisation (FISH) using a centromeric probe of the chromosome X to look for low-level mosaicism of X-chromosome monosomy. Hundred and eight chromosomal abnormalities (10.8%) were found using karyotype analysis. Anomalies were detected in 61 cases out of 432 primary amenorrhea patients (14.12%) and 47 cases out of 568 secondary amenorrhea patients (8.27%). In 23 POF patients among 200 (11.5%) with 46,XX normal karyotype and explored using interphase FISH analysis, the percentage of cells with X-chromosome monosomy was significantly higher as compared with controls in the same age. The cytogenetic study of POF patients showed a high prevalence of chromosome anomalies either in primary or in secondary amenorrhoea. Mosaic X-chromosome s aneuploïdy was the most frequent abnormality and some patients with POF may be attributable to low-level 45,X/46,XX mosaicism detectable using FISH analysis.

Cytogenetic Analysis of 65 Women with Premature Ovarian Insufficiency

“…There is no clear evidence to indicate the effect of an X trisomy on human fertility, as the strong relationship between an X trisomy and POI is clearly revealed [22]. In fact, our data may support that women with X chromosome mosaicism may experience premature menopause [13,20]. The prevalence of 47,XXX in cases with mosaic pattern was 10.7 %, which is higher than the prevalence reported by Goswami et al [5] (3.8%) and Jiao et al [12] (1.5%), respectively.…”

“…The different prevalence in these studies probably results from selection biases because women with primary amenorrhea were included for analysis in some of the studies from different countries. The strong relationship between X chromosome and ovarian function and the etiology of POI is commonly highlighted in the literature [5,13]. A Dutch study also indicated the relationship between X chromosome and the broader spectrum of menopausal age and POI [19].…”

“…When compared to our results, some studies reported higher frequency while others reported lower frequency of chromosomal abnormalities. The prevalence of chromosomal abnormalities reported in previous studies is presented in Table 3 [1,4,[12][13][14][15][16][17][18]. The different prevalence in these studies probably results from selection biases because women with primary amenorrhea were included for analysis in some of the studies from different countries.…”

Possible influence of menstrual cycle on lymphocyte X chromosome mosaicism

“…Although fluorescence in situ hybridization (FISH) may be the most appropriate method for detecting low level X chromosome mosaicism [9,14] we evaluated the presence of aneuploid metaphases by routine G-banding chromosome analysis, in order for the results to be comparable with some previous studies [5,6,12]. However, according to the International System for Human Cytogenetic Nomenclature (ISCN), numerical and structural abnormalities still have to be excluded at a banding level appropriate to the referral's guidelines [1,25,26].…”

“…Some authors consider it to be the presence of ≤10 % of aneuploid cells [4][5][6], others the presence of <6 % of aneuploid cells [7]. It can be found in women with premature ovarian failure, infertility or a history of recurrent pregnancy loss [4][5][6][8][9][10][11][12][13][14]. In the general population X chromosome loss correlated with age has been described [1,3,15].…”