Fertility in Turner Syndrome
Turner syndrome affects 1 in 2000 liveborn females and is associated with partial or complete loss of one X chromosome in a 46,XX foetus or of loss of a Y chromosome in a 46,XY foetus, resulting in monosomy of the X chromosome.[8–10] It is characterized by ovarian failure, which occurs prior to puberty in most cases. Approximately 30% of women with TS have a mosaic peripheral blood karyotype, where 45,X is present only in some cells. Women with 45,X mosaicism have a 45,X cell line which coexists with at least one non-45,X cell line, for example, 45,X/46,XX, 45,X/47,XXX, 45,X/46,XX/47,XXX, 45,X/46,X,i(Xq), 45,X/46,XY. Mosaicism is thought to account for much of the variability in phenotype, including the degree of ovarian dysfunction. Rigorous analysis for mosaicism can be performed with karyotype of an adequate number of peripheral blood leucocytes (e.g. 100 cells), analysis of cells from more than one tissue type or via fluorescence in situ hybridization (FISH) with X and Y probes.[11,13]
Women with TS and a mosaic karyotype containing a Y chromosome, for example, 45,X/46,XY, usually have complete gonadal dysgenesis and streak gonads. In these gonads, which are unlikely to have potential for fertility or significant hormone production, the risk of germ cell malignancy is 10–15% due to presence of Y chromosomal material.[14,15] Risk-reducing gonadectomy should be considered in this group after diagnosis.
Spontaneous puberty occurs in 15–30% of girls with TS and 2–5% experience menarche. Approximately 2–5% of women with TS are able to conceive.[7,17] It has therefore been recommended that counselling for young TS women who undergo spontaneous pubertal development should include potential for spontaneous unintended pregnancy, contraception, and education regarding complications in pregnancy.
Current evidence suggests that 45,X germ cells are unable to complete meiosis and are eliminated during germ cell development.[18,19] When ovarian follicles are observed, they originate from small numbers of 46,XX germ cells and not from 45,X cells.[18,20] The likelihood of functional ovarian tissue in women with TS therefore relies on the presence of 46,XX germ cells in the ovaries. As expected, fertility is more likely to be retained in women with 45,X/46,XX mosaicism rather than complete monosomy 45,X.[7,17,21] Even in the presence of initially functioning ovarian tissue, development of premature ovarian failure remains common, and the risk of chromosomal abnormality in the offspring of women with mosaic TS appears to be increased compared with the general population.[22,23]
It is worth noting that a completely nonmosaic 45,X karyotype in peripheral blood leucocytes does not preclude the coexistence of 45,X/46,XX mosaicism in the ovary. A significant proportion of 45,X conceptions are thought to result from postzygotic loss of the second sex chromosome, implying that mosaicism is frequently present, even when not detectable in blood. Such phenomena may explain a report describing multiple spontaneous pregnancies in two women with 45,X TS. In one of the women, both karyotype and FISH analysis confirmed classical monosomy X in peripheral blood. The other woman had monosomy 45,X in 199 of 200 metaphases, with 47,XXX found in one.
Approximately 40% of women with TS have a structural abnormality of the second X chromosome, resulting in partial X monosomy, such as deletion Xp, ring X and isochromosome Xq. For these categories, mosaicism with 45,X or 46,XX cell lines is common. Some structural abnormalities of the X chromosome, for example, loss of the distal part of Xp, are compatible with spontaneous menarche and fertility, and there are examples of mother–daughter transmission. Risk to offspring is increa-sed: male embryos that inherit the structurally abnormal X will usually be nonviable, and female offspring are at risk of a more severe phenotype if X-inactivation does not favour the intact X.
Clin Endocrinol. 2013;79(5):606-614. © 2013 Blackwell Publishing