SUN-263 Evidence for Diminished Ovarian Reserve in Youth with Trisomy X

Abstract

Background: An additional X chromosome occurs in 1 in 1,000 females resulting in a 47,XXX karyotype also known as Trisomy X. Abnormal ovarian function was suggested from a cohort of 10 females with Trisomy X followed from birth through young adulthood who had later age of menarche and one girl who developed secondary amenorrhea with elevated gonadotropin levels (1). There have since been several case reports of premature menopause in women with Trisomy X, and 3.8% of women with premature ovarian insufficiency (POI) have been reported to have Trisomy X (2). Ovarian reserve can be estimated by serum anti-mullerian hormone (AMH) concentrations, with low AMH concentrations concerning for diminished ovarian reserve and poor fertility prospects. Ovarian function in youth with Trisomy X has not been evaluated. The purpose of this study was to evaluate AMH as a marker of ovarian reserve in girls with Trisomy X. Methods: Parents and youth with Trisomy X seen at a tertiary care referral center were counselled on the risk for POI and AMH was offered as a screen for ovarian reserve. All participants provided informed consent to use their clinical data for research purposes. A total of 11 girls with a non-mosaic 47,XXX karyotype had AMH measured by chemiluminescent assay (Esoterix Laboratory Services) between December 2015 and October 2018. Results: The median age of participants was 13.3 years (IQR 12.4 – 17.9) and 9 of 11 girls had experienced menarche at a median age of 12.5 years (IQR 11.5-12.6); none had primary or secondary amenorrhea. The median AMH concentration was 0.7 ng/ml (IQR 0.2-1.7), significantly lower than the laboratory provided median of 5.23 ng/ml (one sample Wilcoxin Signed Rank Test p=0.001). 72% had an AMH below 1.05 ng/ml, the lower limit of normal for age. Discussion: Despite normal menarchal timing and ongoing menses, the majority of youth with Trisomy X had a low AMH concerning for diminished ovarian reserve and potentially impaired fertility. Although there is great interest in fertility preservation for girls with oncological diagnoses and Turner syndrome, there is limited awareness of ovarian dysfunction in Trisomy X. Research on ovarian function and fertility in Trisomy X is needed across the lifespan, as well as investigation into the mechanisms of the additional X chromosome leading to the diminished ovarian reserve observed in this adolescent sample. (1) Ratcliffe et al, 1990, Birth Defects: Original Article Series, 26(4): 1-44. (2) Goswami et al, 2003, Fertil Steril, 80(4): 1052-4.