Karyotype is associated with timing of ovarian failure in women with Turner syndrome

Abstract

Abstract Objective To characterize the age of ovarian failure in Turner Syndrome (TS) patients by karyotype. Methods Retrospective cohort study of individuals with TS at an academic university hospital. Subjects were seen in TS Clinic at UNC Hospital between 2014 and 2018. Individuals were analyzed by karyotype category (45X, 45X/46XX mosaicism, miscellaneous) and percentage of 45X cells. Age at follicle-stimulating hormone> 30 was defined as the age at loss of ovarian function. Results A total of 79 patients were identified after excluding individuals with unknown ovarian function and those with Y chromosome material. Thirty-eight percent were 45X monosomic, 62% were 45X/46XX mosaic or miscellaneous karyotypes. Fifty-five of 79 (70%) patients had evidence of ovarian failure, median age of failure 11 years (IQR: 4,12). Ovarian failure was more prevalent among individuals with 45X karyotype (100%). The median age of ovarian failure for 45X patients (n=30) was 10 years old, which is significantly younger than other karyotypes (n=49), with a median of 15 years, p<0.01. Linear regression analysis found that 1 percentage point increase in 45X cells in the peripheral karyotype is associated with a 0.09 year decrease in age of ovarian failure (p value=0.01). Only 9% of individuals were referred for fertility counseling. Conclusions There is a lower prevalence of ovarian failure among individuals with mosaic TS karyotypes, and referral rate for fertility counseling of patients with TS is low. These findings are in line with published literature. The finding that percentage of 45X cells in peripheral karyotype is associated with earlier age of ovarian failure is novel and warrants further investigation in a larger prospective cohort.