ESPE Abstracts

Introduction: Turner syndrome (TS) significantly impacts the reproductive lifespan of affected girls due to premature ovarian insufficiency (POI). To improve fertility counseling for (parents of) girls with TS, it is important to predict the ovarian reserve at an early age. However, this is challenging since data on longitudinal hormone parameters related to ovarian function are scarce. This study aims to initiate a first step towards a prediction model for ovarian function in prepubertal girls with TS.

Methods: A retrospective cohort study of females with TS born between 1964 and 2019. Levels of serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, anti-Mullerian hormone (AMH), testosterone and inhibin B, and information on karyotype and puberty were extracted from the medical records. A survival analysis was used to study the occurrence of POI during the follow up period. A mixed effects model was used to model the association between POI and longitudinal hormone levels.

Results: A total of 368 girls were included at a mean age of diagnosis 8.9 ± 4,5 years, and followed up for 13.2 ± 5,1 years. Among the cohort, 43% had a monosomic karyotype, 17% had a 45,X/46,XX karyotype, 14% had an isochromosome, and 26% had an ‘other’ karyotype. At the end of the study, 82 girls were still prepubertal, 114 (41%) had experienced a spontaneous thelarche and 81 (28%) a spontaneous menarche. Girls who experienced a spontaneous thelarche had a significant lower FSH (4.3 ± 7.9 U/L versus 12.6 ± 18.5 U/L (P <0.001)) and higher AMH (1.9 ± 1.6 ug/L versus <0.10 ± 0.01 ug/L (P <0.001)) compared to girls with induced puberty before the age of 10 years. POI after spontaneous thelarche occurred in 38% of the girls at a mean age of 17.7 ± 6.5 years. The occurrence and timing of POI showed significantly large differences between different AMH levels at pubertal onset (AMH<0,1; 0,1-1; 1-2 and > 2 ug/l) and between karyotype groups. A joint model was developed using longitudinal measurements of AMH and FSH levels to predict the onset of POI, although the predicted risk of POI varied widely.

Discussion: AMH and FSH levels contribute to understanding ovarian reserve at an early age (< 10 years) in girls with TS. Longitudinal follow up of hormonal markers in prepubertal girl with TS improves prediction of reproductive lifespan and with that supports the fertility counseling process.