P-485 The TurnerFertility study: data on fertility preservation (FP) by ovarian tissue cryopreservation (OTC) in young girls with Turner syndrome (TS)
Authors: Fleischer K , Nadesapillai S , Van der Velden J , Schleedoorn M , Van der Coelen S , Braat D , Peek R 
Published: June 2022

Study question

Which girls with TS could benefit from FP by OTC, based on the presence of follicles in relation to karyotype, clinical and hormonal data?

Summary answer

Girls with TS who have favourable predictive parameters (e.g 46,XX cell line, a measurable AMH or spontaneous puberty) could benefit from FP by OTC.

What is known already

Infertility due to premature ovarian insufficiency is a major concern for girls with TS and their parents. Physicians are often asked about possible options to preserve their fertility. However, evidence for successful FP by OTC in these girls is lacking. Without evidence on the effectiveness of OTC in TS girls, it should only be offered in a research setting.

Study design, size, duration

A national prospective exploratory intervention study. Ovarian cortex will be obtained after unilateral ovariectomy from 106 girls with TS aged 2-18 years. Patients will be included between 2017 and 2022.

Participants/materials, setting, methods

All girls with TS who have completed the diagnostic work up of TS were included. After unilateral ovariectomy, one fragment of the ovarian cortex was used to determine the number of follicles by serial sectioning and staining. Karyotyping of ovarian cells, lymphocytes, buccal cells and urine cells was performed by Fluorescence in situ hybridization (FISH). Blood samples obtained before oophorectomy and during the yearly clinical visit after oophorectomy will provide information on hormonal parameters.

Main results and the role of chance

Currently, we have received 106 informed consent forms and 86 TS patients (age 3-19) had a unilateral ovariectomy. Oocytes were found in 32,6% (n = 28; age 5-19) of which 11 were prepubertal, 16 had a spontaneous puberty, 22 had numerical chromosome X aberrations, of whom one 45,X monosomy and 6 had structural chromosome X aberrations. In 6 patients with structural aberrations we found a low follicle density. In 24/28 patients AMH was measurable (0.1 - 4.79µg/L) and 25/28 patients had a FSH below 15 E/L.

FISH was used to karyotype the ovarian cortex cells of 12 patients with a numerical aberration and revealed that 112 of the 119 oocytes (94,1%) had a normal X-chromosomal content. Granulosa cells were largely 45,X, but showed different levels of X chromosome mosaicism, not only between patients but also between individual follicles of the same patient. Despite the level of aneuploidy (0–80%) of ovarian stromal cells, no obvious morphological/histological abnormalities were observed in the ovarian cortex tissue.

Hormone values and the chromosome pattern were found to be predictive parameters for the presence of follicles. The chance of finding follicles in girls with a 46,XX cell line was three times higher than in girls without a 46,XX cell line.

Limitations, reasons for caution

The final analysis will be performed when the dataset of 106 TS girls is completed. Further research is necessary to determine the effects of ovarian mosaicism on folliculogenesis, i.e. are follicles capable to grow to antral stages, and to elucidate if OTC is an effective method for FP in TS.

Wider implications of the findings

A combination of clinical, hormonal and karyotypic data could provide predictive parameters to define which girls with TS might benefit from fertility preservation. These parameters could help physicians during FP counselling to determine if OTC is an option for a certain girl with TS.

Trial registration number

NCT03381300