Puberty progression in girls with Turner syndrome after ovarian tissue cryopreservation.

Abstract

Objective: To study the impact of unilateral ovariectomy for ovarian tissue cryopreservation (OTC) on the function of the remaining ovary in girls with Turner syndrome.

Design: A prospective cohort study as a follow-up of OTC in a research setting (the TurnerFertility trial, NCT03381300).

Setting: University Hospital.

Patient(s): A total of 28 girls with Turner syndrome with follicles in their cryopreserved ovarian cortex tissue, aged 5-19 years. Of the 28 girls, 21 had a 45,X/46,XX mosaic karyotype; 5 had structural aberrations of the X chromosome; 1 had a 45,X monosomy; and 1 had a 45,X/47,XXX karyotype.

Intervention(s): Girls were monitored annually after OTC for pubertal development and levels of antimüllerian hormone (AMH), follicle-stimulating hormone, luteinizing hormone, estradiol, and inhibin B.

Main outcome measure(s): Thelarche, menarche, and onset of premature ovarian insufficiency.

Result(s): The girls were monitored for a median duration of 3.4 years (maximum 6.6 years). The pubertal development of five prepubertal girls is still unknown; all were aged <10 years and had low gonadotropin and estradiol levels at the end of the follow-up. Seven of the eight girls of approximately pubertal age (10-12 years) experienced spontaneous thelarche, although one received medication to induce puberty. Eleven of the 14 girls between the ages of 14-17 years experienced spontaneous menarche; three other girls with thelarche still had ongoing puberty at the end of follow-up with normal gonadotropins and AMH levels above the detection limit. Approximately 6-12 months after OTC, a decline in AMH concentration was observed in 57% (16/28) of girls, followed by an increase in AMH concentration in the following years. Six of the total 28 girls started hormone replacement therapy because of symptoms of premature ovarian insufficiency, and all had AMH levels <0.50 μg/L before OTC.

Conclusion(s): Pubertal development progressed after unilateral ovariectomy for OTC in most girls with Turner syndrome. Hormone replacement therapy was required within a few years for girls with unfavorable parameters before OTC, such as AMH levels <0.50 μg/L. Decisions regarding OTC should be personalized, considering the girl's preferences and specific characteristics.

Clinical trial registration number: NCT03381300-Preservation of ovarian cortex tissue in girls with Turner syndrome-Full Text View-ClinicalTrials.gov. Registered on: December 21, 2017. The first patient was recruited on January 1, 2018.