TurnerFertility trial: fertility preservation in young girls with Turner syndrome by freezing ovarian cortex tissue—a prospective intervention study

Abstract

Which girls with Turner syndrome (TS) could benefit from fertility preservation by ovarian tissue cryopreservation (OTC) based on karyotype, puberty status and hormonal data? Prospective intervention study. Participants were included between 2018 and 2020. In total, 106 girls with TS, aged between 2 and 18 years were included. Girls with minor X chromosome deletions, Y chromosomal content, active infections, or contra-indications for surgery were excluded. Laparoscopic unilateral ovariectomy was performed to obtain ovarian cortical tissue for cryopreservation. One tissue fragment per participant was used to determine the number of follicles per ovary by serial sectioning and staining. Chromosome analysis was performed on lymphocytes and buccal cells. A blood sample was taken before ovariectomy for hormonal analysis. The presence of follicles in ovarian cortex tissue from girls with TS in relation to karyotype, puberty status, and hormonal data. Unilateral ovariectomy was performed in 93 girls with TS. Complications after surgery occurred in 5 girls, including luxation of psychological symptoms in 2 girls. In 13 girls (14%), a 46,XX cell line was found in buccal cells which was absent in lymphocytes. Follicles were observed in 30/93 girls (32%) and were mainly found in girls with a 46,XX cell line in lymphocytes or buccal cells (correlation ϕ=0.55, P < 0.001). Spontaneous onset of puberty (ϕ=0.59, P < 0.001), Anti-Müllerian hormone (AMH; r=0.82, P < 0.001), inhibin B (r=0.67, P< 0.001) and FSH (r=-0.46, P < 0.001) were also strongly correlated with the presence of follicles. Furthermore, AMH had a significant correlation with the number of follicles per ovary (r=0.66, P < 0.001). Favorable predictive markers for the presence of follicles included either a 46,XX cell line, spontaneous onset of puberty or combination of a measurable AMH and normal FSH.