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.

To report a case of a young girl initially diagnosed with exclusively 45,X Turner syndrome (TS), but with a cryptic mosaicism in the ovary. Case report. Radboud University Medical Center in the Netherlands. A 14-year-old girl with TS showing an exclusively 45,X cell line in lymphocytes, buccal cells, and urine cells in the presence of ovarian follicles. Laparoscopic unilateral oophorectomy was performed to obtain ovarian cortex tissue for fertility preservation purposes. One cortex fragment was used to determine the number of follicles by serial sectioning and staining, to perform fluorescence in situ hybridization (FISH) analysis and an in vitro growth (IVG) assay. FISH analysis of ovarian cells and the capacity of unilaminar follicles to develop to secondary follicles. FISH analysis revealed that most oocytes had a normal tetraploid X chromosomal content, the stromal cell compartment had both 45,X and 47,XXX cell lines, and all follicular granulosa cells had a 45,X karyotype. IVG assay showed that unilaminar follicles were capable of maturing to secondary follicles, but that the granulosa layers and membrana granulosa were distorted. We report a case where follicles were found in a girl with monosomic TS, in the presence of a cryptic mosaicism. Karyotyping of extraovarian cells was not predictive of the karyotype of ovarian cells in the same patient. Despite the presence of normal oocytes, our observation that all analyzed follicles contained exclusively 45,X granulosa cells embedded in mosaic 45,X/47,XXX stromal tissue may have functional consequences for follicular development. NCT03381300.

Introduction: Ovarian tissue cryopreservation (OTC) has proven to be effective in other patient groups, but the effectiveness in girls with Turner syndrome (TS) is still unclear. Guidelines for counselling about OTC in TS are lacking. The aim of this study was to gain insight into the experiences of patients, parents, and healthcare providers with the decision-making process regarding OTC in girls with TS. Methods: Within a year after counselling, a survey was sent to 132 girls with TS and their parents. Furthermore, focus groups were conducted with (1) gynaecologists with subspeciality reproductive medicine, (2) paediatric endocrinologists, (3) parents of girls aged 2–12, and (4) parents of girls aged 13–18. Transcripts were analysed using a thematic analysis approach. Results: The response rate of the survey was 45%. Of the survey respondents, 90% appreciated counselling regarding their future parenting options and considered it an addition to existing healthcare. Girls with TS and their parents indicated that the option of OTC raised hope for future genetic offspring and instantly made them feel that their only option was to seize this opportunity. Gynaecologists and paediatricians found it challenging to truly make families grasp a realistic perspective of OTC in girls with TS. Discussion and Conclusion: Offering young girls with TS the possibility of fertility preservation in an experimental setting raised high hopes and led to challenges for healthcare providers in ensuring a considered decision. The appropriate moment for counselling should be tailored to the individual and discussed with patient, parents, and paediatrician.

Background: Turner syndrome (TS) is accompanied with premature ovarian insufficiency. Oocyte vitrification is an established method to preserve fertility. However, data on the oocyte yield in women with TS who vitrify their oocytes and the return rate to utilize the oocytes are scarce. Methods: Retrospective multicenter cohort study. Data was collected from medical records of women with TS who started oocyte vitrification between 2010 and 2021. Results: Thirty-three women were included. The median cumulative number of vitrified oocytes was 20 per woman. Complications occurred in 4% of the cycles. Significant correlations were found between the cumulative number of vitrified oocytes and AMH (r = 0.54 and p < 0.01), AFC (r = 0.49 and p < 0.01), percentage of 46,XX cells (r = 0.49 and p < 0.01), and FSH (r = −0.65 and p < 0.01). Spontaneous (n = 8) and IVF (n = 2) pregnancies occurred in 10 women ± three years after vitrification. So far, none of the women have returned to utilize their vitrified oocytes. Conclusions: Oocyte vitrification is a feasible fertility preservation option for women with TS, particularly in those with 46,XX cell lines or sufficient ovarian reserve. Multiple stimulation cycles are recommended to reach an adequate number of vitrified oocytes for pregnancy. It is too early to draw conclusions about the utilization of vitrified oocytes in women with TS.

What are the considerations of girls with Turner syndrome and their parents to opt for or against ovarian tissue cryopreservation (OTC)? Semi-structured in-depth interviews were conducted with girls with Turner syndrome and their parents until data saturation was reached. Participants were recruited through purposive sampling. Data were analysed using a thematic analysis approach. Thirteen parents and five girls who opted for OTC, and seven parents and three girls who declined OTC, were interviewed. Parents and girls mentioned that OTC offered hope, an opportunity to have genetic offspring and clarity about their current fertility status. Most participants were not afraid of the risks of surgery and trusted healthcare providers with this procedure. In contrast, families had to deal with uncertainties, owing to the lack of information on the success rate and long-term consequences of OTC in this group. Families indicated that they had to go through an important decision-making process in a short period of time, because of the limited number of participants in the OTC study. A new opportunity and hope for future fertility were considerations for opting for OTC. However, OTC also came with uncertainties owing to the experimental nature of this procedure in girls with Turner syndrome. Healthcare providers could share these experiences with girls with Turner syndrome and their parents to improve fertility-preservation counselling in this group.