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.

BACKGROUND: Girls with Turner syndrome (TS) lack a partial or complete sex chromosome, which causes an accelerated decline of their ovarian reserve. Girls have to deal with several dilemmas related to their fertility, while only a limited number of them are referred to a fertility specialist and counselled about options of family planning on time. OBJECTIVE AND RATIONALE: This scoping review provides an update of the literature on fertility in girls with TS throughout their lifespan and aims to propose a clinical practice guideline on fertility in TS. SEARCH METHODS: Databases of PubMed, Embase, and Web of science were searched using the following key terms: Turner syndrome, fertility, puberty, pregnancy, sex-hormones, karyotype, fertility preservation, assisted reproductive techniques, and counselling, alongside relevant subject headings and synonymous terms. English language articles published since 2007 were critically reviewed. Pregnancies after using donated oocytes and data about girls with TS with Y-chromosomal content were excluded. OUTCOMES: This search identified 1269 studies of which 120 were extracted for the review. The prevalence of natural conception ranged from 15% to 48% in women with 45,X/46,XX, 1% to 3% in women with 45,X, and 4% to 9% in women with other TS karyotypes. When assessing a girl’s fertility potential, it was crucial to determine the karyotype in two cell lines, because hidden mosaicism may exist. In addition to karyotype, assessment of anti-Müllerian hormone (AMH) played a significant role in estimating ovarian function. Girls with AMH above the detection limit were most likely to experience spontaneous thelarche, menarche, and ongoing ovarian function during the reproductive lifespan. Fertility preservation became more routine practice: vitrification of oocytes was reported in 58 girls with TS and a median of five oocytes were preserved per stimulation. Ovarian tissue cryopreservation has demonstrated the presence of follicles in approximately 30% of girls with TS, mostly in girls with mosaic-TS, spontaneous puberty, and AMH above the detection limit. Although girls and their parents appreciated receiving counselling on fertility in TS, only one in ten girls with TS received specialized counselling. Unfamiliarity with fertility preservation techniques or uncertainties regarding the eligibility of a girl for fertility preservation constituted barriers for healthcare professionals when discussing fertility with girls with TS. WIDER IMPLICATIONS: There currently is a high demand for fertility preservation techniques in girls with TS. A reliable prognostic model to determine which girls with TS might benefit from fertility preservation is lacking. Only a minority of these girls received comprehensive fertility counselling on the full spectrum of fertility, including uncertainties of fertility preservation, pregnancy risks, and alternatives, such as adoption. Fertility preservation could be a viable option for girls with TS. However, the question remains whether enough oocytes can be obtained for a realistic prospect of a live birth. It is important that girls and parents are empowered with the necessary information to make a well-informed decision.

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.

To study the impact of unilateral ovariectomy for ovarian tissue cryopreservation (OTC) on the function of the remaining ovary in girls with Turner syndrome. A prospective cohort study as follow up of OTC in a research setting (The TurnerFertility trial, NCT03381300). University hospital in Nijmegen, the Netherlands. 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 girls had a 45,X/46,XX mosaic karyotype, five had structural aberrations of the X-chromosome, one girl had a 45,X monosomy, and one girl had a 45,X/47,XXX karyotype. Girls were monitored annually after OTC for pubertal development and levels of anti-Müllerian hormone (AMH), Follicle Stimulating Hormone, Luteinizing Hormone, Estradiol, and Inhibin B. Thelarche, menarche and onset of premature ovarian insufficiency. 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 under the age of 10 and had low gonadotropins and estradiol levels at the end of the follow-up. Seven of the eight girls around pubertal age (10-12 years) experienced spontaneous thelarche, while one received medication to induce puberty. Eleven of the fourteen girls between the age 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. Around six to twelve months after OTC, a decline in AMH concentration was observed in 57% of girls (16/28 girls), followed by an increase in AMH concentration in the following years. Six of the total 28 girls started hormone replacement therapy due to symptoms of premature ovarian insufficiency, and all had AMH levels below 0.50 μg/L before OTC. 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 below 0.50 μg/L. Decisions regarding OTC should be personalized, considering the girl's preferences and specific characteristics.

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.