Introduction The preservation of fertility is an integral part of care of children requiring gonadotoxic treatments for cancer or non‐malignant diseases. In France, the cryopreservation of ovarian tissue has been considered and has been offered as a clinical treatment since its inception. The aim of this study is to review 20 years of activity in fertility preservation by ovarian tissue cryopreservation (OTC) for children and the feasibility of oocyte isolation and cryopreservation from the ovarian tissue at a single center. Material and methods Retrospective study including patients aged 15 years or younger who underwent OTC, combined for some with oocyte cryopreservation of isolated oocytes, before a highly gonadotoxic treatment for malignant or non‐malignant disease was initiated. We describe the evolution of activities in our program for fertility preservation and patient characteristics at the time of OTC and follow up. Results From April 1998 to December 2018, 418 girls and adolescents younger than 15 years of age underwent OTC, representing 40.5% of all females who have had ovarian tissue cryopreserved at our center. In all, 313 patients had malignant diseases and 105 had benign conditions. Between November 2009 and July 2013, oocytes were isolated and also cryopreserved in 50 cases. The mean age of patients was 6.9 years (range 0.3‐15). The most frequent diagnoses in this cohort included neuroblastoma, acute leukemia and hemoglobinopathies; neuroblastoma being the most common diagnosis in very young patients. During follow up, three patients requested the use of their cryopreserved ovarian tissue. All had undergone ovarian tissue transplantation, one for puberty induction and the two others for restoring fertility. So far, no pregnancies have been achieved. Eighty‐four patients who had OTC died. Conclusions Ovarian tissue cryopreservation is the only available technique for preserving fertility of girls. To our knowledge this is the largest series of girls and adolescents younger than 15 years so far reported on procedures of OTC before highly gonadotoxic treatment in a single center.

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In vitro folliculogenesis could be a new technology to produce mature oocytes from immature follicles that have been isolated from cryopreserved or fresh ovarian tissue. This technique could also be a tool for evaluation of oocyte quality and/or for determination of follicular parameters during follicular growth. Our objective was to characterize in mice the secretion profiles of follicles that had been isolated mechanically during in vitro follicular growth and in relation to the growth curve. Early preantral follicles from fresh prepubertal and adult mouse ovaries or frozen-thawed prepubertal mouse ovaries were cultured individually in microdrops under oil for 12 days. Each day, two perpendicular diameters of the follicles were measured. From day-3 to day-12 of culture, culture medium was collected and preserved for determination of inhibin B, anti-Müllerian hormone (AMH) and estradiol levels. At the end of the culture, after maturation, the status of the oocyte was evaluated. Follicular growth and their individual hormone production did not always correlate. Inhibin B was never secreted from follicles of less than 200 μm diameter, whether the follicles were examined when fresh or after freezing-thawing. Estradiol secretion was never observed in frozen-thawed follicles. AMH was mainly secreted between day-3 and day-9. Despite similar morphological aspects at the start of culture, follicles selected for in vitro folliculogenesis were found to be heterogeneous and differed in their ability to grow and to produce hormones, even if they had similar growth curves. Follicles from frozen-thawed ovaries developed slowly and produced fewer hormones than freshly collected follicles.

Study question To evaluate the feasibility and results of a fertility preservation program for transgender men. Summary answer Ovarian stimulation outcomes are similar between transgender men and oocyte donation candidates, leading to a satisfactory mean number of cryopreserved oocytes. What is known already The reproductive potential of transgender people may be impaired by gender-affirming hormone treatment (GAHT) and is obviously suppressed in case of gender-affirming surgery involving bilateral ovariectomy and/or hysterectomy. The evolution of medical support for transgender people has made fertility preservation strategies possible. Fertility preservation in transgender men mainly relies on oocyte cryopreservation following controlled ovarian stimulation. However, few data are available to date on the subject, concerning small sample sizes, so no reliable conclusions can be drawn about the feasibility and efficiency of fertility preservation procedures in trans men. Study design, size, duration This retrospective study reports the results of fertility preservation counselling in 118 transgender men referred to our fertility centre from September 2018 to December 2022. Among them, 16 benefited from oocyte cryopreservation. Ovarian stimulation outcomes were compared with those of cisgender oocyte donors. Participants/materials, setting, methods Sixteen transgender men benefited from oocyte cryopreservation following ovarian stimulation and were matched 1:1 to cisgender oocyte donors according to age and body mass index. Antral follicle count and serum AMH levels were systematically measured. Primary outcomes included duration of the stimulation, total FSH dose, peak serum estradiol, oocyte yield, number of mature oocytes, and maturity rate (mature oocytes/total oocytes collected). Results were compared using Fisher’s exact or Wilcoxon’s rank sum tests. Main results and the role of chance One hundred and eighteen transgender men were referred in our centre for fertility preservation counselling. Among them, 95 asked for a medical consultation, and 86 came to the appointment. Following the consultation, only 16 (18.6%) finally decided to benefit from oocyte cryopreservation following ovarian stimulation, including 2 that had already started testosterone therapy. Sixteen presumably fertile oocyte donors were matched based on age and BMI. Mean age of trans’ men was 23.9 ± 5.0. Basal ovarian reserve tests showed satisfactory results in trans’ men and oocyte donors, with similar AMH (4.5 ± 2.3 vs. 4.4 ± 3.2, respectively, NS) but lower AFC in trans’men than in oocyte donors (13.8 ± 11.0 vs. 26.7 ± 10.1, p = 0.033). This result may be explained by a more frequent use of the abdominal approach to assess AFC in the transgender group. Ovarian stimulation outcomes were comparable, with no differences in the duration of stimulation, total FSH dose and peak estradiol levels, leading to a comparable mean number of mature oocyte (15.4 ± 9.9 vs. 17.2 ± 10.6, respectively, NS). Thirteen out 16 transgender men had 10 or more cryopreserved mature oocyte following a single procedure. Limitations, reasons for caution Only a low percentage of trans men that were referred to our centre finally chose to perform oocyte cryopreservation, leading to a small sample size. The majority of them had not started any GAHT, preventing us to evaluate the potential consequences of these treatments on ovarian stimulation outcomes. Wider implications of the findings While parenthood strategies for transgender people have long been ignored, fertility preservation is an important issue to consider, especially because medical treatments and surgeries may be undertaken in very young adults. Oocyte cryopreservation seems to represent a feasible way for trans men to preserve their fertility for future biological parenting. Trial registration number N/A