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15 GENERAL INTRODUCTION AND THESIS OUTLINE 1 However, not for everybody fertility preservation is available prior to the start of gender- affirming treatment. Due to limited capacity of gender identity clinics, waiting lists for access to gender-affirming care are often long. Therefore, many transgender people seek alternative routes and even start using illicitly obtained hormones. Besides, some trans women choose to keep the male gonads and discontinue gender-affirming medication when an active desire for children emerges.Very little is known about the long-term effects of hormone treatment on gonadal function and gametes, and therefore the feasibility of fertility preservation in trans women who already started GAHT remains uncertain. Theoretically, serum testosterone concentrations will increase after cessation of GAHT which will provide for adequate circumstances for restoration of spermatogenesis, but data on semen quality after prolonged GAHT and outcomes of children born from these gametes are limited. 39 For some trans women, semen cryopreservation prior to, or after discontinuation of, GAHT is not a realistic option,such as for peoplewho start medical transition in an earlypubertal stage (Tanner stage 2) when they do not have complete spermatogenesis yet. In this group, choices regarding fertility may pose a difficult dilemma as they often feel an extreme pressure to transition early in order to prevent irreversible development of secondary sex characteristics, such as lowering of the voice and facial hair growth. Therefore, cryopreservation of germ cells harvested from testicular tissue that is removed during GAS may be their only option for genetically related offspring. How, and if, these germ cells can be used for procreation depends on their maturation phase. Mature spermatozoa can directly be used for assisted reproductive techniques. The use of immature germ cells, conversely, relies on the possibility of in vitro spermatogenesis. Unfortunately, complete in vitro spermatogenesis has only been successfully demonstrated in mouse models, and still unsuccessful in human. 40 However, if in vitro spermatogenesis becomes available in the future, cryopreservation of immature germ cells might be a promising option for fertility preservation in those who started their medical transition in early pubertal stage. Currently, limited data is available on the effect of GnRHa and GAHT on testicular histology and the most advanced germ cell type that can be harvested form testicular tissue obtained at time of GAS. Moreover, previous studies that have been conducted on this topic showed contrasting results, ranging from a complete absence of germ cells to full spermatogenesis. 29 Risk for cancer of the male genital tract during gender-affirming hormone use Where limited research is published on the effect of GAHT on testicular histology and spermatogenesis, even less is reported about the influence on the occurrence of testicular cancer in trans women using GAHT, and only a few cases have been described. 41-45 As mentioned previously, exposure to exogenous estrogens is suggested to play a stimulating role in testicular cancer development. Since the abolition of transgender laws that required sterilization for legal gender recognition, an increasing number of people with non-binary identities or less need to confirm to binary cis presentation choose to keep their male gonads. As a consequence, in the future we might be faced with a growing population of young trans women using GAHT, who are still at risk for testicular cancer.