Iris de Nie

84 C H A P T E R 6 INTRODUCTION Gender dysphoria refers to the distress experienced by people with an incongruence between their sex assigned at birth and their gender identity. 70 People assigned male at birth with a female gender identity are referred to as transgender women. Many transgender women seek medical treatment to avoid (further) masculinization and induce feminization, and hereby align their physical characteristics with their gender identity. The preferred treatment protocol depends on the person’s age at time of start of medical treatment. For adolescents ( < 18 years), treatment can be initiated when a person reaches puberty (Tanner stage 2 or higher, determined by the development of secondary sex characteristics). It aims to suppress further pubertal development by administration of a gonadotropin-releasing hormone agonist (GnRHa) which reversibly inhibits the production of sex hormones. Hereby, adolescents have more time to explore options and to live in the experienced gender before deciding whether or not to proceed with additional, sometimes irreversible, treatments. At the age of approximately 16 years, treatment can be supplemented with estrogens to induce the development of female secondary sex characteristics. 2 For transgender women presenting at adult age ( ≥ 18 years), treatment usually does not consist of a phase of hormone suppression only, but immediately involves a combination of anti-androgens and estrogens, to achieve feminization. The combination of testosterone suppressing therapy and estrogen supplementation is referred to as gender affirming hormonal treatment (GAHT). Transgender women of 18 years or older who have used GAHT for at least one year, can opt for genital gender affirming surgery (gGAS) if no surgical contra-indications are present. gGAS may comprise vaginoplasty, gender confirming vulvoplasty or bilateral orchiectomy, depending on the desires of the individual. 110 The use of testosterone suppressing therapy results in a severely impaired reproductive function, since spermatogenesis - the differentiation of spermatogonial stem cells into spermatozoa - requires adequate levels of intratesticular testosterone. 39 This reproductive loss is permanent after gGAS. Although gender affirming treatment significantly improves quality of life, reproductive loss may be an unwanted consequence. 60,73,94 Therefore, it is important that (future) desire for biological children and the options for fertility preservation are discussed and offered prior to the start of medical treatment. 2 The currently available option for fertility preservation in transgender women is cryopreservation of spermatozoa from a semen sample, obtained through ejaculation. Cryopreservation of surgically obtained spermatozoa through testicular sperm extraction (TESE) may serve as an alternative for those who are unable to ejaculate or in case of azoospermia. 111 A complicating factor for contemporary fertility preservation in transgender female adolescents is the requirement of complete spermatogenesis, which only develops from Tanner stage 3 onwards, under the influence of increasing intratesticular testosterone