Gonadotropin-releasing hormone agonists (GnRHa) are often used to suppress pubertal development in transgender youth who are not yet ready for gender-affirming hormone therapy (GAHT). With prolonged use, GnRHa bind to their receptors in the pituitary, leading to endocytosis and downregulation of GnRH receptors.1 This decreases the release of gonadotropins, which leads to decreased sex hormone production to prepubertal levels. The pubertal suppression is considered reversible as puberty resumes after the discontinuation of the GnRHa therapy.2

Depending on individual patient goals, gender-affirming care can progress directly from pubertal suppression with GnRHa to GAHT without a pause to experience natural puberty. GAHT may impair fertility by a decrease in sperm count and testicular size and impairments in gonadal histology.3 Counseling regarding fertility preservation is important before GnRHa treatment and GAHT.4 In fact, a study showed that 36% of transgender youth report wanting biological children.5 Despite this fact, the documented rates of fertility preservation among transgender youth remain low.6 Spermarche has been reported to occur as early as Tanner stage 3. A threshold testicular volume of ≥10 mL consistent with Tanner 3 is a predictor of successful sperm retrieval via biopsy; however, a similar threshold has not been reported in ejaculated semen.3

Conventionally, fertility preservation is performed via cryopreservation of ejaculated sperm. The first successful conception using sperm that had been cryopreserved occurred in 1964.7 In adolescents, however, ejaculated sperm can be more challenging to obtain as some transgender females do not know how to masturbate, cannot masturbate due to significant dysphoria, or do not yet have sperm in an ejaculated specimen. To manage these issues, it is critical to involve a pediatric urologist or another fertility provider in the counseling of these youth. For transgender girls who cannot masturbate due to dysphoria or other concerns, penile vibratory stimulation or electroejaculation under anesthesia can be offered as a minimally invasive but effective means of collecting ejaculated sperm. If these are not successful, families can elect to proceed with surgical retrieval of sperm. This can be done via a small scrotal incision under general anesthesia. Testicular tissue from 1 or both testes is removed and processed to extract and cryopreserve sperm. This procedure was developed for infertile cisgender men in the 1990s but has since been used for cryopreservation of sperm for patients undergoing chemotherapy or GAHT.8 This has successfully been undertaken in transgender girls at the time of pubertal suppression implant placement.9 At this time, cryopreservation of testicular tissue for prepubertal with the possibility of future in vitro maturation of spermatozoa is considered experimental but can be discussed with families.10

In some cases, families may elect to wait for the progression of puberty and in vivo maturation of sperm, before initiation of GAHT.

In current guidelines, the Endocrine Society suggests that treatment with GnRHa to suppress puberty may be initiated after signs of pubertal development.4 The goal of pubertal blockade is to temporarily halt the development of virilizing secondary sexual characteristics. In transgender girls, these characteristics include facial hair, facial features, voice change, and laryngeal prominence. Many of these changes are irreversible but occur in later puberty.

Before GnRHa treatment or GAHT, we evaluated transgender female patients who underwent sperm analysis to assess the presence of virilizing secondary sex characteristics at the time of sperm collection and to correlate the viability of sperm with the degree of virilization.