Rates of Fertility Preservation Use Among Transgender Adolescents

Abstract

This cohort study examines medical records of pediatric transgender patients undergoing gender-affirming care to characterize their use of fertility preservation.

Transgender adolescents are increasingly seeking hormonal intervention to achieve a body consistent with their gender identity. These treatments include gonadotropin-releasing hormone agonists (GnRHa) to suppress puberty and the gender-affirming hormones testosterone and estrogen. Given that these interventions affect reproductive function, current treatment guidelines recommend prior fertility counseling and access to fertility preservation (FP).¹ However, despite a previous report that 36% of transgender adolescents want biological children in the future,² 3 recent North American studies^3,4,5 identified that less than 5% of transgender adolescents accessed FP. Whether these low rates reflect service barriers (eg, cost and availability), unwillingness to delay hormonal treatment for FP, and/or an intrinsic lack of desire for FP is unclear.

We performed a retrospective review to examine FP use among transgender adolescents receiving hormonal intervention at our pediatric gender service in Australia. We hypothesized that the nature of our clinic, which is publicly funded and located alongside a pediatric oncofertility center, might reduce barriers and increase FP uptake.

Methods

Our statewide service sees transgender individuals who are 18 years or younger. To assess FP use, we conducted a retrospective review of all individuals with gender dysphoria who had commenced receiving GnRHa and/or gender-affirming hormones from January 1, 2003, until June 1, 2017. Information on birth-assigned sex, age, hormonal treatment, fertility counseling, and FP use was extracted from the medical record. The Royal Children’s Hospital Human Research Ethics Committee approved the study, which included a waiver of informed consent because the study was a secondary use of medical data. Data were analyzed between August 2017 and July 2019. The P value threshold considered significant was .05 (2-tailed), and statistical analysis was performed using Prism version 7.0 (GraphPad).

Results

One hundred two patients received fertility counseling from their pediatrician prior to commencing hormones. Of 53 individuals who were assigned male at birth (AMAB), 23 received counseling prior to taking GnRHa and 30 prior to taking estrogen, and 14 received additional consultation from an andrologist. Of 49 individuals assigned female at birth (AFAB), 3 received counseling prior to taking GnRHa and 46 prior to taking testosterone, and 47 received additional consultation from a gynecologist. The mean age at counseling was 15.6 years (range, 10.8-18.3 years), with no significant difference between sexes.

Among 49 individuals who were AFAB, none attempted FP, with 16 stating no reason; among the other 33, the main reason was a plan to reassess fertility options when older (Figure). Conversely, 33 of 53 individuals who were AMAB (62%) pursued FP (Table), of whom 22 successfully froze sperm after providing a masturbatory sample (mean [SD] age, 15.6 [1.4] years). The remaining 11 underwent testicular biopsy (which is well suited to those in early puberty), and this group was significantly younger (mean [SD] age, 13.9 [1.5] years; P = .003). Five of these 11 individuals were found to have mature sperm, while the other 6 had germ cells only, all of which were cryopreserved.

Figure. Reasons for Declining Fertility Preservation.

To understand why some patients chose not to pursue fertility preservation, we examined reasons recorded in the medical record. Of the 49 young people assigned female at birth (AFAB) who declined FP, 16 gave no reason. The remaining 33 gave a variety of responses, the proportions of which are displayed. Of the 19 young people assigned male at birth (AMAB) who declined FP, 9 gave no reason. The remaining 10 gave a variety of responses, the proportions of which are displayed. The item “experimental nature of procedure” refers to the procedure for those in early puberty who have yet to start producing mature gametes, in whom cryopreservation of immature testicular or ovarian tissue harvested via biopsy is offered within a governed pathway that emphasizes that this practice is experimental and requires further technological advances for the tissue to be successfully used for reproductive purposes.

Table. Rates of Cryopreservation Between Patients Assigned Male or Female at Birth.

Method of fertility preservation	No. (%)
	Prior to commencing gonadotropin-releasing hormone agonistsa	Prior to commencing estrogen or testosteronea
Transgender adolescents assigned male at birth (n = 53)	23 (43.4)	30 (56.6)
Masturbatory semen collection with sperm cryopreservation	7 (30.4)	15 (50.0)
Testicular tissue biopsy
Sperm and testicular tissue cryopreservation	3 (13.0)	2 (6.7)b
Testicular tissue cryopreservation only	4 (17.4)	2 (6.7)b
No fertility preservation	9 (39.1)	11 (36.7)
Transgender adolescents assigned female at birth (n = 49)	3 (6.1)	46 (93.9)
Oocyte retrieval and cryopreservation	0	0
Ovarian tissue biopsy and cryopreservation	0	0
No fertility preservation	3 (100)	46 (100)

^aIt is important to note that gonadotropin-releasing hormone agonists, estrogen, and testosterone have differential associations with reproductive function. For example, prolonged use of estrogen in patients assigned male at birth has been associated with impaired spermatogenesis, with the reversibility still unclear. Meanwhile, testosterone administration in patients assigned female at birth can similarly impair reproductive function, although this outcome appears reversible. Finally, gonadotropin-releasing hormone agonists can be expected to inhibit reproductive development, and although this should also be reversible, most adolescents who undergo pubertal suppression subsequently proceed to gender-affirming hormones.

^bThree of these individuals had received puberty-blocker therapy prior to commencing estrogen (1 with sperm cryopreservation and 2 with tissue only).

Discussion

Whereas all our patients who were AFAB declined FP, 62% of patients who were AMAB pursued FP, suggesting that most transfeminine adolescents have an intrinsic desire to preserve their fertility. This result stands in stark contrast to recent North American studies in which FP rates among the AMAB population were 0% to 14%.^3,4,5 Given that our cohort had a similar age and rate of andrology consultation as those in previous reports, the most likely explanation is differences in FP access. Specifically, patients who were AMAB within our service obtain FP in a timely manner (<1 week for masturbatory specimens; <1-2 months for testicular biopsies). This is probably important, given an unwillingness to delay hormone treatment is a common reason for forgoing FP.^2,3,5 Furthermore, FP costs for patients who were AMAB at our clinic are relatively affordable (testicular biopsy is free, semen analysis costs approximately $66 [AU $100], and annual sperm storage costs approximately $132 [AU $200]). Consistent with this, a recent Dutch study in which FP costs were also largely covered by insurance observed that 12 of 32 transgender individuals who were AMAB (38%) froze sperm prior to starting hormones.⁶ Notably, this rate was still considerably lower than ours. One likely reason is that testicular biopsy, which is likely to be less dysphoria-inducing than masturbation and also more suitable for younger adolescents, was not an option for the patients in the Netherlands, highlighting the importance of providing different FP options.