Fertility Concerns of the Transgender Patient

Philip J. Cheng; Alexander W. Pastuszak; Jeremy B. Myers; Isak A. Goodwin; James M. Hotaling


Transl Androl Urol. 2019;8(3):209-218. 

In This Article

Fertility Preservation in Prepubertal Transgender Youth

Maturation of oocytes or sperm occurs during puberty, but for prepubertal individuals who opt for FP prior to initiating hormonal therapy, options are more limited since they do not have mature gametes to preserve. FP options in these individuals are still investigational; accordingly, these procedures should only be performed under an institutional review board-approved protocol at an expert center.[21]

Ovarian Tissue Cryopreservation

For prepubertal FTM transgender individuals, the only option for FP is ovarian tissue cryopreservation (OTC). OTC with subsequent ovarian autotransplantation is currently experimental and has been performed primarily in prepubertal girls who require gonadotoxic cancer treatments.[33–36] Ovarian tissue obtained via biopsy or oophorectomy is cryopreserved. When patients opt to restore fertility, the tissue is thawed and autotransplanted. If an ovary is still present, the tissue can either be fixed to the decorticated medulla[34] or inserted under the cortex.[35] If bilateral oophorectomy was performed, then the ovarian tissue is placed in a peritoneal window.[37] If primordial follicles were present, ovarian activity was restored in 100% of cases.[33] At least 60 live births worldwide have been reported using this technique.[33] In a study of 20 women who underwent OTC with ovarian autotransplantation, 53% conceived and 32% had at least one live birth.[35] There has been one documented live birth following autotransplantation of ovarian tissue cryopreserved before menarche.[36] Orthotopic ovarian tissue reimplantation allows for the possibility of restoration of fertility and natural conception. However, for FTM individuals, restoration of ovarian function may be undesirable given that it may have feminizing effects.

An alternative method of using the preserved ovarian tissue that does not require restoration of ovarian function is to perform in vitro follicle growth and oocyte maturation.[38] The follicles from the ovarian tissue are grown in vitro using a special culture medium with alginate hydrogels. Several studies showed the success of in vitro maturation of oocytes to metaphase II, which demonstrated that this is a promising method for FP.[38] If oocytes can successfully mature in vitro, they can potentially be used for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) using either a gestational surrogate or in an FTM individual with a preserved uterus.

Cryopreservation of Testicular Tissue

Prepubertal MTF transgender individuals cannot bank sperm, but a potential method of FP is cryopreservation of immature testicular tissue (ITT), which has been performed under experimental protocols. ITT contains spermatogonial stem cells (SSCs) from which spermatozoa derive. Controlled slow-freezing with dimethyl sulfoxide (DMSO) has been used to preserve ITT and protect the tissue architecture.[39] This process allows survival and proliferation of spermatogonia after transplantation of isolated testicular stem cells to germ cell-depleted testes in mice.[39] Vitrification is a potential alternative technique that uses high concentrations of cryoprotectant and ultrafast cooling speeds to minimize cellular damage in the long-term storage of ITT.[40] In one study, spermatogonia were able to survive and proliferate, but only partial differentiation occurred after vitrification and xenotransplantation.[40] Another study showed that long-term propagation of SSCs could occur in vitro in a special culture medium.[41] Further studies are necessary to improve the ability of SSCs to differentiate, but this is a promising technology that could potentially be used in prepubertal transgender individuals in the future.