Background: Transgender and gender diverse individuals including transgender women (TW) often retain a desire for procreation [1]. Gender affirming hormone therapy (GAHT) suppresses spermatogenesis, hence, sperm cryostorage is encouraged prior to GAHT. Uptake remains poor so some TW may subsequently seek fertility after established GAHT [2]. However, the potential and extent of recovery of sperm after GAHT is not well understood.
Methods: A literature review (PubMed) of sperm outcomes after at least 4 weeks of suspended GAHT identified seven ejaculated sperm studies [3-9] and seven studies on orchidectomy specimens [10-16].
Results: GAHT impairs sperm concentration, motility and cryosurvival compared to control men and TW not on GAHT [5, 8]. In TW after ceasing GAHT, semen (37.5 - 100%) and orchidectomy samples (3.7-50%) displayed recovery of sperm production. Yet, despite reduced sperm output, 78-100% of fresh samples and 38-93% of thawed samples were sufficient for intrauterine insemination or in-vitro fertilisation. Recovery trajectory is heterogeneous with partial recovery within 1–3 months, additional recovery by 6–12 months, and delayed recovery beyond 12 months in some.
Histological recovery of spermatogenesis was best predicted by testicular volume [15]. Spermatogenesis is more impaired by cyproterone acetate and estradiol exposure in adults than GnRH-analog in adolescents [17]. Neither serum or intratesticular testosterone concentrations nor duration of GAHT were reliable indicators of recovery. Initiating GAHT in early puberty (Tanner 2-3) is associated with poorer recovery compared to commencement at later stages (Tanner 4-5) [17]. Overall, the small sample size and heterogeneity in treatments limited analysis of the specific effects of anti-androgen, estradiol or progesterone.
Conclusion: Spermatogenesis may recover within months after cessation of GAHT in some individuals but up to 6–12 months in others. Even partial recovery can facilitate fertility through assisted reproductive techniques.