Iris de Nie

96 C H A P T E R 6 DISCUSSION The results of our study imply that there may be options for fertility preservation for transgender women who are unable to pursue semen cryopreservation, by using testicular tissue from orchiectomy specimens obtained during gGAS. In a small percentage of transgender women who initiated medical treatment in Tanner stage 4 or higher, complete spermatogenesis was observed in the orchiectomy specimen. For this group, it would theoretically be possible to perform TESE and cryopreserve the harvested spermatozoa from this specimen. Furthermore, the vast majority of transgender women still had immature germ cells in their orchiectomy specimen. This is the first study to report on people who initiated medical treatment in Tanner stage 2-3, and it was found that in 100% of their orchiectomy specimens immature germ cells were present. If maturation techniques like in vitro spermatogenesis become available in the future, cryopreservation of testicular tissue containing spermatogonial stem cells might be a promising option for this group to retain the possibility to have biological children. A complete absence of germ cells was only observed in transgender women who commenced GAHT as adult. Cessation of GAHT prior to gGAS did not affect the possibilities for fertility preservation, neither was there an effect of the duration of GAHT prior to gGAS. Although some previous studies have been conducted on the influence of GAHT on spermatogenesis and testicular architecture, this is the first study taking age and pubertal stage at time of initiation of medical treatment into account. Between 1970 and 1990, several small studies were conducted reporting on 4 to 11 transgender women per study. 28,114-118 Therefore, no strong conclusions could be drawn, but results showed high proportions of tubular hyalinization and reduced spermatogenesis in all transgender women. The first large cohort study on this topic was performed in 2015 and assessed orchiectomy specimens of 108 transgender women from three clinics with different pre- operative treatment protocols (6 weeks, 2 weeks, or no discontinuation of GAHT prior to gGAS). 27 Their results on testicular histology and spermatogenic state were highly heterogeneous and did not show a relation with treatment strategy. Remarkably, a high number of transgender women (24% of their study cohort) had complete spermatogenesis at time of gGAS. This finding was confirmed by Jiang et al. who even observed complete spermatogenesis in 40% of the 72 included transgender women. 107 However, several other recent studies found lower percentages of complete spermatogenesis ranging from 0 to 11% of the study cohort. 103,104,106,119 It must be noted that hormonal and pre- operative treatment protocols vary considerably within, and between, the different studies conducted on this topic. Therefore, for the current study it was decided to only include transgender women who used estradiol in combination with testosterone suppressing therapy (triptorelin when initiated in adolescence, cyproterone acetate when initiated in adulthood), and to report results for those who continued GAHT until gGAS separate from those who discontinued four weeks prior to gGAS. Since a study performed by Vereecke et al. also adhered strict in- and exclusion criteria that are similar to those in our adult subgroup, their results allow for the most accurate comparison. 103 In addition, their method of analysis using immunohistochemistry to