Introduction

Gender dysphoria, defined as the persistent discomfort with one's gender identity or biological sex, affects between 0.5 and 1.4% of adult males.  Treatment aims at congruence, to allow those who experience it to find comfort within their gendered self, which optimises psychological wellbeing and self‐fulfilment. Although many experiencing gender dysphoria require partial treatment or social transition, others only find comfort following surgical intervention to change their external genitalia and sexual characteristics. Traditionally, infertility has been an unfortunate consequence of the realignment of a transgender person's body with their gender identity.

Following a successful clinical trial investigating uterine transplantation (UTx) in Sweden, resulting in eight live births so far, UTx appears to be a viable therapeutic option for women with absolute uterine factor infertility (AUFI). More than 42 UTx procedures have now been performed globally, and at least 12 live births have been reported. Following the establishment of the International Society of Uterine Transplantation (ISUTx), and the formation of research teams globally, it is anticipated that UTx will make the transition from research to clinical care in the future. Following these developments, speculation has escalated regarding the possibility of performing UTx in male to female (M2F) transgender women, which would enable them to gestate and give birth to their own children.

Ethically, the consideration of performing UTx in transgender women is primarily motivated by the considerations of justice and equality. Like all women, psychological harm may arise secondary to a mismatch between reproductive capacity and aspiration. Transgender women have AUFI, and therefore they cannot experience gestation, which may play an integral role in the expression and consolidation of a female identity, and is considered by many to constitute a transformative experience.6 Legally, under the Equality Act (2010) transgender people are afforded explicit protection from both direct and indirect forms of discrimination through the characterisation of ‘gender reassignment’ as a protected characteristic. As such, M2F transgender women cannot be subjected to discrimination on the basis of this characteristic. Subsequently, if UTx becomes an established treatment option for women with AUFI, UK and EU legislation would make it legally impermissible to refuse to perform UTx in transgender women solely because of their gender identity. Performing UTx in this population, however, raises a number of anatomical, physiological, fertility, and obstetric considerations. The aim of this manuscript is to discuss these factors and provide an initial framework for assessing the feasibility of UTx in M2F transgender women.

Anatomical considerations

Uterine transplantation entails the transplantation of the uterus, including the cervix, a cuff of vagina, the surrounding ligamentous and connective tissues, as well as the major blood vessels to the level of the internal iliac vessels. The uterus is then placed orthotopically in the pelvis of the recipient, where it is structurally supported using the uterosacral, round and broad ligaments laterally, the bladder peritoneum anteriorly, and the vagina and paravaginal tissues inferiorly.

Vascular anastomosis

Most UTx procedures performed to date have achieved revascularisation through bilateral internal iliac artery to external iliac end‐to‐side anastomoses. To determine the plausibility of retrieving a graft from a woman, with subsequent implantation into a natal male pelvis, the intersex differences in pelvic vascular anatomy require consideration. Fătu et al. assessed the morphometry of the internal iliac arteries between sexes, and concluded there was no difference in internal iliac artery length, with a mean length of 49 mm. However, the calibre of the vessels was noted to be 1.6 mm wider in females than in males (6.2 versus 7.8 mm). Although a significant funnelling effect could predispose to thrombosis, this difference could be negated by anastomosing further proximally, where the vessels are similarly sized. With regard to the external iliac arteries, data from lower limb angioplasties show there is no significant difference in external iliac artery calibre between sexes.

Vaginal anastomosis

In all UTx cases performed to date, the recipient's vagina has been anastomosed to a vaginal cuff, of varying length, which is retrieved as part of the graft. This restores reproductive anatomy and allows physiological excretion of discharge and menstruation, but also allows direct visualisation of the cervix and access to take biopsies, which is the only reliable way to detect rejection following UTx.9 In the M2F transgender model, it would therefore only be possible following gender reassignment surgery (GRS), which traditionally includes orchidectomy, penectomy, clitoroplasty, and labiaplasty, with the subsequent creation of a neovagina. The inverted penile skin flap is the standard technique for neovagina creation, to line a newly created space between the bladder/prostate and the rectum. However intestine, or pelvic peritoneum,12 have also be utilised, particularly in cases with penoscrotal hypoplasia, which can be an iatrogenic consequence of feminising hormones. However, the absence of a physiologically functioning vaginal mucosa may be problematic. The vagina is lined by multiple layers of stratified squamous epithelium, the top layer of which removes adherent micro‐organisms by desquamation into the vaginal lumen.  Vaginal epithelium also facilitates the recognition of pathogens and stimulates production of antimicrobial peptides and pro‐inflammatory cytokines. These protective mechanisms contribute to the creation of a commensal microflora, predominantly consisting of lactobacilli, which provides an optimal physiological environment to prevent infection and maintain pregnancy. In M2F transgender women, the pH in penile skin‐lined neovaginas is elevated, owing to an inability to support the growth of acidic lactobacilli, with colonisation of bacteria from skin or intestinal microfloras instead. Following M2F transgender UTx, the presence of a skin or intestinal neovagina, in the context of immunosuppression, may increase susceptibility to recurrent neovaginal infections and create a hostile environment that may be incapable of sustaining pregnancy. This was exemplified in the UTx case performed in Turkey in a recipient with an intestinal neovagina. Despite multiple embryo transfers and at least six early pregnancy miscarriages, she has yet to achieve a live birth.17Moreover, the only woman in the Swedish series to have not yet given birth following successful UTx, despite suffering at least five miscarriages, has a skin neovagina. Although it appears the absence of a physiologically functioning vagina is detrimental, albeit to a currently unquantified extent, small numbers of live births have been reported in women with skin neovaginas, including two following UTx in the Swedish series, highlighting that successful pregnancy is possible.

To overcome this anatomical hindrance in M2F transgender women, a utero‐vaginal transplant could be performed, utilising as much donor vagina as possible, en‐bloc with the uterus (Figure 1). This would be achievable using a similar technique to that employed at radical hysterectomy, with preservation of the vaginal branches of the uterine vessels. This would necessitate retrieval from deceased donors, excluding female living donors. An alternative donor pool may be female to male (F2M) transgender men undergoing hysterectomy and vaginectomy, although the increased radicality of the hysterectomy may not be acceptable. However, recent evolution of the surgical technique, following cases in China and Dallas has potentially significantly reduced donor risk. The modified technique utilises venous drainage of the graft via the ovarian or utero‐ovarian veins, as opposed to the unpredictable and tortuous uterine venous plexus which leads to the internal iliac veins. This negates the need for the complex and time‐consuming ureteric dissection away from the uterine veins, reducing surgical risk. Moreover, it reduces operative times from 12 hours to 4–5 hours, which in turn decreases potential venous thromboembolism (VTE) risk. This dissection also favours minimally invasive retrieval techniques, which should enhance recovery and reduce potential morbidity further. As most F2M transgender men will also undergo bilateral oophorectomy, whereas the ovaries it would not be transplanted, it would allow the retrieval of elongated ovarian vascular pedicles to facilitate the implantation.