Chapter 30 – Uterine Transplantation for Trans Women: Prerequisites and Limitations

Summary

Uterine transplantation to date is still an experimental technique, and a lot of future research is necessary to confirm its success and safety. Although indications for its use will have to be defined once it is accepted in cis women, in the future however it could very well be that uterine transplantation will be a possibility for all women with uterine factor infertility, including trans women. This chapter deals with the prerequisites and limitations of potential uterine transplantation in transwomen.

30.1 Introduction

Uterus transplantation (UTx), as a way of providing fertility in women with no uterus, proved to be a feasible option in 2014, by the first live birth after a UTx procedure, which took place the year before in Sweden [Reference Brännstrom, Johannesson and Bokström1]. This proof-of-concept birth was after a live donor UTx procedure, and some years later the concept of UTx was also established after deceased donor Utx [Reference Ejzenberg, Andraus and Baratelli Carelli Mendes2]. In early 2021 more than 80 UTx attempts have been performed worldwide and more than 30 children have been born from it (personal communication with more than 20 UTx centers around the world). Thus, UTx has become a rapidly expanding field, with numbers exceeding those of other composite tissue allotransplant procedures, such as transplantations of the upper extremity and the face. A majority of ongoing clinical UTx trials have only accepted inclusion of women with congenital aplasia of the uterus. This has been a logical group to start with, since they have a major congenital malformation that would be temporarily cured by UTx. Some UTx trials have single cases where the recipient has lost the uterus because of previous life-saving hysterectomy, secondary to cervical cancer or massive obstetric bleeding [Reference Brännstrom, Johannesson and Dahm-Kähler3,Reference Fageeh, Raffa, Jabbad and Marzouki4]. There are however several more causes of congenital or acquired uterine factor infertility that in the future could be considered for the UTx procedure.

30.2 Principles of Uterine Transplantation

Uterine factor infertility (UFI) stems from the anatomical or physiological inability of a uterus to sustain gestation; it is a condition that affects about 5% of all infertile couples. Often the term absolute uterine factor infertility (AUFI) is used, thus indicating that the chance of pregnancy is zero.

The condition of UFI can have anatomical or physiological causes. Typical anatomical causes are the congenital absence of the uterus or the presence of a congenital abnormal uterus (primary UFI), but also the absence of the uterus as a result of a hysterectomy and the presence of a defective uterus as a result of Asherman syndrome or multiple fibroids (secondary UFI) are common anatomical causes. Examples of physiological UFI causes are conditions such as endometrial non-receptivity (primary or secondary), adenomyosis, or other uterine diseases (secondary). Only in case of an absent uterus can we truly talk of AUFI.

In 2012, after the first two cases of UTx in humans, the Montreal criteria for ethical feasibility of uterine transplantation were drawn up (Table 30.1.) [Reference Lefkowitz, Edwards and Balayla5]. Concerning the recipient, the following recommendations were then made: it should be a genetic female of reproductive age with no medical contraindication for transplantation, who has documented congenital or acquired UFI which has failed conservative therapy, has a personal or legal contraindication for surrogacy or adoption and desires a child or seeks UTx solely as a measure to experience gestation with an understanding of its limitations. Furthermore, the candidate should be psychologically stable and suited for motherhood and responsible enough to consent, informed enough to make a responsible decision, and not under coercion. Approximately, a year later these guidelines were slightly updated, adding a phrase about the compliancy to take immunosuppressive medication and to stay under the follow-up of the transplantation team [Reference Lefkowitz, Edwards and Balayla6]. Moreover, “other populations,” such as transgender people, were also discussed.

Table 30.1. Montreal Criteria for ethical feasibility of Uterine transplant [Reference Lefkowitz, Edwards and Balayla5,Reference Lefkowitz, Edwards and Balayla6]

∎ Genetic female of reproductive age
∎ No medical contraindication for transplantation
∎ Documented congenital or acquired UFI which has failed conservative therapy (e.g. Asherman syndrome)
∎ A personal or legal contraindication for surrogacy or adoption and desires a child or seeks UTx solely as a measure to experience gestation
∎ An understanding of the limitations of the procedure
∎ Responsible enough to consent, informed enough to make a responsible decision and not under coercion
∎ Psychologically stable
∎ Suited for motherhood

2013 complemented by:

▪ Compliancy to take immunosuppressive medication
▪ Ready to stay under the follow-up of the transplantation team

Important questions, however, still remain: should we give recommendations about the removal of the uterus after one or two successful pregnancies, in order to decrease the time on immunosuppression with its associated side-effects? Should we only treat women who have their own oocytes, or can donor oocytes be used? What about women who already have children? What about the recommendation that there has to be a contraindication for surrogacy and adoption? What about 46XY women with complete androgen insensitivity syndrome (AIS) and what about other XY women such as trans women?

When addressing these questions, we must keep in mind that there is indeed an ethical tension between the principles of “non-maleficence” and “autonomy of the individual” [Reference Olausson, Johannesson and Brattgård7]. In our role as medical professionals, the principle of “non maleficence” is of utmost importance. Thus, we have to keep in mind that UTx is a potentially life-threatening experimental treatment without the aim of improving the physical health of the individual, let alone saving their life. That individual, however, has the fundamental right to reproduce even if there are risks involved. On the other hand, no single clinician has the obligation to grant their cooperation to such a desire. Nowadays, we perform infertility treatments in women with pre-existing medical conditions (congenital heart disease, cystic fibrosis, organ failure with secondary solid organ transplant, etc.) that pose danger to themselves and/or their prospective fetuses/children. As physicians we always have to weigh the potential benefits (even if psychosocial) of an intervention against its medical risks.

Up until today, UTx has been performed in women with the Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome (congenital UFI) and women who have had hysterectomy (acquired UFI). Other causes of acquired UFI are quite a difficult group in relation to indication for UTx. First of all, in most cases, the uterine infertility which results is not absolute but relative, such as women with Asherman syndrome, adenomyosis, and fibroids. Several questions remain in this group: for example, how many years of failed conception should they undergo before UTx can be brought up as an alternative. How many documented pregnancy losses should they have? As for other non-life-saving transplantations (face, hand, larynx, penis), the indication for this group of relative UFI will always be debatable.

Even more difficult is the question of UTx in other types of congenital absence of the uterus, namely, people with disorders of sexual differentiation (DSD) and trans women. Several arguments against performing this procedure in this group of patients can be put forward, and some of them are mentioned in the updated version of the Montreal criteria for the ethical feasibility of uterine transplantation [Reference Lefkowitz, Edwards and Balayla6]. Up until today, apart from the anecdotal case of Lili Elbe (1882–†1931) (Figure 30.1), a transgender woman who is said to have died of complications after a uterus transplantation, no experiments in any species involving UTx to non-genetic female individuals have been performed.