Uterine allografts: A new era in reproduction

Uterine transplantation (UTx) has rapidly moved from a theoretical construct to a clinical reality. Over just the past 5 years, the world has witnessed several notable milestones in this quickly-evolving field. With healthy live birth being the ultimate goal of a reproductive transplant, the 14 babies born to date following UTx for which reports exist and the additional ongoing pregnancies represent proof of concept for the viability of this experimental procedure. 

Options for AUFI
UTx represents the first and only treatment for women with absolute uterine factor infertility (AUFI). AUFI can be either congenital (e.g., Mayer Rokitansky Kuster Hauser syndrome) or acquired. Estimated to affect one in 500 women, AUFI has previously only been addressed using in vitro fertilization (IVF) with gestational carriers, fostering, adoption, or planning a life without children.¹ For some women, these may be acceptable options, but for others, these alternatives may not be desired, often due to personal, social, cultural or religious beliefs. Choices for women with AUFI are especially limited in parts of the world where gestational carriers and even adoption may be socially unacceptable, highly restricted, or banned completely. Interviews of women with AUFI in a uterine transplant trial indicate that the diagnosis of AUFI can be a devastating and life-altering experience and that achieving reproductive autonomy is a key desire of women with this condition.²

AUFI Milestones
The advent and rapid ascent of UTx have been marked by innovation. Initial international attempts in humans performed outside of clinical trials were not successful, and technical success for the Swedish team was ultimately achieved following decades of preparatory work in small mammals and non-human primates. As with any new surgical procedure, the technical elements have quickly advanced and evolved (Table 1). 

In case you missed it: Uterine transplantation from deceased donor results in livebirth

Together with documented technical success and increased media attention has come improved public perception and enhanced physician awareness and support for the procedure. Sixty percent of American Association of Gynecologic Laparoscopists (AAGL) and American Society for Reproductive Medicine (ASRM) members support UTx as a treatment for AUFI.¹⁰ A 2018 study of public perception of UTx in the United States indicated that 78% of respondents supported UTx and 45% believed it should be covered by insurance.¹¹ Another recent study indicated that 74% of women would donate their uterus for transplant.¹² It is unclear what the cost of a uterine transplant will be, and how or whether insurance will cover this reproductive procedure. As the discussion evolves along with the science, questions regarding access, cost, and safety will be paramount. 

Slow initial acceptance of UTx may be due to the fact that, unlike other transplants, UTx is not a life-saving transplant. Like face, hand, and other vascularized composite allographs, the uterine transplant can be life-enhancing and indeed can be life-giving. Also distinct from other known organ transplants, UTx is an “ephemeral” transplant.¹³ This means that the uterus will be removed after one or two live births are achieved and is not intended to be a lifelong transplant. This means that women receiving a UTx will not be exposed to immunosuppression once the uterus has been removed after childbearing. 

Despite growing numbers of live births, UTx remains a significant undertaking for both recipients and living donors. The procedure for donor hysterectomy is similar to radical hysterectomy, and donor complications have been reported in the literature.^14,15 Historically, donor surgeries have involved long operating room times (10-13 hours in the original Swedish series) and large incisions, although this may change as laparoscopic and robotic approaches are pioneered. Although a deceased donor model obviates this risk completely, most live births to date have been achieved with living donors. Deceased donor UTx represents a more ethical choice by eliminating donor risk, however, it has the limitations of organ availability, less convenient scheduling, and more restricted medical history on the donor.¹ It is unknown how outcomes from deceased donor trials will compare with living donor trials and whether one approach will demonstrate superiority over the other or whether both approaches will coexist. Recent studies suggest no recipient preference for a living vs a deceased donor.²