Ethical and Practical Considerations of Transplantation in Male-to-Female Patients Hilliard T. T. Brydges1 and Miguel I. Dorante2, MD, MBE 1. Boston University School of Medicine, Boston, MA 2. Department of Plastic & Reconstructive Surgery, Lahey Hospital & Medical Center, Burlington, MA

Societal Impact & Broader Ethical Considerations Research Ethics and Future Innovations The experience of gender dysphoria is individualized and requires goals of • Health Questionnaire Research of uterus transplantation in transgender patients needs to care to be personalized to each patient. No uniform clinical course or set of Pre-Inclusion • Information on Trial and Surgery - including known demonstrate a safe reproductive option without compromising ethical procedures is capable of meeting the needs of every transgender person. Phase risks and benefits principles. Results and findings will help the profession and society • Counseling on fertility and options Uterus transplantation has the potential to expand capacity and quality of care better evaluate the question of ”can vs. should” UTx be performed. available in addressing gender dysphoria. Transgender surgery and reconstructive transplants challenge modern Current options for male-to-female gender confirmation surgery focus on Selection • Medical Work-up and Evaluation medicine to include improvement to quality of life in outcome Phase • Consultation, Imaging & Laboratory testing addressing gender dysphoria by modifying the patient’s physical form to • Comprehensive Psychosocial evaluation assessments. Labeling a combination of these procedures a ”success” resemble the socially accepted female form. Uterus transplantation deviates necessitates the development of novel measurement tools. This from the norm by reconstructing the patient’s form to support a uniquely endeavor should involve a broad group of interdisciplinary researchers female function: gestation. • Multidisciplinary Listing Meeting with expertise ranging from basic science to translational and clinical Consultation • Organization Phase • In-Vitro Fertilization research. As this is a departure from previous treatment paradigms it is important to consider the ethical implications for all stakeholders involved: • Informed Consent Pre- Biochemical Modifications Psychological Assessments Patient • Psychosocial Re-assessment Transplantation • Risks of immunosuppressive therapy • Pre-operative Preparation Implementation of Hormone similarity • Risks of gestational state standardized between cisgender • Childrearing as gender identity • Rehabilitation & Regimen psychological Post- Tailoring women with complete evaluation of UTx Transplantation • In-Vitro Fertilization uterine factor recipients, partners, and • Gestation & Hormonal Regulation and transgender women Offspring Consent living donors10 • Potential risk to psychological health • Unpredictable hormonal interactions Development of tools to Implementation Considerations Generation of gametes evaluate impact on • Predetermined assent that align with gender Medical Team gender dysphoria and identity9 A procedure of this complexity requires an interdisciplinary medical team with quality of life Society and Culture combined experience in transplantation, reconstructive surgery, and transgender care. Members might include plastic surgeons, reconstructive gynecologists and • Acceptance of transgender individuals urologists, endocrinologists, psychiatrists, social workers, pharmacologists and • Reconstructive transplants growing in popularity immunologists. • Paradigm shift in healthcare policy Citations Medical Center 1. Sampson A, Kimberly LL, Goldman KN, Keefe DL, Quinn GP. Uterus transplantation in women who are genetically XY. Journal A medical center that has an established culture of providing transgender care is of 2019;medethics-2018-105222. 2. Brännström M, Dahm Kähler P, Greite R, Mölne J, Díaz-García C, Tullius SG. Uterus Transplantation: A Rapidly Expanding Field. Professional Virtues an appropriate environment for this procedure. A supportive staff throughout all Transplantation 2018;102(4):569–77. phases of care affirms the institution’s commitment to this patient population. 3. De Sutter P. Gender reassignment and assisted reproduction. Human Reproduction 2001;16(4):612–4. • Ability to treat hinges on public trust 4. Puntambekar S, Telang M, Kulkarni P, et al. Laparoscopic-Assisted Uterus Retrieval From Live Organ Donors for Uterine Transplant: Our Experience of Two Patients. Journal of Minimally Invasive Gynecology 2018;25(4):622–31. • Duty to treat for public’s best interest 5. Kantar RS, Ceradini DJ, Gelb BE, et al. Facial Transplantation for an Irreparable Central and Lower Face Injury: A Modernized Patient & Community Approach to a Classic Challenge. Plastic and Reconstructive Surgery 2019;144(2):264e–83e. • Transparency will be critical Fastidious patient selection is crucial to the success of any operation. This 6. Johannesson L, Wall A, Putman J, Zhang L, Testa G, Diaz-Garcia C. Rethinking the time interval to embryo transfer after uterus transplantation—DUETS (Dallas UtErus Transplant Study). BJOG: An International Journal of Obstetrics & Gynaecology procedure is as unique as the individual and can only succeed in a supportive [Internet] 2019 [cited 2019 Sep 2];Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/1471-0528.15860 7. Jones B, Williams N, Saso S, et al. Uterine transplantation in transgender women. BJOG: An International Journal of Obstetrics & community where transgender patients are given honest informed consent of Gynaecology 2019;126(2):152–6. risks, benefits, and realistic expectations of undergoing this experimental 8. Taran F-A, Schöller D, Rall K, et al. Screening and evaluation of potential recipients and donors for living donor uterus Miguel I. Dorante MD, MBE Hilliard T. T. Brydges transplantation: results from a single-center observational study. Fertility and Sterility 2019;111(1):186–93. • Email: • Email: operation. 9. Cutas D, Smajdor A. “I am Your Mother and Your Father!” In Vitro Derived Gametes and the Ethics of Solo Reproduction. Health [email protected] [email protected] Care Analysis 2017;25(4):354–69. 10. Järvholm S, Warren AM, Jalmbrant M, Kvarnström N, Testa G, Johannesson L. Preoperative psychological evaluation of uterus This patient selection framework was adapted for transgender patients.8 transplant recipients, partners, and living donors: Suggested framework. American Journal of Transplantation 2018;18(11):2641–6. Ethical and Practical Considerations of Uterus Transplantation in Male-to-Female Transgender Patients Hilliard T. T. Brydges1 and Miguel I. Dorante2, MD, MBE 1. Boston University School of Medicine, Boston, MA 2. Department of Plastic & Reconstructive Surgery, Lahey Hospital & Medical Center, Burlington, MA

Role of Uterus Transplantation in Transgender Care Surgical options for patients with gender dysphoria aim to reduce associated psychosocial stress by aligning the patients’ phenotypic preferences with their genotypic expression to aid with integration into society. Patients have the opportunity to undergo a variety of procedures altering facial, body and genital structures.

Uterus transplantation would be unique in large part due to its potential for gestation. Such did Lili Elbe desire the experience of gestating that she became the first transgender recipient of UTx;1 albeit, it led to her untimely death. Almost 90 years later, UTx has successfully been performed and has led to multiple live births.2 A gender transition plan must consider known risks in cisgender females and patient preferences for other gender confirmation surgery.

It is critical that providers distinguish reproductive desire in transgender patients exploring surgical options. Recommendations for bottom surgery could follow two treatment paths based on the goals of care discussions. Patients unsure of their future gestational preferences may choose to delay bottom surgery until their decisions have solidified.

Political & Legal Considerations for Childrearing in Transgender Women Anatomical and Physiological Considerations Differences between gynecoid and non-gynecoid pelvic anatomy have been Adoption In Vitro Fertilization discussed. Propositions have included adapting vasculature anastomosis and Currently, no laws explicitly prohibit the adoption of children by transgender No explicit legal barriers exist for transgender individuals seeking to become structural support sites. The complex interactions of transgender hormone women. Protection is scarce as only 5 states, Guam and Washington D.C. have parents via in vitro fertilization and . Only 11 states and Washington therapy and reconstructive transplantation could conflate viability laws which explicitly prohibit discrimination against prospective adoptive parents D.C. recognize non-gestational parents as legal guardians regardless of assessments and increase risks to mother and child. Adoption of novel based off gender identity; meanwhile, 42 states and 3 territories are silent on the marital status. This limits access for transgender women that transitioned and techniques and further research could increase safety and likelihood of issue. Notably, 10 states allow child welfare agencies to refuse prospective parents cannot contribute genetic material to gestation;3 and, may prohibit legal success of UTx in a non-gynecoid pelvis. on the basis of religious beliefs. recognition as parents should they chose to have a child through IVF. Surgical Technique • Adoption of laparoscopic procurement could improve allograft quality and increase living donor organ pool4 Imaging Technique • Advances in preoperative computerized surgical planning, 3D printing technologies, and intraoperative navigation have been used in face transplant5

Immunosuppressive Technique • Minimize time and risks by optimizing immunosuppression to facilitate earlier embryo transfer6 Transplantation Technique • Creation of optimized gestational environment with an en bloc 7 Movement Advancement Project. (current as of: 2019, August 22). Equity Maps/Foster and Adoption Law. Retrieved from http://www.lgbtmap.org/equality-maps/foster_and_adoption_laws Movement Advancement Project. (current as of: 2019, August 22). Equity Maps/Other Parental Recognition Laws. Retrieved from http://www.lgbtmap.org/equality-maps/other_parenting_laws utero-vaginal allograft