Emerging Technologies: Uterus Transplantation

Acknowledgments

The author would like to acknowledge Dr. Michal Silber for her critical review of this manuscript. This work was supported in part by Health Resources and Services Administration contract HHSH250-2019-00001C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Introduction

Assisted reproductive technologies (ART) have been developed to help overcome many causes of infertility; however, uterine factor infertility (UFI) remains an intractable condition with limited treatments. Prior to 2014, adoption and the use of a gestational carrier were the only possible paths to parenthood that existed for women with UFI. The use of a gestational carrier is the only alternative that allows an individual or couple to have a child genetically related to the intended parent(s). The advent of uterus transplantation (UTx) has provided patients with UFI a potentially curative intervention that is rapidly transitioning out of the research realm given its safety, efficacy, and reproducibility. A successful UTx on the recipient side involves a number of significant steps that will be discussed in detail below including comprehensive screening, undergoing IVF for embryo banking, major abdominal/pelvic surgery, daily antirejection medication while the uterus is in place, embryo transfer, pregnancy, Cesarean delivery, and finally hysterectomy. Despite promising initial results, the development and adoption of UTx comes with many important ethical, medical and financial considerations.

UTx involves surgically removing the uterus, cervix, and top of the vagina from the donor and placing it in the pelvis of an individual with UFI ( Fig. 40.1 ). The goal is for the recipient to achieve pregnancy and deliver a healthy baby or babies. Donor uteri may come from living or deceased donors (DDs) and regardless of the type of donor, procuring the uterus requires complex dissection of the arterial supply to the uterus and the delicate venous network. The initial recipient surgery involves laparotomy (at most centers), establishment of bilateral vascular anastomoses (which are responsible for uterine blood flow), and fixation of the recipient vagina to the donor vagina in order to reestablish typical anatomy. Pregnancy in the setting of uterus transplant requires in vitro fertilization (IVF) as the Fallopian tubes are not transplanted with the uterus. The rationale for this is nonhuman primate studies demonstrated high rates of tubal blockage following uterotubal autotransplantation. Therefore, prior to receiving a uterus transplant, individuals must generate and store embryos. Once they are selected for uterus transplant and a suitable match is found, the transplant is performed. At the time of transplant, the recipient must start on an immunosuppressive regimen in order to prevent organ rejection. Six to twelve months after the transplant, attempts at pregnancy can be initiated with embryo transfers. Once pregnancy is achieved, the mother and fetus are monitored until approximately 37 weeks (or earlier if medically indicated) at which time a Cesarean delivery is performed. Following the birth of 1 to 2 live-born children, the uterus is removed and the immunosuppressive regimen is discontinued.

Fig. 40.1, Overview of the key steps involved in the pre-transplant, post-transplant, and transplant phases for uterus transplant. The dotted box surrounds a potential second attempt at pregnancy and delivery which may be pursued depending on center, patient preference, and medical considerations.

Indication for UTx

UFI may be congenital or acquired
Congenital absence of the uterus affects approximately 1 in 5000 women
In addition to Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome uterine factor infertility may occur secondary to hysterectomy, uterine fibroids, adenomyosis, or Asherman syndrome

UFI is defined as infertility resulting from either an abnormality of the uterus preventing achieving and/or carrying of a pregnancy or a complete absence of the uterus. It is estimated that UFI affects 3% to 5% of the general population. UFI can be congenital or acquired as discussed. Congenital absence of the uterus (also known as Müllerian agenesis/aplasia or Mayer-Rokitansky-Kuster-Hauser syndrome) affects approximately 1 in 5000 women. Given there are 74 million women of reproductive age (15–49 years of age) in the US (US Census Bureau, 2019 data), we estimate that 14,800 women of reproductive age in the US have congenital UFI.

UFI may also be acquired when hysterectomy is required prior to initiation/completion of childbearing secondary to abnormal uterine bleeding, obstetric complications (primarily postpartum hemorrhage), premalignancy and malignancy, pelvic pain, and/or endometriosis. In an attempt to define the number of women who acquired AUFI, Nair and colleagues reviewed national hysterectomy data in a number of different subgroups and concluded that 9.5 million (15.4%) women of reproductive age may have acquired absolute UFI. However, using national hysterectomy data to estimate the number of women with AUFI is limited by the fragmented nature of the datasets available. ^, Therefore, the number of women with acquired UFI secondary to hysterectomy is unknown. There are multiple other potential causes of UFI including uterine fibroids, adenomyosis, and Asherman syndrome. It is difficult to determine the number of women who experience UFI related to these conditions as the degree to which they contribute to an individual’s infertility varies and is at times unknown.

To date, most uterus transplants have been performed in women with MRKH; however, patients with a history of Asherman syndrome and hysterectomy secondary to obstetrical hemorrhage and malignancy have also received uterus transplants. As the procedure is optimized and additional centers develop programs, the cause of UFI for which individuals undergo UTx will likely expand. Future indications for UTx may include complete Androgen Insensitivity Syndrome (karyotype 46, XY) and identification as transgender female.

Preclinical and Clinical Research

Proof of principle for uterus transplant was first demonstrated in multiple animal models
Following extensive research in animals, a Swedish team from Gothenburg led by Dr Mats Brannstrom initiated the first successful human uterus transplant clinical trial in 2012
As of 2020, over 70 uterus transplants have been performed in over 10 countries and >20 children have been born to women following UTx
The United Network for Organ Sharing (UNOS) oversees all organ transplant activities and programs, including uterus transplants, in the US.

The success of human uterus transplant was built on a solid foundation of over a decade’s worth of rigorous research in both small and large animal models. These preclinical studies first examined surgical technique, ^, effect of ischemic time, ^, and immunosuppression. Once graft survival was established, function was demonstrated via establishment of pregnancy and/or livebirths in rodents, rabbits, sheep, ^, and finally nonhuman primates.

The first uterus transplant in humans was performed in 2000 in Saudi Arabia. The recipient had a hysterectomy due to an obstetric complication and the uterus came from a nondirected living donor (LD). Approximately three months posttransplant, the recipient developed an acute vascular occlusion that appeared to be caused by inadequate uterine structure support requiring hysterectomy. The second human uterus transplant was performed in 2011 by a Turkish team and involved a recipient with MRKH and a DD. Despite multiple embryo transfers, no ongoing pregnancies were achieved until 2020 when the recipient delivered a baby boy.

The first human uterus transplant clinical trial was led by Dr. Mats Brannstrom and a Swedish team from Gothenburg. The team performed four LD UTx in 2012 and five in 2013. Graft failure occurred in two transplants secondary to vascular occlusion in one recipient and intractable infection in the other requiring hysterectomies. Of the seven women who had graft survival, six delivered live-born children, with two recipients delivering a second liveborn child following UTx.

Following this initial success, UTx using LD was pursued almost exclusively. The rationale for this was likely multifactorial and included but was not limited to perceived limited donor availability, access to suitable LD in the Swedish trial, the success with living donation in the Swedish trial, and finally the extensive preoperative evaluation and coordination that is afforded by the use of an LD. However, given the potential risk of harm to an LD, other centers were reticent to pursue LD and pursued DD UTx.

The first uterus transplant from a DD was performed in 2016 at the Cleveland Clinic Foundation and was given to a recipient with MRKH. The recipient developed a candida infection that ascended and interrupted one of the vascular anastomoses, requiring emergent hysterectomy. The first live birth from a uterus transplant from a DD took place in Brazil in 2017 and was in a recipient born with MRKH.

The number of centers that have performed uterus transplants has rapidly expanded in the past 5 years. As of 2020, worldwide >70 uterus transplants have been performed in >10 countries including Saudi Arabia, Turkey, Sweden, the United States (Cleveland Clinic Foundation [Cleveland, OH], Baylor University Medical Center [Dallas, TX], and the University of Pennsylvania [Philadelphia, PA]), Brazil, Czech Republic, Germany, France, China, Lebanon, Serbia, and India. The field of uterus transplant has progressed at an incredible speed; <10 years from when the International Federation of Gynecology and Obstetrics (FIGO) Committee Opinion on Uterus Transplant stated uterine transplantation “may reach human clinical experimentation stage,” more than 20 children have been born to women who have received uterus transplants.

In the United States, all organ transplant programs and activities must operate under the guidance of the United Network for Organ Sharing (UNOS). UNOS is a nonprofit, scientific, and educational organization that administers the Organ Procurement and Transplantation Network (OPTN). UNOS’ activities include managing the national transplant waiting list, matching donors to recipients, maintaining a database containing organ transplant data, managing the national transplant waiting list, matching donors to recipients, maintaining a database containing organ transplant data, monitoring organ transplant outcomes nationally and at a programmatic level as well as engaging with the public about the importance of organ donation. UTx is categorized as a vascularized composite allograft (VCA) transplant as opposed to a solid organ transplant. Other structures that fall underneath the VCA classification include limbs, face, abdominal wall, trachea, larynx, and penis. VCAs are a developing field in transplant medicine and are considered life-enhancing rather than life-saving. VCAs are regulated in the same fashion as solid-organ transplants by UNOS however, they required consent by the donor family authorizing the donation of the particular organ and acknowledgment that the VCA is being donated for research purposes. Organ Procurement Organizations (OPOs) are not-for-profit organizations responsible for recovering organs from DDs for transplantation. The OPO is responsible for obtaining consent for donation of all organs including VCAs.

Living Versus Deceased Donor in Uterus Transplant

Although more than 75% of all UTx performed to date have used LDs, live births have been achieved from uterus transplants using DD and LD. ^,
The primary advantage of the use of a living uterus donor is the ability to perform a comprehensive evaluation while the most significant disadvantage is the potential risk to the donor.
The use of a DD forgoes the risk to a LD at the expense of pretransplant assessment and potentially increased organ ischemic time.

Living Donors

As previously stated, the first successful human UTx was performed in the Swedish trial using exclusively LDs. A number of factors drove the team’s decision to pursue an LD UTx trial: the center (Sahlgrenska University Hospital) had extensive experience in both LD transplantation and in performing radical hysterectomy for cervical cancer. Additionally, the use of LDs makes scheduling the procedure ahead of time possible which is more than just a matter of convenience. Scheduling the procedure ahead of time facilitates a comprehensive evaluation of the donor and ensures the team members (including doctors, nurses, and operating room staff) who have trained for the procedure are available to perform the case. Other cited advantages of LDs include proposed improved graft quality and reduced cold ischemic time due to the geographic proximity of the donor and recipient at the time of surgery.

The most significant disadvantage of LD UTx is the potential risk to the donor. Although no life-threatening events have been reported following LD UTx thus far, regardless of approach, the type of hysterectomy required will always be of significant length (likely shortest duration is 6 hours) and will run the risk of physical and psychosocial morbidity and even mortality. Additionally, in LDs, blood flow to the pelvis and lower extremities must be maintained. This can limit the size/length of the vessels taken with the graft which may impede blood flow to and from the uterus.

Deceased Donors

The risk to the donor can be eliminated by limiting uterus donation to DDs. Deceased organ donors can donate following brainstem death (DBD) or circulatory death (DCD). DCD donors have their organs procured for the purpose of transplantation following death diagnosed and confirmed using cardio-respiratory criteria (i.e., non-heartbeating organ donor). DBD describes a donor who had primary brain death in whom cardiac circulation and respiration remain intact or are maintained artificially for the purpose of transplantation. DCD donors have not been included in uterus transplant trials given the increased warm ischemic time, which damages the organ, and other challenges involved in including this population. In the DD model, the living next of kin (LNOK) must consent to organ donation, and specifically, uterus donation

In addition to reduced risk to an LD, advantages of the use of DDs include increased length and number of vascular pedicles that can be harvested and the younger average age of DDs, which may improve blood flow and organ quality. In LDs, the options for venous outflow are the uterine vein and the superior uterine vein (or the uteroovarian vein). ^, The options for arterial inflow are the uterine artery with patches/segments of the anterior portion of the internal iliac arteries. ^, In LDs alternative venous drainage through the ovarian (gonadal) vein cannot be used or the blood flow to the donor’s ovaries will be compromised. This is not a concern in DDs, which makes the ovarian vein, a more accessible vessel than the uterine artery, a viable option for outflow. In terms of arterial supply, in DD the internal iliac can be harvested on both sides rather than a patch of it or the smaller uterine artery. ^, ^, The age of the donor may also be an advantage to DD UTx. The average age of donation in DD UTx was 38 years compared to 45 years in LD cases. Given vessel narrowing has been noted in the pelvic vasculature in older donors, younger donors may result in improved blood supply to the uterine graft.

The most significant disadvantage of DD UTx is the inability to perform a comprehensive preoperative assessment. Diagnostic testing, including imaging, is often limited, as is a complete medical, obstetric, and gynecologic history as this information may not be known by the LNOK. Additionally, the number of uteri suitable for transplant may be insufficient to meet the demand for UTx.

Given the overall small number of UTx that have been performed, any comparison of outcomes between LD and DD would lack statistical power. However, some have suggested that outcomes using LDs are likely to be superior in UTx as they are in other solid organ transplants. In general, living donation has been demonstrated to be associated with better outcomes including improved graft and patient survival. This is primarily thought to be due to superior organ quality, better HLA matching, shorter cold ischemia (CI) time, and negation of negative donor-related factors (e.g., brain death, cardiovascular instability, use of vasoconstrictive agents). An important caveat to this line of reasoning is that, unlike all other transplants, uterus transplants are temporary; hysterectomy is performed when the individual has delivered 1 to 2 liveborn children. As a result, long-term graft function is less important in UTx. Furthermore, given the uterus is not required for survival, the improved graft quality and patient survival associated with a living donation in other organ transplants may not be significant in UTx.

Preoperative Considerations

Pretransplant evaluation of recipients and LDs includes a full medical, surgical, psychosocial, laboratory, and radiologic assessment by a multidisciplinary team.
Given the goal of UTx is live birth, recipients must have adequate reproductive potential which in most cases is deduced from age and number and quantity, and/or euploid status of embryos cryopreserved prior to transplant.
As with other organ transplants, ABO and HLA typing as well as antibody crossmatching must be done prior to UTx.

Recipient

UTx recipients must be healthy individuals of reproductive age with AUFI who desire to have children. Additional suggested exclusion criteria for UTx recipients include but are not limited to active smoking status, history of significant systemic disease, prior recent malignancy, substance abuse, and history of multiple abdominal/pelvic surgeries. Given the goal of UTx is for individuals with UFI to carry and deliver a live-born child, candidates must have adequate reproductive potential. Reproductive potential is difficult to define and markers of ovarian reserve, such as AMH, are poor markers of reproductive potential in the general population. Centers have attempted to better ensure adequate recipient reproductive potential by imposing age limits on participation and/or requiring specific numbers of high-quality embryos to be generated and frozen prior to undergoing a uterus transplant. Specific age range and requisite number, quality, and known ploidy status vary by center.

Medical conditions that may impact vascular integrity (e.g., diabetes, vasculitis, etc.) and surgical history that may increase the risk of adhesion formation and surgical complications (i.e., multiple abdominopelvic surgeries, or appendectomy in the setting of rupture) often preclude participation in existing UTx programs. Additionally, prior history of malignancy is commonly cited as exclusion criteria given that the established increased risk posttransplant of cancer recurrence and mortality that were seen in recipients with a pretransplant history of malignancy undergoing solid organ transplants.

Additional potential exclusion criteria include BMI > 30–35 kg/m ² , recent smoking history, history of HIV, Hepatitis B or C, history of significant and/or untreated psychiatric illness, chemical and/or alcohol dependence or abuse, and allergy to expected immunosuppressive agents. The use of some of the factors detailed above will likely change and new criteria will emerge as UTx transitions to clinical practice.

A comprehensive psychosocial assessment is critical in assessing suitability for an organ transplant. Mental health disorders are common in the infertility population (prevalence ∼30%) and specifically in women with MRKH; 75% of these patients show depressive symptoms, and 33% are at risk for depressive disorders. Moreover, mood disorders may be well managed with both pharmacologic and/or nonpharmacologic interventions. As such, mental illness in and of itself is not listed as exclusion criteria by most uterus transplant programs. However, understanding current and past mental health conditions as well as assessing how past and future stressors have impacted mental well-being is important prior to transplant. Obtaining documentation from current mental health providers, if a recipient is in active treatment, is prudent. Additionally, ensuring any current treatment continues before and after UTx is recommended. Alternatively, a comprehensive evaluation by a medical health professional may uncover severe or untreated psychopathology, substance abuse, and/or domestic violence that would preclude participation due to the risk of the psychological strain of transplant exacerbating the individual’s underlying mental health disorder.

Social support can generally be defined as the services, assistance, care, or encouragement provided by social network members (e.g., spouses or partners, family, and friends). In accordance with the Centers for Medicare and Medicaid Policy (CMS) and professional societies, inadequate social support has been used as a contraindication to transplant by most centers performing UTx. However, given the subjectivity in this criterion’s assessment and its uncertain impact on posttransplant outcomes, its use raises questions related to transparency and justice.

Determining if individuals interested in receiving a uterus transplant meet the inclusion and exclusion criteria listed above requires a rigorous multidisciplinary preoperative evaluation. The preoperative evaluation includes laboratory, imaging, and clinical assessments (see Table 40.1 ).

Table 40.1

UTx Recipient Preoperative Evaluation

Clinical Assessment	Gynecology
	Reproductive endocrinology & infertility
	Transplant surgery
	Maternal fetal medicine
	Psychology
	Anesthesiology
	Social work
	Nutrition
	Pharmacy
Laboratory	Complete blood count
	Comprehensive metabolic panel
	ABO, Rh, and antibody screen
	Prothrombin time
	Activated partial thromboplastin time
	Cytomegalovirus
	Epstein-Barr virus
	Varicella virus
	Rubella virus
	Rubeola virus
	Human immunodeficiency virus
	Hepatitis A, B, C
	Chlamydia
	Human papilloma virus
	Gonorrhea
	Syphilis
	Pap test
	Anti-müllerian hormone
	Thyroid stimulating hormone
Radiology	Pelvic ultrasound
	MRI (abdomen and pelvis)

The immunosuppressive regimen used following organ transplant is nephrotoxic and therefore renal assessment should be performed on all candidates with Mullerian anomalies given the association between MRKH and structural renal abnormalities. Renal anomalies, the most common extragenital abnormalities, are found in 30% to 40% of all MRKH patients. Unilateral renal agenesis (∼50%), pelvic kidney, duplex kidney, and horseshoe kidney have been observed. The presence of renal abnormalities may be important because tacrolimus, one of the most commonly used immunosuppressants in UTx, is renally cleared. Given the potential for calcineurin-inhibitor-related renal damage, some research protocols exclude patients with renal anomalies. However, there have been at least four UTx recipients with renal malformations, including single kidneys and unilateral pelvic kidneys. ^, There was a disproportionately higher rate of preeclampsia after UTx in patients with single kidneys necessitating preterm delivery (∼75%) between 31 and 35 weeks’ gestation, compared to those without renal abnormalities, although given the small numbers it is not clear if this is a significant increase.

Donor

The quality of the donated uterus, in particular its vasculature, is critical to the viability of the graft posttransplant (surgical success) as well as pregnancy and/or delivery outcomes. Many factors that contribute to organ quality are also factors that would make an individual a good medical/surgical candidate and therefore there is overlap between inclusion and exclusion criteria for UTx donors and recipients with some notable exceptions.

The age of the donor is important in UTx; however, the rationale is related to quality of the vasculature rather than reproductive potential. The age minimum and cutoffs differ by center and donor type (the average age for LD is 45 compared to 38 years old for DD). Although live births following UTx have been achieved using postmenopausal LD, it is important to recognize that age is an independent risk factor for arterial calcification and stiffness, which may compromise vascular anastomoses. Abortion of a transplant after graft procurement in a 61-year-old woman, with cardiovascular risk factors of obesity and type II diabetes mellitus, occurred after inability to flush the graft’s vessels due to atherosclerotic disease. Additionally, in the Swedish trial, the grafts of two LDs (age 62 and 58 years) failed secondary to what was attributed to be suboptimal arterial flow due to intimal hyperplasia or atherosclerosis.

Again, medical conditions that may impact vascular integrity (e.g., diabetes, vasculitis, etc.) and surgical history that may increase the risk of adhesion formation and surgical complications (i.e., multiple abdominopelvic surgeries, or appendectomy in the setting of rupture) or the risk of pregnancy complications (i.e., myomectomy or endometrial ablation) may result in an individual being consider a suboptimal or poor candidate for uterus donation. It is important to note that this information and much of the information below may not be available or may be incomplete in the setting of a DD.

The parity of the donor is preferred as it demonstrates the ability of the uterus to sustain implantation and pregnancy; however, live birth has been achieved from nulliparous DDs. Along the same line, a history of miscarriage alone does not preclude uterus donation as pregnancy loss is common (occurs in 15%–25% of pregnancies). However, a history of recurrent pregnancy loss (defined as ≧3 losses) occurs in <1% of women and therefore should prohibit uterus donation. Additionally, a history of obstetric complications such as placenta previa, placental abruption, and preterm delivery are conditions that should prevent donation.

The structural integrity of the uterus must be assessed prior to UTx. In LDs, multiple imaging modalities can be used prior to donation to assess for structural abnormalities including pelvic ultrasound, saline-infused sonohysterogram, and hysteroscopy. The imaging modalities available are more limited in DD. Although computerized tomography of the thorax and abdomen is often performed to exclude pathology prior to solid organ donation, the pelvis is not consistently imaged. Additionally, CT or MRI may not detect subtle intracavitary findings (e.g., fibroids, polyps, septums) that may impact pregnancy. Preoperative hysteroscopy may be possible and its use has been reported prior to DD UTx.

A gross inspection of the uterus and cervix can be done at the time of organ procurement and most structural abnormalities that are visible would result in excluding the uterus for transplant. Importantly, cervical cancer may not be grossly visible and a history of cervical cancer or abnormal pap test would ideally be an exclusion criteria for uterus donation. In the case of LD, a pap test can be obtained prior to transplant if needed. In DD, pap history may not be known and the result of a pap test may not be able to be obtained prior to transplant. In this setting, a pap test can be obtained at the time of transplant and the decision can be made whether to proceed with the transplant following the stratification of risk for development of invasive cervical cancer and recipient counseling.

The inclusion of LDs enables imaging to detect structural abnormalities in the reproductive tract and also evaluate the vasculature supplying the uterus, pelvis, and lower extremities. In the Dallas trial (Dallas UtErus Transplant Study [DUETS]), predonation imaging included dual-phase computed tomography (CT) angiograms of the abdomen and pelvis in the arterial and venous phases and >50% of donors underwent multiphasic pelvic MR angiograms. Interestingly, 33% of donors evaluated were excluded due to suboptimal quality of the pelvic vasculature including small uterine arteries, the presence of atherosclerosis, or small size/poor quality of the uterine or uteroovarian veins, or both.

A comprehensive psychosocial assessment is as critical in assessing suitability for uterus donation as it is for potential uterus recipients. Approximately one in five individuals in the general population live with mental illness ; therefore, a history of well-controlled mental health disorders do not typically warrant exclusion from uterus donation. However, the presence of poorly controlled or untreated mental health disorders in the donor increases the risk of harm to the donor postdonation. For other living organ donors, substance abuse is a contraindication to donation and, therefore, this recommendation should be extended to uterus donors. Similar to UTx recipients, additional exclusion criteria may include significant medical comorbidities, BMI > 30–35 kg/m ² , smoking history, history of HIV, Hepatitis B or C, and/or active viremia.

Importantly, LD is considered morally justifiable based on the autonomy of the donor provided the following conditions are met : the donor (1) is medically and psychologically competent, (2) has been informed about risks of donation as well as risks, benefits, and alternatives for the recipient, and (3) is free from coercion. Paying for human organs is illegal in almost every country and is strictly banned by the National Organ Transplant Act. An assessment at one point in time does not ensure donation is voluntary. Procedural steps that have been proposed to safeguard voluntariness in donation include: (1) facilitating an open relationship between a potential donor and an independent donor advocate early in the evaluation process, (2) allowing for a “cooling off period” after initial exchange and planned donation, (3) describing mechanisms for opting out while assuring confidentiality of reasons for withdrawal.

Donor/Recipient Matching

The major physiologic barrier in transplantation is the potential for the recipient’s immune system to recognize the transplanted organ as foreign and provoke an immune response that damages the tissue. Histocompatibility testing is used to reduce donor-specific immune responses in the recipient. The type of histocompatibility testing performed varies, depending on the organ or tissue that has been transplanted. The reason for this variability is the immunogenicity of distinct organ types differs. A transplanted heart elicits a more robust response from the donor immune system than a transplanted liver. As a result, additional HLA testing must be done to ensure the donor and recipient match closely and independent of matching, higher doses of immunosuppression are required to prevent rejection following heart transplant than liver transplant. The immunogenicity of the uterus is not known at this time.

The ABO and human leukocyte antigen (HLA) systems have been identified as the major transplantation antigens and therefore are taken into consideration most when matching donor organs to recipients. Basic ABO typing is used to denote the presence of one, both, or neither of the A and B antigens on red blood cells. If an ABO-incompatible graft is transplanted, hyperacute rejection may occur. Interestingly, Rho antigens are not expressed on endothelial tissue and, therefore, play no apparent role in graft rejection or survival. HLA typing is also done prior to organ transplant. There are three general groups of HLA: HLA-A, HLA-B, and HLA-DR. There are many different proteins within each of these groups. Although individuals do not have to have all of the same HLA antigens expressed, ensuring a close HLA match reduces the risk of inciting an immune reaction that can result in rejection. Cell surface proteins other than HLA can also incite immune reactions and therefore in addition to HLA typing, a crossmatch is performed prior to transplant. The purpose of the crossmatch is to detect the presence of antibodies in the recipient against antigens on donor cells. Even if donor and recipient are immunologically compatible, immunosuppressive regimens must be used. The only exception to this is in the case of monozygotic twins which have identical ABO and HLA profiles.

Surgical Technique

Uterus transplant involves removing the internal iliac artery and vein (or its downstream branches) from the donor and connecting it to the external iliac artery and vein in the recipient.
Venous drainage of the uterus is technically difficult and vascular occlusion is the most common indication of graft failure.
Ideal surgical techniques and approaches are rapidly evolving, the ultimate goal of which is to achieve living donation through minimally invasive surgery

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