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Original Research ajog.

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OBSTETRICS
Living uterus donation and transplantation: experience of
interest and screening in a single center in the United States
Liza Johannesson, MD, PhD; Kristin Wallis, BSN; E. Colin Koon, MD, PhD; Greg J. McKenna, MD; Tiffany Anthony, MD;
Sara G. Leffingwell, BS; Goran B. Klintmalm, MD, PhD; Robert T. Gunby Jr, MD; Giuliano Testa, MD

BACKGROUND: Little is known about attitudes toward uterus donation with a congenital uterine absence were in general younger than the
and transplantation in society and the interest of the women the treatment women in the group whose uterus had been removed (mean of 28 and 33
is aimed to assist. years, respectively). In every step of the initial screening and evaluation
OBJECTIVE: This study examined the interest of recipients and living process, there were donor and recipient candidates that chose not to
donors in our uterus transplantation program; it describes the screening continue the process. The reasons for self-withdrawal after expressing
protocol we developed and the results of the screening and reports de- interest were not returning phone calls or e-mails (17 donors and 76
mographic data and characteristics of screened candidates. recipients); after initial phone screening, no longer interested (1 donor
STUDY DESIGN: Initial screening and evaluation included physical and 9 recipients); in step 1, health history questionnaire not returned after
examinations by a gynecologist and a transplant surgeon; psychological 1 reminder (10 donors and 9 recipients); step 2, not right in their current
evaluation; imaging (x-ray, computed tomography, ultrasound); blood life situation (2 donors and 2 recipients), and in step 3, chose another way
tests; immunological testing; viral, bacterial, and fungal testing; drug to achieve motherhood (1 recipient). Most donor and recipient candidates
screen; hormonal testing; Papanicolau smear; urinalysis; and electro- (52% and 78%, respectively) could be screened out (because of self-
cardiogram. For selected recipients, the process also included in vitro withdrawal or transplant team’s decision) during the noninvasive and
fertilization. cost-efficient initial screening.
RESULTS: A total of 351 women contacted our department with in- CONCLUSION: Our initial experience shows a great interest in
terest in participating in uterus transplantation; 272 were potential re- participating in a trial of uterus transplantation by both potential recipients
cipients and 79 were potential donors. Among these women, 179 and donors. It is the first study to show interest in nondirected donation. A
potential recipients and 62 potential donors continued the evaluation after sufficient but thoughtful screening process of living donors and recipients
the initial telephone screening. The mean age of the donor candidates is essential and should aim both to assure donor/recipient safety and to
was 40 years; all had completed their own family, and 80% were provide good quality grafts.
nondirected. Most recipient candidates (92%) had an anatomical lack of
the uterus, and of these, 36% had a congenital malformation. The women Key words: donor, infertility, interest, recipient, uterus transplantation

I n 2014, the first baby was delivered by


a mother born without a uterus.1 The
birth was facilitated by a uterus trans-
have no functional uterus but want to
have a child are currently given only
adoption or surrogacy as options.
While public attitudes toward tradi-
tional organ donation are favorable and
uterus transplantation is considered a
plantation almost 2 years prior to the Uterus transplantation is unique in promising treatment option among
delivery. While uterus transplantation is several ways. Rather than being life health care professionals, little is known
still in an experimental stage, it is a saving, it enhances quality of life and is about attitudes toward uterus donation
promising potential treatment for potentially life giving. It is the first tem- and transplantation in society and the
women with absolute uterine-factor porary organ transplantation, with interest of the women the treatment is
infertility. Approximately 1 in 500 planned removal after childbirth. It can aimed to assist. In this paper, we present
women are affected by absolute uterine- be performed with both living and our initial experience with the interest of
factor infertility2; based on the popula- deceased donors, although to date the potential recipients and donors for
tion, we estimate that there are about birth of a child has occurred only after uterus transplantation, the development
80,000 reproductive-age women with living-donor transplants. of a screening protocol, and the de-
absolute uterine-factor infertility in the The first attempt at uterus trans- mographic data and characteristics of
United States. The many women who plantation in the United States in our screened candidates.
2016 was unfortunately unsuccessful.3
The transplant was conducted with a Materials and Methods
Cite this article as: Johannesson L, Wallis K, Koon EC, deceased-donor uterus, and the graft Our clinical uterus transplantation trial
et al. Living uterus donation and transplantation: expe- had to be removed less than 2 weeks (Project 015-158) was performed at
rience of interest and screening in a single center in the
after the transplant. Six months after Baylor University Medical Center
United States. Am J Obstet Gynecol 2017;xxx:xx-xx.
this initial uterus transplantation, we (Dallas, TX) and was approved by the
0002-9378/$36.00 performed the first living-donor institutional review board. The policy
ª 2017 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.ajog.2017.11.594 uterus transplantation in the United of the program is to present all poten-
States. tial uterus recipients with the possibility

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Original Research OBSTETRICS ajog.org

of both living and deceased donor


TABLE 1
transplants at the time of evaluation for
Evaluation of candidates for in vitro fertilization
transplantation.
Type Test The candidates (both potential donors
Health care professional Physical examination and recipients) independently contacted
evaluation our institution. There was no advertising
or recruiting for the clinical trial aside
Pelvic examination
from information on the hospital web
Psychological evaluation (including in-depth interview site and a local press conference to
and standardized questionnairesa)
announce the start of the trial, during
Imaging Chest x-ray which contact information was provided
Computed tomography, abdomen and pelvis (e-mail and phone number) as well as
Vaginal ultrasound
the listing on clinicaltrials.gov (clinical
number NCT02656550).
Doppler ultrasound The first contact with the potential
Transabdominal ultrasound recipient or donor was through a nurse
Blood tests Complete blood count with differential coordinator (with >10 years of experi-
ence in women’s health) assigned to
Comprehensive metabolic panel
the program. The candidates were
Gamma-glutamyl transferase informed at the initial contact about
Lipid panel the experimental nature of the program,
Prothrombin time/international normalized ratio the worldwide experience/outcome of
uterus transplantation, details of the
Partial thromboplastin time
surgery, postoperative care, and poten-
Hemoglobin A1c tial complications. They were also
Immunological testing ABO blood groups Rh antigens informed that participation in the uterus
Human leukocyte antigens transplantation trial possibly could
render costs for them.
Viral, bacterial, and fungal Syphilis The trial would cover investigations,
testing
surgery, hospital stay, medications, and
Chlamydia and gonorrhea (Neisseria gonorrhoeae follow-up visits but would not cover
culture)
in vitro fertilization (IVF), travels, ac-
Herpes simplex virus 1 and 2 commodation, or loss of income. No
Hepatitis C virus RNA by polymerase chain reaction compensation for participating in the
Surface antigen of the hepatitis B virus
trial would be handed out. A basic initial
screening also took place during this first
Cytomegalovirus IgM and IgG contact, with exclusion criteria being age
Epstein-Barr virus IgM and IgG (limit of 65 years for donors and 35 years
HIV for recipients), body mass index (BMI)
limit of 30 kg/m2, medical comorbid-
Fungal screening
ities, and obstetric history. The candi-
Urine culture dates considered to be initially suitable
Rubella and interested in participation pro-
Tuberculosis (T-SPOT) ceeded to the first step of evaluation.
Drug screen Serum alcohol test
Step 1: subjective health screening
Urine drug test
The candidates received an informed
Other tests Papanicolau smear with cotesting for human consent form for screening and a health
papillomavirus
history questionnaire. Candidates were
Urinalysis also encouraged to send any related
Electrocardiogram medical records, if present. Based on the
health history questionnaires, the pri-
Johannesson et al. Uterus transplantation interest. Am J Obstet Gynecol 2017. (continued)
mary investigator (transplant surgeon)

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the IVF process. During the IVF, intra-


TABLE 1 cytoplasmic sperm injection was used,
Evaluation of candidates for in vitro fertilization (continued) and on day 5e6 the blastocysts were
Type Test biopsied for PGS testing. Once the po-
Hormonal testingb Follicle-stimulating hormone
tential recipient had obtained at least 2
day 5e6 blastocysts of satisfactory
Luteinizing hormone quality (may require 1 or more stimu-
Estradiol lations), she was listed for trans-
Prolactin plantation and donor matching.
Anti-Müllerian hormone
Step 5: final selection committee
Thyroid-stimulating hormone meeting
Ig, immunoglobulin. If the potential recipient had a named
a
For recipients only: Fertility Quality of Life Questionnaire. For both recipients and donors: Millon Behavioral Medicine Diag- donor, the donor would have to go
nostic; Hospital Anxiety and Depression Scale; Posttraumatic Strerss Disorder Checklist for Diagnostic and Statistical Manual
of Mental Disorders, fifth edition; 36-Item Short Form Survey; Brief Coping Orientation to Problems Experienced Question- through evaluation steps 1e3 before
naire; Connor-Davidson Resilience Scale 10; Drug Use Questionnaire, and Dyadic Adjustment Scale; b Hormonal testing being approved. If the potential recipient
occurred in step 4; all other testing occurred in step 2.
Johannesson et al. Uterus transplantation interest. Am J Obstet Gynecol 2017.
did not have a donor, she was put on a
list for altruistic donor matching. The
matched donor-recipient pair was pre-
sented at a second selection committee
decided which candidates were eligible psychological evaluation included an in- meeting during which final approval to
for step 2. The decision on eligibility was depth interview and standardized psy- go through with donation/trans-
based on the inclusion and exclusion chological questionnaires (Fertility plantation was given and scheduled. In
criteria of the uterus transplantation trial Quality of Life Questionnaire for re- the event the potential recipient did not
and excluded, for example, vaginal cipients only; Millon Behavioral Medi- have a named donor or could not be
grafts, hormonal replacement therapy, cine Diagnostic, Hospital Anxiety and matched with an existing altruistic
kidney malformations, and severe Depression Scale, Posttraumatic Strerss donor, she was put on a list for deceased
endometriosis. The candidates were Disorder Checklist for Diagnostic and donor matching.
notified and an evaluation schedule Statistical Manual of Mental Disorders,
arranged. fifth edition, 36-Item Short Form Sur- Results
vey, Brief Coping Orientation to Prob- Within a year, 351 women (272 potential
Step 2: objective health screening lems Experienced Questionnaire, recipients and 79 potential donors)
The second step of the evaluation pro- Connor-Davidson Resilience Scale 10, contacted our department with interest
cess consisted of a medical workup. A Drug Use Questionnaire, and Dyadic in participating in the uterus trans-
second informed consent form was given Adjustment Scale for both recipients and plantation trial (>85% contacted the
to the candidates before the process donors). The medical workup took place department during the first 2 months
started. The candidates were informed of over a 2 day period and is detailed in after the trial was announced in a press
the procedure by both transplant sur- Table 1. conference). The characteristics of the
geons and gynecological oncologists 179 potential recipients and 62 potential
separately. They were informed of the Step 3: initial selection committee donors who passed the initial screening
known complications of previously meeting are summarized in Table 2. Of this
performed cases of living donor uterus The 8 potential donors and 11 potential group, 48% of the donor candidates and
donation and transplantation world- recipients screened through step 2 were 22% of the recipient candidates
wide. They were also informed about presented at a selection committee continued to the first step of evaluation
postoperative hospital stay, post- meeting made up of transplant surgeons, (Figure).
operative restrictions, and readjustment gynecologists, obstetricians, a repro- Among the 62 donor candidates who
to normal life. They were thoroughly ductive endocrinologist, a psychologist, went through the initial screening, 74%
informed about the experimental nature and a nurse coordinator. The candidates were altruistic/nondirected. The 16
of the uterus transplantation trial and considered suitable for donation or for directed donor candidates were referred
that there is an unknown outcome for the next step in recipient evaluation were by 5 recipient candidates. The mean age
both recipients and donors. They had the notified. of the donor candidates was 40 years
opportunity to see a psychologist after (range, 21e64 years), and 90% had
receiving the information. Step 4: in vitro fertilization for delivered at least 1 child. All donors had
Clinical evaluations were performed potential recipients completed their own family, and 19
by a transplant surgeon, a gynecological Potential recipients were referred to the (31%) had gone through permanent
oncologist, and a psychologist. The reproductive endocrinologist to begin pregnancy prevention, either female

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had an anatomical lack of the uterus


TABLE 2
(Table 3). Of these women, 36% had
Characteristics of candidates for uterus donation and transplantation
a congenital malformation (Mayer-
Characteristics Recipients Donors Rokitansky-Küster-Hauser syndrome
Candidates included in initial phone screening, n 179 62 [MRKH]). The women with MRKH
were in general younger than the women
Age, y, mean (range) 32 (19e59) 40 (21e64)
in the group whose uterus had been
2
Body mass index, kg/m , mean (range) 27 (18e60) 26 (18e41) removed (mean of 28 and 33 years,
Smoking, n 9 0 respectively). In the group of women
Previous children, n, % 89 (50%) 56 (90%) with a previous hysterectomy, 73% had
their uterus removed because of benign
Biological, n 85 73
causes, 16% because of obstetric com-
Gestational surrogacy (biological), n 3 0 plications, and 11% because of gyneco-
Adopted, n 1 0 logical malignancies (Table 3).
Selected candidates for donation and transplantation, n 10 6
In addition, 47% of the interested
recipient candidates had at least 1 child
Age, y, mean (range) 30 (22e34) 42 (34e55) prior to expressing interest in the clinical
2
Body mass index, kg/m , mean (range) 25 (19e30) 24 (19e28) trial. The selected recipient candidates
Smoking, n 0 0 (n ¼ 10) had a mean age of 30 years and a
Marital status BMI of 25 kg/m2. All selected recipients
were either married or in a committed
Married 9 3
relationship. The majority (70%) were
Divorced 0 2 white/non-Hispanic and had at least a
Committed relationship 1 1 high school education. Detailed charac-
Race/ethnicity teristics of the selected recipients are
shown in Table 2.
White/not Hispanic 7 5
In every step of the initial screening
Hispanic 1 1 and evaluation process, there were donor
Black 1 0 and recipient candidates who chose not
American Indian 1 0 to continue the process. The reasons for
self-withdrawal were, after expressing
Religion
interest, not returning phone calls or
No preference 2 2 e-mails (17 donors and 76 recipients);
Christian 5 4 after initial phone screening, no longer
Muslim 1 0 interested (1 donor and 9 recipients); in
step 1, health history questionnaire not
Unknown 2 0
returned after 1 reminder (10 donors
Geographic origin and 9 recipients); step 2, not right in
United States/Texas 3 6 their current life situation (2 donors and
United States/other state 7 0 2 recipients); and in step 3, chose
another way to achieve motherhood (1
Education level
recipient). None of the donors or re-
High school 2 0 cipients were excluded based on the
Technical school 1 0 psychological evaluation (in-depth
Associate’s degree 1 0 interview and standardized psychologi-
cal questionnaires).
Bachelor’s degree 5 4
Master’s degree 1 2 Comment
Johannesson et al. Uterus transplantation interest. Am J Obstet Gynecol 2017. (continued) Uterus transplantation as a treatment for
certain kinds of infertility is a new,
rapidly growing area of transplantation,
(tubal ligation, 63%) or male (partner/ were nondirected. Detailed characteris- augmented by the first successful de-
husband vasectomy, 37%). The selected tics of the selected donors are shown in livery after a uterus transplant in 2014.1
donor candidates (n ¼ 6) had a mean age Table 2. This is the first study that describes not
of 42 years and a BMI of 24 kg/m2. All of Of the recipient candidates who went only the interest of potential recipients in
the donors had previous children, and all through the initial screening, 164 (92%) uterus transplantation but also the

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ajog.org OBSTETRICS Original Research

favored more than gestational surrogacy


TABLE 2 but less than adoption (35%, 18%, and
Characteristics of candidates for uterus donation and transplantation 62%, respectively).
(continued) Kisu et al6 also showed that for
Characteristics Recipients Donors candidate donors and recipients,
Employment deceased donors and congenital uterine
agenesis were favored. In our study, at
Student 1 0
this initial state of uterus trans-
Not employed 2 1 plantation, we chose to continue the
Part time 1 0 evaluation process (step 1) with women
Full time 6 5 who had MRKH (congenital agenesis)
and women who had a previous hyster-
Number of previous children, mean (range) 0 3 (2e4)
ectomy because of obstetric complica-
Nondirected donor NA 6 tions, who together represented 42% of
Johannesson et al. Uterus transplantation interest. Am J Obstet Gynecol 2017. the potential recipients interested in
participating. It was also required that
the women with MRKH have 2 func-
tioning kidneys and nongrafted vaginas.
interest of potential donors at a single donors (23% of 351). It is difficult to A recent publication from the team
center at the launch of a new transplant judge whether the interest shown from behind the first uterus transplantation in
program. potential donors and recipients corre- the United States showed great interest
The screening and evaluation pro- lates to that of the general population, in uterus transplantation, with >250
cesses (steps 1e5) were based on a suc- but a few studies have been published potential recipients of reproductive age
cession from least to most invasive that support the fact that there is a strong who contacted that center prior to the
examinations. We also aimed to identify and positive interest in the general pop- first transplant.7 The study showed a
key examinations that would help detect ulation toward uterus transplantation.4-6 high percentage (64%) of acquired
unsuitable candidates as early as possible A study of public attitudes in the uterine-factor infertility within the study
in the process, thus saving time and ex- United States toward vascularized com- population, with a high proportion of
penses both for the candidates and the posite allograft donation and trans- hysterectomies for a benign cause
program. plantation had 1485 participants, of (50%).7
In our study, 52% of potential donors whom 736 were women (median age, 32 In our study, the corresponding
and 78% of potential recipients were years).4 The survey showed that as many numbers were similar or higher (58%
rejected on initial screening, and a as 74% of women were willing to donate and 78%, respectively). The mean age of
further 29% and 12%, respectively, were their uterus. Among those who were not the women who had a hysterectomy of
rejected during the first step of the willing to donate their uterus, the main benign cause was 34 years, and the main
evaluation. The main reason for elimi- reasons were vague psychological reasons for the hysterectomy were
nation during the initial phone screening discomfort, nonspecific, or body part is endometriosis, fibroids, and heavy
was that the potential donors and re- not viable (41%, 32%, and 23%, respec- bleeding. The relatively high proportion
cipients did not meet the basic inclusion tively). Only 1% stated identity loss as a of young women of child-bearing age
criteria of the trial (50% and 86%, cause for not being willing to donate. who underwent a hysterectomy for
respectively). Of the potential donors Support for uterus transplantation has benign causes was noted by Arian et al,7
and recipients who continued to step 1, been reported previously. In the United who commented on the US culture of
the main reason for not proceeding to Kingdom, a survey of 528 health care hysterectomy, which results in infertility.
step 2 was self-withdrawal (56% and professionals showed great support It is interesting to note that most po-
41%, respectively) and comorbidities for (94%) for uterus transplantation as a tential donors and recipients who con-
potential recipients (27%). Because no possible therapeutic option for absolute tacted our program did so after it was
medical examinations are included in uterine-factor infertility.5 Another study publicly known that the first uterus
the initial screening or step 1, the ex- of 3098 women (mean age, 32 years) transplantation in the United States
penses are minimal. explored the attitudes of Japanese failed.3 Despite the news of the failed first
After registration of our clinical trial, women of reproductive age toward attempt, interest in the clinical trial
we hoped to receive interest from po- uterus transplantation.6 The survey remained strong.
tential recipients, but as the trial became showed 44% in favor of uterus trans- Arian et al7 also pointed to the fact
common knowledge, we were also con- plantation; 47% had no opinion, and 8% that 17% of potential recipients in their
tacted by interested potential altruistic were against. Uterus transplantation was study had at least 1 biological child to

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Original Research OBSTETRICS ajog.org

FIGURE
Results of initial screening and evaluation process for candidates

Results of the initial screening and evaluation process for candidates of uterus donation and transplantation, showing causes for not continuing evaluation
for both donors and recipients. Administrative reasons included insurance/financial issues or the candidate or spouse being unable to relocate.
BMI, body mass index; HPV, human papillomavirus; HSV, herpes simplex virus; STD, sexually transmitted disease.
Johannesson et al. Uterus transplantation interest. Am J Obstet Gynecol 2017.

dispute the argument that uterus trans-


TABLE 3 plantation would exploit a vulnerable
Causes of infertility among the 179 recipient candidates screened for uterus population unable to have children
transplantation another way. In our study, almost half of
the interested potential recipients had at
Cause N
least 1 child prior to showing interest in
Absent uterus 164 (92%) the clinical trial (biological, n ¼ 85;
Congenital uterine-factor infertility/MRKH 59 adopted, n ¼ 3; biological through sur-
Acquired uterine-factor infertility 104 rogacy, n ¼ 1).
In conclusion, this study shows a great
Hysterectomy for obstetric complications 17
interest in participation in uterus trans-
Hysterectomy for malignancy 11 plantation, both by potential recipients
Hysterectomy for benign conditions 76 and donors. This study is the first to
Transgender female 1 show that interest in donating a uterus is
great, even for nondirected donors. A
Present uterus 15 (8%)
sufficient but thoughtful screening pro-
Undiagnosed infertility 11 cess of living donors and recipients is
Ovarian-factor infertility 2 essential. The process should aim both to
Fallopian tubeefactor infertility 2 assure donor/recipient safety and to
MRKH, Mayer-Rokitansky-Küster-Hauser syndrome.
provide good-quality grafts for the re-
Johannesson et al. Uterus transplantation interest. Am J Obstet Gynecol 2017. cipients. The screening and evaluation
process is time consuming and

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ajog.org OBSTETRICS Original Research

expensive. Hence, one of the greatest 3. Flyckt RL, Farrell RM, Perni UC, Tzakis AG, 7. Arian SE, Flyckt RL, Farrell RM, Falcone T,
challenges is to recognize patient char- Falcone T. Deceased donor uterine trans- Tzakis AG. Characterizing women with interest
plantation: innovation and adaptation. Obstet in uterine transplant clinical trials in the United
acteristics and examinations that would Gynecol 2016;128:837-42. States: who seeks information on this experi-
identify unsuitable candidates as early in 4. Rodrigue JR, Tomich D, Fleishman A, mental treatment? Am J Obstet Gynecol
the process as possible. n Glazier AK. Vascularized composite allograft 2017;216:190-1.
(VCA) donation and transplantation: a survey of
Acknowledgment public attitudes in the United States. Am J Author and article information
Transplant 2017;17:2687-95. From the Annette C. and Harold C. Simmons Transplant
This observational study had a trial registration
5. Saso S, Clarke A, Bracewell-Milnes T, et al. Institute (Drs Johannesson, McKenna, Anthony, Klint-
number of NCT02656550.
Survey of perceptions of health care pro- malm, and Testa), Baylor Research Institute (Ms Wallis
fessionals in the United Kingdom toward and Ms Leffingwell), and Department of Obstetrics and
References uterine transplant. Prog Transplant 2015;25: Gynecology (Drs Koon and Gunby), Baylor University
1. Brannstrom M, Johannesson L, Bokstrom H, 56-63. Medical Center, Dallas, TX.
et al. Livebirth after uterus transplantation. Lan- 6. Kisu I, Banno K, Soeda E, et al. Survey of Received Aug. 22, 2017; revised Nov. 7, 2017;
cet 2015;385:607-16. attitudes toward uterus transplantation accepted Nov. 29, 2017.
2. Sieunarine K, Zakaria FB, Boyle DC, et al. among Japanese women of reproductive The authors report no conflict of interest.
Possibilities for fertility restoration: a new surgical age: a cross-sectional study. PLoS One Corresponding author: Liza Johannesson, MD, PhD.
technique. Int Surg 2005;90:249-56. 2016;11:e0156179. liza.johannesson@BSWHealth.org

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