Initiation of a Deceased Donor Uterine Transplantation Program at the University of Nebraska Medical Center
Information source: University of Nebraska
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Uterus Transplant
Intervention: Uterine Transplant (Procedure)
Phase: N/A
Status: Not yet recruiting
Sponsored by: University of Nebraska Official(s) and/or principal investigator(s): Alexander T Maskin, MD, Principal Investigator, Affiliation: UNMC
Overall contact: Alexander T Maskin, MD, Phone: 402-559-3382, Email: alexander.maskin@unmc.edu
Summary
This study will explore the feasibility of initiating a uterine transplant program at UNMC.
Using the procedural templates established by a successful Swedish team, the investigators
will identify emotionally and socially stable females of reproductive age with intact
ovaries who are unable to gestate a child due to congenital or acquired uterine factor
infertility (UFI). Women will be 21 to 35 years of age upon entry into the protocol, with
normal ovarian reserve and otherwise healthy for pregnancy. After careful screening,
participants will undergo egg harvest, in-vitro fertilization, and embryo cryopreservation
using standard methods. Women who successfully complete in vitro fertilization and
cryopreservation of at least six embryos will be eligible to receive implantation of a
deceased donor uterus. After a period of observation to ensure normal menstrual cycling and
graft viability, embryo implantation will be undertaken. Gestations will be carefully
monitored by our high-risk pregnancy specialists. Medical research interventions include
uterine harvest from a deceased donor, surgical implantation of the organ utilizing standard
transplant techniques, careful post-transplant follow-up including immune suppression
therapy tailored to minimize fetal compromise, and careful management of pregnancy. After
childbearing is complete (at most two gestations), the donor uterus will be removed. In
addition, open-ended interviews and written surveys will be conducted to elicit ethical and
psychosocial concerns arising from the experience of subjects and their families, health
care providers, and the wider community. The investigators intent is to monitor outcomes
lifelong for transplant recipients and live-born infants.
Clinical Details
Official title: Initiation of a Deceased Donor Uterine Transplantation Program at the University of Nebraska Medical Center
Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Successful Uterine Transplant
Detailed description:
Uterine transplantation was developed as a surgical/medical procedure to ameliorate the
condition of absolute uterine factor infertility. As a condition, the congenital or acquired
state renders fertile-age women the inability to have a child via conventional birth. It is
estimated that this condition may affect near 1 in 500 women. The alternative, namely
gestational surrogacy or adoption, can be fraught with legal, ethical, or religious issues.
Significant research and progress has been obtained in Europe (namely Sweden) in
facilitating uterine transplantation. Recently, they were able to obtain a successful live
childbirth using a donated uterus from a living relative. Based on significant background
research already performed, the aim of this research study is to expand upon their gains by
successfully establishing a deceased donor uterus transplantation program at UNMC.
Prior to the success of the Swedish team, two other European/Asian medical research groups
have attempted deceased donor uterus transplantation. The first resulted in organ failure
from unclear pathology. The second was a successful transplant, but failed to yield a
childbirth due to multiple miscarriages. In 2004 however, the team from the Sahlgrenska
Institute in Gothenburg instituted a rigorous research undertaking in order to study the
phenomenon and to obtain a childbirth. Using established immunological knowledge, and
practical experience using animal models, the investigators were able over a course of a
decade, to start an active transplant program.
From a medical/obstetrics and gynecology standpoint, potential subjects were screened using
a rigorous physical and psychosocial evaluation. This involved meeting with multiple members
of the research team, in addition to independent monitors familiar with the field and the
risks and benefits of participation. To facilitate success, all women and their partners
underwent investigation to rule out any sterility factors that could have been related to
fertility. Next, egg harvesting and embryo transfer was undertaken according to currently
accepted protocols. Of note, all women who had uterine agenesis had some type of neo-vaginal
recreation in order to facilitate IVF. Finally, donor and recipient HLA matching was done
using standard transplantation methods in order to avoid unacceptable matches.
During surgery, the donor underwent an extensive procedure in order to successfully dissect
out the artery and venous supply of the organ. The vagina was transected caudal to the
fornix, thus allowing a donor specimen which was attached by only the vascular pedicles.
(The process of removing a uterus from a living donor is infinitely more complex than that
of a deceased donor, hence our initial plan at UNMC is to focus on organs derived from the
latter.) Once the organ was removed, it was flushed with preservation solution using
standard transplantation protocols. The recipient surgery was also performed in standard
fashion, with the donor iliac vessels anastomosed to the recipients. The vaginal rim of the
graft was sutured to the recipient's vagina in standard fashion. Routine intra-operative
examinations with Doppler (to assess blood flow) were then performed prior to the
termination of the operation.
Maintenance immunosuppression was given to the recipients using standard accepted protocols
with close monitoring of drug levels. Serial Doppler US were done both during
hospitalization and in follow up to assess uterine viability. Clinical examination from an
obstetrician was performed at pre-determined intervals and biopsies of uterine tissue were
taken to assess for organ viability and to rule out rejection. Those few patients who did
have rejection were treated with standard transplantation protocols with increased steroids
only.
Embryo transfer was done at approximately 1 year post transplant, in order to ensure
continued viability and normal menstruation of the organ. Post transfer, hormonal
stimulation was done using standard reproductive endocrinology protocols. Serial monitoring
of the fetus was done at routine intervals through the 9 month gestational period. Finally,
a caesarean section was performed in routine fashion at time of birth.
Our groups rationale at UNMC is to continue to build on the accepted protocols developed by
the Swedish team and apply them to deceased donors. The investigators believe our vast
experience in transplant and obstetrics/gynecology combined with reproductive endocrinology
facilitates undergoing this exciting new medical and surgical therapy.
Eligibility
Minimum age: 21 Years.
Maximum age: 35 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- For transplantation, the criteria are as follows:
1. Female of reproductive age with intact native ovaries and no medical
contraindication to transplantation, including surgical procedure and subsequent
immunosuppression, and no medical contraindication to reproduction and gestation
in a transplanted uterus. Evaluation for a medical contraindication will be
determined by a maternal-fetal medicine specialist at UNMC.
2. Diagnosed with either congenital or acquired uterine factor infertility (UFI)
and counseled about alternate options for family building including gestational
surrogacy and/or adoption and provided access to these alternate services.
Acquired circumstances may include nonfunctional uterus and hysterectomy due to
benign disease (uterine fibroids, Asherman's syndrome, pelvic infection,
postpartum hemorrhage) or gynecologic malignancy of the uterus or cervix.
Additionally, UFI may be a result of congenital anomaly of the uterus and
uterine agenesis.
3. If uterine removal was for uterine or cervical cancer a minimum 5 year
recurrence-free time period will be required.
4. If MRKH Syndrome (Mayer-Rokitansky-Kuster-Hauser) or Mullerian agenesis is
present, the patient has a negative evaluation for other relevant congenital
abnormalities (such as a pelvic kidney). Additionally, women with Mulllerian
agenesis who have absence of the vagina must have had neovaginal creation
surgery prior to uterine transplant in order to allow for embryo transplantation
and monitoring of the organ after transplant.
5. Ovaries are intact with adequate ovarian reserve as determined by accepted
markers including anti-Mullerian hormone level (AMH), astral follicle count
and/or early follicular follicle stimulating hormone (FSH) levels.
6. Desires a biological child and is unable or unwilling to consider gestational
surrogacy, and / or seeks uterine transplantation as a means to experience
gestation, with an understanding of the limitations provided by the uterine
transplant in this respect.
7. Meets psychological evaluation criteria, e. g.,stable, committed relationship
with an individual who supports uterine transplant and intends to co-parent;
emotionally mature with good coping skills and no significantly adverse mental
health history; normal intellect allowing careful analysis of risks and
benefits; no evidence of coercion; no significant evidence of previous
noncompliance with medical care; no evidence of frank unsuitability for
motherhood (e. g., previous conviction for child abuse).
8. Likely to comply with medical management, including antirejection immune
suppression, frequent follow-up with surgical team, time-sensitive reproductive
endocrinology management, high-risk pregnancy management, possible high-risk
neonatal management.
9. Likely to be able to accommodate potential adverse outcomes such as loss of
graft, inability to conceive, loss of pregnancy, adverse fetal or neonatal
outcome.
10. Willing to consider transplant hysterectomy or termination of pregnancy if
medically necessary.
11. Willing to undergo oocyte harvest and in-vitro fertilization prior to
transplantation, with at least six viable embryos cryopreserved in anticipation
of post-transplant implantation.
12. Financially able to cover anticipated expenses of assisted reproductive
services, either through third party coverage or through personal assets.
Exclusion Criteria:
- For transplantation: Exclusions include genetic males, and women who do not meet the
inclusionary criteria above. Residence in the greater Omaha area during the
implantation and pregnancy period is required because of the time-sensitive nature of
transplantation and assisted reproductive technology, as well as the frequent medical
monitoring which will be required of transplant subjects.
Locations and Contacts
Alexander T Maskin, MD, Phone: 402-559-3382, Email: alexander.maskin@unmc.edu
University of Nebraska Medical Center, Omaha, Nebraska 68198, United States
Additional Information
Starting date: September 2015
Last updated: April 3, 2015
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