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Active, not recruitingNCT03307356UNTILUpdated Aug 27, 2026

The University of Pennsylvania Uterus Transplant for Uterine Factor Infertility Trial

An interventional study of Uterine Transplant in Mayer Rokitansky Kuster Hauser Syndrome, Uterine Agenesis and Infertility, Female, of Uterine Origin, sponsored by University of Pennsylvania. Active, not recruiting at 1 site in United States. Open to female participants aged 21 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-27.

Sponsored by University of Pennsylvania · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
10
Allocation
Not applicable
Ages
21 Years to 40 Years
Sex
Female
01

Study summary

Options for childbearing are limited for the thousands of women in the United States who suffer from absolute uterine factor infertility. Uterine transplantation is an emerging treatment that provides hope for these individuals.

In the Penn UNTIL trial, the investigators plan to perform uterus transplants on five women who will ultimately undergo embryo transfer, pregnancy, delivery, and then transplant hysterectomy.

This trial is accepting women in need of a transplant and also women who are interested in being a live donor.

For more information please visit: https://clinicalresearch.itmat.upenn.edu/clinicaltrial/4821/congenital-abnormalitiesfemale-infertility-penn-ut/

Read the detailed description

BACKGROUND The inability to conceive children can be one of the most devastating and traumatic situations to arise in the life of an individual or couple. While assisted reproductive technologies have been developed that help overcome many causes of infertility, uterine factor infertility has remained an intractable condition. Absolute uterine factor infertility (AUFI) occurs when the uterus is either not present (congenitally absent or surgically removed) or is present but is not capable of sustaining a pregnancy. AUFI can result from either congenital absence of a uterus (Mayer-Rokitansky-Kuster-Hauser [MRKH] syndrome) or other Müllerian anomalies. MRKH occurs in 1:4000 of females. It is difficult to determine the exact number of women that suffer from AUFI, however estimates are as high as 7 million women between the ages of 15-34 may suffer from this condition in the United States.

Existing options for individuals with AUFI to achieve parenthood are adoption and the use of a gestational carrier. 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). These options are considered acceptable to many women with AUFI; however, there are a number of significant limitations to these alternatives. The use of a gestational carrier is fraught with ethical, legal, and social controversy because it shifts the burden of gestation from one woman to another, usually for payment. Additionally, adoption and/or surrogacy may not be permissible to a couple due to social, ethical, moral or religious considerations. If these alternatives are acceptable to a couple, they may not be affordable. Finally, these alternatives may not be accessible as barriers to domestic and international adoption have increased and the use of a compensated gestational carrier is not legally protected in most states (and is illegal in some states). The limitations of these alternatives may account for the extraordinary interest in UTx by women with AUFI, as 92% of women with AUFI would undergo UTx as first line management for their AUFI, above adoption and surrogacy.

Understanding the limitations of these alternatives, uterine transplantation (UTx) began to be explored as a concept in animal studies in the 1970s. In 2012, a Swedish team led by Dr. Mats Brannstrom started the first human uterine transplantation trial. The first live birth after successful UTx occurred in Sweden in 2014. As of September 2021, the investigators estimate 33 uterus transplants have been performed in the United States and >10 babies have been born to these women.

Unlike all other transplants, uterine transplantation is "ephemeral". This means that a uterine transplant is only maintained during the individual's child-bearing period which, in the case of uterine transplantation, will be the time necessary to produce one or two children (\<10 years). Although pregnancy after transplant is considered high risk, more than 15,000 babies have been born to female recipients of solid organ transplants that were immunosuppressed with no reported increased risk of fetal malformations.

STUDY DESIGN Recognizing that the University of Pennsylvania has been a leader in all of the domains required to build a successful uterus transplant program, planning for the Penn UNTIL trial began in October 2016. The UNTIL trial is is a nonrandomized, interventional human study whose goal is to achieve live birth after donor uterus transplantation. The investigators plan to perform approximately five uterus transplants in this pilot trial. Prior to being listed for transplant, the participants will need to create embryos through ovarian stimulation, oocyte retrieval and in vitro fertilization that will be cryopreserved. After undergoing donor uterus transplantation, participants will be monitored for rejection, infection and other complications for twelve months.

If the graft is clinically stable and any complications that arise are successfully treated 6 months after transplantation, the embryos created prior to transplantation will be directly placed into the uterus in order for the women to achieve pregnancy. If pregnancy is achieved the participant will be monitored by a Maternal Fetal Medicine specialist (high-risk obstetrician) with goal to deliver at 37-39 weeks unless otherwise indicated. All deliveries will occur via cesarean delivery. If the participant and partner wish to attempt an additional pregnancy and the medical team feel it is safe to proceed, attempts at a second pregnancy will be undertaken. Again, if pregnancy is achieved following embryo transfer the participant will be monitored for the duration of her pregnancy by a Maternal Fetal Medicine specialist with goal to deliver at 37-39 weeks through repeat cesarean delivery unless otherwise indicated. Hysterectomy will either be performed at the time of cesarean delivery or shortly following the final cesarean delivery.

The transplanted uteri will be from either living or deceased donors. Interested potential donors will be screened and evaluated and if eligible with continued interest in participation, will undergo radical hysterectomy for the purpose of uterus transplant into a woman with AUFI. Deceased donors will be considered and screened with the organ procurement organization Gift of Life Donation Program.

For more information please visit: https://clinicalresearch.itmat.upenn.edu/clinicaltrial/4821/congenital-abnormalitiesfemale-infertility-penn-ut/

02

Conditions studied

  • Mayer Rokitansky Kuster Hauser Syndrome
  • Uterine Agenesis
  • Infertility, Female, of Uterine Origin
  • Uterine Factor Infertility

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Keywords

  • Uterine Transplant
  • MRKH
03

Who can participate

Ages eligible
21 Years to 40 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Eligibility criteria

Uterine Transplant Recipient Participant Inclusion Criteria:

  1. XX-bearing individual diagnosed with Uterine Factor Infertility (UFI) a
  2. Age 21-40
  3. Lives in Philadelphia region for the duration of the trial
  4. Received counseling regarding alternatives to uterine transplant such as adoption or surrogacy
  5. Intact ovaries
  6. Vaginal length >6 cm (average vaginal length established with dilators)
  7. Body mass index \<35 kg/m2
  8. Fluent in the English Language
  9. If cervix present/previously present, human papillomavirus (HPV)) negative or received vaccination for HPV
  10. Willing to comply with screening, protocol and all required procedures
  11. Has adequate social support
  12. Has undergone controlled ovarian hyperstimulation, egg retrieval, in vitro fertilization, and embryo freezing and has frozen embryos of sufficient embryo quality/quantity (≥2 high quality blastocysts); (Required for Transplant Phase, not Screening or Evaluation Phases)

Uterine Transplant Recipient Participant Exclusion Criteria:

  1. Previous multiple major abdominal/pelvic surgery
  2. Severe endometriosis
  3. History of hypertension, diabetes mellitus, thrombophilia or other clotting or bleeding disorders, significant heart, liver, kidney or central nervous system disease
  4. History of prior malignancy except for cervical cancer in stage 1a or 1b (must be in remission for 3 years)
  5. History of significant psychiatric illness
  6. Allergy, hypersensitivity, or intolerance of expected immunosuppressive agents (i.e. Thymoglobulin®, tacrolimus, etc.)
  7. Allergy, hypersensitivity, or intolerance of heparin or aspirin
  8. Presence of active documented systemic infection or recent systemic infection within the past 3 months
  9. Seropositivity for HIV, HBV core antibody or antigen, HCV
  10. Current smoker (smoking cessation must have occurred 3 months prior to enrollment)
  11. Chemical and/or alcohol dependency or abuse
  12. Psychosocial problems (including alcoholism, drug abuse, documented behavioral disorders)
  13. Renal abnormalities, specifically single kidney or pelvic kidneys (imaging confirmation of 2 normal kidneys is required for MRKH subjects)
  14. Contraindications to pregnancy
  15. Unwilling to receive a transfusion of blood or blood products

Living Donor Participant Inclusion Criteria:

  1. Age 30-50
  2. Has definitively completed childbearing
  3. Live birth to miscarriage ratio ≥1
  4. Body mass index \<35 kg/m2
  5. Normal uterine anatomy
  6. Normal pap test and Human papillomavirus (HPV) negative
  7. Negative infection screen (HIV, HepB, HepC, Syphilis, gonorrhea, chlamydia)
  8. Received counseling regarding alternatives to uterus donation such as adoption and gestational surrogacy
  9. Fluent in the English Language
  10. Willing to comply with screening, protocol and all required procedures
  11. Has adequate social support
  12. Compatible blood type with recipient
  13. Negative flow cytometric crossmatch with recipient
  14. Has current health insurance
  15. Able to stay in the Philadelphia region for 3 weeks following uterus donation

Living Donor Participant Exclusion Criteria:

  1. Previous multiple major abdominal/pelvic surgery
  2. Severe endometriosis
  3. History of hypertension, diabetes mellitus, thrombophilia or other clotting or bleeding disorders, significant heart, liver, kidney or central nervous system disease
  4. History or obvious evidence of previous multiple/significant uterine surgery. Defined as >1 cesarean delivery and/or myomectomy
  5. History of previous cervical surgery (cone biopsy or loop electrosurgical excision procedure)
  6. Significant systemic disease (diabetes or systemic lupus erythematosus)
  7. Previous obstetric problem including delivery \<34 weeks and abnormal placental location (i.e. placenta Previa/accreta/increta/percreta)
  8. Pregnancy
  9. Abnormal uterine cavity
  10. Vascular calcification on imaging tests
  11. History of significant psychiatric illness
  12. Current smoker (smoking cessation must have occurred 3 months prior to enrollment)
  13. Chemical and/or alcohol dependency or abuse
  14. Psychosocial problems (including alcoholism, drug abuse, documented behavioral disorders)
  15. Unwilling to receive a transfusion of blood or blood products
  16. Evidence of coercion or exchange of money or goods for donating the organ

Deceased Donor Inclusion Criteria:

  1. Hemodynamically stable donor
  2. Age between 18 to 50 years
  3. Compatible blood type with recipient
  4. Negative flow cytometric crossmatch with recipient
  5. Live birth to miscarriage ratio ≥1
  6. Normal gross uterine anatomy (as visually assessed by gynecologic surgeon at time of organ procurement)
  7. Macroscopically normal cervix (polyp acceptable)
  8. Negative infection screen (HIV, HepB, HepC, Syphilis)
  9. Cytomegalovirus (CMV)- matched based on rapid donor screening. A CMV positive donor may be used in a CMV negative recipient. A CMV negative donor may be used in either a CMV positive or negative recipient.
  10. Donates after brain death

Deceased Donor Exclusion Criteria:

  1. Current malignancy or history of malignancy active within the past 5 years (Except adequately treated localized basal or squamous cell carcinoma of skin without evidence of recurrence)
  2. No history or obvious evidence of previous multiple/significant uterine surgery. Defined as >1 cesarean delivery and/or myomectomy
  3. No history or obvious evidence of previous cervical surgery (cone biopsy or loop electrosurgical excision procedure)
  4. Significant systemic disease (i.e. diabetes, peripheral vascular or cardiovascular disease, autoimmune disease, renal or liver failure, etc.)
  5. Previous obstetric problem including delivery \<34 weeks and abnormal placental location (i.e. placenta Previa/accreta/increta/percreta)
  6. Pregnancy
  7. BMI >35 kg/m2
  8. Donates after cardiac death (DCD)
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
10 participants (actual)

Study arms

  • Experimental
    Uterine Transplantation

    Women will undergo extensive medical and psychological screening. Five women that meet all inclusion and exclusion criteria will undergo ovarian stimulation, oocyte retrieval and will create embryos that will be stored for future use. Women will then undergo uterine transplantation from a donor. Following transplant women will be closely monitored for complications (including infection and rejection). If no complications arise, or complications that do arise can be treated, attempts at pregnancy will begin approximately 6 months after transplant. Pregnancy in the setting of uterine transplant requires directly placing embryos directly into the uterus.

    Other: Uterine Transplant

Interventions

  • OtherUterine Transplant

    Transplant of a uterus from a donor, deceased or living

    Also known as: Donor Uterine Transplant

05

What researchers measure

Primary outcomes

  1. Recipient: Successful engraftment of deceased or living donor uterus

    Uterus remains in recipient with no complications (i.e. infection or rejection) or any complications that did arise could be successfully treated.

    Time frame: Assessed 6 months after transplant

  2. Recipient: Live-born child per embryo transfer

    Time frame: Assessed up to 35 weeks post-embryo transfer

  3. Living Donor: Survival post-donation

    Living or deceased

    Time frame: Assessed at 2 years post-hysterectomy

Secondary outcomes

  1. Recipient: Neonatal growth

    Birth weight percentile at delivery

    Time frame: Assessed at birth

  2. Recipient: Pregnancy complications

    Including but not limited to preeclampsia, gestational hypertension, gestational diabetes, and cholestasis of pregnancy.

    Time frame: Assessed up to 35 weeks post-embryo transfer

  3. Recipient: Surgical or medical complications following cesarean delivery

    Time frame: Assessed up to 6 months after delivery

  4. Recipient: Surgical or medical complications following hysterectomy

    Time frame: Assessed 2 years after hysterectomy

  5. Recipient: Child height percentile

    Time frame: Assessed at 2 years

  6. Recipient: Child weight percentile

    Time frame: Assessed at 2 years

  7. Living Donor: Intraoperative/postoperative/pregnancy/postpartum complications

    Time frame: Assessed at 2 years post-hysterectomy

  8. Living Donor: Symptomatic claudication of buttock or legs

    yes or no

    Time frame: Assessed at 2 years post-hysterectomy

  9. Living Donor: Genitourinary tract complications

    Time frame: Assessed at 2 years post-hysterectomy

  10. Living Donor: Need for reoperation

    Time frame: Assessed at 2 years post-hysterectomy

06

Study locations

1 site
  • University of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
07

References and documents

Publications

  • Griffin JE, Edwards C, Madden JD, Harrod MJ, Wilson JD. Congenital absence of the vagina. The Mayer-Rokitansky-Kuster-Hauser syndrome. Ann Intern Med. 1976 Aug;85(2):224-36. doi: 10.7326/0003-4819-85-2-224. PubMed 782313 ↗
  • White PM. "One for Sorrow, Two for Joy?": American embryo transfer guideline recommendations, practices, and outcomes for gestational surrogate patients. J Assist Reprod Genet. 2017 Apr;34(4):431-443. doi: 10.1007/s10815-017-0885-7. Epub 2017 Feb 9. PubMed 28185120 ↗
  • Ethics Committee of the American Society for Reproductive Medicine. Consideration of the gestational carrier: a committee opinion. Fertil Steril. 2013 Jun;99(7):1838-41. doi: 10.1016/j.fertnstert.2013.02.042. Epub 2013 Mar 29. PubMed 23541404 ↗
  • Drabiak K, Wegner C, Fredland V, Helft PR. Ethics, law, and commercial surrogacy: a call for uniformity. J Law Med Ethics. 2007 Summer;35(2):300-9. doi: 10.1111/j.1748-720X.2007.00139.x. PubMed 17518856 ↗
  • O'Leary JA, Feldman M, Gaensslen DM. Uterine and tubal transplantation. Fertil Steril. 1969 Sep-Oct;20(5):757-60. doi: 10.1016/s0015-0282(16)37148-5. No abstract available. PubMed 5822860 ↗
  • Brannstrom M, Bokstrom H, Dahm-Kahler P, Diaz-Garcia C, Ekberg J, Enskog A, Hagberg H, Johannesson L, Kvarnstrom N, Molne J, Olausson M, Olofsson JI, Rodriguez-Wallberg K. One uterus bridging three generations: first live birth after mother-to-daughter uterus transplantation. Fertil Steril. 2016 Aug;106(2):261-6. doi: 10.1016/j.fertnstert.2016.04.001. Epub 2016 Apr 25. PubMed 27125227 ↗
  • Nair A, Stega J, Smith JR, Del Priore G. Uterus transplant: evidence and ethics. Ann N Y Acad Sci. 2008 Apr;1127:83-91. doi: 10.1196/annals.1434.003. PubMed 18443334 ↗
  • McKay DB, Josephson MA. Pregnancy in recipients of solid organs--effects on mother and child. N Engl J Med. 2006 Mar 23;354(12):1281-93. doi: 10.1056/NEJMra050431. No abstract available. PubMed 16554530 ↗
  • Saso S, Clarke A, Bracewell-Milnes T, Saso A, Al-Memar M, Thum MY, Yazbek J, Del Priore G, Hardiman P, Ghaem-Maghami S, Smith JR. Psychological Issues Associated With Absolute Uterine Factor Infertility and Attitudes of Patients Toward Uterine Transplantation. Prog Transplant. 2016 Mar;26(1):28-39. doi: 10.1177/1526924816634840. PubMed 27136247 ↗
  • Brannstrom M. Uterus transplantation and beyond. J Mater Sci Mater Med. 2017 May;28(5):70. doi: 10.1007/s10856-017-5872-0. Epub 2017 Mar 29. PubMed 28357688 ↗
  • Flyckt RL, Farrell RM, Perni UC, Tzakis AG, Falcone T. Deceased Donor Uterine Transplantation: Innovation and Adaptation. Obstet Gynecol. 2016 Oct;128(4):837-842. doi: 10.1097/AOG.0000000000001617. PubMed 27607877 ↗
  • Testa G, Koon EC, Johannesson L, McKenna GJ, Anthony T, Klintmalm GB, Gunby RT, Warren AM, Putman JM, dePrisco G, Mitchell JM, Wallis K, Olausson M. Living Donor Uterus Transplantation: A Single Center's Observations and Lessons Learned From Early Setbacks to Technical Success. Am J Transplant. 2017 Nov;17(11):2901-2910. doi: 10.1111/ajt.14326. Epub 2017 May 23. PubMed 28432742 ↗
  • Johannesson L, Humphries LA, Porrett PM, Testa G, Anderson S, Walter JR, Rush M, Ferrando CA, O'Neill K, Richards EG. Classification and treatment of vaginal strictures at the donor-recipient anastomosis after uterus transplant. Fertil Steril. 2024 Sep;122(3):525-534. doi: 10.1016/j.fertnstert.2024.04.019. Epub 2024 Apr 16. PubMed 38636770 ↗
  • Walter JR, Johannesson L, Falcone T, Putnam JM, Testa G, Richards EG, O'Neill KE. In vitro fertilization practice in patients with absolute uterine factor undergoing uterus transplant in the United States. Fertil Steril. 2024 Sep;122(3):397-405. doi: 10.1016/j.fertnstert.2024.04.017. Epub 2024 Apr 15. PubMed 38631504 ↗

Individual participant data

Plan to share: Undecided — Select trial data may be shared with the International Society of Uterine Transplantation (ISUTx) Registry. No protected health information will be shared.

08

Registry details

Key details

Study ID
NCT03307356
Lead sponsor
University of Pennsylvania
Responsible party
Sponsor
First posted
Oct 11, 2017
Start date
Jan 10, 2018
Primary completion
Jul 1, 2029 (estimated)
Completion
Jul 1, 2029 (estimated)
Last update
Aug 27, 2026

Study contacts

Kathleen E O'Neill, MD, MTR
principal investigator · University of Pennsylvania

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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