<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03307356</url>
  </required_header>
  <id_info>
    <org_study_id>827853</org_study_id>
    <nct_id>NCT03307356</nct_id>
  </id_info>
  <brief_title>The University of Pennsylvania Uterus Transplant for Uterine Factor Infertility Trial</brief_title>
  <acronym>UNTIL</acronym>
  <official_title>The University of Pennsylvania Uterus Transplant for Uterine Factor Infertility Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Options for childbearing are limited for the thousands of women in the United States who&#xD;
      suffer from absolute uterine factor infertility. Uterine transplantation is an emerging&#xD;
      treatment that provides hope for these individuals.&#xD;
&#xD;
      In the Penn UNTIL trial, the investigators plan to perform uterus transplants on five women&#xD;
      who will ultimately undergo embryo transfer, pregnancy, delivery, and then transplant&#xD;
      hysterectomy.&#xD;
&#xD;
      This trial is accepting women in need of a transplant and also women who are interested in&#xD;
      being a live donor.&#xD;
&#xD;
      For more information please visit:&#xD;
      https://clinicalresearch.itmat.upenn.edu/clinicaltrial/4821/congenital-abnormalitiesfemale-in&#xD;
      fertility-penn-ut/&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND The inability to conceive children can be one of the most devastating and&#xD;
      traumatic situations to arise in the life of an individual or couple. While assisted&#xD;
      reproductive technologies have been developed that help overcome many causes of infertility,&#xD;
      uterine factor infertility has remained an intractable condition. Absolute uterine factor&#xD;
      infertility (AUFI) occurs when the uterus is either not present (congenitally absent or&#xD;
      surgically removed) or is present but is not capable of sustaining a pregnancy. AUFI can&#xD;
      result from either congenital absence of a uterus (Mayer-Rokitansky-Kuster-Hauser [MRKH]&#xD;
      syndrome) or other Müllerian anomalies. MRKH occurs in 1:4000 of females. It is difficult to&#xD;
      determine the exact number of women that suffer from AUFI, however estimates are as high as 7&#xD;
      million women between the ages of 15-34 may suffer from this condition in the United States.&#xD;
&#xD;
      Existing options for individuals with AUFI to achieve parenthood are adoption and the use of&#xD;
      a gestational carrier. Use of a gestational carrier is the only alternative that allows an&#xD;
      individual or couple to have a child genetically related to the intended parent(s). These&#xD;
      options are considered acceptable to many women with AUFI; however, there are a number of&#xD;
      significant limitations to these alternatives. The use of a gestational carrier is fraught&#xD;
      with ethical, legal, and social controversy because it shifts the burden of gestation from&#xD;
      one woman to another, usually for payment. Additionally, adoption and/or surrogacy may not be&#xD;
      permissible to a couple due to social, ethical, moral or religious considerations. If these&#xD;
      alternatives are acceptable to a couple, they may not be affordable. Finally, these&#xD;
      alternatives may not be accessible as barriers to domestic and international adoption have&#xD;
      increased and the use of a compensated gestational carrier is not legally protected in most&#xD;
      states (and is illegal in some states). The limitations of these alternatives may account for&#xD;
      the extraordinary interest in UTx by women with AUFI, as 92% of women with AUFI would undergo&#xD;
      UTx as first line management for their AUFI, above adoption and surrogacy.&#xD;
&#xD;
      Understanding the limitations of these alternatives, uterine transplantation (UTx) began to&#xD;
      be explored as a concept in animal studies in the 1970s. In 2012, a Swedish team led by Dr.&#xD;
      Mats Brannstrom started the first human uterine transplantation trial. The first live birth&#xD;
      after successful UTx occurred in Sweden in 2014. As of September 2021, the investigators&#xD;
      estimate 33 uterus transplants have been performed in the United States and &gt;10 babies have&#xD;
      been born to these women.&#xD;
&#xD;
      Unlike all other transplants, uterine transplantation is &quot;ephemeral&quot;. This means that a&#xD;
      uterine transplant is only maintained during the individual's child-bearing period which, in&#xD;
      the case of uterine transplantation, will be the time necessary to produce one or two&#xD;
      children (&lt;10 years). Although pregnancy after transplant is considered high risk, more than&#xD;
      15,000 babies have been born to female recipients of solid organ transplants that were&#xD;
      immunosuppressed with no reported increased risk of fetal malformations.&#xD;
&#xD;
      STUDY DESIGN Recognizing that the University of Pennsylvania has been a leader in all of the&#xD;
      domains required to build a successful uterus transplant program, planning for the Penn UNTIL&#xD;
      trial began in October 2016. The UNTIL trial is is a nonrandomized, interventional human&#xD;
      study whose goal is to achieve live birth after donor uterus transplantation. The&#xD;
      investigators plan to perform approximately five uterus transplants in this pilot trial.&#xD;
      Prior to being listed for transplant, the participants will need to create embryos through&#xD;
      ovarian stimulation, oocyte retrieval and in vitro fertilization that will be cryopreserved.&#xD;
      After undergoing donor uterus transplantation, participants will be monitored for rejection,&#xD;
      infection and other complications for twelve months.&#xD;
&#xD;
      If the graft is clinically stable and any complications that arise are successfully treated 6&#xD;
      months after transplantation, the embryos created prior to transplantation will be directly&#xD;
      placed into the uterus in order for the women to achieve pregnancy. If pregnancy is achieved&#xD;
      the participant will be monitored by a Maternal Fetal Medicine specialist (high-risk&#xD;
      obstetrician) with goal to deliver at 37-39 weeks unless otherwise indicated. All deliveries&#xD;
      will occur via cesarean delivery. If the participant and partner wish to attempt an&#xD;
      additional pregnancy and the medical team feel it is safe to proceed, attempts at a second&#xD;
      pregnancy will be undertaken. Again, if pregnancy is achieved following embryo transfer the&#xD;
      participant will be monitored for the duration of her pregnancy by a Maternal Fetal Medicine&#xD;
      specialist with goal to deliver at 37-39 weeks through repeat cesarean delivery unless&#xD;
      otherwise indicated. Hysterectomy will either be performed at the time of cesarean delivery&#xD;
      or shortly following the final cesarean delivery.&#xD;
&#xD;
      The transplanted uteri will be from either living or deceased donors. Interested potential&#xD;
      donors will be screened and evaluated and if eligible with continued interest in&#xD;
      participation, will undergo radical hysterectomy for the purpose of uterus transplant into a&#xD;
      woman with AUFI. Deceased donors will be considered and screened with the organ procurement&#xD;
      organization Gift of Life Donation Program.&#xD;
&#xD;
      For more information please visit:&#xD;
      https://clinicalresearch.itmat.upenn.edu/clinicaltrial/4821/congenital-abnormalitiesfemale-in&#xD;
      fertility-penn-ut/&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">January 10, 2018</start_date>
  <completion_date type="Anticipated">July 1, 2029</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2029</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recipient: Successful engraftment of deceased or living donor uterus</measure>
    <time_frame>Assessed 6 months after transplant</time_frame>
    <description>Uterus remains in recipient with no complications (i.e. infection or rejection) or any complications that did arise could be successfully treated.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recipient: Live-born child per embryo transfer</measure>
    <time_frame>Assessed up to 35 weeks post-embryo transfer</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Living Donor: Survival post-donation</measure>
    <time_frame>Assessed at 2 years post-hysterectomy</time_frame>
    <description>Living or deceased</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recipient: Neonatal growth</measure>
    <time_frame>Assessed at birth</time_frame>
    <description>Birth weight percentile at delivery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recipient: Pregnancy complications</measure>
    <time_frame>Assessed up to 35 weeks post-embryo transfer</time_frame>
    <description>Including but not limited to preeclampsia, gestational hypertension, gestational diabetes, and cholestasis of pregnancy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recipient: Surgical or medical complications following cesarean delivery</measure>
    <time_frame>Assessed up to 6 months after delivery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recipient: Surgical or medical complications following hysterectomy</measure>
    <time_frame>Assessed 2 years after hysterectomy</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recipient: Child height percentile</measure>
    <time_frame>Assessed at 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recipient: Child weight percentile</measure>
    <time_frame>Assessed at 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Living Donor: Intraoperative/postoperative/pregnancy/postpartum complications</measure>
    <time_frame>Assessed at 2 years post-hysterectomy</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Living Donor: Symptomatic claudication of buttock or legs</measure>
    <time_frame>Assessed at 2 years post-hysterectomy</time_frame>
    <description>yes or no</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Living Donor: Genitourinary tract complications</measure>
    <time_frame>Assessed at 2 years post-hysterectomy</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Living Donor: Need for reoperation</measure>
    <time_frame>Assessed at 2 years post-hysterectomy</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">5</enrollment>
  <condition>Mayer Rokitansky Kuster Hauser Syndrome</condition>
  <condition>Uterine Agenesis</condition>
  <condition>Infertility, Female, of Uterine Origin</condition>
  <condition>Uterine Factor Infertility</condition>
  <arm_group>
    <arm_group_label>Uterine Transplantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Uterine Transplant</intervention_name>
    <description>Transplant of a uterus from a donor, deceased or living</description>
    <arm_group_label>Uterine Transplantation</arm_group_label>
    <other_name>Donor Uterine Transplant</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Uterine Transplant Recipient Participant Inclusion Criteria:&#xD;
&#xD;
          1. XX-bearing individual diagnosed with Uterine Factor Infertility (UFI) a&#xD;
&#xD;
          2. Age 21-40&#xD;
&#xD;
          3. Lives in Philadelphia region for the duration of the trial&#xD;
&#xD;
          4. Received counseling regarding alternatives to uterine transplant such as adoption or&#xD;
             surrogacy&#xD;
&#xD;
          5. Intact ovaries&#xD;
&#xD;
          6. Vaginal length &gt;6 cm (average vaginal length established with dilators)&#xD;
&#xD;
          7. Body mass index &lt;35 kg/m2&#xD;
&#xD;
          8. Fluent in the English Language&#xD;
&#xD;
          9. If cervix present/previously present, human papillomavirus (HPV)) negative or received&#xD;
             vaccination for HPV&#xD;
&#xD;
         10. Willing to comply with screening, protocol and all required procedures&#xD;
&#xD;
         11. Has adequate social support&#xD;
&#xD;
         12. Has undergone controlled ovarian hyperstimulation, egg retrieval, in vitro&#xD;
             fertilization, and embryo freezing and has frozen embryos of sufficient embryo&#xD;
             quality/quantity (≥2 high quality blastocysts); (Required for Transplant Phase, not&#xD;
             Screening or Evaluation Phases)&#xD;
&#xD;
        Uterine Transplant Recipient Participant Exclusion Criteria:&#xD;
&#xD;
          1. Previous multiple major abdominal/pelvic surgery&#xD;
&#xD;
          2. Severe endometriosis&#xD;
&#xD;
          3. History of hypertension, diabetes mellitus, thrombophilia or other clotting or&#xD;
             bleeding disorders, significant heart, liver, kidney or central nervous system disease&#xD;
&#xD;
          4. History of prior malignancy except for cervical cancer in stage 1a or 1b (must be in&#xD;
             remission for 3 years)&#xD;
&#xD;
          5. History of significant psychiatric illness&#xD;
&#xD;
          6. Allergy, hypersensitivity, or intolerance of expected immunosuppressive agents (i.e.&#xD;
             Thymoglobulin®, tacrolimus, etc.)&#xD;
&#xD;
          7. Allergy, hypersensitivity, or intolerance of heparin or aspirin&#xD;
&#xD;
          8. Presence of active documented systemic infection or recent systemic infection within&#xD;
             the past 3 months&#xD;
&#xD;
          9. Seropositivity for HIV, HBV core antibody or antigen, HCV&#xD;
&#xD;
         10. Current smoker (smoking cessation must have occurred 3 months prior to enrollment)&#xD;
&#xD;
         11. Chemical and/or alcohol dependency or abuse&#xD;
&#xD;
         12. Psychosocial problems (including alcoholism, drug abuse, documented behavioral&#xD;
             disorders)&#xD;
&#xD;
         13. Renal abnormalities, specifically single kidney or pelvic kidneys (imaging&#xD;
             confirmation of 2 normal kidneys is required for MRKH subjects)&#xD;
&#xD;
         14. Contraindications to pregnancy&#xD;
&#xD;
         15. Unwilling to receive a transfusion of blood or blood products&#xD;
&#xD;
        Living Donor Participant Inclusion Criteria:&#xD;
&#xD;
          1. Age 30-50&#xD;
&#xD;
          2. Has definitively completed childbearing&#xD;
&#xD;
          3. Live birth to miscarriage ratio ≥1&#xD;
&#xD;
          4. Body mass index &lt;35 kg/m2&#xD;
&#xD;
          5. Normal uterine anatomy&#xD;
&#xD;
          6. Normal pap test and Human papillomavirus (HPV) negative&#xD;
&#xD;
          7. Negative infection screen (HIV, HepB, HepC, Syphilis, gonorrhea, chlamydia)&#xD;
&#xD;
          8. Received counseling regarding alternatives to uterus donation such as adoption and&#xD;
             gestational surrogacy&#xD;
&#xD;
          9. Fluent in the English Language&#xD;
&#xD;
         10. Willing to comply with screening, protocol and all required procedures&#xD;
&#xD;
         11. Has adequate social support&#xD;
&#xD;
         12. Compatible blood type with recipient&#xD;
&#xD;
         13. Negative flow cytometric crossmatch with recipient&#xD;
&#xD;
         14. Has current health insurance&#xD;
&#xD;
         15. Able to stay in the Philadelphia region for 3 weeks following uterus donation&#xD;
&#xD;
        Living Donor Participant Exclusion Criteria:&#xD;
&#xD;
          1. Previous multiple major abdominal/pelvic surgery&#xD;
&#xD;
          2. Severe endometriosis&#xD;
&#xD;
          3. History of hypertension, diabetes mellitus, thrombophilia or other clotting or&#xD;
             bleeding disorders, significant heart, liver, kidney or central nervous system disease&#xD;
&#xD;
          4. History or obvious evidence of previous multiple/significant uterine surgery. Defined&#xD;
             as &gt;1 cesarean delivery and/or myomectomy&#xD;
&#xD;
          5. History of previous cervical surgery (cone biopsy or loop electrosurgical excision&#xD;
             procedure)&#xD;
&#xD;
          6. Significant systemic disease (diabetes or systemic lupus erythematosus)&#xD;
&#xD;
          7. Previous obstetric problem including delivery &lt;34 weeks and abnormal placental&#xD;
             location (i.e. placenta Previa/accreta/increta/percreta)&#xD;
&#xD;
          8. Pregnancy&#xD;
&#xD;
          9. Abnormal uterine cavity&#xD;
&#xD;
         10. Vascular calcification on imaging tests&#xD;
&#xD;
         11. History of significant psychiatric illness&#xD;
&#xD;
         12. Current smoker (smoking cessation must have occurred 3 months prior to enrollment)&#xD;
&#xD;
         13. Chemical and/or alcohol dependency or abuse&#xD;
&#xD;
         14. Psychosocial problems (including alcoholism, drug abuse, documented behavioral&#xD;
             disorders)&#xD;
&#xD;
         15. Unwilling to receive a transfusion of blood or blood products&#xD;
&#xD;
         16. Evidence of coercion or exchange of money or goods for donating the organ&#xD;
&#xD;
        Deceased Donor Inclusion Criteria:&#xD;
&#xD;
          1. Hemodynamically stable donor&#xD;
&#xD;
          2. Age between 18 to 50 years&#xD;
&#xD;
          3. Compatible blood type with recipient&#xD;
&#xD;
          4. Negative flow cytometric crossmatch with recipient&#xD;
&#xD;
          5. Live birth to miscarriage ratio ≥1&#xD;
&#xD;
          6. Normal gross uterine anatomy (as visually assessed by gynecologic surgeon at time of&#xD;
             organ procurement)&#xD;
&#xD;
          7. Macroscopically normal cervix (polyp acceptable)&#xD;
&#xD;
          8. Negative infection screen (HIV, HepB, HepC, Syphilis)&#xD;
&#xD;
          9. Cytomegalovirus (CMV)- matched based on rapid donor screening. A CMV positive donor&#xD;
             may be used in a CMV negative recipient. A CMV negative donor may be used in either a&#xD;
             CMV positive or negative recipient.&#xD;
&#xD;
         10. Donates after brain death&#xD;
&#xD;
        Deceased Donor Exclusion Criteria:&#xD;
&#xD;
          1. Current malignancy or history of malignancy active within the past 5 years (Except&#xD;
             adequately treated localized basal or squamous cell carcinoma of skin without evidence&#xD;
             of recurrence)&#xD;
&#xD;
          2. No history or obvious evidence of previous multiple/significant uterine surgery.&#xD;
             Defined as &gt;1 cesarean delivery and/or myomectomy&#xD;
&#xD;
          3. No history or obvious evidence of previous cervical surgery (cone biopsy or loop&#xD;
             electrosurgical excision procedure)&#xD;
&#xD;
          4. Significant systemic disease (i.e. diabetes, peripheral vascular or cardiovascular&#xD;
             disease, autoimmune disease, renal or liver failure, etc.)&#xD;
&#xD;
          5. Previous obstetric problem including delivery &lt;34 weeks and abnormal placental&#xD;
             location (i.e. placenta Previa/accreta/increta/percreta)&#xD;
&#xD;
          6. Pregnancy&#xD;
&#xD;
          7. BMI &gt;35 kg/m2&#xD;
&#xD;
          8. Donates after cardiac death (DCD)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Female sex; specifically XX-bearing individual</gender_description>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kathleen E O'Neill, MD, MTR</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalresearch.itmat.upenn.edu/clinicaltrial/4821/congenital-abnormalitiesfemale-infertility-penn-ut/</url>
    <description>Please visit the UPENN Study Web Page</description>
  </link>
  <reference>
    <citation>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.</citation>
    <PMID>782313</PMID>
  </reference>
  <reference>
    <citation>White PM. &quot;One for Sorrow, Two for Joy?&quot;: 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.</citation>
    <PMID>28185120</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>23541404</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>17518856</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>5822860</PMID>
  </reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>27125227</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>18443334</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>16554530</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>27136247</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>28357688</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>27607877</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>28432742</PMID>
  </results_reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>October 5, 2017</study_first_submitted>
  <study_first_submitted_qc>October 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>October 13, 2022</last_update_submitted>
  <last_update_submitted_qc>October 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Uterine Transplant</keyword>
  <keyword>MRKH</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
    <mesh_term>Infertility, Female</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Select trial data may be shared with the International Society of Uterine Transplantation (ISUTx) Registry. No protected health information will be shared.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03307356
org study id: 827853
nct id: NCT03307356
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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-in
      fertility-penn-ut/
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-in
      fertility-penn-ut/
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recipient: Successful engraftment of deceased or living donor uterus
time frame: Assessed 6 months after transplant
description: Uterus remains in recipient with no complications (i.e. infection or rejection) or any complications that did arise could be successfully treated.
measure: Recipient: Live-born child per embryo transfer
time frame: Assessed up to 35 weeks post-embryo transfer
measure: Living Donor: Survival post-donation
time frame: Assessed at 2 years post-hysterectomy
description: Living or deceased
measure: Recipient: Neonatal growth
time frame: Assessed at birth
description: Birth weight percentile at delivery
measure: Recipient: Pregnancy complications
time frame: Assessed up to 35 weeks post-embryo transfer
description: Including but not limited to preeclampsia, gestational hypertension, gestational diabetes, and cholestasis of pregnancy.
measure: Recipient: Surgical or medical complications following cesarean delivery
time frame: Assessed up to 6 months after delivery
measure: Recipient: Surgical or medical complications following hysterectomy
time frame: Assessed 2 years after hysterectomy
measure: Recipient: Child height percentile
time frame: Assessed at 2 years
measure: Recipient: Child weight percentile
time frame: Assessed at 2 years
measure: Living Donor: Intraoperative/postoperative/pregnancy/postpartum complications
time frame: Assessed at 2 years post-hysterectomy
measure: Living Donor: Symptomatic claudication of buttock or legs
time frame: Assessed at 2 years post-hysterectomy
description: yes or no
measure: Living Donor: Genitourinary tract complications
time frame: Assessed at 2 years post-hysterectomy
measure: Living Donor: Need for reoperation
time frame: Assessed at 2 years post-hysterectomy
arm group label: Uterine Transplantation
arm group type: Experimental
description: 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.
intervention type: Other
intervention name: Uterine Transplant
description: Transplant of a uterus from a donor, deceased or living
arm group label: Uterine Transplantation
other name: Donor Uterine Transplant
criteria: 
gender: Female
gender based: Yes
gender description: Female sex; specifically XX-bearing individual
minimum age: 21 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kathleen E O'Neill, MD, MTR
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
url: https://clinicalresearch.itmat.upenn.edu/clinicaltrial/4821/congenital-abnormalitiesfemale-infertility-penn-ut/
description: Please visit the UPENN Study Web Page
citation: 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.
PMID: 782313
citation: 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.
PMID: 28185120
citation: 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.
PMID: 23541404
citation: 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.
PMID: 17518856
citation: 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.
PMID: 5822860
citation: 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.
PMID: 27125227
citation: 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.
PMID: 18443334
citation: 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.
PMID: 16554530
citation: 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.
PMID: 27136247
citation: 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.
PMID: 28357688
citation: 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.
PMID: 27607877
citation: 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.
PMID: 28432742
responsible party type: Sponsor
mesh term: Infertility
mesh term: Infertility, Female
sharing ipd: Undecided
ipd description: Select trial data may be shared with the International Society of Uterine Transplantation (ISUTx) Registry. No protected health information will be shared.