Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study will examine the feasibility of initiating a uterine transplant program for Absolute Uterine Factor Infertility (AUFI) at Brigham and Women's Hospital. The investigators plan to screen 30 patients with a goal of enrolling 10 patients. (5 donors and 5 recipients) After careful screening, appropriate candidates will undergo IVF, Uterine Transplantation, Embryo Transfer, Pregnancy and Delivery. Once the uterus is explanted, five years of follow-up is planned.
There are approximately 9.5 million women in the United States with Absolute Uterine Factor Infertility (AUFI).Congenital uterine infertility in women is linked to a malformed or absent mullerian system termed MRKH - Rokitansky's or Mayer-Rokitansky-Kuster-Hauser Syndrome). Additional causes of acquired uterine infertility include a hysterectomy subsequent to life-threatening hemorrhage during childbirth or as a consequence to a hysterectomy related to cervical cancer or for large symptomatic fibroids. Additional causes may include intrauterine adhesions subsequent to surgical abortion or infection.
Uterine transplantation will provide a much needed medical option for many women in the U.S. and overseas who are unable to carry their own children based on uterine infertility. Centers outside of the US have initiated uterus transplant programs. Initial attempts were reported from Saudi Arabia. While the deceased donor transplant had been successful, successful pregnancies were not achieved. Another deceased donor transplant had been performed in Turkey with a uterus procured from a deceased donor. Although several IVF attempts had been performed, they had not resulted in live births.
Uterus transplants from live donors have been successful. In October 2014, Swedish doctors treating a woman born without a uterus, announced the world's first live birth of a healthy baby boy after a live donor uterine transplantation. Since then, an additional three babies have been born in Sweden to mothers who received live donor uterus transplants. A fifth baby is at term and a 6th pregnancy has been reported.
For this study, the investigators plan to screen 30 patients in order to enroll 10 patients, 5 recipients and their respective donors. Prospective recipients will undergo comprehensive medical and psychological evaluation. If deemed an appropriate candidate, In Vitro Fertilization would be started with the goal of obtaining 6 normal embryos for implantation. The uterus of a suitable live donor would then transplanted into the recipient. The recipient would need to take potent anti-rejection drugs and undergo regular assessments for rejection. After one year, embryo transfer to the transplanted uterus would be tried. Up to 6 cycles would be attempted hopefully resulting in pregnancy. If pregnancy results, the recipient would be followed by the high risk pregnancy team. Delivery will be by Caesarian Section. A woman may have up to 2 pregnancies with the transplanted uterus. The uterus is later removed so the recipient no longer has to take anti-rejection drugs.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Women with AUFI | Experimental | Women with AUFI must meet criteria for uterine transplant. In vitro fertilization to obtain 6 (screened) healthy embryos for cryo-preservation precedes uterine transplant from an appropriate donor The recipient will be required to take potent anti rejection medications including Thymoglobulin, Prednisone, Tacrolimus, Mycophenolate Mofetil (MMF) , later substituted with Azathioprine to avoid birth defects. One year later, up to 6 attempts using 1 screened embryo at a time will be tried to achieve pregnancy. During pregnancy, the high risk pregnancy and transplant teams will follow the recipient. The goal is a full term baby and delivery will be by Caesarian section. A second pregnancy may be attempted. Afterward, the uterus will be explanted. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Uterine Transplant | Procedure | Treating Absolute Uterine Factor Infertility by Uterus Transplant. Potential recipients undergo IVF to obtain 6 embryos for cryopreservation followed by live donor uterine transplant. After 1 year, embryo transfer is done to achieve pregnancy. Delivery is by Caesarian section. The recipient may have up to 2 children by these methods and then the uterus is removed so that immunosuppression can be stopped. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of successful live births following uterus transplant/embryo transfer | Full term live birth by caesarian section after uterus transplant and IVF | 2 years after uterine transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of complications during pregnancy in uterus transplant recipient | Close monitoring for pre-eclampsia, hypertension, diabetes, and pre-term delivery. Monitoring for signs of rejection, should it occur, you would first be treated with steroids | 9 months after pregnancy achieved by embryo transfer |
| Rate of complications following uterine donation |
Not provided
Uterine Transplant Inclusion/Exclusion Criteria
RECIPIENT:Inclusion Criteria
Exclusion Criteria :
DONOR:Inclusion criteria
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Stefan G Tullius, M.D. | Contact | 617-732-6866 | stullius@partners.org |
| Name | Affiliation | Role |
|---|---|---|
| Stefan G Tullius, M.D. | Brigham and Womens Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Recruiting | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9747668 | Background | Armenti VT, Moritz MJ, Davison JM. Drug safety issues in pregnancy following transplantation and immunosuppression: effects and outcomes. Drug Saf. 1998 Sep;19(3):219-32. doi: 10.2165/00002018-199819030-00005. | |
| 24582522 | Background | Brannstrom M, Johannesson L, Dahm-Kahler P, Enskog A, Molne J, Kvarnstrom N, Diaz-Garcia C, Hanafy A, Lundmark C, Marcickiewicz J, Gabel M, Groth K, Akouri R, Eklind S, Holgersson J, Tzakis A, Olausson M. First clinical uterus transplantation trial: a six-month report. Fertil Steril. 2014 May;101(5):1228-36. doi: 10.1016/j.fertnstert.2014.02.024. Epub 2014 Feb 27. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D007247 | Infertility, Female |
| D007246 | Infertility |
| ID | Term |
|---|---|
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
Monitoring for excessive bleeding, infection and bladder dysfunction. Also monitoring blood clots in the legs. |
| Up to 2 years post donation |
| Impact of uterine donation on donor quality of life | Measured by serial SF 36 QOL survey by psychiatrist at pre-donation and at follow-up appointments. The SF-36 evaluates general health perception, perceived change in health over time, physical functioning, role limitations due to physical or emotional health, and activity limitations. Emotional well-being will also be assessed using the Hospital Anxiety and Depression Scale (HADS), a validated questionnaire scored from 0 to 3 per item. | Up to 2 years post donation |
| Cost comparison for uterine transplant vs. surrogacy vs adoption | At the end of the study, investigators will calculate average cost of each modality, i.e. transplant vs surrogacy vs adoption to compare the three alternatives to infertility | Up to 5 years after uterine transplant |
| Impact of uterine transplant on quality of life | Measured by serial SF 36 QOL survey by psychiatrist pre-transplant and at follow-up appointments.. | Up to 5 years after uterine transplant |
| Background | Christensen, M, Kronberg, CJ, Knudsen UB: Pre-eclampsia and arterial stiffness - a 10 year follow-up of previous pre-eclamptic women. Pregnancy Hyprtens 2015; 5: 72-73. |
| 23202992 | Background | Del Priore G, Saso S, Meslin EM, Tzakis A, Brannstrom M, Clarke A, Vianna R, Sawyer R, Smith JR. Uterine transplantation--a real possibility? The Indianapolis consensus. Hum Reprod. 2013 Feb;28(2):288-91. doi: 10.1093/humrep/des406. Epub 2012 Nov 30. |
| 23978550 | Background | Josephson MA, McKay DB. Women and transplantation: fertility, sexuality, pregnancy, contraception. Adv Chronic Kidney Dis. 2013 Sep;20(5):433-40. doi: 10.1053/j.ackd.2013.06.005. |
| 22356169 | Background | Lefkowitz A, Edwards M, Balayla J. The Montreal Criteria for the Ethical Feasibility of Uterine Transplantation. Transpl Int. 2012 Apr;25(4):439-47. doi: 10.1111/j.1432-2277.2012.01438.x. Epub 2012 Feb 23. |
| 15121619 | Background | Le Ray C, Coulomb A, Elefant E, Frydman R, Audibert F. Mycophenolate mofetil in pregnancy after renal transplantation: a case of major fetal malformations. Obstet Gynecol. 2004 May;103(5 Pt 2):1091-4. doi: 10.1097/01.AOG.0000124986.32858.ba. |
| 16554530 | Background | 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. |
| 19897849 | Background | Brannstrom M, Wranning CA, Altchek A. Experimental uterus transplantation. Hum Reprod Update. 2010 May-Jun;16(3):329-45. doi: 10.1093/humupd/dmp049. Epub 2009 Nov 7. |
| 6132996 | Background | Szekeres-Bartho J, Csernus V, Hadnagy J, Pacsa AS. Immunosuppressive effect of serum progesterone during pregnancy depends on the progesterone binding capacity of the lymphocytes. J Reprod Immunol. 1983 Mar;5(2):81-8. doi: 10.1016/0165-0378(83)90003-7. |
| 26088636 | Result | Balayla J, Dahdouh EM, Lefkowitz A; Montreal Criteria for the Ethical Feasibility of Uterine Transplantation Research Group. Livebirth after uterus transplantation. Lancet. 2015 Jun 13;385(9985):2351-2. doi: 10.1016/S0140-6736(15)61096-0. No abstract available. |
| D000091662 | Genital Diseases |