Uterine Transplant in Absolute Uterine Infertility (AUIF)

Female Infertility Clinical Trial

Official title:

Uterine Transplant in Absolute Uterine Infertility (AUIF)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02741102
• Other study ID #: 2015P002552
• Status: Not yet recruiting
• Phase: N/A
• First received: February 22, 2016
• Last updated: April 27, 2016
• Start date: June 2016
• Est. completion date: January 2023

Study information

• Verified date: April 2016
• Source: Brigham and Women's Hospital
• Contact: Stefan G Tullius, M.D.
• Phone: 617-732-6866
• Email: stullius[@]partners.org
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: January 2023
• Est. primary completion date: June 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Uterine Transplant Inclusion/Exclusion Criteria

RECIPIENT:Inclusion Criteria

• Age 18-40

• Clinical evidence of AUFI (Absolute Uterine Factor Infertility)

• Able to produce at least 6 normal embryos by IVF for future use

• Reasonable weight with BMI (Body Mass Index) less than 30.

• Normal kidney function

• Able to undergo transplant and be compliant with treatment

• Has stable partner and social supports

• Partner willing to undergo psychological evaluation and receive immunizations as recommended

• Stable home environment to support a child

Exclusion Criteria :

• Active smoking, alcohol use or use of illicit drugs

• Inability to comply with required treatment (taking pills, having biopsies, frequent appointments )

• Having a condition that would make pregnancy or taking anti rejection medicines too risky.

• Active infection: Human Immunodeficiency Virus (HIV) , Tuberculosis, Hepatitis B, Hepatitis C

• History of extensive abdominal or pelvic surgery

• History of abnormal Papanicolaou test (PAP smear) or genital warts

• History of pelvic inflammatory disease

DONOR:Inclusion criteria

• Age over 40 up to age 60

• Has completed having a family

• Previous pregnancies were carried to term (no miscarriages)

• Able to take a birth control pill containing estrogen

• Weight reasonable with BMI (Body Mass Index) of 30 or less

• Good social supports

Exclusion Criteria:

• Active smoking, alcohol use or use of illicit drugs

• Psychiatric illness

• Cervical or endometrial polyps (growths) or tumors in the uterus muscle

• History of more than 1 Caesarean section

• History of abnormal PAP smear or genital warts

• Internal scarring from extensive abdominal or pelvic surgery

• Hypertension, Coronary artery disease, Chronic Obstructive Lung disease (emphysema) and Diabetes

• Active cancer or incompletely treated cancer

• Active infection including Human Immunodeficiency Disease (HIV) , Tuberculosis, Hepatitis B or Hepatitis C

• Significant history of either blood clots or bleeding tendencies

• Evidence of coercion or exchange of money or goods for donating the organ

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Female Infertility
• Infertility
• Infertility, Female

Intervention

Procedure:
• Uterine Transplant
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

References & Publications (11)

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. Review. — View Citation

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. — View Citation

Brännström M, Johannesson L, Dahm-Kähler P, Enskog A, Mölne J, Kvarnström N, Diaz-Garcia C, Hanafy A, Lundmark C, Marcickiewicz J, Gäbel 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. — View Citation

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.

Del Priore G, Saso S, Meslin EM, Tzakis A, Brännström 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. — View Citation

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. Review. Erratum in: Adv Chronic Kidney Dis. 2014 Jan;21(1):114. — View Citation

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. — View Citation

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. — View 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. Review. — View Citation

Nair, A, et al: Ann NY Acad Sci 2008; 1127:83-91, Brannstroem, M, et al.: Experimental uterus transplantation. Hum Reprod Update 2010; 16:329-345).

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Rate of complications during pregnancy in uterus transplant recipient	Monitoring for pre-eclampsia, hypertension, pre-term delivery	9 months after pregnancy achieved by embryo transfer	Yes
Secondary	Rate of complications following uterine donation	Monitoring for excessive bleeding , infection and bladder dysfunction	Up to 2 years post donation	Yes
Secondary	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	Up to 2 years post donation	No
Secondary	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	No
Secondary	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	No