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.
