Trasplante uterino: resultados actuales. Preparación de un equipo multidisciplinario en Argentina / Uterine transplant: current results. Preparation of a multidisciplinary team in argentina

El factor uterino absoluto como causa de infertilidad, ya sea la ausencia de útero o la presencia de útero no funcional, es actualmente una patología con posibilidad de tratamiento. El primer intento de trasplante uterino en humanos fue en el año 2000, este falló y el útero necrótico tuvo que ser removido luego de 99 días. Este caso pionero inspiró a varios grupos de investigación alrededor del mundo para comenzar estudios en animales para investigar el trasplante uterino en relación a cirugía, inmunosupresión, rechazo y resultados obstétricos. El primer estudio clínico de trasplante uterino comenzó en Suecia en el año 2013 donde se realizaron nueve procedimientos a partir de donantes vivas. El primer nacido vivo en el mundo a partir de un trasplante uterino se reportó en septiembre del año 2014, luego se comunicaron dos nacimientos más en noviembre de ese mismo año. Desde ese momento se han reportado nacimientos de trasplantes uterinos en Suecia, Estados Unidos y Brasil. El caso de nacido vivo en Brasil es el primer y único nacimiento en el mundo cuya donante fue cadavérica. Todos los casos publicados de trasplante uterino y nacidos vivos serán revisados en detalle en este artículo. En el año 2016 se realizó el primer simposio de trasplante uterino en América Latina bajo el auspicio de la Asociación Latinoamericana de Medicina Reproductiva (ALMER). En ese encuentro, el equipo de la Universidad de Gotemburgo, Suecia, compartió su experiencia en trasplante uterino en humanos. Este fue nuestro puntapié para comenzar un trabajo colaborativo entre nuestro equipo en Rosario y el equipo de Suecia, con la intención de preparar un estudio científico de trasplante uterino en Argentina. Los pasos importantes para este procedimiento serán revisados en este artículo (AU)

Absolute uterine factor infertility, due to absence or non-function of the uterus, is now treatable. The first attempt of human uterus transplantation was in year 2000, but it failed and a necrotic uterus had to be removed after 99 days. This pioneering case inspired several research groups around the globe to initiate animal-based studies to investigate uterus transplantation in relation to surgery, immunosuppression, rejection and pregnancy outcome. The first clinical trial of uterus transplantation was initiated in Sweden in 2013 and involved nine live donor procedures. The world ́s first live birth was reported from that trial in September 2014 and this was followed by two more births within the trial in November 2014. Births after uterus transplantation has since then been reported from Sweden, USA and Brazil. The live birth in Brazil is the first and only birth from a deceased donor so far. All published cases of uterus transplantation and the live births will be review in detail.In 2016 there was the first symposium on uterus transplantation in Latin-America under the auspice of ALMER. At the meeting, the Swedish team shared their experiences of human uterus transplantation. This was the starting point for a collaboration work between our team in Rosario and the Swedish team, with the aim to prepare for a scientific trial of uterus transplantation in Argentina. The important steps in this procedure will be reviewed (AU)

Description and evaluation of experimental models for uterine transplantation in pigs / Descrição e avaliação de modelos experimentais para transplante uterino em suínos

ABSTRACT Objective: To evaluate the technique of uterine transplantation and the use of drugs used in the process of immunosuppression. Methods: We included 12 sows, and immunosuppression was performed with minimal doses of cyclosporine, and cross-match was done to exclude the possibility of blood incompatibility. Hysterectomy was performed in the donor under general anesthesia, with the removal of the aorta and inferior vena cava in monobloc, and anastomosis of these vessels was made in the recipient. Results: Six experiments were performed, and on the immediate postoperative period, five animals had good reperfusion. However, on the seventh postoperative day, histological analysis showed rejection in five animals. Conclusion: The experimental model of uterine transplantation is feasible, but monitoring doses of immunosuppressants is pivotal to prevent rejection episodes.

RESUMO Objetivo: Avaliar a técnica de transplante uterino e o uso de drogas no processo de imunossupressão. Métodos: Foram incluídas 12 porcas, sendo realizada imunossupressão com doses mínimas de ciclosporina, e prova cruzada para afastar a possibilidade de incompatibilidade sanguínea. Realizou-se, na doadora, histerectomia sob anestesia geral, com a retirada, em monobloco, da aorta e da veia cava inferior, de tal forma que, na receptora, fosse possível realizar a anastomose com estes vasos. Resultados: Foram realizados seis experimentos e, no pós-operatório imediato, houve boa reperfusão em cinco animais. Entretanto, no sétimo dia de pós-operatório, as análises histológicas demonstraram rejeição em cinco deles. Conclusão: O modelo experimental de transplante uterino é factível, mas a monitorização das doses de imunossupressores é importante, a fim de impedir os episódios de rejeição.

Sheep Model for Uterine Transplantation: The Best Option Before Starting a Human Program

OBJECTIVE: This study reports the first four cases of a uterine transplant procedure conducted in sheep in Latin America. The aim of this study was to evaluate the success of uterine transplantation in sheep. METHOD: The study was conducted at Laboratory of Medical Investigation 37 (LIM 37) at the University of São Paulo School of Medicine. Four healthy mature ewes weighing 40-60 kg were used as both the donor and recipient for a transplant within the same animal (auto-transplant). Institutional guidelines for the care of experimental animals were followed. RESULTS: The first two cases of auto-transplant were performed to standardize the technique. After complete uterine mobilization and isolation of the blood supply, the unilateral vascular pedicle was sectioned and anastomosed on the external iliac vessels. After standardization, the protocol was implemented. Procurement surgery was performed without complications or bleeding. After isolation of uterine arteries and veins as well as full mobilization of the uterus, ligation of the distal portion of the internal iliac vessels was performed with subsequent division and end-to-side anastomosis of the external iliac vessels. After vaginal anastomosis, the final case presented with arterial thrombosis in the left uterine artery. The left uterine artery anastomosis was re-opened and flushed with saline solution to remove the clot from the artery lumen. Anastomosis was repeated with restoration of blood flow for a few minutes before another uterine artery thrombosis appeared on the same side. All four animals were alive after the surgical procedure and were euthanized after the experimental period. CONCLUSION: We describe the success of four uterine auto-transplants in sheep models.

Uterine transplantation: a systematic review

Up to 15% of the reproductive population is infertile, and 3 to 5% of these cases are caused by uterine dysfunction. This abnormality generally leads women to consider surrogacy or adoption. Uterine transplantation, although still experimental, may be an option in these cases. This systematic review will outline the recommendations, surgical aspects, immunosuppressive drugs and reproductive aspects related to experimental uterine transplantation in women.

A meta-analysis on uterine transplantation: Redefining the limits of reproductive surgery / Uma metanálise sobre o transplante de útero: redefinindo os limites da cirurgia reprodutiva

SUMMARY In September 2014, the first baby grown in a transplanted uterus was born, which represented an astonishing scientific progress that will mark the history of human reproduction. The recipient was a 32-year-old woman with Rokytanski syndrome who became pregnant after a successful embryo transfer and had an uneventful pregnancy, giving birth to a healthy newborn and marking the beginning of a new era. Patients who do not have a uterus or have a dysfunctional uterus now have the chance of dreaming with pregnancy and motherhood. Combining principles of solid organ transplantation and techniques of human reproduction, uterus transplantation is the first ephemeral transplant performed in order to promote reproductive potential of women and may be removed after successful pregnancy. Worldwide, 11 uterine transplantations were performed in patients. Of these, seven maintained their reproductive potential, with viable transplanted uteri and regular menstrual cycles.

RESUMO Em 2014, nasce o primeiro bebê oriundo de um útero transplantado, um avanço científico que ficará marcado na história da reprodução humana. A paciente, portadora da síndrome de Rokytanski, engravidou após transplante de útero e transferência de embrião. Teve uma gestação sem complicações e deu à luz um recém-nascido saudável, marcando o início de uma nova realidade. Pacientes que não possuem útero ou possuem útero disfuncional agora podem sonhar em ser mães e gestar um filho. Combinando princípios de transplante de órgão sólido e técnicas de reprodução humana, o transplante de útero consiste no primeiro transplante efêmero realizado com o intuito de promover potencial reprodutivo à mulher, podendo ser removido após gestação bem-sucedida. Mundialmente, 11 transplantes de útero foram realizados em humanos. Dentre os casos, sete mantêm potencial reprodutivo, com úteros viáveis e ciclos menstruais regulares.

La migración de la burbuja de aire postransferencia embrionaria es un evento al azar / Air bubble migration post embrionary tranferir is a random event

Demostrar que la migración de la burbuja de aire postransferencia embrionaria es un evento al azar que no depende de la posición del paciente. Estudio prospectivo multicéntrico. Se practicó transferencia embrionaria a 69 pacientes bajo guía ultrasonográfica. Se cargó el catéter de transferencia con una o dos burbujas junto con el medio conteniendo los embriones usando catéter de Frydman o catéter de Wallace y luego se les hizo seguimiento ecográfico en posición horizontal, 20-25 minutos más tarde y luego a los 90 minutos postransferencia en posición vertical para verificar movimiento y configuración de las burbujas. Centro Médico Docente La Trinidad, Caracas. Nortwestern University Feimberg School of medicine, Chicago, IL. EE.UU. En 50 (72,46 por ciento) de las pacientes se observó movimiento de las burbujas. En posición de pie se demostró una distribución al azar sin efecto visible de la gravedad. Las burbujas de aire se mueven y dividen frecuentemente posterior a la transferencia con la paciente en posición horizontal y de pie, lo que sugiere actividad contráctil uterina. No fue común observar movimiento de burbujas relacionada con la gravedad, lo que sugiere que el descanso horizontal postransferencia embrionaria puede ser innecesario.

To demonstrate that air bubble migration is a random event after embryo transfer regardless of the position of patient. Multicenter prospective study. Sixty nine embryo transfers were performed under ultrasound guidance. Transfer catheter was loaded with one or two air bubbles and medium containing embryos, either Wallace catheter or Frydman catheter were used, ultrasound tracking of air bubble was performed to verify movement and configuration inmediately, 20-25 minutes in horizontal position and 90 minutes on standing position after embryo transfer. Centro Medico Docente La Trinidad, Caracas. Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Movement was observed in 50 (72,46 percent) of the patients. Movement was not observed related to gravity while standing up. Air bubbles move and split frequently after embryo transfer with the patient in the horizontal position and on standing, suggestive of active uterine contractions. Gravity related bubble motion was uncommon, suggesting that horizontal rest post embryo transfer may be unnecessary.

Evaluation of the macroscopic growth degree of experimental endometriosis in rats

PURPOSE: To evaluate macroscopically the growth degree of self-transplantation of endometriosis in rats. METHODS: Forty female rats, after a 7-day period for adpating and evaluating of the estrous cycle regularity, underwent tail abdominal midline laparotomy with 3-cm cuts. The average third of the left uterine horn was removed, 4mm x 4mm patches in liquid environment were made, and self-transplanted in the rat mesenterium with a single stitch, and the endometrial surface of the endometriotic implant facing the lumen of the peritoneal cavity. The rats were programmed to die after three weeks. The abdominal cavity displaying was held and self-transplants were identified and classified. RESULTS: The results achieved were: one case for degree 0 (2,5 percent), three cases for degree 1 (7,5 percent), eleven cases for degree II (27,5 percent) and twenty-five cases for degree III (62,5 percent). CONCLUSION: The experimental endometriosis development, through the self-transplantation technique, showed to be most common in degrees 3 and 2 of development.

OBJETIVO: Avaliar macroscopicamente o grau de crescimento de autotransplantes de endometriose em ratos. MÉTODOS: Quarenta ratos fêmeas, após período de sete dias para adaptação e avaliação da regularidade do ciclo estral, foram submetidas à laparotomia mediana abdominal caudal com incisões de três cm. Foi retirado o terço médio do corno uterino esquerdo, feito retalhos de quatro mm x quatro mm em meio líquido, sendo em seguida autotransplantado no mesentério da rata com ponto simples, tomando o cuidado de manter a superfície mucosa voltada para luz abdominal. Após o período de três semanas as mortes das ratas foram programadas. Realizou-se a exposição da cavidade abdominal com identificação e classificação dos autotransplantes. RESULTADOS: os resultados encontrados foram: grau 0 obteve um caso (2,5 por cento), o grau I foi observado em três casos (7,5 por cento), o grau II com onze casos (27,5 por cento) e o grau III foi visto em vinte cinco casos (62,5 por cento). CONCLUSÃO:Desenvolve-se a endometriose experimental pela técnica do autotransplante com a maioria dos casos em grau 3 e 2 de desenvolvimento.