Early initiation of embryo transfers after uterus transplantation to shorten the administration of immunosuppressive therapy.

Uterus transplantation seems to be a promising method for the causal treatment of absolute uterine factor infertility in women with an absent or non-functional uterus. Since uterus transplantation is still experimental in nature, there are no strict guidelines regarding each step of this comprehensive treatment method. Prior to uterus transplantation, ovarian stimulation and in vitro fertilization are performed on the potential uterus recipient, and the obtained embryos are cryopreserved and stored for the transfers after transplantation when only non-fetotoxic maintenance immunosuppressants are administered. In the first human uterus transplantation study, the start of embryo transfers was set at 12 months after transplantation. Due to the growing experience, especially with early rejections after transplantation and the course of pregnancy, several ongoing studies have experimentally shortened the uterus transplant-to-embryo transfer interval to 6 months. Shortening the total time of immunosuppression administration after uterus transplantation is the main reason for early initiation of embryo transfers after transplantation. However, the safety of an interval of less than one year between uterine transplantation and the first post-transplant embryo transfer should be further studied.

Current ethical aspects of absolute uterine factor infertility treatment using uterus transplantation.

OBJECTIVE: An analysis of ethical studies related to uterus transplantation in the treatment of absolute uterine factor infertility. METHODS: Literary research using the Web of Science, Google Scholar and Pubmed databases with the following keywords: absolute uterine factor infertility, ethics, deceased donor, living donor, and uterus transplantation. An analysis of articles published in impact and reviewed journals between 2000-2021. RESULTS: Uterus transplantation is a promising treatment method for women with absolute uterine factor infertility. In the experimental studies, an ultimate goal of this complex treatment was repeatedly achieved: childbirth through a caesarean section. An important milestone towards the application of uterus transplantation in human was the Montreal criteria of its ethical feasibility, published in 2012-2013. In 2012, the first uterus transplant study from a living donor started in Sweden and, in 2016, further studies were initiated worldwide. The first childbirth from the transplanted uterus in 2014 increased the interest of ethicists in various aspects of this experimental treatment, and this trend continues. Current ethical analyzes are focused particularly on the comparison of advantages and disadvantages related to the utilization of living and deceased donors of uterus; comparing ethical aspects of gestational surrogacy and uterus transplantation; uterus transplantation as an extremely radical form of assisted reproduction; its impact on adoptions; uterus transplantation in trans-gender women; the importance of establishing an international registry for uterus transplants; and other important ethical issues associated with this complex form of assisted reproduction. CONCLUSION: Uterus transplantation is still in an experimental stage. The ethical analysis of the individual steps of this comprehensive method in the treatment of female infertility should be carried out continuously, in connection with the gradually presented outcomes of ongoing scientific research studies.

Revaluation and lessons learned from the first 9 cases of a Czech uterus transplantation trial: Four deceased donor and 5 living donor uterus transplantations.

Although uterus transplantation is still in the experimental stage, it has promising potential as a treatment for women with absolute uterine factor infertility based on the childbirths from living donor trials conducted in Sweden and the United States. We report the main characteristics and perioperative and postoperative courses of both recipients and donors following 4 deceased donor and 5 living donor uterus transplantations. Three main priorities differentiate this study from the previously reported uterus transplantations. First, clinical experience with the largest worldwide group of deceased donor uterine transplants is described. Second, in the majority of living donor uterine recipients, only 2 ovarian veins were used for venous blood outflow. All of these recipient procedures were surgically successful, and follow-up posttransplant ultrasound examinations revealed normal uterine blood supply and outflow. Third, in only one living and one deceased donor recipient, the transplanted uterus relied on only 2 uterine veins for venous outflow with a 50% surgical success rate. In all other recipients, 2 uterine and 2 ovarian veins were utilized. Although a successful pregnancy has not yet been achieved, the presented surgical and functional results of our trial are promising.

Clinical pregnancy after deceased donor uterus transplantation: Lessons learned and future perspectives.

AIM: To describe our first clinical pregnancy following a uterus transplant from a brain-dead donor and to discuss current issues with deceased donor uterus transplantation as they relate to obstetrical success. METHODS: In August 2016, a 26-year-old woman with Mayer-Rokitansky-Küster-Hauser syndrome was the fourth person worldwide to receive a uterine transplant from a deceased donor and was the second in our trial. in vitro fertilization treatments using the long gonadotropin-releasing hormone agonist protocol preceded the transplantation procedure. Frozen embryo transfers were performed in months 12, 13, 16, 19 and 23 after transplant. RESULTS: Recovery of the uterus of a 24-year-old brain-dead nulliparous donor and the transplant procedure itself was uncomplicated. No abnormalities were revealed on Pap smears, which were performed every 6 months during the post-transplant period, and cervical biopsies showed no epithelial dysplasia. The fifth frozen embryo transfer resulted in a clinical pregnancy. Three weeks after embryo transfer, an intrauterine gestational sac containing an embryo with a heartbeat was detected. One week later, signs of a missed abortion were revealed by ultrasound. Two weeks later, spontaneous bleeding occurred, and an ultrasound examination performed a week later confirmed an empty uterine cavity. CONCLUSION: In light of present research, both deceased donor uterine procurement and transplantation surgeries are technically feasible; however, more experience is needed to determine the pregnancy success rate associated with this method. Thus, additional trials of deceased donor uterine transplantation should be performed in the future to continue research related to this promising concept for the treatment of absolute uterine factor infertility.

[Possibility of uterus transplantation trial in Czech Republic - indications, research and clinical experience]. / Moznosti transplantace delohy v Ceské republice - indikace, výzkum a klinické zkusenosti.

Uterus transplantation is a novel experimental method of female infertility treatment. It is an appropriate treatment modality for women with absolute uterine factor infertility - congenital uterine malformations, absent uterus, hysterectomized women and non-functional uterus.Successful animal studies confirming the safety and efficacy were performed before introduction of uterus transplantation into human medicine. The first clinical trial was performed in 2012-2013 in Gothenburg, Sweden. The first child from the transplanted womb was delivered in 2014. Concerning the promising results of Swedish trial it is essential to perform trials in some other world centers.In 2015 Czech Ministry of Health permitted uterus transplantation trial in cooperation of two Prague hospitals - namely Institute for Clinical and Experimental Medicine and University Hospital Motol. The aim of the Czech trial is to reassert feasibility, efficacy and safety of uterus transplantation in two groups of women - 10 recipients from living and 10 from deceased brain donor. We believe that detailed and precise long-term theoretic and practical preparation and perfectly arranged trial are the main conditions of the successful uterine transplantation survey. The first Czech uterus transplantation was performed in April 30, 2016.Up to December 2016 four transplantations out of planned 20 (2 in living donor and 2 in deceased brain donor arm) were carried out by our team.

[Ethical aspects of uterus transplantation]. / Etické aspekty transplantace delohy.

Uterus transplantation is an experimental treatment method with an ambition to become accepted treatment modality for women with absolute uterine factor infertility. The only legal alternative for these women to get parenthood is adoption which is accepted by most world societies and countries. Surrogate pregnancy is connected with many medical, ethical, legal, religious and social controversies in the great part of the world.Donors (in living donation), recipients, partners and also unborn children must be incorporated into the analysis of ethical risks and benefits of uterus transplantation. The main ethical risks for the recipient are surgery, immunosuppression, pregnancy and delivery. All the potential recipients have to be advised about further ethical issues like organ rejection, infection, side effects of the drugs, unsatisfactory fertilization and different complications during pregnancy.Uterus procurement in donor takes longer time than in standard hysterectomy due to preparation of uterine arteries and veins. Vessels with 2 mm diameter and their anatomical collision with ureter are connected with higher peroperative risk of uneventful surgical complications. Ethical issues might be connected with the uterus procurement in dead brain donors identically.The deliveries after uterus transplantation are fruitful but the risk of preterm delivery and immaturity of the newborns cannot be underestimated as well.

[Psychological evaluation of uterus transplantation trial participants]. / Psychologické hodnocení úcastníku studie transplantace delohy.

Uterus transplantation is a life-giving and quality-of-life enhancing transplantation. Life with transplanted uterus is a transitional phase of life for both recipients and their partners. Six deliveries of healthy children from five transplanted mothers out of 9 uterus transplantations in Sweden may encourage untimely hopes of thousands of women with absolute uterine factor infertility worldwide. Psychological evaluation might be included into all trials regarding new treatment methods and treatment procedures. Main psychological issues connected with the infertility treatment in women with absent uterus are clearly defined (especially in vitro fertilization, uterus transplantation, compliance with immunosuppressive treatment, ultrasound examinations of uterine vascular perfusion, rejection signs surveillance, embryo transfer, pregnancy, cesarean section, preterm delivery risk, puerperium, hysterectomy and immunosuppressive treatment termination). The role of psychological evaluation of participants before the admission to complicated treatment process is to choose those who will be able to cope all mentioned difficulties and unexpected complications including potential failure of the whole treatment without serious negative impact on their psychological situation. Up to now experience with psychological stability of our 7 uterus recipients and 3 uterus living donors are good although post-transplant period is especially in recipients connected with everyday psychological adaptation on the significant life changes. We are aware that psychological evaluation of our study participants will require further 3 years of follow up with publication of our results.

Assisted Reproductive Techniques and Pregnancy Results in Women with Mayer-Rokitansky-Küster-Hauser Syndrome Undergoing Uterus Transplantation: the Czech Experience.

STUDY OBJECTIVE: This study aimed to evaluate the reproductive potential of patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) who were candidates for uterus transplantation (UTx) before inclusion in the experimental trial, and to summarize the existing experience with posttransplantation embryo transfers in functionally successful cases. DESIGN AND SETTING: A prospective study at a tertiary medical center. PARTICIPANTS: Ten pre-UTx women with MRKHS and 7 successful UTx cases. INTERVENTIONS AND MAIN OUTCOME MEASURES: Ovarian stimulations, frozen embryo collection, embryo transfers, and incidence of pregnancy in MRKHS women in the pre- and posttransplantation periods. RESULTS: The average number of ovarian stimulations to collect the required frozen embryos was 1.9 (1-3). On average, the number of aspirated oocytes was 16.4 (7-38), 12.6 (5-26) oocytes were fertilized, and 7.0 (1-18) embryos were cryopreserved per cycle. To date, the average number of embryo transfers per recipient was 4.9 (3-8), and the embryo transfer/pregnancy rate was 8.8% (3 of 34). Three pregnancies have been achieved to date, including a missed abortion in the 8th week, a birth in the 35th week, and an ongoing pregnancy in the 30th week. CONCLUSIONS: Despite the small number of UTx cases, our data indicated that women with MRKHS showed a good response to ovarian stimulation and blastocyst formation. Although the procedures for fertilization, cryopreservation, and transfer of the embryos were standardized, the success rate per embryo transfer achieved in the study group has been low to date.