The fertility sparing therapy in ectopic pregnancy.

OBJECTIVE: A review of current knowledge on the possibilities of fertility sparing therapy in case of ectopic pregnancy. METHODS AND RESULTS: Ectopic pregnancy is defined as implantation of an embryo outside the endometrial cavity, most often in the fallopian tube. This dia-gnosis is very common among young women. Ectopic pregnancies can be treated using the following three approaches, which can be combined: expectantly, pharmacologically or surgically. Fertility-sparing salpingostomy may be performed during surgical treatment. Medical (pharmacological) treatment consists in the application of methotrexate with a success rate of 75-96%, depending on the initial level of the free beta subunit of human chorionic gonadotropin (b-hCG). This is a safe treatment with minimal side effects. There is no standardization of the blood b-hCG level limits or of the size of the ectopic pregnancy mass for choosing expectant, surgical or medical treatment. A considerable increase in the rate of Cesarean sections over the last decades has led to an increase in the occurrence of the implantation of the gestational sac in the hysterotomy scar. There are several options to address this dia-gnosis, but none is clearly preferred. This issue is also discussed in the article. CONCLUSION: The goal of ectopic pregnancy treatment is to choose a safe and effective therapy with a low incidence of side effects and maintaining the maximum fertility of women. Properly set indication criteria are most important when choosing the right option.

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.

Uterine transplantation in an era of successful childbirths from living and deceased donor uteri: Current challenges.

BACKGROUND AND AIMS: Uterine transplantation (UTx) is an experimental sterility treatment method in women with absolute uterine factor infertility. This article describes the current trends and risks in UTx and provides an overview of our experience with this method, to date. METHODS: Based on our experience with the Czech UTx trial and the published results of other trials, we describe the possibilities and risks of this perspective method in the treatment of absolute uterine factor infertility (AUFI). RESULTS: Twelve healthy babies were born in 2014-2018 after more than 40 uterine transplantations. There is no general consensus whether it is more suitable to transplant uteri from living or deceased donors, and nulliparous or parous women (with proven obstetrical functionality). Most centers prefer to collect at least ten frozen embryos from in vitro fertilization (IVF) cycles before transplantation. The serious complication of a surgically successful uterine transplantation is posttransplant partial stenosis of the uterine-vaginal anastomosis that may be a technical problem for embryo transfer, outflow of menstrual blood, and sexual satisfaction due to the narrowed and shortened vagina. This paper concludes that, currently, procurement of the uterus and the transplant procedure are surgically feasible and that none of the transplanted uteri have been lost due to rejection but only because of graft thrombosis or infection. CONCLUSION: Uterine transplantation, after optimization of surgical methods, selection of suitable donors, standardization of immunosuppressive therapy, adjustment of assisted reproductive technologies and obstetrical proceedings might be an effective therapeutic method for women with AUFI who wish to have their own biological child.

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.

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.

Comparison of impact of two decontamination solutions on the viability of the cells in human amnion.

Human amniotic membrane (HAM) is used as an allograft in regenerative medicine or as a source of pluripotent cells for stem cell research. Various decontamination protocols and solutions are used to sterilize HAM before its application, but little is known about the toxicity of disinfectants on HAM cells. In this study, we tested two decontamination solutions, commercial (BASE·128) and laboratory decontamination solution (LDS), with an analogous content of antimycotic/antibiotics for their cytotoxic effect on HAM epithelial (EC) and mesenchymal stromal cells (MSC). HAM was processed in a standard way, placed on nitrocellulose scaffold, and decontaminated, following three protocols: (1) 6 h, 37 °C; (2) 24 h, room temperature; (3) 24 h, 4 °C. The viability of EC was assessed via trypan blue staining. The apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). The mean % (±SD) of dead EC (%DEC) from six fresh placentas was 12.9 ± 18.1. Decontamination increased %DEC compared to culture medium. Decontamination with BASE·128 for 6 h, 37 °C led to the highest EC viability (81.7%). Treatment with LDS at 24 h, 4 °C resulted in the lowest EC viability (55.9%) in the set. MSC were more affected by apoptosis than EC. Although the BASE·128 expresses lower toxicity compared to LDS, we present LDS as an alternative decontamination solution with a satisfactory preservation of cell viability. The basic formula of LDS will be optimised by enrichment with nutrient components, such as glucose or vitamins, to improve cell viability.

[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.

Oncological and pregnancy outcomes after high-dose density neoadjuvant chemotherapy and fertility-sparing surgery in cervical cancer.

OBJECTIVE: 28 women under 35years with early-stage cervical cancer and strong desire for fertility preservation that do not fulfil standard criteria for fertility-sparing surgery (tumour larger than 2cm or with deep of infiltration more than half of stroma) were included in prospective study. METHODS: Dose-dense neoadjuvant chemotherapy (NAC) was performed on all 28 patients in 10-day intervals: cisplatin plus ifosfamide in squamous cell cancer (15 women-53.6%) or cisplatin plus doxorubicin in adenocarcinoma (13 women-46.3%). Patients underwent laparoscopic lymphadenectomy and vaginal simple trachelectomy after NAC. Patients with positive lymph nodes or inadequate free surgical margins underwent radical hysterectomy. RESULTS: No residual disease was found in 6 women (21.4%), microscopic disease was observed in 11 women (39.3%) and macroscopic tumour in was observed in 11 women (39.3%). Ten women (35.7%) lost fertility. Four women (20%) after fertility-sparing surgery recurred, two died of the disease (10%). Fertility was spared in 20 (71.4%) women and 10 of them became pregnant (50%). Eight women delivered ten babies (6 term and four preterm deliveries). There were two miscarriages in second trimester (in one woman) and one in first trimester. One woman underwent four unsuccessful cycles of IVF, one failed to become pregnant and one recurred too early. Two women underwent chemoradiotherapy for recurrence and lost chance for pregnancy. CONCLUSIONS: Downstaging by NAC in IB1 and IB2 cervical cancer before fertility-sparing surgery is still an experimental procedure, but shows some promise. Long-term results in relation to oncological outcome for this concept are still needed.