Uterus human leucocyte antigen expression in the perspective of transplantation.

AIM: To describe class I and II human leucocyte antigen (HLA) expression using different uterine tissues in the perspective of uterus transplantation. METHODS: Human uterine tissues were obtained from 12 women who had undergone hysterectomy for the treatment of benign disease. HLA class I and HLA-antigen D related (DR) expression were assessed via immunochemistry. HLA class I expression in the uterus was compared with expression in other organs and tissues, including kidney and myocardium samples. RESULTS: HLA class I expression was strong in the endometrial glands and mild in the myometrium. Staining of endometrial glands was similar to glomerular staining in the kidney. The myometrium seems to express HLA class I similarly to hepatocytes and myocardial cells. HLA class I expression in the uterus did not differ in younger or post-menopausal women. HLA-DR was expressed in the endometrial glands, but not in the myometrium. A lack of HLA-DR expression seemed to be correlated with cell proliferation. CONCLUSION: HLA expression in the endometrium and myometrium is different. The endometrium should be the major target of alloreactive response. As for other transplanted organs, assessment of HLA unacceptable antigens and multiple immunosuppressive treatments is necessary in uterus transplantation.

Pelvic magnetic resonance imaging in the ewe: a model for experimental gynecologic research.

AIM: Our goal was to demonstrate the feasibility of pelvic magnetic resonance imaging (MRI) in the ewe. MATERIAL AND METHODS: Two ewes underwent a pelvic 3 Tesla MRI scan, under light anesthesia, with T2-weighted fast spin-echo images and T1-weighted spoiled gradient-echo images. Multiplan T1 weighted images were also obtained after the intravenous injection of a contrast product. One ewe was anestrous and the other one had undergone ovarian stimulation. RESULTS: No incident occurred during the examination. Both the uterus (with two horns) and the ovaries were identified. The intensity of the endometrial, myometrial and ovarian signals was similar to that encountered in women. The uterus and ovaries could be enhanced in both cases. Pelvic vasculature was also studied. In the case of hormonal stimulation, the endometrium was thicker, follicular growth was identified and enhancement seemed greater. CONCLUSION: MRI in the ewe is feasible and could be helpful in experimental gynecologic research, especially in uterus transplantation.

Uterine Factor Infertility, a Systematic Review.

Uterine factor infertility (UFI) is defined as a condition resulting from either a complete lack of a uterus or a non-functioning uterus due to many causes. The exact prevalence of UFI is currently unknown, while treatments to achieve pregnancy are very limited. To evaluate the prevalence of this condition within its different causes, we carried out a worldwide systematic review on UFI. We performed research on the prevalence of UFI and its various causes throughout the world, according to the PRISMA criteria. A total of 188 studies were included in qualitative synthesis. UFI accounted for 2.1 to 16.7% of the causes of female infertility. We tried to evaluate the proportion of the different causes of UFI: uterine agenesia, hysterectomies, uterine malformations, uterine irradiation, adenomyosis, synechiae and Asherman syndrome, uterine myomas and uterine polyps. However, the data available in countries and studies were highly heterogenous. This present systematic review underlines the lack of a consensual definition of UFI. A national register of patients with UFI based on a consensual definition of Absolute Uterine Factor Infertility and Non-Absolute Uterine Factor Infertility would be helpful for women, whose desire for pregnancy has reached a dead end.

Uterine junctional zone at magnetic resonance imaging: a predictor of in vitro fertilization implantation failure.

AIM: To prospectively study the influence of the uterine junctional zone thickness measured on pelvic magnetic resonance imaging (MRI), on implantation rates during in vitro fertilization (IVF). METHODS: A prospective clinical-imaging study was conducted and included 152 female patients. Patients had a positive diagnosis of infertility and an indication for IVF. All patients had a pelvic MRI scan on a 1.5T magnet with T2-weighted sequences prior to IVF. The average junctional zone thickness value and the maximal junctional zone thickness values were measured. Implantation outcomes were correlated with junctional zone values and with infertility subtypes (endometriosis, tubal, dysovulation, male, unexplained). RESULTS: The mean number of embryo transfers per patient was 1.63, with a total pregnancy rate of 54%. Junctional zone thickness increase was significantly correlated with implantation failure at IVF: implantation failure rate was 95.8% for patients with an average junctional zone superior to 7 mm and a maximal junctional zone superior to 10 mm, versus 37.5% in other patient groups (P < 0.0001), independently from the cause of infertility or patients' age. CONCLUSION: In a group of infertile patients engaged in an IVF program, a pelvic MRI scan showing a thickened uterine junctional zone is a negative predictive factor for embryo implantation after IVF.

Description of an initiation program to robotic in vivo gynecological surgery for junior surgeons.

INTRODUCTION: Most gynecological residents or junior surgeons do not practice nor experience robotic surgery due to lack of access during residency or poor knowledge about this growing surgical technology. This study evaluated the feasibility and safety of a 3-half-day experiencing and training session for robot-assisted gynecological surgery designed for residents and fellows. MATERIEL AND METHODS: This is a prospective, single-center observational study about a training course aimed at residents or fellows at the university teaching hospital of Limoges (France). It spreads over three consecutive half-days: one dedicated to simulation exercises involving the Da Vinci Skills Simulator© and the other two, to practice in two robot-assisted procedures with dual-console equipment supervised by a senior surgeon (as it is usually performed in a university teaching hospital). Complications during surgery, patient's medical records as well as the participants' performances during in vivo suturing acts were gathered. Feedback on the session was obtained with a questionnaire at the end of the course. RESULTS: Twelve sessions involving 24 patients operated on by 34 trainees from 16 different teaching university hospitals across the country took place. No conversion to laparotomy nor any major peri- or post-operative complication was reported. Time for stitching decreased significantly (p=.016) between the first and the second in vivo surgery. Use of the dual console was found helpful and most attendees (96.8%) would recommend this training session. CONCLUSION: We showed this training course with both simulation and in vivo surgery was feasible, safe and was a well-liked initiation program for robotic surgery.

Organizing a uterus transplantation programme: The designation of Uterus Transplantation Centres in France.

Absolute uterine factor infertility affects several thousand young women in France. The first healthy child delivered to a uterus transplant recipient took place in 2014, and uterus transplantation is developing rapidly in many countries. The French College of Gynaecologists and Obstetricians (CNGOF) formed a uterus transplantation committee (CETUF) in 2015 to advance this technology in France. The CETUF sets out the criteria for the designation of Uterus Transplantation Centres. The objectives, requirements, operation and responsibilities of these centres have been described. Their responsibilities for organizing geographical coverage, continuity of care, communication, training, research and evaluation have been defined. This document will serve as a guide for the authorities concerned, to ensure that the means are provided to adequately manage patients with absolute uterine factor infertility who require uterus transplantation.

The Key Role of Warm and Cold Ischemia in Uterus Transplantation: A Review.

Introduction: Uterus transplantation (UTx) is a promising treatment for uterine infertility that has resulted in several births since 2014. Ischemia is a key step in organ transplantation because it may lead to changes jeopardizing graft viability. Method: We performed a systematic review of animal and human studies relating to uterine ischemia. Results: We retained 64 studies published since 2000. There were 35 studies in animals, 24 in humans, and five literature reviews. Modest preliminary results in large animals and humans are limited but encouraging. In small animals, pregnancies have been reported to occur after 24 h of cold ischemia (CI). In ewes, uterine contractions have been detected after 24 h of CI. Furthermore, it has been shown in animals that uterine tolerance to CI and to warm ischemia (WI) can be increased by pharmacological products. In women, mean CI time in studies of births from uteri obtained from live donors was between 2 h 47 min and 6 h 20 min from a deceased donor; with only one birth in this case. Muscle contractions have also been demonstrated in myometrial samples from women, after six or more hours of CI. Conclusion: The uterus seems to be able to tolerate a prolonged period of CI, of at least six hours. Studies of the ischemia tolerance of the uterus and ways to improve it are essential for the development of UTx, particularly for procedures using grafts from deceased donors.

Which Donor for Uterus Transplants: Brain-Dead Donor or Living Donor? A Systematic Review.

BACKGROUND: The aim of this systematic review was to evaluate and compare the pros and cons of using living donors or brain-dead donors in uterus transplantation programs, 2 years after the first worldwide live birth after uterus transplantation. METHODS: The Medline database and the Central Cochrane Library were used to locate uterine transplantation studies carried out in human or nonhuman primates. All types of articles (case reports, original studies, meta-analyses, reviews) in English or French were considered for inclusion. RESULTS: Overall, 92 articles were screened and 44 were retained for review. Proof of concept for human uterine transplantation was demonstrated in 2014 with a living donor. Compared with a brain-dead donor strategy, a living donor strategy offers greater possibilities for planning surgery and also decreases cold ischemia time, potentially translating into a higher success rate. However, this approach poses ethical problems, given that the donor is exposed to surgery risks but does not derive any direct benefit. A brain-dead donor strategy is more acceptable from an ethical viewpoint, but its feasibility is currently unproven, potentially owing to a lack of compatible donors, and is associated with a longer cold ischemia time and a potentially higher rejection rate. CONCLUSIONS: The systematic review demonstrates that uterine transplantation is a major surgical innovation for the treatment of absolute uterine factor infertility. Living and brain-dead donor strategies are not mutually exclusive and, in view of the current scarcity of uterine grafts and the anticipated future rise in demand, both will probably be necessary.

Uterus retrieval process from brain dead donors.

OBJECTIVE: To describe the feasibility of human uterus retrieval after donation after brain death. DESIGN: Single-center, prospective study. SETTING: University hospital. PATIENT(S): Female brain dead donors. INTERVENTION(S): The families of female brain dead donors were informed about consent to uterus donation. A specific organ retrieval procedure was performed. At the end of the procedure the uterus was removed together with the hypogastric vessels, parametria, and vaginal fornix. The tolerance of the uterus to cold ischemia was evaluated with histology and TUNEL reaction up to 24 hours. MAIN OUTCOME MEASURE(S): Rate of uterus donation refusal. RESULT(S): Between August 1, 2012 and July 31, 2013, seven uteri were retrieved from 14 female multiorgan donors. No refusal to uterus donation occurred. Our surgical protocol did not interfere with vital organ retrieval and was readily accepted by the other transplantation teams. The hypogastric vessels could be preserved in all cases but for one vein loss in the first retrieval. Histology studies did not find major morphologic changes after 24 hours of cold ischemia. Apoptosis was rare. CONCLUSION(S): Uterus retrieval could be part of a reproducible multiorgan procurement procedure. Uterus donation seems readily accepted. This preliminary study is a necessary step before any transplantation project.

Children born after autotransplantation of cryopreserved ovarian tissue. a review of 13 live births.

INTRODUCTION. Premature ovarian failure (POF) can occur naturally at an early age or be due to iatrogenic agents. Indeed, ovaries are very sensitive to cytotoxic treatment, especially to radiation and alkylating agents. METHODS. Several options are currently available to preserve fertility in cancer patients and allow them to conceive when they have overcome their disease: embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation. Cryopreservation of ovarian tissue is the only option available for pre-pubertal girls and women who cannot delay the start of chemotherapy. FINDINGS. Since the first live birth after autotransplantation of cryopreserved ovarian tissue in humans was reported in 2004, orthotopic reimplantation has led to the birth of 13 healthy babies. Restoration of ovarian activity and prognostic factors are evaluated by comparison with 7 cases of fresh ovarian tissue transplantation. We report 13 live births after orthotopic transplantation of frozen-thawed ovarian tissue in cancer patients (n = 8) and in patients treated with high doses of chemotherapy for benign diseases (n = 2) (microscopic polyangiitis, sickle cell anemia). INTERPRETATION. Based on our review, we believe that ovarian cortex cryopreservation, associated or not with cryopreservation of immature oocytes, should be offered before gonadotoxic chemotherapy in all cases where there is a high risk of POF and where emergency IVF is not possible.

[Chemotherapy and women fertility preservation]. / Chimiothérapie et préservation de la fertilité féminine.

Agressive chemotherapy can lead to premature ovarian failure and loss of fertility in women and children. Embryo cryopreservation is an established clinical procedure of fertility preservation but with several limitations. Others options are available. Cryopreservation ovarian cortex tissu have to be suggested in case of high gonadotoxic treatment. It doesn't require puberty and delay in initiation of chemotherapy. The first birth in France after orthotopic graft of ovarian tissu thawed have been recently described with a promising process. Oocyte cryopreservation is available for women without partner but the experience is limited. Gonadotrophin-releasing hormone (GnRH) agonist therapy as ovarian protectants seem interesting. Follicular growth and maturation in vitro are still experimental.

Live birth after ovarian tissue autograft in a patient with sickle cell disease treated by allogeneic bone marrow transplantation.

OBJECTIVE: To report the first case of restoration of ovarian activity and live birth after cryopreserved ovarian tissue autograft in a patient without cancer treated by allogeneic bone marrow transplantation. DESIGN: Case report. SETTING: University hospital. PATIENT(S): One woman with homozygous sickle cell anemia. INTERVENTION(S): An orthotopic autotransplantation of ovarian cortical strips was performed after freeze-thawing. MAIN OUTCOME MEASURE(S): Cryopreservation of ovarian tissue, bone marrow transplantation, ovarian autograft, and restoration of ovarian function. RESULT(S): In autumn 2005, biopsy samples of ovarian tissue were cryopreserved before chemotherapy followed by bone marrow transplantation. In spring 2008, because the patient had been menopausal for 2.5 years as a result of the conditioning therapy, an orthotopic autotransplantation of thawed ovarian cortex was performed. The patient conceived spontaneously in a natural cycle in autumn 2008, and delivered a healthy female child in June 2009. CONCLUSION(S): Cryopreservation of ovarian tissue with subsequent autotransplantation is an emerging procedure for preserving the fertility of young patients with a high risk of premature ovarian failure (POF) resulting from gonadotoxic treatment. This case opens up new perspectives in cases of nonmalignant diseases.