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International audience; 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.

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.

International audience; 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.

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.

To describe class I and II human leucocyte antigen (HLA) expression using different uterine tissues in the perspective of uterus transplantation.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.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.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.

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.

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

Resume Plusieurs cas de greffe d’organes non vitaux ont ete decrits lors de la derniere decennie dans le but d’ameliorer la qualite de vie des patients. La greffe d’uterus pourrait etre une alternative a la grossesse de substitution ou a l’adoption pour les femmes ayant une absence d’uterus acquise ou congenitale, desireuses de mener une grossesse. Differentes experimentations animales sur la souris, la brebis ou le singe ont montre la faisabilite du prelevement uterin en bloc elargi aux vaisseaux iliaques et de la transplantation avec la realisation de macroanastomoses vasculaires. Une tentative isolee de greffe uterine a ete realisee sans succes chez l’humain avec donneur vivant. La tolerance du greffon uterin a l’ischemie froide a ete testee chez la souris, la brebis et l’humain. Actuellement, des grossesses sur greffon uterin n’ont ete publiees qu’apres allogreffe chez des souris syngeniques. Les resultats de grossesse apres allogreffes sous traitement immunosuppresseur chez la brebis et le singe sont en attente avant d’envisager la possibilite d’une grossesse apres transplantation uterine chez l’humain.

Ovarian tissue cryopreservation (OTCP) is a new procedure of medically assisted procreation, still at the experimental stage, whose primary aim is to store female gametes as sperm cryopreservation permits to do for male gametes. Ovarian tissue is removed very simply by laparoscopy. It survives well to freezing if the medium contains a cryoprotective agent and the rate of freezing is slow. In contrast, thawing must be rapid. There are three processes for the utilization of ovarian tissue after thawing. In vitro maturation and xenografting remain impossible for technical and ethical reasons. Autologous transplantation (orthotopic or heterotopic) of the tissue is therefore the only foreseeable method over the short term. Indications for OTCP must remain rare as long as no pregnancy has been obtained in human. At the present time, only female patients who would inevitably suffer the loss of their fertility should be able to take advantage of OTCP. Basically, this would mean women subjected to castrating anticancer therapy. It would seem reasonable to set the age limit at 35-years for carrying out OTCP. Lastly, female patients should be clearly informed that the method is still at the research stage, and in France samples must be taken in accordance with the laws governing clinical research.

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.

International audience; 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.

Objective: A report is given of a series of 126 laparoscopically-assisted vaginal hysterectomies (LAVH) for benign lesions, carried out between September 1990 and December 1995. Materials and method: The mean age of the patients was 50.3 years, and the main indications for hysterectomy were metrorrhagia (88). The main reasons why LAVH was chosen from among other hysterectomy techniques were a large uterus (55), associated ovarian surgery (45), and a difficult vaginal approach (35). The surgical technique always began with a laparoscopic stage followed by a vaginal stage. The laparoscopic stage generally finished at the lower part of the broad ligament. The vagina was opened and the uterine arteries were ligatured by a vaginal approach (116). Only 10 total laparoscopic hysterectomies were performed. Results: The mean duration of the operation was 72 ± 28 min, mean blood loss was 1.89 g/dl, and mean uterus weight was 224 g (maximum = 1093 g). Operative complications consisted of two bladder wounds and two switches to abdominal hysterectomy. Postoperative complications were urinary infections (17), hemorrhages needing second-look operations [2] and abscess of the vaginal section requiring evacuation [3]. Conclusion: LAVH should never be carried out instead of vaginal hysterectomy (VH), since VH is the best procedure when it is easy to perform. The authors use LAVH when VH is difficult or contraindicated (the aim being to avoid laparotomy) and actually carry out less than 5% of hysterectomies for benign lesions by laparotomy.

L’information aux jeunes femmes et aux parents dejeunes filles concernant les techniques de préservationde la fertilité en cas de traitements gonadotoxiques estune obligation médico-légale. En cas de stade précocedes cancers gynécologiques, une chirurgie conservatrice peut parfois être discutée. La congélationembryonnaire et/ou ovocytaire est réservée auxpatientes pubères et nécessitent une stimulation ovarienne incompatible avec un traitement urgent. Lamaturation ovocytaire in vitro semble séduisante. Lacryoconservation de tissu ovarien a l’avantage de pouvoir être proposée chez les jeunes filles non pubères etne retarde pas le traitement. Quant à la protection ducapital folliculaire par les analogues GnRH, les résultats d’études randomisées sont en attente.

Summary of results of oestradiol, FSH, LH, inhibin B, and AMH from the day of transplantation to day 4 (D4) of the second spontaneous menstrual period future pubic hair, between the abdominal skin and the abdominal muscle. An abdominal pocket was opened and three thawed ovarian fragments were deposited inside. Hormonal investigations (fi gure) on the fi rst day of the ovarian transplantation showed FSH 89 IU/L, LH 36 IU/L, oestradiol less than 37 pmol/L, and AMH less than 0∙18 pmol/L. 2 months after the graft, breast growth started bilaterally, and she had reached Tanner stage S2 4 months after the graft. At this time, pubic and axillary hair appeared. H er fi rst menstruation was 8 months af ter transplantation, lasting 4 days. Breast development reached Tanner stage S3. At 3 years and 3 months after ovarian autotransplantation, our patient was 172 cm tall and weighed 52 kg. Her menstruation was regular for 2 years after the graft and irregular thereafter. Her breasts were completely developed with normal shape.Cryopreservation of ovarian tissue before potentially sterilising treatment can preserve ovarian function. 13 children have been born worldwide after auto-transplantation of ovarian fragments.

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.

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).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).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 (P0.0001), independently from the cause of infertility or patients' age.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.

International audience; 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.

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.

Sperm cryopreservation permits young men, undergoing cancer treatments, to preserve their fertility. Ovarian tissue cryopreservation have the same goal for young women and could also be an option for children. However, only primordial follicles survive after freezing and a follicular maturation is needed after thawing. This maturation has not yet been realized in humans, pregnancies have only been obtained in animal models. As cryopreservation is yet effective in humans, many teams have already cryopreserved the ovarian tissue of patients who have nothing to lose as their follicular reserve would have been destroyed or severely depleted by cancer treatment. The preservation of fertility is rarely an issue in gynecologic oncology because it usually concerns post-menopausal women. However, they are early-onset forms of gynecologic cancers and in these cases fertility is often threatened. Ovarian tissue cryopreservation may be performed when curative or prophylactic ovariectomy must be undergone, when chemotherapy with high-dose alkylating agents is planned or when pelvic radiation is needed (particularly in cases requiring chemotherapy combined with radiotherapy). In some of these situations it would be dangerous to graft back the tissue to the patient as cancer cells could remain within the grafts, the best solution in this case would be the in vitro follicular maturation.

Abstract 4482 One major drawback of myeloablative allogeneic stem cell transplantation is the near 100% risk of profound fertility impairment leading to early menopause and sterility in most female patients. This toxic effect is especially critical in patients without malignant disease, i.e hemoglobinopathies or other inherited diseases. Cryopreservation of ovarian tissue with subsequent autotransplantation is an emerging procedure to preserve the fertility of young patients with a high risk of premature ovarian failure resulting from radiotherapy or chemotherapy for cancer. We report the restoration of ovarian activity and pregnancy with live birth after an orthotopic transplantation of frozen/thawed ovarian tissue in a 23 year old female patient given a transplant for sickle cell disease. In spring 2005, the patient of S/S hemoglobin genotype experienced a central nervous system stroke with unilateral central retinal artery occlusion. Monthly exchange transfusions were started from then and a pretransplant procedure was undertaken with a 10/10 matched sibling male donor who was heterozygous for HbS. In autumn 2005, biopsy samples of ovarian tissue were cryopreserved prior to conditioning. The patient received a conditioning regimen with IV busulfan (12.8 mg/kg total dose), cyclophosphamide (200 mg/kg total dose) and antilymphocyte globulin (15 mg/kg total dose) followed by allogeneic bone marrow transplantation (BMT). A stable 100% donor chimerism was obtained from D60.The patient developed grade II acute GVHD treated by steroids, then followed by limited chronic GVHD treated by a combination of mycophenolate-mofetil and ciclosporin. The treatment was tapered and stopped 7 months after BMT. After BMT, the patient presented clinical menopause with amenorrhoea and hot flushes due to premature ovarian failure. FSH and LH concentrations rose to menopausal levels. Hormone replacement therapy with oestro-progestogens was started 6 months after BMT and was maintained until ovarian function restoration after ovarian transplantation. In spring 2008, as the patient had been menopausal for 2.5 years as a result of the conditioning chemotherapy, an orthotopic autotransplantation of ovarian cortex was performed. The cortical fragments were grafted according to the following procedure: a first laparoscopy was performed to create a peritoneal windows between the right iliac vessels and an ovarian window in the remaining left ovary with the aim of further inducing angiogenesis. One thawed strip of ovarian cortex was cut in fragments, that were fixed in the ovarian incision and deposited in the peritoneal window. Three days later, a second laparoscopy was performed and three thawed cortical strips were fixed into the left ovary and one into the peritoneal window. Ovarian function recovery was evaluated by hormonal levels and follicular development was observed by ultrasound. The patient conceived spontaneously in a natural cycle in autumn 2008, and delivered a healthy female child in June 2009. This first case report of pregnancy and delivery after ovarian autograft in a patient treated by allogeneic BMT suggests that cryopreservation of ovarian tissue should be offered prior to SCT not only to women of childbearing age but also to prepubertal patients, as primordial follicles are already present in the post natal ovaries. This technique still deserves further investigations in leukemias but appears safe in non malignant diseases. Time line of treatment Disclosures: No relevant conflicts of interest to declare.