Ovarian tissue cryopreservation (OTC) is recommended by scientific societies for women undergoing highly gonadotoxic cancer treatments. Following transplantation, the restoration of ovarian function is typically characterised by the resumption of spontaneous menstruation. Yet, a few studies have looked at the longitudinal hormonal variations following transplantation. This study aims to investigate the fluctuation of gonadotropins and granulosa/theca cells secretions during the interval between ovarian transplantation and the recovery of menstrual function in two young women with no residual ovarian activity. We selected two patients diagnosed with Hodgkin’s lymphoma, initially referred for OTC at the ages of 19 and 15, respectively, and who had both undergone two consecutive stem cell transplants due to recurrent disease episodes. Both patients presented with premature ovarian failure and returned at ages 29 and 26, respectively, for ovarian cortex transplantation. Hormonal secretions and menstrual function were closely monitored both prior and in the months following the ovarian transplantation. Menstruation resumed at 7 and 5 months post-transplantation, respectively. FSH and LH levels significantly decreased as early as 1 and 3 months before the first menstruation. As for ovarian hormonal secretion, AMH, measured with an ultra-sensitive assay (“pico AMH”), and Inhibin B were the first to increase, starting 1 month before the resumption of menstruation. Subsequently, AMH levels consistently remained very low throughout the follow-up, as did androgens, which showed a slight increase after the graft but remained at postmenopausal levels. Pico AMH, measured by an ultra-sensitive assay, Inhibin B and estradiol are the first ovarian hormones to be secreted following an ovarian graft, with levels rising 1 month prior the return of menstruation. However, the earliest hormonal indicators of graft success are the significant drops in FSH and LH levels, accompanied by a rise in estradiol levels, which occur 1–3 months before menstruation resumes.

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(C) 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. (C) 2019 Elsevier Masson SAS. All rights reserved.

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.

BACKGROUND:Sterility is a major late effect of radiotherapy and chemotherapy treatments. Iatrogenic sterility is often permanent and greatly impacts long-term quality of life. Ovarian tissue cryopreservation (OTC) performed before gonadotoxic treatments with subsequent autograft is a method of fertility preservation available for girls and women. Its application in prepubertal girls is of particular value as it is the only possible approach in this patient group. In addition, it does not require a delay in cancer therapy and no ovarian stimulation is needed.OBJECTIVE:The primary aim of this protocol is to help increase the implementation of ovarian tissue autografting in France. Knowledge is still lacking regarding the efficacy of ovarian transplantation in restoring ovarian function and regarding the safety of this procedure, especially the risk of cancer cell reseeding in certain types of cancer. A secondary aim of this study is to generate data to improve our understanding of these two essential aspects.METHODS:The DATOR (Development of Ovarian Tissue Autograft in Order to Restore Ovarian Function) study is ongoing in 17 university hospitals. The DATOR protocol includes the autograft of ovarian cortex fragments. Candidates are identified from an observational prospective cohort (called the Prospective Cohort of Patients Candidates for Ovarian Tissue Autograft [PERIDATOR]) of patients who have undergone OTC. Enrollment in the study is initiated at the patient's request and must be validated by the center's multidisciplinary team and by the study steering committee. The DATOR study begins with a total medical checkup. Ovarian tissue qualification and residual disease detection, if required, are performed.RESULTS:The study is ongoing. Currently, 38 patients have provided informed consent and have been entered into the DATOR study. Graft has been performed for 34 of these patients. An interim analysis was conducted on the first 25 patients for whom the period of at least 1 year posttransplantation was achieved. Out of these 25 patients, 11 women succeeded in becoming pregnant (pregnancy rate=44% [11/25]; delivery rate=40% [10/25]). Among these, 6 women conceived twice, and 1 pregnancy led to a miscarriage.CONCLUSIONS:Our preliminary analysis appears to be coherent with the accumulating body of evidence indicating the potential utility of ovarian tissue autograft for patients with premature ovarian failure. All these elements justify the pursuit of our study.TRIAL REGISTRATION:ClinicalTrials.gov NCT02846064; https://clinicaltrials.gov/ct2/show/NCT02846064.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/12944.

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.

Postpartum hemorrhage remains the leading cause of maternal death in France. Parturients in western French Guiana have specific sociodemographic features and a high rate of pathological pregnancies. The objective of this study was to determine the incidence of immediate postpartum hemorrhage (IPPH) in western French Guiana, and to describe the etiologies and risk factors.A case control study with incident cases was conducted in the Maternity Department of the Western French Guiana Hospital over a period of one year. The cases included women giving birth to a child of 22 weeks' GA and/or a child weighing 500 g, and who presented with IPPH. Two control subjects were included per case (after pairing for mode of delivery). The data were collected by questionnaire and from medical records. Multivariate analyses by logistic regression were conducted.154 cases and 308 controls were included. The incidence rate of IPPH was 6.7%. The primary etiologies were: atony, placenta retention, and cervico-vaginal lesions. The factors associated with IPPH were: past history of IPPH (ORadj = 3.36 [1.65–6.87]), pre-eclampsia (ORadj = 2.56 [1.07–6.14]), labor induction by oxytocin (ORadj = 2.03 [1.03–3.99]), the absence of managed placental delivery (ORadj = 2.46 [1.24–4.91]), a gap of more than 30 min between birth and placental delivery (ORadj = 10.92 [2.17–54.99]), and macrosomia (ORadj = 6.38 [1.97–20.67]).The incidence rate of IPPH is similar to that found in metropolitan France and in the literature. The risk factors identified here will enable the development of appropriate preventive protocols.

To evaluate the long term anatomical and reproductive outcomes of hysteroscopic treatment for T shaped uterus in patients presenting with reproductive failure.This prospective cohort study included 56 patients with a history of long-standing unexplained infertility, recurrent implantation failure (RIF), and/or recurrent pregnancy loss (RPL) who were eligible for metroplasty by office hysteroscopy. Office hysteroscopy under conscious sedation was performed. Anatomical outcomes were assessed with pre- and postoperative measurements of the transostial, isthmic and myometrial diameters and the uterine volume using three-dimensional transvaginal sonography (3D-TVS). Reproductive outcome was assessed after spontaneous or assisted conception.Hysteroscopic treatment significantly increased the volume of the uterus from a mean of 2.5 + 1 mL before surgery to 3.2 ± 1 mL by the end of 1 year as measured by 3D-TVS. According to the main indication to perform metroplasty, 20 of 32 (62.5%) patients with long standing unexplained infertility, 9 of 14 (64%) patients with RIF, and 8 of 10 (80%) patients with RPL conceived either spontaneously or with assisted reproduction.Office hysteroscopic metroplasty results in a significant long-term expansion of the uterine cavity and improved reproductive outcomes in women presenting with a T shaped uterus and poor reproductive history.

Uterine transplantation is an evolving procedure to allow for childbearing in paitents with absolute uterine factor infertility. The objective of this study was to review the existing literature using a comprehensive PubMed literature search. A systematic medical subheadings search strategy was used with the terms "uterus transplant" and "uterine transplantation". Of the 75 full-text articles assessed for eligibility, 68 were included in the qualitative synthesis. Of these, 9 were included in the meta-analysis on living donor uterine transplant, 5 on deceased donor uterine transplant, and 6 case reports of single uterine transplants. In conclusion, uterus transplant is a nascent field undergoing a rapid rate of evolution as programs mature their data and increase the number of procedures performed. The most recent publications and advances are thus summarized in this article to capture the most up-to-date information.

In Brief 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. Uterine transplantation is a major surgical innovation for the treatment of absolute uterine factor infertility, and both living and brain-dead donors will probably be necessary in view of the current scarcity and future rise in demand of uterine grafts.

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: 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.

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. (C) 2014 by American Society for Reproductive Medicine.

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.

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.

In November, 2003, a 10-year-old girl with severe homozygous sickle-cell disease was referred to our reproductive biology unit requesting cryopreservation of ovarian tissue before a myeloablative conditioning regimen followed by allogeneic haemopoietic stem-cell transplantation. 1 Bernaudin F Socie G Kuentz M et al. Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood. 2007; 110: 2749-2756 Crossref PubMed Scopus (379) Google Scholar Ovarian failure is a common adverse effect after such conditioning. 2 Thibaud E Rodriguez-Macias K Trivin C Esperou H Michon J Brauner R Ovarian function after bone marrow transplantation during childhood. Bone Marrow Transplant. 1998; 21: 287-290 Crossref PubMed Scopus (143) Google Scholar She was 142 cm tall, weighed 31 kg, and had no signs of puberty. Right oophorectomy was done by laparoscopy under general anaesthesia. The ovarian tissue was transferred to the reproductive laboratory where the cortex was isolated and dissected into 23 ovarian fragments, which were cryopreserved by the slow cooling protocol. 3 Gosden R Baird DT Wade JC Webb R Restoration of fertility to oophorectomized sheep by ovarian autografts stored at −196 degrees C. Hum Reprod. 1994; 9: 597-603 PubMed Google Scholar Microscopic analysis of one ovarian fragment showed a density of 8·6 primordial follicles per mm2.

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.

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. (Fertil Steril (R) 2010;93:2413.e15-e19. (C) 2010 by American Society for Reproductive Medicine.)