Immune Checkpoint Inhibitor Use During Pregnancy and Outcomes in Pregnant Individuals and Newborns.

Importance: With the widespread use of immune checkpoint inhibitors (ICIs), concerns about their pregnancy outcomes through maternal exposure have emerged, and clinical comparative data are lacking. Objective: To assess the risk of pregnancy-, fetal-, and/or newborn-related adverse outcomes associated with exposure to ICIs compared with exposure to other anticancer agents. Design, Setting, and Participants: In this cohort study, all reports mentioning a pregnancy-related condition and an antineoplastic agent (Anatomical Therapeutic Chemical classification group L01) used for a cancer indication registered in the World Health Organization international pharmacovigilance database VigiBase up to June 26, 2022, were extracted. Exposure: Anticancer agents, including ICIs, used during pregnancy for a cancer indication. Immune checkpoint inhibitors included blockers of programmed cell death 1 (PD1) or its ligand (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Main Outcomes and Measures: The main outcome was the reporting odds ratio (ROR) for maternal, fetal, or newborn complications in patients treated with ICIs vs any other anticancer drug. Adverse events, categorized into 45 individual maternofetal adverse outcomes, were directly mapped to Medical Dictionary for Regulatory Activities preferred terms in VigiBase. Results: A total of 3558 reports (ICI: 91 [2.6%]; other anticancer drugs: 3467 [97.4%]) were included in the analysis. In the ICI group, most reports were from the US (60 [65.9%]), and the mean (SD) patient age was 28.9 (10.2) years; in 24 of 55 reports with data on cancer type (43.6%), patients were treated for melanoma. The molecules involved in the ICI group were anti-PD1 (58 reports [63.7%]), anti-PD1 plus anti-CTLA4 (15 [16.5%]), anti-CTLA4 (13 [14.3%]), anti-PD-L1 (4 [4.4%]), and anti-PD1 plus anti-lymphocyte activation gene 3 (1 [1.1%]). An ICI was used in combination with a non-ICI anticancer agent in 10 participants (11.0%). Compared with other anticancer drugs, none of the 45 adverse outcomes identified were overreported in the group exposed to ICIs. However, preterm birth was significantly overreported for the anti-PD1 plus anti-CTLA4 combination compared with other anticancer drugs (12 of 15 [80.0%] vs 793 of 3452 [23.0%]; ROR, 13.87; 95% CI, 3.90-49.28; P < .001) but not for anti-PD-L1 or anti-CTLA4 monotherapy. Three reports of possibly immune-related maternofetal events were identified: 1 case of maternal antiphospholipid syndrome leading to spontaneous abortion, 1 case of pneumonitis leading to neonatal respiratory distress syndrome and death, and 1 case of transient congenital hypothyroidism. Conclusions and Relevance: In this cohort study of 91 individuals exposed to ICIs during pregnancy, ICI exposure was not associated with overreporting of specific adverse pregnancy, fetal, and/or newborn outcomes compared with other anticancer treatments. However, due to possible rare immune-related neonatal adverse events, ICI use in pregnant women should be avoided when possible, especially the anti-PD1 plus anti-CTLA4 combination.

Postmenopausal endometriosis: a challenging condition beyond menopause.

IMPORTANCE AND OBJECTIVE: Postmenopausal endometriosis is a complex condition that challenges the conventional belief that endometriosis resolves with menopause. Despite the cessation of menstruation, a subset of women continues to experience or develop endometriosis-related symptoms during the postmenopausal period. Thus, this review aimed to shed light on postmenopausal endometriosis, exploring its clinical features, diagnostic considerations, management approaches, and the potential impact on women's health. METHODS: PubMed/Medline, Scopus, and Web of Science databases were used for the research, with only articles in English language, using the following terms: "postmenopausal endometriosis," "menopause," "management," "treatment," and "quality of life," from inception to 2023. DISCUSSION AND CONCLUSION: The clinical features of postmenopausal endometriosis include persistent or recurrent pelvic pain, dyspareunia, bowel, or urinary symptoms and, occasionally, abnormal vaginal bleeding. The absence of menstrual cycles presents a diagnostic challenge, as the traditional diagnostic criteria for endometriosis rely on menstrual patterns. Visual cues may be less evident, and the symptoms often overlap with other gynecological conditions, necessitating a thorough evaluation to differentiate postmenopausal endometriosis from other potential causes. Management approaches for postmenopausal endometriosis encompass surgical intervention, hormonal therapies, pain management, and individualized care. Postmenopausal endometriosis significantly impacts the quality of life, sexual health, and long-term well-being of women. Understanding the clinical features, diagnostic challenges, and management approaches of postmenopausal endometriosis is crucial for healthcare professionals to provide effective care and to improve the quality of life of women affected by this condition.

Pollution and endometriosis: A deep dive into the environmental impacts on women's health.

BACKGROUND: The interaction between pollution and endometriosis is a pressing issue that demands immediate attention. The impact of pollution, particularly air and water pollution, or occupational hazards, on hormonal disruption and the initiation of endometriosis remains a major issue. OBJECTIVES: This narrative review aims to delve into the intricate connection between pollution and endometriosis, shedding light on how environmental factors contribute to the onset and severity of this disease and, thus, the possible public health policy implications. DISCUSSION: Endocrine-disrupting chemicals (EDCs) in pollutants dysregulate the hormonal balance, contributing to the progression of this major gynaecological disorder. Air pollution, specifically PM2.5 and PAHs, has been associated with an increased risk of endometriosis by enhancing chronic inflammation, oxidative stress, and hormonal imbalances. Chemical contaminants in water and work exposures, including heavy metals, dioxins, and PCBs, disrupt the hormonal regulation and potentially contribute to endometriosis. Mitigating the environmental impact of pollution is required to safeguard women's reproductive health. This requires a comprehensive approach involving stringent environmental regulations, sustainable practices, responsible waste management, research and innovation, public awareness, and collaboration among stakeholders. CONCLUSION: Public health policies have a major role in addressing the interaction between pollution and endometriosis in a long-term commitment.

Association of severe postpartum hemorrhage and development of psychological disorders: Results from the prospective and multicentre HELP MOM study.

OBJECTIVE: Post-partum hemorrhage (PPH) is the leading preventable cause of worldwide maternal morbidity and mortality. Risk factors for psychological disorders following PPH are currently unknown. HELP-MOM study aimed to determine the incidence and identify risk factors for psychological disorders following PPH. METHODS: HELP-MOM study was a prospective, observational, national, and multicentre study including patients who experienced severe PPH requiring sulprostone. The primary endpoint was the occurrence of psychological disorders (anxiety and/or post-traumatic disorder and/or depression) following PPH, assessed at 1, 3, and 6 months after delivery using HADS, IES-R, and EPDS scales. RESULTS: Between November 2014 and November 2016, 332 patients experienced a severe PPH and 236 (72%) answered self-questionnaires at 1, 3, and 6 months. A total of 161 (68%) patients declared a psychological disorder following severe PPH (146 (90.1%) were screened positive for anxiety, 96 (58.9%) were screened positive for post-traumatic stress disorder, and 94 (57.7%) were screened positive for post-partum depression). In multivariable analysis, the use of intra-uterine tamponnement balloon was associated with a lower risk to be screened positive for psychological disorder after severe PPH (OR = 0.33 [IC95% 0.15-0.69], p = 0.004, and after propensity score matching (OR=0.34 [IC95% 0.12-0.94], p = 0.04)). Low hemoglobin values during severe PPH management were associated with a higher risk of being screened positive for psychological disorders. Finally, we did not find differences in desire or pregnancy between patients without or with psychological disorders occurring in the year after severe PPH. DISCUSSION: Severe PPH was associated with significant psychosocial morbidity including anxiety, post-traumatic disorder, and depression. This should engage a psychological follow-up. Large cohorts are urgently needed to confirm our results. REGISTRATION: ClinicalTrials.gov under number NCT02118038.

[Uterine transplantation: a treatment for absolute uterine infertility]. / Transplantation utérine : un traitement pour l'infertilité absolue d'origine utérine.

UTERINE TRANSPLANTATION: A TREATMENT FOR ABSOLUTE UTERINE INFERTILITY. Uterine transplantation (UT) is the first proposed treatment for absolute uterine infertility. It is also the first organ transplant of a transitory nature performed for a non-vital indication: the ability to carry a child and give birth. Today, with about one hundred transplants performed worldwide, uterine transplantation is at the crossroads between the experimental phase and current practice. The first uterine transplant was performed in France in 2019 at the Foch Hospital (Suresnes). It allowed the birth of two healthy little girls in 2021 and 2023. The second transplant was performed in September 2022. A state of the art allows to review the steps necessary for a successful transplantation from donor and recipient selection to surgery, immunosuppressive treatment and pregnancies. Potential future developments could make it possible to simplify this complex surgery, which is not without raising ethical questions.

TRANSPLANTATION UTÉRINE : UN TRAITEMENT POUR L'INFERTILITÉ ABSOLUE D'ORIGINE UTÉRINE. La transplantation utérine est le premier traitement proposé pour traiter l'infertilité absolue d'origine utérine. C'est également la première transplantation d'organe de nature transitoire réalisée pour une indication non vitale : la possibilité de porter un enfant et de lui donner naissance. Aujourd'hui, avec une centaine de greffes réalisées dans le monde, la transplantation utérine se situe à un carrefour entre la phase expérimentale et la pratique clinique. La première transplantation utérine a été réalisée en France en 2019 à l'hôpital Foch (Suresnes). Elle a permis la naissance de deux petites filles en bonne santé en 2021 et 2023. La deuxième greffe a été réalisée en septembre 2022. Un état de l'art permet de faire le point sur les étapes nécessaires au succès de la greffe, de la sélection des donneuses et des receveuses à la chirurgie en passant par le traitement immunosuppresseur et les grossesses. Des évolutions potentielles pourraient permettre à l'avenir de simplifier cette chirurgie complexe, qui n'est pas sans soulever des questions éthiques.

Uterus transplantation: from research, through human trials and into the future.

Women suffering from absolute uterine factor infertility (AUFI) had no hope of childbearing until clinical feasibility of uterus transplantation (UTx) was documented in 2014 with the birth of a healthy baby. This landmark accomplishment followed extensive foundational work with a wide range of animal species including higher primates. In the present review, we provide a summary of the animal research and describe the results of cases and clinical trials on UTx. Surgical advances for graft removal from live donors and transplantation to recipients are improving, with a recent trend away from laparotomy to robotic approaches, although challenges persist regarding optimum immunosuppressive therapies and tests for graft rejection. Because UTx does not involve transplantation of the Fallopian tubes, IVF is required as part of the UTx process. We provide a unique focus on the intersection between these two processes, with consideration of when oocyte retrieval should be performed, whether, and for whom, preimplantation genetic testing for aneuploidy should be used, whether oocytes or embryos should be frozen and when the first embryo transfer should be performed post-UTx. We also address the utility of an international society UTx (ISUTx) registry for assessing overall UTx success rates, complications, and live births. The long-term health outcomes of all parties involved-the uterus donor (if live donor), the recipient, her partner and any children born from the transplanted graft-are also reviewed. Unlike traditional solid organ transplantation procedures, UTx is not lifesaving, but is life-giving, although as with traditional types of transplantation, costs, and ethical considerations are inevitable. We discuss the likelihood that costs will decrease as efficiency and efficacy improve, and that ethical complexities for and against acceptability of the procedure sharpen the distinctions between genetic, gestational, and social parenthood. As more programs wish to offer the procedure, we suggest a scheme for setting up a UTx program as well as future directions of this rapidly evolving field. In our 2010 review, we described the future of clinical UTx based on development of the procedure in animal models. This Grand Theme Review offers a closing loop to this previous review of more than a decade ago. The clinical feasibility of UTx has now been proved. Advancements include widening the criteria for acceptance of donors and recipients, improving surgery, shortening time to pregnancy, and improving post-UTx management. Together, these improvements catalyze the transition of UTx from experimental into mainstream clinical practice. The procedure will then represent a realistic and accessible alternative to gestational surrogacy for the treatment of AUFI and should become part of the armamentarium of reproductive specialists worldwide.

Monkeypox Virus Infection in 18-Year-Old Woman after Sexual Intercourse, France, September 2022.

A monkeypox virus outbreak has spread worldwide since April 2022. We report a young woman in France positive for monkeypox virus transmitted through oral and vaginal sex. Ulceronecrotic lesions developed intravaginally and around her vulva. Health professionals should become familiar with all aspects of infection from this virus, including possible vertical transmission.

Transgender Males as Potential Donors for Uterus Transplantation: A Survey.

Uterus transplantation is a new treatment for patients with absolute uterine infertility that is conducted in order to enable them to carry their own pregnancy. One of the limitations for its development is donor availability. Some transgender males undergo a hysterectomy in the gender-affirming surgery process, and might be interested in donating their uterus for transplantation. In this manuscript, we report the results of a survey designed to determine the attitudes of such individuals regarding donation of their uterus for this purpose. Over 32 years (January 1989-January 2021), 348 biological women underwent hysterectomy at our hospital as part of gender-affirming surgery. The survey was sent to 212 of the 348 prospective participants (for 136, we lacked postal or email addresses). Among the 212 surveys sent, we obtained responses from 94 individuals (44%): 83 (88.3%) stated they would agree to donate, of whom 44 would do so for altruism, 23 for the usefulness of the gesture and 16 out of understanding of the desire to have a child; 63 (75.5%) wanted to know the recipient and 45 (54.2%) wanted to know the result of the donation. According to this survey, a high proportion of transgender males surveyed would be interested in donating their uterus for uterus transplantation.

Improvement of Post-Operative Quality of Life in Patients 2 Years after Minimally Invasive Surgery for Pain and Deep Infiltrating Endometriosis.

This study addressed the improvement in the quality of life of patients 2 years after minimally invasive surgery for painful deep infiltrating endometriosis (DIE), evaluated with EHP-5 (Endometriosis Health Profile-5) scores and the intensity of dysmenorrhea and dyspareunia. This was a retrospective study, performed in a referral centre for endometriosis, between January 2010 and January 2019. EHP-5 scores were complete for 54 patients, and two subgroups were analysed: classic laparoscopy (CL) vs. robotic laparoscopy (RL), and conservative surgery (ConservS) vs. total surgery (TS). There was an important decrease in 2-year post-operative EHP-5 scores in the global population (pre-op: 61.36 (42.18−68.75) and 2-year post-op: 20.45 (0−38.06); p < 0.001). The Visual Analogic Scale (VAS) was also lower for dysmenorrhea (pre-op: 8 (7−9.75) vs. 2-year post-op: 3 (2−5.25); p < 0.001) and dyspareunia (pre-op: 6 (3.1−8.9) vs. 2-year post-op: 3 (0−6); p < 0.001). In the subgroup analysis, EHP-5 scores were improved in the RL group (pre-op: 65.9 (59.09−71.02) vs. 2-year post-op: 11.4 (0−38.06); p < 0.001) and the CL group (pre-op: 50 (34.65−68.18) vs. 2-year post-op: 27.27 (14.20−40.90); p < 0.001), with a slight advantage for RL (p = 0.04), and the same improvements were found for ConservS (pre-op: 61.4 (38.06−71.59) vs. 2-year post-op: 22.7 (11.93−38.07); p < 0.001) and TS groups (pre-op: 61.59 (51.70−68.75) vs. 2-year post-op: 13.63 (0−44.30); p < 0.001). Minimally invasive surgery improved the quality of life for DIE patients 2 years after surgery, and conservative surgery showed comparable results to total surgery.

Analysis of Predictive Factors for Successful Vascular Anastomoses in a Sheep Uterine Transplantation Model.

Uterine transplantation is becoming an increasingly realistic therapeutic for uterine infertility. Surgical training on large animal models such as sheep is a prerequisite for establishing a program in humans. The objective of our study was to analyze the predictive factors for successful vascular anastomoses. We performed 40 autotransplants that involved end-to-side anastomoses from the uterine to the external iliac vessels. We analyzed vessel results in terms of success or failure; a total of 78.7% of arterial and 82.9% of venous anastomoses were successful in the immediate postoperative period. In multivariate analysis, independent factors associated with immediate successful vein anastomoses were as follows: a short warm ischemia time (<2 h, OR = 0.05; 95% CI [0.003−0.88], p = 0.04), the absence of any anastomotic complications (OR = 0.06; 95% CI [0.003−0.099], p = 0.049), and their realization by a vascular surgeon (OR = 29.3; 95% CI [1.17−731.9], p = 0.04). Secondly, we showed that an increase in lactate levels greater than 2.72 mmol/L, six hours after reperfusion was predictive of failure, with a sensibility of 85.7% and a specificity of 75.0%. In order to perfect the management of vascular anastomoses by a vascular surgeon, training on animal models and in microsurgery are mandatory in establishing a uterine transplantation program in humans.

Plasticity of natural killer cells in pregnant patients infected with SARS-CoV-2 and their neonates during childbirth.

The COVID-19 pandemic has occurred due to infection caused by the SARS-CoV-2 coronavirus, which impacts gestation and pregnancy. In SARS-CoV-2 infection, only very rare cases of vertical transmission have been reported, suggesting that fetal immune imprinting due to a maternal infection is probably a result of changes in maternal immunity. Natural killer (NK) cells are the leading maternal immune cells that act as a natural defense system to fight infections. They also play a pivotal role in the establishment and maintenance of pregnancy. While peripheral NK cells display specific features in patients infected with SARS-CoV-2 in the general population, information remains elusive in pregnant mothers and neonates. In the present study, we analyzed the characteristics of NK cells isolated from both neonatal umbilical cord blood and maternal peripheral blood close to the time of delivery. Phenotype and functions were compared in 18 healthy pregnant women and 34 COVID-19 patients during pregnancy within an ongoing infection (PCR+; N = 15) or after recovery (IgG+PCR-; N = 19). The frequency of NK cells from infected women and their neonates was correlated with the production of inflammatory cytokines in the serum. The expression of NKG2A and NKp30, as well as degranulation of NK cells in pregnant women with ongoing infection, were both negatively correlated to estradiol level. Furthermore, NK cells from the neonates born to infected women were significantly decreased and also correlated to estradiol level. This study highlights the relationship between NK cells, inflammation, and estradiol in patients with ongoing infection, providing new insights into the impact of maternal SARS-CoV-2 infection on the neonate.

Evolving clinical challenges in uterus transplantation.

Before the first live birth following uterus transplantation (UTx) in 2014, the 1-2% of women with an absent or non-functional uterus had no hope of childbearing. With 64 cases of UTx and 34 births reported in the scientific literature, this emerging technology has the potential for translation into mainstream clinical practice. However, limitations currently include donor availability, recipient suitability, surgical challenges regarding success and complications, and recipient management after UTx and during pregnancy. This review considers these challenges and ways to overcome them so that UTx could become part of the reproductive specialist's armamentarium when counselling patients with uterine factor infertility.

Pregnancies and Gynecological Follow-Up after Solid Organ Transplantation: Experience of a Decade.

In recent years, solid organ transplantations, such as kidney or lung grafts, have been performed worldwide with an improvement of quality of life under immunosuppressive therapy and an increase in life expectancy, allowing young women to consider childbearing. In the current study, we conduct a retrospective study in two French centers for kidney and lung transplantations to evaluate the rate and outcomes of pregnancies, contraception and gynecological monitoring for women under 40 years old who underwent solid organ transplantation. Among 210 women, progestin was the most widely used contraceptive method. Of the 210 women, 24 (11.4%) conceived 33 pregnancies of which 25 (75.8%) were planned with an immunosuppressant therapy switch. Of the 33 pregnancies, 7 miscarried (21.2%) and 21 (63.7%) resulted in a live birth with a high rate of pre-eclampsia (50%). No graft rejections were observed during pregnancies. Among the deliveries, 19 were premature (90.5%, mostly due to induced delivery) and the C-section rate was high (52.4%). No particular pathology was identified among newborns. We conclude that pregnancies following solid organ transplantation are feasible, and while they are at an increased risk of pre-eclampsia and prematurity, they should still be permitted with close surveillance by a multidisciplinary care team.

Impact of COVID-19 on Subclinical Placental Thrombosis and Maternal Thrombotic Factors.

BACKGROUND: In the context of the SARS-CoV-2 pandemic, our interest was to evaluate the effect of COVID-19 during pregnancy on placenta and coagulation factors. METHODS: a prospective cohort study between January and July 2021 of 55 pregnant women stratified into: Group O, 16 patients with ongoing SARS-CoV-2 infection at delivery; Group R, 21 patients with a history of SARS-CoV-2 infection during pregnancy but who recovered prior to delivery; Group C, 18 control patients with no infection at any time. All women had nasopharyngeal SARS-CoV-2 RT-PCR tests performed within 72 h of delivery. Obstetrical complications were recorded and two physiological inhibitors of coagulation, protein Z (PZ) and dependent protease inhibitor (ZPI), were analyzed in maternal and cord blood. All placentae were analyzed by a pathologist for vascular malperfusion. RESULTS: No patient in any group had a severe COVID-19 infection. More obstetrical complications were observed in Group O (O: n = 6/16 (37%), R: n = 2/21 (10%), C: n = 1/18 (6%), p = 0.03). The incidence of placental vascular malperfusion was similar among the groups (O: n = 9/16 (56%), R: n = 8/21 (42%), C: n = 8/18 (44%), p = 0.68). No PZ or ZPI deficiency was associated with COVID-19. However, an increased ZPI/PZ ratio was observed in neonates of Group R (O: 82.6 (min 41.3-max 743.6), R: 120.7 (29.8-203.5), C: 66.8 (28.2-2043.5), p = 0.04). CONCLUSION: COVID-19 was associated with more obstetrical complications, but not an increased incidence of placental lesions or PZ and ZPI abnormalities.

Case Report: Post-Partum SARS-CoV-2 Infection After the First French Uterus Transplantation.

Absolute uterus factor infertility, whether congenital or acquired, renders the woman unable to carry a child. Although uterus transplantation (UTx) is being increasingly performed as a non-vital procedure to address this unfortunate condition, the immunosuppression required presents risks that are further compounded by pregnancy and during the puerperium period. These vulnerabilities require avoidance of SARS-CoV-2 infection in pregnant UTx recipients especially during the third trimester, as accumulating evidence reveals increased risks of morbidity and mortality. Here we describe a successful UTx case with delivery of a healthy child, but in which both mother and neonate developed asymptomatic SARS-CoV-2 infection seven days after RNA vaccination, on day 35 post-partum. Although the patient was successfully treated with a combination therapy comprised of two monoclonal antibodies, this case highlights the challenges associated with performing UTx in the era of Covid-19. More broadly, the risks of performing non-vital organ transplantation during a pandemic should be discussed among team members and prospective patients, weighing the risks against the benefits in improving the quality of life, which were considerable for our patient who achieved motherhood with the birth of a healthy child.

Impact of COVID-19 infection in pregnancy and neonates: A case control study.

OBJECTIVE: To evaluate maternal and neonatal outcomes of pregnant women who were infected by COVID-19 during pregnancy. STUDY DESIGN: A Case control retrospective study was conducted in an Obstetrical Department of a west Parisian area during the first year of COVID-19 pandemic. Maternal and neonatal outcomes were compared between a group of women infected by the SARS-CoV-2 virus during pregnancy (March 2020- February 2021) and a control group of women delivering before pandemic. They were matched according to age and parity. Subgroups of SARS-CoV-2 infection occurring before vs after 37 weeks of gestations and symptomatic vs asymptomatic patients were analyzed. The rate of preterm birth, preeclampsia, placental abruption and stillbirth were compared between the year of pandemic and the year before for all deliveries. RESULTS: Maternal and neonatal outcomes were similar. Among the 86 pregnant women with SARS-CoV-2 infection, five were admitted to Hospital (5.8%). One was transferred in intensive care unit for respiratory distress (1.2%). All patients had favorable outcomes. Patients with symptoms had more associated comorbidities (34.5%, n = 20/58, with symptoms, vs 9,1%, n = 2/22, without symptoms, p = 0.023). No differences in preeclampsia, placenta abruption and stillbirth, but less preterm births (4.9%, n = 160/3383 vs 6.2%, n = 209/3235, p = 0.04) were observed between the year of pandemic and the year before. CONCLUSION: There were few complications associated with COVID-19 infection among pregnant patients and their neonates. A low rate of associated comorbidities, a good access to healthcare services in this area and the small sample size of patients could explain these results.

Involving Animal Models in Uterine Transplantation.

Background: Absolute uterine factor infertility affects 0. 2% women of childbearing age around the world. Uterine transplantation (UTx) is a promising solution for many of them since the first birth from UTx was described by the Swedish team in 2014. The success of Utx in humans has become possible after a systematic and meticulous approach involving years of research on animal models. To date, more than 80 UTx procedures have been performed worldwide and 30 children were born. Material and Method: This review summarizes the research preparation conducted in animals before beginning UTx in humans. It focuses on the advantages and limits of each animal model, their place in surgical training, and current contribution in research to improve UTx successes in humans. The different steps in the process of UTx have been analyzed, such as imaging, surgery, ischemia-reperfusion effects, rejection markers, immunosuppressive treatment, and pregnancy. Conclusion: Animal models have played an essential role in the implementation of UTx, which is a highly complex procedure. While respecting the 3R requirements (replacement, refinement, and reduction), the surgical training using large animal models, such as notably ewes remain irreplaceable for teams wishing to initiate a UTx program. Furthermore, animal models are still mandatory in current research to improve the success rates of UTx in humans as well as to reduce the morbidity associated with this experimental infertility treatment.

Procurement of Uterus in a Deceased Donor Multi-Organ Donation National Program in France: A Scarce Resource for Uterus Transplantation?

Uterus transplantation is a new possibility for women suffering from absolute uterine infertility to become pregnant and have children. In the case of a deceased donor, a list of exclusion criteria is defined to ensure the high quality of the uterus graft. This study evaluates the number of potentially available uterus grafts based on the pre-defined exclusion criteria in a national deceased donor multi-organ donation program in France. We analyzed the data reported in the CRISTAL database regarding all women aged 18 to 60 on whom organ procurement was performed between 2014 and 2019. Potential deceased women donors were classified into three categories: very ideal donor, ideal donor, and expanded criteria donor. Between 2014 and 2019, 4544 women underwent organ procurement. Using the very ideal donor, ideal donor, and expanded criteria donor classification, we found that, respectively, only 124, 264, and 936 donors were potentially eligible for UTx. This represents 2.8 per million people (PMP) very ideal donors, 3.8 PMP ideal donors, 8.6 PMP expanded criteria donors (ECDs). The restricted number of grafts requires a complementary strategy of living and deceased donors to meet the demand of all women with AUI.