ABSTRACT
BACKGROUND: Uterus transplantation (UTx) is an emerging therapy for women with uterine infertility. However, critical questions remain with this procedure including the mechanisms involved in graft rejection. METHODS: In this study, we analyzed the immune profile of ectocervical biopsies from 5 patients after UTx before and during their first episode of rejection using RNA sequencing, quantitative polymerase chain reaction, and imaging mass cytometry. RESULTS: We identified 530 upregulated and 207 downregulated genes associated with graft rejection. Enrichment databases revealed abnormalities of skin-associated genes and the immune system, in particular activation of T and B lymphocytes, and macrophages. Imaging mass cytometry confirmed these observations; in cervical biopsies of 3 women, rejection was associated with the presence of B-cell structures linked to tertiary lymphoid structures, and 2 biopsies from 1 woman with severe rejection episodes and poor prognosis of graft function (repeated miscarriage and implantation failures) were associated with an accumulation of HLA-DR- macrophages, producing granzyme B at the surface of the epithelium. CONCLUSIONS: We showed that rejection of a UTx graft was associated with major alterations of immune markers including the involvement of tertiary lymphoid structures, the most organized of which may be a sign of chronic rejection, and with an increase in HLA-DR- macrophages expressing granzyme B in the case of grade 3 rejection episodes according Mölne's classification. We identified potential emerging biomarkers to predict or diagnose graft rejection (Keratin 1 granzyme B, IL1ß). These findings could lead to development of improved strategies for the identification, prevention, and/or treatment of uterus graft rejection.
ABSTRACT
Adenomyosis is a benign condition commonly encountered in patients with infertility. While the definitive surgical management is hysterectomy, conservative surgical management is gaining attention in patients desiring future fertility. This review explores whether the surgical treatment of adenomyosis affects fertility outcomes for patients trying to conceive. The PubMed and Medline databases were searched using the keywords: "adenomyosis", "surgery", "radiofrequency", "infertility", "pregnancy", "sterility", "conception", "miscarriage", and "endometrial receptivity". Abstracts were screened, and relevant articles were selected for review. This review reveals that surgery appears to improve fertility outcomes with or without medical therapy; however, the risk of uterine rupture remains high and the best technique to reduce this risk is still not known. More studies are needed to formulate the best surgical approach for preserving fertility in treating adenomyosis and to establish standardized guidelines.
ABSTRACT
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.
Subject(s)
Endometriosis , Postmenopause , Quality of Life , Humans , Endometriosis/therapy , Endometriosis/complications , Endometriosis/diagnosis , Female , Postmenopause/physiology , Dyspareunia/etiology , Dyspareunia/therapy , Pelvic Pain/etiology , Pelvic Pain/therapy , Women's Health , Middle AgedABSTRACT
Fertility preservation for cancer has existed for three decades. The advent of highly effective oocyte cryopreservation by vitrification has paved the way for social fertility preservation. The options are discussed.
Subject(s)
Fertility Preservation , Humans , Cryopreservation , Oocytes , Counseling , VitrificationABSTRACT
The improvements accomplished in assisted reproductive technology have emphasized more than ever the role played by chronological age, notably for predicting oocyte quality. Studies in cellular aging have directed research on telomere length measurements as possible markers of functional aging and, notably, female reproductive outcomes. Although further research is still needed, encouraging results are already available on the possibility that leucocyte telomere length may be a useful parameter for assessing reproductive potential in aging women.
Subject(s)
Aging , Reproduction , Female , Humans , Aging/genetics , Reproduction/genetics , Cellular Senescence/genetics , Oocytes , Telomere/geneticsABSTRACT
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.
Subject(s)
Air Pollution , Endometriosis , Environmental Pollutants , Female , Humans , Endometriosis/etiology , Environmental Pollutants/toxicity , Women's Health , Air Pollution/adverse effects , EnvironmentABSTRACT
Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments have been proposed, but still, no guidelines directing the management of adenomyosis are available. While a hysterectomy is typically regarded as the definitive treatment for adenomyosis, the scarcity of high-quality data leaves patients desiring fertility with limited conservative options. Based on the available data, the levonorgestrel-IUD appears to offer the most favorable outcomes. Other treatments, including GnRH antagonists, dienogest, prolactin, and oxytocin modulators, show promise; however, further data are required to establish their efficacy definitively. Furthermore, there are many emerging therapies that have been developed that seem worthy of consideration in the near future. The aim of this narrative review was to explore the current medical treatments available for adenomyosis and to provide a glimpse of future therapies under assessment. For this scope, we performed a literature search on PubMed and Medline from incept to September 2022 using the keywords: "medical treatment", "non-steroidal anti-inflammatory", "progesterone intrauterine device", "dienogest", "combined oral contraceptives", "gonadotropin releasing hormone agonist", "gonadotropin releasing hormone antagonist", "danazol", "aromatase inhibitors", "ulipristal acetate", "anti-platelet therapy", "dopamine", "oxytocin antagonists", "STAT3", "KRAS", "MAPK", "micro-RNA", "mifepristone", "valproic acid", "levo-tetrahydropalamatine", and "andrographolide". The search was limited to articles in English, with subsequent screening of abstracts. Abstracts were screened to select relevant studies.
ABSTRACT
Endometriosis, traditionally associated with cisgender women, should be recognized as a significant issue for transgender men. This perspective highlights the need to address the unique experiences and challenges faced by transgender men with endometriosis. Diagnostic difficulties arise due to hormone therapy and surgical interventions, which can alter symptoms. Limited research in transgender men undergoing hysterectomy further complicates the understanding of endometriosis in this population. Healthcare providers must be aware of these challenges and adapt the diagnostic approaches accordingly. Education and inclusive care are essential to ensure timely and appropriate management of endometriosis in transgender men, ultimately improving their quality of life.
ABSTRACT
Objectives: The goal of this study was to assess the effect of unilateral salpingectomy on the number of mature follicles in the ipsilateral ovary during an assisted reproductive technology (ART) stimulation cycle, as compared to the contralateral ovary. Methods: This was a retrospective, single-center, case-control cohort study conducted from 2017 to 2022. Patients from 18 to 43 years old who underwent at least one ART cycle before and after a unilateral salpingectomy were included. The number of recruited follicles, including mature (≥16 mm) and intermediate follicles (13-15.5 mm), on the salpingectomy side (case) were compared to those present on the contralateral ovary (control) during an ART attempt. To take into account the inter-ovarian variability, the comparison was performed on two ART cycles, performed before then after the salpingectomy. Results: Overall, 24 patients were included in our study. While the number of mature follicles was similar in both ovaries before surgery, the mean number of mature follicles was significantly reduced after salpingectomy in the operated side, as compared to the control side, being, respectively 3.00 vs. 5.08 (p = 0.048). There was no significant difference between the intermediate and total recruited follicles. Conclusions: Our study suggests that salpingectomy may impact the follicle recruitment on the ipsilateral side by altering the vascularization during mesosalpinx coagulation. Gynecologists should be mindful of this concept and accurately set surgical indications. Beyond the indication, this emphasizes the critical role of having infertility surgeons sensitive to fertility preservation for optimal management of ART patients. Further studies with larger patient populations are required to confirm these results.
ABSTRACT
Adenomyosis is a commonly diagnosed benign condition characterized by the presence of ectopic endometrial glands within the underlying myometrium. The most common presenting signs and symptoms are abnormal uterine bleeding, chronic pelvic pain, and infertility. The clinical relevance of this condition is evident in both medical and surgical care. Histopathology and imaging studies are used for the diagnosis and classification of adenomyosis, which are hallmarks of the advancement of our ability to diagnose adenomyosis. Importantly, the diagnosis and classification of adenomyosis lacks standardization due to the nature of imaging techniques, features of adenomyosis, and the clinical spectrum of adenomyosis. We reviewed the literature to summarize the available classification systems for adenomyosis and highlight the different imaging approaches and histologic criteria used in diagnosis. Despite the high prevalence of the disease, there is no clear consensus on one classification system. We provide a review of some of the classification systems available and discuss their strengths and limitations.
Subject(s)
Adenomyosis , Endometrial Neoplasms , Endometriosis , Female , Humans , Endometriosis/diagnosis , Adenomyosis/complications , Adenomyosis/diagnosis , EndometriumABSTRACT
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.
Subject(s)
Infertility, Female , Pregnancy , Animals , Child , Humans , Female , Infertility, Female/surgery , Infertility, Female/etiology , Uterus/transplantation , Living Donors , Embryo Transfer/adverse effects , Live BirthABSTRACT
McCune-Albright syndrome (MAS) is a rare genetic disease affecting multiple organs, including endocrine tissues. This endocrinopathy is sometimes responsible for infertility, as it may induce an independent functioning of the ovaries leading to anovulatory cycles. This case report describes the infertility journey of a 22-year-old female who had early puberty and irregular periods with high estrogen and progesterone levels, low FSH and LH (on day 3 of her menstrual cycle), and a multi-cystic right ovary. She received several infertility treatments: initially in vitro oocyte maturation (IVM) followed by cyst transvaginal ultrasound-guided aspiration, all unsuccessful. A right hemi-ovariectomy was performed that eventually restored regular cycles and made it possible to perform ovarian stimulation (OS) and in vitro fertilization (IVF). Live birth was obtained after the first embryo transfer.
Subject(s)
Fibrous Dysplasia, Polyostotic , Infertility, Female , Infertility , Female , Humans , Fibrous Dysplasia, Polyostotic/complications , Fibrous Dysplasia, Polyostotic/genetics , Fertilization in Vitro/adverse effects , Ovary , In Vitro Oocyte Maturation Techniques , Infertility/complications , Infertility, Female/therapy , Infertility, Female/etiologyABSTRACT
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.
Subject(s)
Infertility , Organ Transplantation , Child , Female , Pregnancy , Humans , Tissue Donors , France , HospitalsABSTRACT
PURPOSE: To assess the value of having an onsite genetic counseling service integrated into an assisted reproductive technology (ART) center. METHODS: Since January 2021, we have offered genetic counseling at our ART center for couples whose medical history suggests risk of transmission of a genetic disorder. The percentage of couples referred for genetic counseling, the distribution of couples according to reasons for consultation, the mode of transmission in cases of Mendelian disorders, and the frequency of mutations for those with identified genetic disorders were determined. RESULTS: In an 18-month period, 150 of 1340 couples (11.2%) enrolled for ART treatment were referred to the genetic counseling unit. Two-thirds (99/150, 66.0%) were referred for a known genetic risk, a family history of a genetic disorder or chromosomal abnormality, a serious condition of unknown cause, or consanguinity. The remaining couples had a putative genetic risk (diminished ovarian reserve, high incidence of oocyte immaturity, recurrent abortion, or severe male infertility). Of the 99 with known genetic risk, 62 (62.7%), were approved for ART treatment, 23 (23.2%) were recommended prenatal or preimplantation testing, and 14 (14.1%) were referred for further testing before undergoing ART. CONCLUSIONS: Our findings reveal great value in having an on-site genetic counseling unit for referral of ART patients. Such a unit makes the ART process smoother and safer for couples, and it lightens the burden of ART staff by removing responsibilities for which they are neither trained, nor should they have to assume.
Subject(s)
Genetic Counseling , Reproductive Techniques, Assisted , Pregnancy , Humans , Female , Male , Prospective Studies , Chromosome Aberrations , MutationABSTRACT
BACKGROUND: Lower rates of successful trial of labor after cesarean (TOLAC) in association with fetal macrosomia were previously reported. This study aimed to compare TOLAC to elective caesarean delivery (CD) in women with estimated fetal weight large for gestational age (eLGA) and a prior CD. Primary outcome was to analyse the mode of delivery in case of TOLAC. Secondary outcome was to compare maternal and foetal morbidity. METHODS: We conducted a retrospective, descriptive, multicentric, cohort study in five maternity units between January and December 2020. Inclusion criteria were: women with a single prior CD and eLGA or neonatal weight > 90th percentile with singleton pregnancy and gestational age ≥ 37 weeks. MAIN OUTCOME MEASURES: rate of vaginal delivery, maternal and fetal morbidity including: shoulder dystocia, neonatal hospitalization, fetal trauma, neonatal acidosis, uterine rupture, 3rd and 4th perineal tears, post-partum hemorrhage, and a need for blood transfusion. RESULTS: Four hundred forty women met inclusion criteria, including 235 (53.4%) eLGA. 170 (72.3%) had a TOLAC (study group) and 65 (27.7%) an elective CD (control). 117 (68.82%) TOLAC had a vaginal delivery. No significant differences were found between the two groups in the rates of: postpartum haemorrhage, transfusion, Apgar score, neonatal hospitalization, and foetal trauma. Cord lactate was higher in the case of TOLAC (3.2 vs 2.2, p < 0.001). Median fetal weight was 3815 g (3597-4085) vs. 3865 g (3659-4168): p = 0.068 in the study vs. controls group respectively. CONCLUSION: TOLAC for eLGA fetuses is legitimate because there is no difference in maternal-fetal morbidity, and the CD rate is acceptable.