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Women suffering from absolute uterine factor infertility (AUFI), due to either lack of a uterus or one unable to sustain neonatal viability, presented as one of the last frontiers in conquering infertility. Following systematic animal research for over a decade, uterus transplantation was tested as a treatment for AUFI in 2012, which culminated in the first human live birth in 2014. The development of uterus transplantation from mouse to human has followed both the Moore criteria for introduction of a surgical innovation and the IDEAL concept for evaluation of a novel major surgical procedure. In this article we review the important preclinical animal and human studies that paved the way for the successful introduction of human uterus transplantation a decade ago. We discuss this in the context of the Moore criteria and describe the different procedures of preparation, surgeries, postoperative monitoring, and use of assisted reproduction in human uterus transplantation. We review the worldwide activities and associated results in the context of the IDEAL concept for evaluation of surgical innovation and appraise the ethical considerations relevant to uterus transplantation. We conclude that rigorous application of the Moore criteria and strict alignment with the IDEAL concept have resulted in the establishment of uterus transplantation as a novel, safe, and effective infertility therapy that is now being used worldwide for the treatment of women suffering from AUFI. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions Uterus transplant (UTx) has emerged as a groundbreaking solution for individuals with uterine factor infertility (UFI). This study is the first in Australia to explore the psychosocial functioning of potential recipients assessed for the nation's initial UTx clinical trial and to compare their psychological profiles with those from international UTx trials.This is a mixed methods prospective study incorporating standardized psychological measures and semi‐structured interviews. Conducted at a tertiary hospital in Sydney, Australia, the study involved 10 female Australian UTx potential recipients with UFI undergoing assessment for UTx surgery. Participants underwent comprehensive psychological evaluation using validated measures and in‐depth semi‐structured interviews. Quantitative measurement tools included the Hospital Anxiety and Depression Scale, Short Form‐36 Health Survey, Fertility Quality of Life, and the Stanford Integrated Psychosocial Assessment for Transplantation. Thematic analysis was conducted on qualitative data from semi‐structured interviews.The Australian UTx potential recipients reported significantly higher Short Form‐36 (SF‐36) scores compared to the Australian general population in general health (p < 0.04), bodily pain (p < 0.02), social functioning (p < 0.02), and emotional well‐being (p < 0.01). Compared with international UTx cohorts, the Australian UTx group showed comparable SF‐36 outcomes, with minor variations observed for general health and physical function domains. Hospital Anxiety and Depression Scale scores revealed lower anxiety, but slightly higher depression levels compared to international UTx trial cohorts. Fertility quality‐of‐life scores were significantly higher in the Australian UTx group compared to women experiencing primary infertility across four domains (p < 0.001). Thematic analysis of interviews highlighted the complex emotional impact of infertility, strong family and social support, and the perception of UTx as a transformative opportunity to achieve wholeness and motherhood.UTx represents a novel treatment option for women with UFI. This is the first qualitative study in Australia, it demonstrates the connection between women with UFI and their motivations for parenthood. These findings highlight the importance of tailored psychological assessments and establish a foundation for future research exploring the psychological characteristics of patient candidacy for UTxs. [ABSTRACT FROM AUTHOR]

To describe the incidence and management of vaginal stricture after uterus transplantation (UTx) in the US, to propose a grading system to classify stricture severity, and to identify risk factors for stricture formation. Prospective cohort study. University Hospital. Recipients undergoing UTx from 2016–2023 at Baylor University Medical Center in Dallas, Cleveland Clinic, the University of Pennsylvania, and the University of Alabama at Birmingham were monitored postoperatively with regular pelvic examinations. Stricture was defined as vaginal narrowing of <3 cm in patients with graft survival of at least 7 days. Demographic and surgery characteristics. Stricture development and severity (grade 1 for diameter 2–<3 cm, grade 2 for 1–<2 cm, or grade 3 for <1 cm). Of the 45 UTx from 2016–2023 (16 deceased donors and 29 living donors), 3 were excluded from the analysis because of graft loss within 7 days. Of the 42 remaining recipients, 39 (92.9%) had Mayer-Rokitansky-Küster-Hauser syndrome and 3 (7.1%) had a prior hysterectomy. Twenty-eight (66.7%) UTx recipients developed postoperative vaginal strictures with a median time to stricture of 33 days (interquartile range 19–53 days). Most strictures were of moderate severity, with 4 (14.3%) strictures categorized as grade 1, 19 (67.9%) as grade 2, and 5 (17.9%) as grade 3. History of Mayer-Rokitansky-Küster-Hauser syndrome and preoperative recipient vaginal length were significant risk factors for stricture, after adjustment for donor and recipient age and body mass index, anastomosis technique, total ischemia time, center, and year. Patients with longer preoperative vaginal length had a lower risk of stricture (hazard ratio 0.45, 0.29–0.70). The severity grading of the stricture was associated with the effectiveness of a nonoperative treatment approach (grade 1 vs. grade 3). No patients with grade 3 strictures improved with self-dilation alone; all required surgical repair and/or dilation under anesthesia. Conversely, for grade 1 or 2 strictures, self-dilation alone was successful in 47.8% (11/23), and no grade 1 strictures required surgical repair. Vaginal stricture is a common postoperative complication after UTx, affecting >65% of recipients. Short preoperative vaginal length and history of müllerian agenesis in the recipient are significant risk factors. Vaginal self-dilation was effective for some mild to moderate strictures, although dilation under anesthesia or surgical repair was required in most cases. Dallas UtErus Transplant Study (DUETS) at Baylor University Medical Center (NCT02656550), Uterine transplantation for the treatment of uterine factor infertility at the Cleveland Clinic (NCT02573415), The University of Pennsylvania Uterus Transplant for Uterine Factor Infertility Trial (UNTIL) (NCT03307356). [ABSTRACT FROM AUTHOR]

Objective: To identify independent risk factors for placenta accreta spectrum among pregnancies conceived with assisted reproductive technology. Design: Retrospective cohort study. Setting: Tertiary hospital. Patient(s): Individuals who conceived with assisted reproductive technology and reached 20 weeks’ gestation or later from 2011 to 2017. Intervention(s): Patient and cycle data was abstracted from hospital records and supplemented with state-level data. Poisson regression was used for multivariate analyses and reported as adjusted relative risks (aRR). Main Outcome Measure(s): Clinical or histologic placenta accreta spectrum. Result(s): Of 1,975 qualifying pregnancies, 44 (2.3%) met criteria for accreta spectrum at delivery. In the multivariate model, significant risk factors included low-lying placenta at delivery (aRR, 15.44; 95% CI 7.76–30.72), uterine factor infertility or prior uterine surgery (aRR, 4.68; 95% CI, 2.72–8.05), initial low-lying placentation that resolved (aRR, 3.83; 95% CI, 1.90–7.73), and use of frozen embryos (aRR, 3.02; 95% CI, 1.66–5.48). When the fresh vs frozen variable was replaced with controlled ovarian hyperstimulation, the final model did not change (aRR, 2.40 for unstimulated cycles, 95% CI, 1.32–4.38). With frozen transfers, the accreta rate was 16% when the endometrial thickness was < 6mm vs 3.8% with thicker endometrium (P=.02). Conclusion(s): Among pregnancies conceived with assisted reproductive technology, accreta spectrum is associated with low placental implantation (even when resolved), uterine factor infertility and prior uterine surgery, and the use of frozen embryo transfer or unstimulated cycles.

Background: Uterus transplantation is an emerging treatment option for uterine factor infertility. Most uterus transplantation research programs use living donors, although this comes with considerable surgical and psychological risks and not all women desiring uterus transplantation will have an available living donor. A deceased donor program eliminates donor risks; however, the availability of deceased uterus donors is currently unknown in Australia. Aims: To establish the feasibility of a deceased donor uterus transplantation program in Australia and consider expanded inclusion criteria for this model. Materials and Methods: A retrospective review of the New South Wales (NSW) Organ and Tissue Donation Service database was undertaken to identify potential deceased uterus donors, with comparison to the broad deceased donor inclusion criteria from three international uterus transplantation trials including female, brain‐dead, multi‐organ donation, no major abdominal surgery, and <60 years of age. Results: Between January 1, 2018, and December 31, 2022, 648 deceased donors were available in NSW. Of these, 43% (279/648) were female and 67% of the women (187/279) were also multi‐organ donors. When the brain‐dead donor‐only and age criteria (<60 years) were applied, a total of 107 deceased donors met the available criteria for uterus transplantation, with an average of 21 deceased donors per year in NSW. Conclusions: There appears to be adequate deceased donor organ availability to establish a deceased uterus transplantation program in NSW, Australia. Should interest in uterus transplantation increase, including criteria such as older and nulliparous donors could increase organ availability for a uterus transplantation program. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Uterus transplantation (UTx) is now an alternative to surrogacy and adoption for women with uterine factor infertility to have children; however, there are still unresolved clinical and technical issues. One of these is that the graft failure rate after transplantation is somewhat higher than that of other life-saving organ transplants, which is a critical concern. Herein, we summarize the details of 16 graft failures after UTx with living or deceased donors using the published literature in order to learn from these negative outcomes. To date, the main causes of graft failure are vascular factors (arterial and/or venous thrombosis, atherosclerosis, and poor perfusion). Many recipients with thrombosis develop graft failure within one month of surgery. Therefore, it is necessary to devise a safe and stable surgical technique with higher success rates for further development in the UTx field. [ABSTRACT FROM AUTHOR]

Uterus transplantation (UTx) is a promising treatment option for women who wish to give birth but suffer from absolute uterine factor infertility. This paper presents an interim analysis of a trial focusing on the causes, prevention, diagnosis, and management of graft thrombosis. Our team analyzed 10 cases of UTx (recipients numbered 1 to 10). Early thrombosis developed in 2 of 10 (20 %) recipients, and thrombectomy and temporary viability preservation were achieved in both cases. However, re-thrombosis developed in both cases, and a graft hysterectomy was carried out. In recipient number 2, vascular changes might have contributed to graft thrombosis. The histopathological finding of the explant revealed subintimal excentric fibrosis with focal sclerotic changes. In recipient number 8, thrombosis was facilitated by external compression of the vascular pedicles by the hematoma as well as production of de novo donor-specific antibodies. Thrombosis led to graft loss in both cases despite an attempt at a thrombectomy. Therefore, the focus must be on the prevention including a thorough evaluation of the donor candidate. In the postoperative course, perfusion is closely followed-up with an ultrasound, Doppler flow monitoring, and macroscopic evaluation of the cervix. In the case that findings are unclear, a relaparotomy should be promptly indicated. If thrombosis is revealed, a thrombectomy and an attempt to salvage of the graft are indicated; however, the role of this strategy is questionable due to the low chance of long-term success. The indication of upfront graft removal and early retransplantation in the treatment of uterine graft remains debatable. [ABSTRACT FROM AUTHOR]

Importance: Patients with uterine factor infertility (UFI) have few options for family building. Uterus transplant is a feasible treatment for some patients; however, cost remains a significant concern., Objective: To compare the cost effectiveness of treatment for patients with absolute uterine factor infertility to achieve 1-2 singleton births by gestational carrier or uterus transplant DESIGN: Decision analysis from the United States healthcare sector perspective, with time horizons to achieve one or two singleton births., Intervention: Gestational carrier or uterus transplant MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratios, comparing the costs (2020 U.S. Dollars) and effectiveness (quality-adjusted life years, QALYs, and live births) to achieve one or two births by gestational carrier and uterus transplant., Results: In the base case of one singleton birth, the overall cost using a gestational carrier was $97,712.90 ($56,985.20-$153084.20) compared $116,137.20 ($67,142.88-$182,290.86) after uterus transplant. QALYs were higher in the gestational carrier arm (0.93) compared to uterus transplant (0.90) and overall rates of live birth were also higher in the gestational carrier arm (94%) compared to the uterus transplant arm (77%). Costs of the gestational carrier and uterus transplant recipient were the most significant cost variables in the model. Monte Carlo simulation showed that uterus transplant had a 37% chance of being the cost-effective strategy for a single live birth at a willingness to pay of $150,000/QALY. In the case of two singleton births, the cost using a gestational carrier was $186,278.56 ($103,597.81-$296,010.27) compared to $164,276.84 ($111,961.91-$229,394.43) after uterus transplant. QALYs were again higher in the gestational carrier arm (0.93) compared to uterus transplant (0.89). Overall rates of two live birth were also higher in the gestational carrier arm (86%) compared to the uterus transplant arm (66%). Monte Carlo simulation showed that uterine transplant has a 62% chance of being the cost-effective strategy for two live births at a willingness to pay of $150,000/QALY., Conclusion: Treatment of uterine factor infertility with a gestational carrier is likely the most cost-effective approach for patients delivering a single child. However, the absolute costs associated uterus transplant were 14% less than a gestational carrier for those having two live singleton births., (Copyright © 2025. Published by Elsevier Inc.)

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. [ABSTRACT FROM AUTHOR]

Uterus transplantation (UTx) provides a new pathway to parenthood for patients with absolute uterine factor infertility. The application of reproductive technologies, such as in vitro fertilization, embryo cryopreservation, and frozen embryo transfers, for this unique population, is particularly nuanced and continually evolving. There are important pretransplant and posttransplant reproductive considerations for physicians and patients anticipating UTx. As with any rapidly evolving medical innovation, efforts to consolidate experiences and knowledge by centers offering UTx is paramount. [ABSTRACT FROM AUTHOR]

Uterine transplantation is an emerging treatment for patients with uterine factor infertility (UFI). In order to determine patient candidacy for transplant, it is imperative to understand how to identify, counsel and treat uterine transplant recipients. In this article, we focus on patient populations with UFI, whether congenital or acquired, including Mayer-Rokitansky-Kuster-Hauser, complete androgen insensitivity syndrome, hysterectomy, and other causes of nonabsolute UFI. Complete preoperative screening of recipients should be required to assess the candidacy of each individual prior to undergoing this extensive treatment option. [ABSTRACT FROM AUTHOR]

Purpose: To provide a comprehensive review of uterus transplantation in 2021, including a discussion of pregnancy outcomes of all reported births to date, the donor and recipient selection process, the organ procurement and transplant surgeries, reported complications, postoperative monitoring, preimplantation preparation, and ethical considerations. Methods: Literature review and expert commentary. Results: Reports of thirty-one live births following uterus transplantation have been published from both living and deceased donors. The proper selection of donors and recipients is a labor-intensive process that requires advanced planning. A multidisciplinary team is critical. Reported complications in the recipient include thrombosis, infection, vaginal stricture, antenatal complications, and graft failure. Graft rejection is a common occurrence but rarely leads to graft removal. While most embryo transfers are successful, recurrent implantation failures in uterus transplant patients have been reported. Rates of preterm delivery are high but appear to be declining; more data, including long-term outcome data, is needed. Conclusions: Uterus transplantation is an emerging therapy for absolute uterine factor infertility, a condition previously without direct treatment options. It is paramount that reproductive health care providers are familiar with the uterus transplantation process as more patients seek and receive this treatment. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the personal, ethical, and financial perspectives of individuals with Mayer-Rokitansky-Küster-Hauser syndrome (MRKH), a congenital uterine factor infertility condition, regarding uterine transplantation (UTx).Design: Cross-sectional, quantitative survey.Setting: A 60-item anonymous electronic questionnaire was disseminated via social media sites.Patients: International members of the Beautiful You MRKH Foundation.Interventions: None.Main Outcome Measures: The survey contained UTx educational materials followed by questions assessing participants' baseline knowledge, global perceptions, financial concerns, and ethical considerations regarding UTx.Results: We received 281 responses, with a mean participant age of 28.2 ± 9.8 years. After reviewing the education material, most participants considered receiving a UTx (73%), believed that it should be an option for all women with uterine factor infertility (86%), and believed that it should be covered by health insurance (78%). Respondents perceived the benefits of the procedure to outweigh the risks (67%) and considered it to be an ethical procedure (82%). Almost one-half (49%) were willing to spend more than $10,000 out of pocket to receive the procedure. When asked to rank the risk of UTx to self, donor, and fetus in order of personal importance, 21% ranked their own safety last.Conclusion: There is a profound desire in the MRKH community for UTx to become more widely available and affordable. MRKH patients may represent a vulnerable population requiring special considerations for informed consent and rigorous evaluation for UTx. Providers caring for MRKH patients should be prepared to provide education about UTx and to thoughtfully engage with news and media outlets to communicate evidence-supported information. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Uterus transplantation (UTx) is now a treatment for women with uterine factor infertility to have a child. However, UTx is still largely at the experimental stage, and many medical issues remain unsolved. Therefore, adequate studies in large animals including non‐human primates are required for validation of these issues. UTx research, especially in non‐human primates, can provide important information for its full establishment in humans due to the anatomical and physiological similarities between the two. We accumulated data from UTx studies using cynomolgus macaques since 2009 and established autologous and allogeneic UTx models which led to deliveries after performing the procedure. In this paper, we summarized key points to develop UTx models in cynomolgus macaques based on our experience. UTx models in non‐human primates can surely contribute new and beneficial knowledge in this field and can be useful for the further development of UTx in humans. [ABSTRACT FROM AUTHOR]

Objective: To present the first live birth after uterine transplantation (UTx) in the People's Republic of China.Design: Case study.Setting: University hospital.Patient(s): A 22-year-old woman with Mayer-Rokitansky-Kuster-Hauser syndrome and previous surgery for vaginal reconstruction and UTx.Intervention(s): Endometrial preparation, frozen embryo transfer, pregnancy follow-up, and cesarean section.Main Outcome Measure(s): Results of in vitro fertilization, frozen embryo transfer, ultrasound measurements during pregnancy, rejection diagnosis and treatment, delivery, live birth, and histology of uterus.Results(s): Frozen embryo (cleavage stage) transfer started 1.5 years after UTx. The first embryo transfer (n = 2) resulted in a biochemical pregnancy. The second, third, and fourth embryo transfer (n = 2, 2, 3) did not result in pregnancy. The fifth embryo transfer (n = 3) resulted in pregnancy with two gestational sacs, but with spontaneous disappearance of one in early pregnancy. During early pregnancy three episodes of vaginal bleedings occurred (gestational weeks 6 + 2, 13 + 1, and 16 + 3), with a spontaneously resorbing subchorionic hematoma diagnosed at the last bleeding episode. Bleeding episodes were treated with corticosteroids and tacrolimus. During pregnancy, blood flow velocity waveforms and fetal growth parameters were normal. A subacute cesarean section was performed at gestational week 33 + 6 due to uterine contraction pattern suggesting imminent labor. A healthy boy (2,000 g) with Apgar scores of 10, 10, 10 was delivered. The uterus was kept for a possible second pregnancy.Conclusion(s): The first live birth after UTx in the People's Republic of China is reported and this occurred after a robotic-assisted laparoscopic uterus retrieval from the mother. [ABSTRACT FROM AUTHOR]

Uterus transplantation is the only known potential treatment for absolute uterine factor infertility. It offers a unique setting for the investigation of immunologic adaptations of pregnancy in the context of the pharmacologic-induced tolerance of solid organ transplants, thus providing valuable insights into the early maternal-fetal interface. Until recently, all live births resulting from uterus transplantation involved living donors, with only 1 prior birth from a deceased donor. The Cleveland Clinic clinical trial of uterus transplantation opened in 2015. In 2017, a 35 year old woman with congenital absence of the uterus was matched to a 24 year old parous deceased brain-dead donor. Transplantation of the uterus was performed with vaginal anastomosis and vascular anastomoses bilaterally from internal iliac vessels of the donor to the external iliac vessels of the recipient. Induction and maintenance immunosuppression were achieved and subsequently modified in anticipation of pregnancy 6 months after transplant. Prior to planned embryo transfer, ectocervical biopsy revealed ulceration and a significant diffuse, plasma cell-rich mixed inflammatory cell infiltrate, with histology interpreted as grade 3 rejection suspicious for an antibody-mediated component. Aggressive immunosuppressive regimen targeting both cellular and humoral rejection was initiated. After 3 months of treatment, there was no histologic evidence of rejection, and after 3 months from complete clearance of rejection, an uneventful embryo transfer was performed and a pregnancy was established. At 21 weeks, central placenta previa with accreta was diagnosed. A healthy neonate was delivered by cesarean hysterectomy at 34 weeks' gestation. In summary, this paper highlights the first live birth in North America resulting from a deceased donor uterus transplant. This achievement underscores the capacity of the transplanted uterus to recover from a severe, prolonged rejection and yet produce a viable neonate. This is the first delivery from our ongoing clinical trial in uterus transplantation, including the first reported incidence of severe mixed cellular/humoral rejection as well as the first reported placenta accreta. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We aimed to present patients with the Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) coming from one center and presenting all the possibilities of its treatment, at the forefront with the uterine transplantation. PATIENTS AND METHODS: The presented work is an example of different types of MRKH syndrome diagnosed in 25 women who were diagnosed in the Department of Gynecological Endocrinology due to the primary amenorrhea from 01/2001 to 06/2018. RESULTS: Patients suffering from MRKH syndrome are capable of having genetic offspring but are unable to give birth to their own child, due to an absence of the uterus, blindly terminated vagina, and normal ovaries. Patients suffering from this syndrome have the opportunity to receive treatment in accordance with their current needs. However, there are many medical, technical, and ethical limitations in achieving the most important therapeutic target: uterine transplantation and childbirth. CONCLUSIONS: Until a few years ago, patients with an absolute uterine factor of infertility, including women with MRKH syndrome, had a real choice of only two equally controversial options giving a chance for motherhood - surrogacy and adoption. However, modern transplantation has shown that a third option - a uterine transplant - exists and is available. [ABSTRACT FROM AUTHOR]

Study Objective: To evaluate 2 cases of uterine transplant surgery that used utero-ovarian veins as outflow channels, internal iliac arteries for perfusion, and the organ harvest surgery performed laparoscopically.Design: Case study (Canadian Task Force Classification III).Setting: An urban, private, tertiary care hospital.Patients: Two patients, ages 30 and 24years, diagnosed with absolute uterine factor infertility secondary to Mayer-Rokitansky-Küster-Hauser syndrome underwent related living donor uterine transplants; donors were their mothers with normal menses.Interventions: Retrieval of organs through minilaparotomy and laparoscopic harvest of donor internal iliac arteries and ovarian veins.Measurements and Main Results: Anastomosis was completed with bilateral donor internal iliac arteries to recipient internal iliac arteries in an end-to-end manner and with bilateral donor ovarian veins to recipient external iliac veins in an end-to-side manner. The lengths of utero-ovarian veins of both donors were 11 and 11cm on both sides; the lengths of the internal iliac arteries of both donors were 10 and 7.5cm on the left side and 10 and 6cm on the right side. The operative times for harvest surgery, bench surgery and transplant surgery were 2:40 and 3:20 hours, 34:32 and 33:30 min and 4:00 and 4:30 hours respectively for recipients 1 and 2. Daily postoperative uterine Doppler was completed through day 8 and then every other day and showed good intrauterine blood flow (i.e., low resistance arcuate vessel flow; resistance index < .5). Cervical biopsies on postoperative days 7 and 14 showed no evidence of rejection in either recipient. Both recipients started menstruating within 2 months of surgery.Conclusion: By using ovarian veins as outflow channels, the challenges involved in dissection along the internal iliac vein are avoided, and harvesting the donor internal iliac artery reduces the tension on vascular anastomosis. The selection of vessels to be harvested could make the technique reproducible, although larger studies are warranted to confirm results. [ABSTRACT FROM AUTHOR]

Background: Despite procedural innovations and increasing numbers of uterus transplant attempts worldwide, the perspectives of uterus transplant (UTx) trial participants are lacking. Methods: We conducted a mixed-methods study with women with absolute uterine factor infertility (AUFI). Participants included women who had previously contacted the Cleveland Clinic regarding the Uterine Transplant Trial and met the initial eligibility criteria for participation. In-depth interviews were conducted in conjunction with FertiQoL, a validated and widely used tool to measure the impact of infertility on the quality of life of infertility patients. Results: All (n = 19) rated their overall health as good; some experienced grief and social isolation. AUFI is a life-framing experience that influences acceptance by family, partners, peers, and one's self. UTx is a means to gain control of reproductive autonomy. UTx allows family-building and the ability to play an active role in prenatal health and well-being. Establishing and maintaining a supportive relationship is a key issue of AUFI and when considering UTx. Risks of UTx are perceived relative to risks to self/child/family posed by adoption/surrogacy. Participants had no overall preference regarding living or deceased donor. Conclusions: The ways in which women with AUFI conceptualize this condition in their lives and choices around UTx and participating in a study of the procedure are multifaceted and textured. These perspectives are critical to understanding its ethical, legal, and social implications. [ABSTRACT FROM AUTHOR]

Abstract: Uterus transplantation (UTx) is now a potential option for women with uterine factor infertility to have a child. However, UTx is still in an experimental stage and basic animal studies including in nonhuman primates are needed for accumulation of data that will provide important information for establishment of UTx in humans. Herein, we summarized our experiences using cynomolgus macaques, with the goal of promoting further development of UTx studies in nonhuman primates. Our basic studies using cynomolgus macaques were summarized, including the results of other teams in nonhuman primates. Our team in Japan launched UTx research in 2009 using cynomolgus macaques and has accumulated a large archive of results in the UTx research field, including examination of uterine blood flow, surgical procedures of autologous and allogeneic UTx, organ perfusion methods in deceased donor models, immunological response and rejection and ischemia/reperfusion injury. We achieved the first delivery after autologous UTx in primates and the first periodic recovery of menstruation after allogeneic UTx in nonhuman primate models. Results from animal studies, including those in nonhuman primates, provide the basis for clinical application of UTx. Therefore, our accumulated data since 2009 and our basic experience in cynomolgus macaque are meaningful for future UTx trials in Japan. In addition, more validation in nonhuman primate models is needed for resolution of medical issues and further development of UTx in humans, despite clinical application of UTx in several countries. [ABSTRACT FROM AUTHOR]

Background In recent years, uterus transplantation ( UTx) has been applied as the treatment for patients with uterine factor infertility worldwide. Thus, the clinical application of UTx in Japan should be considered through both the history of UTx technology development in the world and future prospects. Methods Recent information on UTx was collected via a literature survey and the Internet. Results Basic research using various animals has been done mainly since 2000. In 2014, the world's first UTx baby was born in Sweden. In total, 24 UTx procedures have been performed at 10 institutes in nine countries and five births were obtained (as of May, 2017). In Japan, the 'Project Team for Uterus Transplantation' initiated UTx experiments in 2008 and the 'Japan Society for Uterus Transplantation' was organized in March, 2014. In the rest of the world, the 'International Society for Uterus Transplantation' was established in January, 2016. Conclusion Uterus transplantation is still under development as a reproductive medicine tool and organ transplant procedure. A collaborative system that is not limited by facilities and specialties should strive to build an 'all-Japan' team. [ABSTRACT FROM AUTHOR]

Study Question: How long is the allowable warm ischemic time of the uterus and what morphological and biochemical changes are caused by uterine ischemia/reperfusion injury in cynomolgus macaques?Summary Answer: Warm ischemia in the uterus of cynomolgus macaques is tolerated for up to 4 h and reperfusion after uterine ischemia caused no further morphological and biochemical changes.What Is Known Already: Uterus transplantation is a potential option for women with uterine factor infertility. The allowable warm ischemic time and ischemia/reperfusion injury of the uterus in humans and non-human primates is unknown.Study Design, Size, Duration: This experimental study included 18 female cynomolgus macaques with periodic menstruation.Participants/materials, Setting, Methods: Animals were divided into six groups of three monkeys each: a control group and groups with uterine ischemia for 0.5, 1, 2, 4 and 8 h. Biopsies of uterine tissues were performed before blood flow blockage, after each blockage time, and after reperfusion for 3 h. Blood sampling was performed after each blockage time, and after reperfusion for 5, 15 and 30 min for measurement of biochemical data. Resumption of menstruation was monitored after the surgical procedure. Morphological, physiological and biochemical changes after ischemia and reperfusion were evaluated.Main Results and the Role Of Chance: Mild muscle degeneration and zonal degeneration were observed in all animals subjected to warm ischemia for 4 or 8 h, but there were no marked differences in the appearance of specimens immediately after ischemia and after reperfusion for 3 h in animals subjected to 4 or 8 h of warm ischemia. There were no significant changes in any biochemical parameters at any time point in each group. Periodical menstruation resumed in all animals with warm ischemia up to 4 h, but did not recover in animals with warm ischemia for 8 h with atrophic uteri.Limitations, Reason For Caution: Warm ischemia in actual transplantation was not exactly mimicked in this study because uteri were not perfused, cooled, transplanted or reanastomosed with vessels. Results in non-human primates cannot always be extrapolated to humans.Wider Implications Of the Findings: The findings suggest that the tolerable warm ischemia time in the uterus is expected to be longer than that in other vital organs.Study Funding/competing Interest(s): This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 26713050. None of the authors has a conflict of interest to declare. [ABSTRACT FROM AUTHOR]

Septate uterus is the most common congenital uterine malformation. It has been associated with poor reproductive outcomes, such as infertility and recurrent miscarriage, in the context of both assisted and non-assisted reproduction, though the exact underlying pathophysiological reasons remain unclear. Diagnosis is based on two-dimensional and three-dimensional ultrasound, magnetic resonance imaging, or laparoscopic/hysteroscopic findings. Hysteroscopic repair of the uterine septum has been shown to confer several benefits to reproductive outcomes, though this fact remains in question, due to inconsistent and or low-quality evidence in the medical literature. An individualized approach to the treatment of infertility patients with septate uteri is imperative, given the plethora of possible underlying factors that may complicate management. In this report, we present the case of a patient with a subseptate uterus and a history of infertility, who, following hysteroscopic metroplasty, managed to conceive and ultimately successfully deliver a healthy child., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Lamari et al.)

Uterine factor infertility affects one in 500 women on reproductive age preventing them from being biological mothers. It is the only cause of sterility for which treatment was not available until uterine transplantation was developed, although it remains an experimental technique. The results of Dr. Brännström’s research group in Sweden are promising. Five healthy babies have been born after uterus transplantation. We expect an imminent demand and social controversy around the ethical and legal aspects that surround uterus transplantation. The alternatives for patients with this kind of sterility are adoption and surrogacy. Both raise significant ethical and legal issues that we review in this article. In the context of the Spanish legislation, surrogacy is prohibited; therefore, uterine transplantation could be an alternative to achieve motherhood in patients with absolute uterine factor infertility. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to examine the allowable warm ischemic time and pathological changes due to ischemia and reperfusion injury in the uterus of the cynomolgus monkey as a model for uterus transplantation.Material and Methods: Six female cynomolgus monkeys were used in the study. The uterus was resected from the vaginal canal and connected through the bilateral ovarian and uterine arteries and veins only. One animal was used as a control. In the other five animals, the bilateral uterine and ovarian vessels were clamped for 0.5, 1, 2, 4 and 8 h, respectively. Biopsy of the smooth muscle tissue of corpus uteri was performed after each ischemic time and after subsequent reperfusion for 3 h. Biopsy samples were observed by light and electron microscopy. Menstruation recovery was monitored.Results: There were no particular findings in both light and electron microscopy after ischemia for up to 2 h and after subsequent reperfusion. There were no marked changes after ischemia for 4 h, but dilated nuclear pores and rough endoplasmic reticulum swelling were found after reperfusion. These changes also occurred, along with mitochondrial swelling and cristae loss after ischemia for 8 h, and plasma membrane loss, nuclear fragmentation and chromatin condensation were found after reperfusion. Periodical menstruation restarted in all animals with ischemia up to 4 h, but the animal with ischemia for 8 h had amenorrhea and uterine atrophy.Conclusions: The uterus of the cynomolgus monkey tolerates warm ischemia for up to 4 h. [ABSTRACT FROM AUTHOR]

Aim Living donor surgery in organ transplantation should be performed in a minimally invasive manner under conditions that are as safe as possible. The objective of this study is to examine whether the procedure for using the ovarian vein makes donor surgery less invasive in a cynomolgus monkey model of potential living-donor surgery of uterus transplantation. Material and methods Twenty-two female cynomolgus monkeys aged 6-9 years and with body weights of 3.55 ± 1.28 kg were used in the study. Vessels and tissues surrounding the uterus were dissected while preserving the uterine artery/vein. The deep uterine vein was used as a venous pedicle in four monkeys (Group 1), and the ovarian vein was used instead of the deep uterine vein in 18 monkeys (Group 2). With the uterine artery/vein and deep uterine vein (Group 1) or ovarian vein (Group 2) connected to the uterus, the vaginal canal was cut. The vessels were then clamped to produce a donor surgery model. Surgical time, intraoperative organ and vascular injury were examined in each animal. Results The average surgical time from laparotomy to clamping of vessels was 230 ± 112 min in all 22 cynomolgus monkeys, and significantly longer in Group 1 ( n = 4) than in Group 2 ( n = 18) (393 ± 71 vs. 194 ± 84 min, p < 0.05). Surgical time in Group 2 showed a tendency to decrease in animals treated later in the study, with a significantly longer time in the first 10 monkeys compared with the last 8 (253 ± 65 vs. 120 ± 26 min, p < 0.05). All monkeys had no complications, including no injuries to other organs and no unanticipated vascular injury. Conclusion The procedure using the ovarian vein was less invasive than that using the deep uterine vein in mimicking living-donor surgery in a cynomolgus monkey model of uterus transplantation. [ABSTRACT FROM AUTHOR]

Current data on uterus allotransplantation research has been reviewed and summarized. Over the past 15 years, progress in uterus transplantation research has increased dramatically. As a consequence, the first pregnancy and delivery following uterus allotransplantation in rats have been reported. The technique has been better defined. Although clinical pregnancy and delivery following uterus allotransplantation has been reported in humans, there are still many questions to be answered before clinical application. Gestational surrogacy still remains an important option for being a genetic parent in selected cases with uterine factor infertility. [ABSTRACT FROM AUTHOR]

Aim To review the medical charts of women who applied for the uterine transplant project from June 2008 to June 2011 in our hospital retrospectively (18-40 years). Methods The data for 144 women were retrieved, and information was collected on the etiology of uterine factor infertility( UFI); ovarian reserve tests; and accompanying anatomic, infectious, genetic and endocrinological problems. Results There were 119 patients with primary amenorrhea and uterovaginal agenesis and 25 patients with a history of hysterectomy. The complete Müllerian agenesis patients formed the largest group of the UFI patients with better anti-Müllerian hormone levels and antral follicle count. Anatomical anomalies such as a solitary pelvic kidney may accompany Mayer- Rokitansky- Kuster- Hauser syndrome ( MRKH) and impede surgery. The mean ages in MRKH, hysterectomy and complete androgen insensitivity syndrome ( CAIS) cases were 24.7, 35.0 and 34.4 years, respectively. The karyotype analysis showed 46 XX ( MRKH) in 109 patients and 46 XY ( CAIS) in 10 of the primary amenorrhea patients. Conclusion Hysterectomy may deteriorate ovarian blood flow and decrease ovarian reserve. Fertility preservation may be considered in young woman undergoing hysterectomy. [ABSTRACT FROM AUTHOR]

Aim Uterine transplantation ( UTx) is a potential option for child-bearing in women with uterine infertility. Recovery of uterine function after allogeneic UTx in non-human primates has not been reported. The objective of this study is to establish the functional uterine transplant model in non-human primates. Methods Uteri of two cynomolgus monkeys were simultaneously removed, cooled at 4° C and perfused with heparin saline. The uteri were interchanged with each other and then orthotopically transplanted. Immunosuppressive protocols included use of three agents (tacrolimus, mycophenolate mofetil and methylprednisolone) in case 1 and two agents (tacrolimus and methylprednisolone) in case 2. Transabdominal ultrasonography, vaginoscopy and biopsy of the transplanted uterine cervix were routinely conducted to monitor rejection after surgery. Results The blood concentration of tacrolimus decreased 11 days after surgery and evidence of rejection was found in biopsy of the uterine cervix in both cases. The suspected rejection disappeared 23 days after surgery in case 1 and temporary menstruation resumed at 3 months after surgery. In case 2, blood flow to the uterine artery gradually decreased and the uterus resulted in atrophy due to ischemia, which has been triggered by rejection. Conclusion Allogeneic UTx in the cynomolgus monkeys resulted in temporary recovery of menstruation with three immunosuppressants and uterine atrophy with two immunosuppressants. This preliminary experience suggests that recovery of uterine function after allogeneic UTx in non-human primates is possible but more experiments are required. [ABSTRACT FROM AUTHOR]

Objective: To present the first clinical pregnancy after uterus transplantation. Design: Case study. Setting: Tertiary center. Patient(s): A 23-year-old Mayer-Rokitansky-Kuster-Hauser syndrome patient with previous vaginal reconstruction and uterus transplantation. Intervention(s): Eighteen months after the transplant, the endometrium was prepared for transfer of the thawed embryos. Main Outcome Measure(s): Implantation of embryo in an allografted human uterus. Result(s): The first ET cycle with one day 3 thawed embryo resulted in a biochemical pregnancy. The second ET cycle resulted in a clinical pregnancy confirmed with transvaginal ultrasound visualization of an intrauterine gestational sac with decidualization. Conclusion(s): We have presented the first clinical pregnancy in a patient with absolute uterine infertility after uterus allotransplantation. Although the real success is the delivery of a healthy near-term baby, this clinical pregnancy is a great step forward and a proof of concept that the implantation phase works. [ABSTRACT FROM AUTHOR]

Objective: To clarify the current status of uterus transplantation (UT) and the medical, ethical, and social problems surrounding UT. Design: Systematic review. Setting: Not applicable. Patient(s): Mainly nonhuman primates and humans. Intervention(s): Not applicable Main Outcome Measure(s): A systematic search of Pubmed with the terms "uterus/uterine transplantation" was performed for English-language articles to review the current status of UT and issues associated with its clinical application, with a focus on nonhuman primate and human studies on UT. Result(s): The first UT procedure in humans was conducted for a patient with absolute uterine infertility in Saudi Arabia in 2000. The transplanted uterus was removed after 99 days owing to prolapse and necrosis. That attempt led to a greater focus on basic UT experiments in animal models, including nonhuman primates. The subsequent accumulation of basic data has led to performance of UT in humans by groups in Turkey and Sweden. However, there has yet to be a pregnancy or delivery after allo-UT in primates. Moreover, there are many medical, ethical, and social problems that require examination before clinical application. Conclusion(s): Clinical application of UT has just begun, but more basic data are needed and medical, ethical, and social problems require thorough discussion before clinical application. [ABSTRACT FROM AUTHOR]

Abstract: This pilot study was performed from March 2008 through February 2010 to demonstrate that pregnancy can be achieved in a uterine allograft in the sheep model with the guidance of assisted reproductive technology. Uterine allotransplantation was performed in 12 sexually mature African sheep (Sudanese and Ethiopian). All animals underwent uterine transplantation via a minilaparotomy incision using a Mobius retractor device. A control group of pregnant Romney Marsh sheep with nontransplanted uteri were used to compare fetal development, uterine and placental histologic findings, and blood samples of progeny of the uterine transplant recipient sheep. Fetal size was obtained from ultrasound measurements during the early (crown-rump length) and late (biparietal diameter and abdominal circumference) gestational periods. The primary end point variables included preoperative and postoperative management, embryo transfer protocol, intraoperative assessments, and physiologic cardiopulmonary changes in the lamb during the first 5 hours of life. Four months after the initial uterine transplantation, 5 of 12 uterine allografts were considered candidates for the embryo transfer procedure. Fresh and frozen blastocyst donors were transferred accordingly to the remaining 5 uterine allografts via a minilaparotomy incision. Three of these resulted in pregnancies. One was an ectopic gestation, 1 sheep carried the pregnancy to 105 days, and 1 delivered a fully developed lamb from the transplanted uterus that was delivered via cesarean section. Neonatal lamb blood gas values and chemistry, gross organ examination, and ventilation and respiratory compliance studies yielded results normal for gestational age. This first reported case demonstrates that pregnancy can be carried in an allotransplanted uterus, with the end result a successful delivery. [Copyright &y& Elsevier]

Absolute uterine infertility affects millions of women in the United States and more throughout the world. For instance, each year in the United States about 5,000 hysterectomies are performed in women under the age of 24. In total, nearly 9 million women of reproductive age have had a hysterectomy. Based on fecundity rates, thousands of these women may be candidates for uterus transplantation. An ongoing study enrolling some of these potential recipients onto a uterus transplant “waiting list” has revealed that most of these women have Rokitansky syndrome, hysterectomy secondary to endometriosis, cervical cancer, or compelling personal accounts justifying their candidacy. Fertility restoration by uterus transplantation was derived from fertility preservation research, including the development of the radical trachelectomy, oxygenation and perfusion of the in situ uterus, and work with organ donor networks. A decade of modern animal research set the foundation for this human work. Ongoing experiments include stable, long-term large animal allografts for investigating immunosuppression regimens and other transplantation details. Each of the animal models has contributed to the current knowledge base. Recently, nonhuman primates have been used to further investigate the possibility of human uterus transplantation. Nonhuman primate anatomy is analogous to that of humans with notable exceptions. The first human uterus transplant surgery took place in 2000, but it did not result in a pregnancy. However, taken in total, the magnitude of the intervening work from multiple groups throughout the world has made uterus transplantation a topic for discussion. It may also soon be a reality. [ABSTRACT FROM AUTHOR]

To define the recipient-related determinants of outcome with donor eggs.Case-control study.Community hospital-based assisted reproductive technology (ART) program.One hundred thirty-four embryo transfers (ETs) in which two recipients were matched to one donor.Controlled ovarian hyperstimulation (COH) and ovum retrieval in donors; IVF and ET to recipients.Recipients'' age, body mass index (BMI), medical conditions, endometriosis, gravidity, uterine pathology, endometrial thickness, egg number, total motile sperm count, intracytoplasmic sperm injection (ICSI), zygote number, fertilization rate, embryos per ET, embryos frozen, embryo quality, difficulty with transfer, and ongoing pregnancies per ET.Forty-one recipient pairs had discordant outcomes. Pregnant patients had a lower frequency (9.7% vs. 31.7%, P=.04) and lesser severity of uterine pathology. Endometrium <8 mm was found solely in failed cycles. Pregnant women had fewer moderate or difficult ETs (9.7% vs. 31.7%, P=.04) and more good embryos (1.8 vs. 1.3, P=.03) than the nonpregnant group.Analysis of recipient pairs with discordant outcomes identifies the recipient-related predictors of success by keeping oocyte quality and the laboratory component constant. Uterine pathology, thin endometrium, transfer difficulty, and number of high-grade embryos are the principal recipient-related determinants of outcome with donor eggs. [Copyright &y& Elsevier]

Uterus transplantation (UTx) is now a potential option to allow women with uterine factor infertility to give birth. However, UTx is still at an experimental stage, and basic animal studies, including in non-human primates, are needed for the accumulation of data prior to clinical application. Considering that UTx may provide new hope to Japanese women, we launched UTx research in 2009 and have since accumulated a large archive of results in the UTx research field. Furthermore, we have carried out various activities aimed at the implementation of clinical applications of UTx in Japan while clarifying the ethical and social issues involved. Currently, the clinical application of UTx in Japan is just around the corner, and it is expected that UTx research will develop further in the future. Herein, we summarize our basic experiences using non-human primates and our activities with the goal of future clinical applications.

Various vaginoplasty procedures have been developed for patients with Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome. Here, we describe a novel laparoscopic vaginoplasty procedure, known as the Kisu modification, using a pull-down technique of the peritoneal flaps with additional structural support to the neovaginal apex using the incised uterine strand in patients with MRKH syndrome. Ten patients with MRKH syndrome (mean age at surgery: 23.9 ± 6.5 years, mean postoperative follow-up period: 17.3 ± 3.7 months) underwent construction of a neovagina via laparoscopic vaginoplasty. All surgeries were performed successfully without complications. The mean neovaginal length at discharge was 10.3 ± 0.5 cm. Anatomical success was achieved in all patients, as two fingers were easily introduced, the neovagina was epithelialized, and the mean neovaginal length was 10.1 ± 1.0 cm 1 year postoperatively. No obliteration, granulation tissue formation at the neovaginal apex, or neovaginal prolapse was recorded. Five of the 10 patients attempted sexual intercourse and all five patients were satisfied with the sexual activity, indicating functional success. Although the number of cases in this case series is few, our favorable experience suggests that the Kisu modification of laparoscopic vaginoplasty procedure is an effective, feasible, and safe approach for neovaginal creation in patients with MRKH syndrome. [ABSTRACT FROM AUTHOR]