Uterus Transplantation: A 50-Year Journey.

This paper provides an analysis of the last 50 years of uterus transplantation (UTx). Animal research on UTx began in the 1960s, aiming to solve tubal factor infertility. The success of in vitro fertilization shifted the focus onto uterine factor infertility. Early research in small and large animals improved following the advent of immunosuppression and established the uterus' ability to tolerate cold ischemia and to function following vessel reanastamosis. Upon the achievement of the first live birth following UTx in 2014, human research has started to focus on reducing donor morbidity, optimal immunosuppression regimes, and the development of deceased donor UTx programmes.

Uterine Transplantation in 2021: Recent Developments and the Future.

Uterine transplantation has evolved rapidly over the last decade. As the number of cases performed increases exponentially worldwide, emerging evidence continues to improve collective knowledge and understanding of the procedure, with the aim of improving both surgical and reproductive outcomes. Although currently restricted to women with absolute uterine factor infertility, increasing awareness as a method of fertility restoration has resulted in a demand for the procedure to be undertaken in transgender women. This manuscript summarizes the recent advances in uterine transplantation, and elaborates further upon the key novel avenues research within the field will focus on over the coming years.

Cumulative outcome of pre-implantation genetic diagnosis for sickle cell disease: a 5-year review.

To review the cumulative outcome of pre-implantation genetic diagnosis (PGD) cycles performed for prevention of sickle cell disease (SCD). Couples referred for PGD for SCD between April 2012 and October 2017 were included. Ovarian stimulation was performed using a short gonadotrophin-releasing hormone (GnRH) antagonist protocol and follicle-stimulating hormone injections. The GnRH agonist was used to trigger oocyte maturation. Oocytes were fertilised using intracytoplasmic sperm injection. Trophectoderm biopsy was performed on day 5 or 6 followed by vitrification. Genetic testing was done using pre-implantation genetic haplotyping. A total of 60 couples started 70 fresh PGD cycles (mean 1·2 cycles/couple) and underwent a total of 74 frozen-embryo-transfer (FET) cycles (mean 1·3 FET/couple). The mean (SD) female age was 33 (4·4) years and the mean (SD) anti-müllerian hormone level was 22·9 (2·8) pmol/l. The cumulative live-birth rate was 54%/PGD cycle started and 63%/couple embarking on PGD. The rate of multiple births was 8%. The cumulative outcome of PGD treatment for prevention of SCD transmission is high and PGD treatment should be offered to all at-risk couples.

The impact of COVID-19 on the motivations of women seeking a uterus transplant.

Aim: The aim of this study was to investigate the change if any, in the motivations of women seeking a UTx and determine the impact of the COVID-19 pandemic. Methods: A cross-sectional survey. Results: 59% of women answered they were more motivated in achieving a pregnancy following the COVID-19 pandemic. 80% strongly agreed or agreed the pandemic had no impact on their motivation for a UTx, and 75% strongly agreed or agreed their desire for a baby strongly outweighs the risks of undergoing a UTx during a pandemic. Conclusion: Women continue to express a high level of motivation and desire for a UTx despite the risks imposed by the COVID-19 pandemic.

Attitudes, knowledge, and perceptions among women toward uterus transplantation and donation in the United Kingdom.

Objective: To assess the motivations and perceptions of the general public in the United Kingdom toward donating their uterus for Uterus Transplantation after death (UTx). Design: A cross sectional study. Setting: A 32-item electronic questionnaire. Population: One hundred fifty nine females over the age of 16 living in the United Kingdom, consented and took part in the study. Main outcome measures: The motivations and perceptions toward UTx among the general public including the willingness to donate and barriers preventing donation. Results: One hundred fifty nine women completed the questionnaire. The majority had never heard of UTx (n = 107, 71%) and most were not aware the uterus could be donated after death (n = 130, 92%). 43% of the cohort were willing to donate their uterus after death (n = 57). 8% stated they wished to donate their organs but not their uterus (n = 10). 30% of women (n = 42) believed the child born following UTx would have genetic links to the donor. Over half of the respondents (n = 65, 51%) strongly agreed or agreed they would feel joy in the knowledge that donation would lead to bringing a new life into the world. A quarter of respondents strongly agreed or agreed (n = 45, 25%) that the use of their uterus by another woman would feel like an extension of life. Conclusion: The findings indicate a favorable opinion toward UTx and a positive attitude toward donation of the uterus after death among the general public in the United Kingdom. The findings also highlight the need for education around UTx now this therapeutic option is available.

The Clinical Application of Platelet-Rich Plasma in the Female Reproductive System: A Narrative Review.

Platelet-rich plasma is an autologous plasma containing platelets prepared from fresh whole blood drawn from a peripheral vein. Through processing, it can be prepared to contain supraphysiologic levels of platelets at three to five times greater than the level of normal plasma. PRP has been explored both in vivo and ex vivo in the human endometrium model in its ability to harness the intrinsic regenerative capacity of the endometrium. Intrauterine autologous PRP infusions have been shown to increase endometrial thickness and reduce the rate of intrauterine adhesions. In the setting of recurrent implantation failure, intrauterine infusion of PRP has been shown to increase clinical pregnancy rate. PRP also appears to hold a potential role in select patients with premature ovarian insufficiency, poor ovarian responders and in improving outcomes following frozen-thawed transplantation of autologous ovarian tissue. Further studies are required to explore the potential role of PRP in reproductive medicine further, to help standardise PRP protocols and evaluate which routes of administration are most effective.

INvestigational Study Into Transplantation of the Uterus (INSITU): a cross-sectional survey among women with uterine factor infertility in the UK assessing background, motivations and suitability.

IMPORTANCE: The study summarises the selection prescreen criteria currently used in the UK for a uterus transplant and highlights the number of women who are suitable to proceed. OBJECTIVES: To assess the demographics, motivations, reasons and suitability among women with absolute uterine factor infertility (AUFI) to undergo uterine transplantation (UTx). DESIGN: A cross-sectional survey. SETTING: An electronic questionnaire was sent via email to women with AUFI who had previously been referred to the UTx research team or approached the Womb Transplant UK Charity. The questions assessed suitability to undergo UTx based on demographic information, perceptions to adoption and surrogacy and reasons why UTx was preferable. Responses were assessed against the study selection criteria. PARTICIPANTS: Women with AUFI. RESULTS: 210 women completed the questionnaire. The most common aetiology of AUFI in our cohort was Mayer-Rokitansky-Küster-Hauser (68%; n=143) whereas 29% (n=62) had previously undergone hysterectomy. 63% (n=132) of the cohort had previously considered adoption, 5% (n=11) had attempted it and 2 (1%) had successfully adopted. The most common reason cited to undergo UTx over adoption was to experience gestation (n=63; 53%), while 37% (n=44) wanted a biologically related child. 76% (n=160) of participants had previously considered surrogacy, 22 (10%) had attempted it and 2 (1%) had successfully become mothers using a surrogate. The most common reason to undergo UTx over surrogacy was to experience gestation (n=77; 54%). 15% (n=21) were concerned about the legal implications, 14% (n=20) identified the financial cost as a barrier and 8% (n=12) could not consider it due to religious reasons. On adhering to the selection criteria, 65 (31%) women were suitable to proceed with the trial. CONCLUSION: The study demonstrates that implementing commonly used selection criteria for a UTx led to an attrition rate of more than two-thirds of women who requested to initially undergo the process. As more studies present outcomes following UTx, critical assessment of the selection criteria currently used is warranted to ensure potential recipients are not being unnecessarily excluded. TRIAL REGISTRATION NUMBER: NCT02388802.

Perceptions and Motivations for Uterus Transplant in Transgender Women.

Importance: Uterus transplant has been demonstrated to be a viable fertility-restoring treatment for women categorized as female at birth with absolute uterine factor infertility. Recent advancements, as well as considerations of fairness and equality in reproductive care, have now led to the possibility of uterus transplant being undertaken in transgender women. Objective: To investigate the reproductive aspirations of transgender women and their perceptions of uterus transplant. Design, Setting, and Participants: This cross-sectional survey study used a 27-item electronic questionnaire to investigate the reproductive aspirations of 182 transgender women older than 16 years, including their perceptions of and motivations for uterus transplant, between May 1 and November 1, 2019. Main Outcomes and Measures: Perceptions of and motivations for uterus transplant, including perceived significance of the ability to gestate, menstruate, and have a physiologically functioning vagina. Results: A total of 182 transgender women completed the questionnaire; most women (109 [60%]) were aged 20 to 29 years. Most did not have children prior to transitioning (167 [92%]) and expressed a desire to have children in the future (171 [94%]). In addition, most respondents agreed or strongly agreed that the ability to gestate and give birth to children (171 [94%]) and menstruate (161 [88%]) would enhance perceptions of their femininity. Similarly, high proportions strongly agreed or agreed that having a transplanted, functioning vagina would improve their sexual experience (163 [90%]), improve their quality of life (163 [90%]), and help them to feel like more of a woman (168 [92%]). Nearly all respondents (180 [99%]) believed that uterus transplant would lead to greater happiness in transgender women. More than three-quarters of the respondents (140 [77%]) strongly agreed or agreed that they would be more inclined to cryopreserve sperm if uterus transplant became a realistic option. Conclusions and Relevance: This study provides insights into the reproductive aspirations of transgender women and reports on their multifaceted motivation to undergo uterus transplant. The survey responses suggest that transgender women would choose to have female physiologic experiences, such as menstruation and gestation, as well as potentially having a physiologically functioning transplanted vagina. If proven feasible and safe in this setting, uterus transplant may facilitate the achievement of reproductive aspirations, improve quality of life, and further alleviate dysphoric symptoms in transgender women.

Options for acquiring motherhood in absolute uterine factor infertility; adoption, surrogacy and uterine transplantation.

KEY CONTENT: Following the diagnosis of absolute uterine factor infertility (AUFI), women may experience considerable psychological harm as a result of a loss of reproductive function and the realisation of permanent and irreversible infertility.Adoption enables women with AUFI, and their partners, to experience social and legal parenthood, also often providing benefits for the adopted child.Surrogacy offers the opportunity to have genetically related offspring. Outcomes are generally positive in both surrogates and the children born as a result.Uterine transplantation is the only option to restore reproductive anatomy and functionality. While associated with considerable risk, it allows the experience of gestation and the achievement of biological, social and legal parenthood. LEARNING OBJECTIVES: To gain an understanding of the routes to parenthood available for women with AUFI experiencing involuntary childlessness, such as adoption, surrogacy and, most recently, uterine transplantationTo consider a suggested management plan to facilitate counselling in women with AUFI who experience involuntary childlessness. ETHICAL ISSUES: In the UK, while the number of children requiring adoption continues to increase, the number being adopted from care is decreasing.Some cultures may hold ethical or religious beliefs that surrogacy is unacceptable, and its legal position in many jurisdictions is problematic.Restrictive selection criteria and high costs may limit future availability of uterine transplantation.

Uterine Transplantation: Review of Livebirths and Reproductive Implications.

Uterine transplantation (UTx) is a fertility restoring treatment for women with absolute uterine factor infertility. At a time when there is no question of the procedure's feasibility, and as the number of livebirths begins to increase exponentially, various important reproductive, fetal, and maternal medicine implications have emerged. Detailed outcomes from 17 livebirths following UTx are now available, which are reviewed herein, along with contextualized extrapolation from pregnancy outcomes in other solid organ transplants. Differences in recipient demographics and reproductive aspirations between UTx and other transplant recipients make extrapolating management strategies and outcomes in other solid organ transplants inappropriate. Whereas preterm delivery remains prominent, small for gestational age or hypertensive disorders do not appear to be as prevalent following UTx when compared to other solid organ transplants. Given the primary objective of undertaking UTx is to achieve a livebirth, publication of reproductive outcomes is essential at this early stage, to reflect on and optimize the management of future cases.

Uterine Transplantation Using Living Donation: A Cross-sectional Study Assessing Perceptions, Acceptability, and Suitability.

A uterine transplantation is a nonvital, quality-of-life-enhancing solid organ transplant. Given improvements in donor risk profile and the anticipated shortage of suitable deceased donors, nondirected donation could facilitate sustainability as uterine transplantation moves from research into the clinical realm. The aim of this article is to determine perceptions and identify motivations of potential nondirected living uterus donors and assess acceptability and suitability. METHODS: A cross-sectional survey using an electronic questionnaire among women who have inquired about donating their uterus for uterine transplantation. RESULTS: The majority of respondents "strongly agreed" or "agreed" that the most prevalent motivations to donate their uterus include helping someone carry and give birth to their own baby (n = 150; 99%), helping others (n = 147; 97%), and because they no longer need their womb (n = 147; 97%). After considering risks of uterus donation, the majority were still keen to donate their uterus (n = 144; 95%), but following a process of exclusion using donor selection criteria, less than a third (n = 42; 29%) were found to be suitable to proceed. CONCLUSIONS: This study demonstrates novel insight into the motivations of women who wish to donate their uterus and displays high levels of acceptability after consideration of the risks involved. Despite the physical risk and transient impact upon ability to undertake activities of daily living, women who donate their uterus expect to gain psychological and emotional benefits from enabling another woman to gestate and give birth to their own future children. However, currently used selection criteria reduce the number of potential donors significantly.

Endometrial autotransplantation in rabbits: Potential for fertility restoration in severe Asherman's syndrome.

OBJECTIVE: Uterine transplantation is now considered a feasible treatment for women with absolute uterine factor infertility and has been successfully performed for a woman with Asherman's syndrome (AS). The endometrium is a clinically and histologically distinct entity from the surrounding myometrium. Endometrial transplantation (ETx) may offer a less invasive option, with less immunogenic impact, to restore fertility in women with severe AS. The objective of this study was to assess the feasibility of ETx by evaluating surgical and reproductive outcomes following endometrial autotransplantation in a rabbit model. STUDY DESIGN: A longitudinal study assessing surgical, biochemical, radiological, reproductive and histological outcomes following endometrial autotransplantation in ten New Zealand white rabbits. RESULTS: Ten procedures were performed, including 8 endometrial auto-transplants (ETx) and 2 endometrial resections (ER), to control against endometrial regeneration. Eight procedures were successful, whereas two rabbits from the ETx group died intra-operatively. Three rabbits were euthanised at 48, 72 and 96 h post-operatively to assess gross and histological appearances. Two rabbits, one from the ETx group and one from the ER group, died four weeks and eight weeks post-operatively. Three rabbits subsequently underwent two cycles of in-vitro fertilization. The first cycle resulted in an implantation rate of 57% in the un-operated uteri. In two rabbits who underwent ETx, an implantation rate of 28.6% was seen. In the second cycle, an implantation rate of 61.9 % (13 implantations) was observed in the control uteri. In the two ETx females, an implantation rate of 14.3 % was seen. No pregnancies were seen in either cycle in the animals who underwent ER. Despite successful implantations in both cycles in the ETx rabbits, no livebirths were achieved. Following death or euthanasia there was gross and microscopic evidence of viable endometrium following ETx, but not following ER. CONCLUSION: This study has revealed, for the first time, the feasibility of ETx with gross and microscopic evidence of viable endometrium, and the demonstration of clinical pregnancies. Whilst further studies are essential, and the achievement of successful livebirths fundamental, ETx may offer a potential fertility restoring opportunity for women with severe, treatment refractory cases of AS.

Psychomotor skills and cognitive load training on a virtual reality laparoscopic simulator for tubal surgery is effective.

OBJECTIVES: Validation of a virtual reality (VR) simulator for the training and assessment of laparoscopic tubal surgery and mapping of cognitive load. STUDY DESIGN: Prospective cohort study conducted at the Imperial College Virtual Reality Surgical Skills laboratory amongst 25 trainees and nine senior gynaecologists. Participants performed two sessions of salpingectomy and salpingotomy procedures on a VR simulator to assess construct validity. Nine novices performed ten such sessions to enable assessment of the learning curve. The relationship between cognitive load and the dexterity parameters was assessed. Simulator fidelity was reported by experienced and intermediate level gynaecologists. Statistical analyses utilised non-parametric tests, Kruskall-Wallis and Mann-Whitney U tests. Learning curves were assessed using the Friedman test and Wilcoxon Signed Ranks test. Relationship between dexterity metrics and cognitive load was performed using Spearman's rank order correlation. RESULTS: Salpingectomy demonstrated construct validity for time taken by experienced, intermediate and novice gynaecologists (median 170 vs. 191 vs. 313s (P=0.003) respectively) and movements (median 200 vs. 267 vs. 376s, P=0.045). Salpingotomy demonstrated construct validity for time taken (median 183 vs. 191 vs. 306s, P=<0.001) and movements (median 210 vs. 233 vs. 328s, P=0.005). Learning curve analysis for salpingectomy displayed a plateau for time taken after the eighth session, and the fourth session for movements. Salpingotomy displayed a plateau after the eighth session for both time taken and movements. Cognitive load correlated significantly with dexterity parameters. The fidelity scores were not significantly different between the two procedures (P=0.619). CONCLUSION: The LAP Mentor VR laparoscopic simulator is a valid and effective tool for training novice surgeons in ectopic pregnancy surgery. Reduction in cognitive load significantly correlates with the learning curves.