Whose (germ) line is it anyway? Reproductive technologies and kinship.

Reproductive biotechnologies can separate concepts of parenthood into genetic, gestational and social dimensions, often leading to a fragmentation of heteronormative kinship models and posing a challenge to historical methods of establishing legal and/or moral parenthood. Using fictional cases, this article will demonstrate that the issues surrounding the intersection of current and emerging reproductive biotechnologies with definitions of parenthood are already leading to confusion regarding social and legal family ties for offspring, which is only expected to increase as new technologies develop. Rather than opposing these new technologies to reassert traditional concepts of the family, however, this article will explore the opportunities that these technologies represent for re-imagining various culturally cherished values of family-making in a way that is inclusive of diverse genders, sexualities and cultures. It will consider IVF, gametogenesis, mitochondrial donation, surrogacy, artificial gestation, CRISPR-Cas9 gene editing, foster care and adoption as some of many possible pathways to parenthood, including for members of the LGBTIAUQ+ community.

Gender-affirming hysterectomy in the United States: A comparative outcomes analysis and potential implications for uterine transplantation.

PURPOSE: Hysterectomy is a gynecological procedure sometimes performed as part of the gender-affirming process for transgender and gender-expansive patients assigned female at birth. Our goal was to compare surgical outcomes between patients undergoing gender-affirming hysterectomy and patients undergoing hysterectomy for benign menstrual disorders. We then explored the implications of gender-affirming hysterectomy for uterine transplantation. METHODS: We performed a retrospective cohort study using data from the American College of Surgeons National Surgical Quality Improvement Program database from 2009 through 2018. We identified patients undergoing hysterectomy in the United States based on Current Procedural Terminology code. We used the International Classification of Diseases 9 or 10 codes to identify patients with benign menstrual disorders (non-gender-affirming group) and gender dysphoria (gender-affirming group). We compared patient characteristics and surgical complications. RESULTS: Of the 40,742 patients that met inclusion criteria, 526 (1.3%) patients were individuals with gender dysphoria. Compared to patients who underwent hysterectomy for benign menstrual disorders, gender-affirming patients were younger, were healthier, had a lower prevalence of diabetes, and were more likely to undergo surgery in the outpatient setting, with shorter time to discharge. Complication rates were similar between groups. Logistic regression controlling for the American Society of Anesthesiology classification determined the difference of return to the operating room was not statistically significant (OR 1.082; 95% CI, 0.56-2.10; p = 0.816). CONCLUSION: Gender-affirming hysterectomy has a safety profile similar to hysterectomy performed for benign menstrual disorders. Researchers should further explore the possibility of uterus donation among these patients as they may be suitable candidates.

First uterine transplant case at the Royal Prince Alfred Hospital.

Uterine transplantation (UT) is an emerging medical treatment for women affected by absolute uterine factor infertility (AUFI). To date there have been over 90 documented cases of UT performed worldwide, with over 50 live births. UT allows women affected by AUFI the opportunity to carry and deliver a childd. The Royal Prince Alfred Hospital (RPAH) introduced a UT study in 2019; however, due to the impacts of the COVID pandemic the study was placed on hold for two years. In February 2023, RPAH performed the centre's first UT from a living unrelated donor to a 25-year-old woman with Mayer-Rokitansky-Küster-Hauser syndrome. The donor and recipient surgeries were uncomplicated and both are recovering well in the early post-operative period.

Donor robotic-assisted laparoscopy for uterus transplantation.

OBJECTIVE: Uterine transplantation has proven to be a viable solution in cases of absolute uterine factor infertility. Performing uterine explant surgery is one of the most difficult gynecologic surgical challenges owing to the complexity of the uterine vascular system. The goal of this video is to demonstrate uterine explant surgery and highlight the critical anatomy involved in this procedure. DESIGN: In this video, we display, narrate, and illustrate key portions of right pelvic dissection, which was subsequently performed bilaterally to achieve hysterectomy from a living donor for the purpose of uterine transplantation. SETTING: University hospital. PATIENT(S): The donor was a 39-year-old woman, and the receptor sister suffers from Rokitansky syndrome. A careful right site pelvic dissection was visualized in this operation during a hysterectomy with the aim of performing a uterine graft implantation in a living donor (Research Ethics Committee and the Assistance Ethics Committee of Hospital Clínic de Barcelona [HCB/2016/0111] and Bioethics Committee of Catalunya Study included in ClinicalTrials.org registry [NCT04314869]). INTERVENTION(S): The donor's surgery was performed entirely using robotic surgery (DaVinci Xi, Intuitive Survival Inc.). MAIN OUTCOME MEASURE(S): Assessment of uterine graft transplant viability. RESULT(S): Good quality arterial and venous pedicles were obtained during the surgery. The difficulty of this procedure is the extensive vascular dissection that has to be done to isolate the veins that drain the uterus until the hypogastric vein. CONCLUSION(S): Pelvic anatomy dissection for obtaining the graft from the donor in uterus transplantation is complex, and robotic-assisted laparoscopic surgery may help to provide a clear and more precise visualization.

Anesthetic Considerations for Cesarean Delivery After Uterine Transplant.

Infertility has many etiologies and can have devastating consequences for young couples attempting to bring children into the world. Uterine factor for infertility is related to either uterine agenesis (Mayer-Rokitansky-Küster-Hauser [MRKH] syndrome), unexpected hysterectomy, or presence of a nonfunctioning uterus. In this review, a patient with MRKH syndrome underwent donor uterus transplantation at the Cleveland Clinic, conceived, and delivered the first healthy baby in the United States and the second worldwide. Additionally, we review the pertinent literature on anesthesia problems. Donor-related uterine transplant is a recent medical innovation requiring multidisciplinary expertise. In patients who deliver successfully, according to the current literature, the transplanted uterus can be used for one more pregnancy only if the mother so desires, otherwise cesarean hysterectomy (C-Hyst) should be performed. In the observed case, C-Hyst was performed because the patient developed placenta accreta and the couple desired no further pregnancy. In summary, with our limited data, careful management of these patients is required to ensure the best outcome for the mother and the newborn fetus.

Uterine transplant: an ethical framework analysis from a Middle Eastern perspective.

BACKGROUND: Significant advances in infertility treatment have been achieved over the past several decades, but women with uterine dysfunction, anomaly, or agenesis still need support to carry a pregnancy to term. Recently, advancements in surgical, anesthetic and immunosuppressive therapy have brought the idea of successful uterine transplant closer to reality, but many challenges must be overcome before uterine transplant can become more common, including ethical challenges related to the study and the conduct of this procedure. METHODS: This was an updated ethical analysis of uterine transplant from a Middle Eastern perspective, using an established ethical framework that has been adapted for the analysis of research in non-Western cultures and developing countries. RESULTS: Using the ethical framework, this analysis explored research developments in uterine transplant to date, using the following categories: collaborative partnership, social value, scientific validity, a fair selection of study population, favorable risk-benefit ratio, independent review, informed consent, and respect for recruited participants. The analysis revealed a significant need for region- and religion-specific ethical guidelines for uterine transplant procedures. CONCLUSIONS: The horizons of research need to expand by addressing and researching the ethical issues related to uterine transplant trials and clinical procedures. LIMITATIONS: Limitations included the challenges related to applying ethical analyses to work in developing countries, and the fact that this analysis was based on the views and interpretations of a single researcher.

Single bilateral ovarian venous return in uterine transplant: Validation in an orthotopic auto-transplant model in the Yucatan minipig.

BACKGROUND: Uterine transplant (UT) represents an opportunity to treat absolute uterine infertility. However, the use of uterine veins for venous return, in addition to ovarian veins, significantly increases the risk of ureteral wounds in the living donor and UT time for the recipient. Our aim was to demonstrate that dual ovarian venous return is sufficient for graft viability and survival. METHODS: Uterine orthotopic auto-transplant was performed under general anaesthesia in six Yucatan minipig sows. The uterus graft was implanted with termino-lateral anastomoses between the ovarian and external iliac veins, and between the uterine and external iliac arteries, respectively. RESULTS: The macroscopic physical aspect of the graft was adequate in 83 % of the sows (5/6) 30 min after reperfusion with a surgical time of 439±54 min (mean anastomosis time: 153±49 min). Two sows died the day after surgery. In the four remaining sows, two uteri were necrotic and two were adequately vascularized on Day 7. CONCLUSIONS: the learning curve was relatively fast, the sole use of bilateral ovarian venous return is possible and might reduce post-surgery morbidity in human living donors as well as UT time for the recipient.

The Missing Uterus, the Missed Diagnosis, and the Missing Care. Mayer-Rokitansky-Küster-Hauser Syndrome in the Lives of Women in Malaysia.

STUDY OBJECTIVE: To explore the effect of the diagnosis of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome on affected Malaysian women. DESIGN: Qualitative study with a quantitative component. SETTING: Pediatric and adolescent gynecology unit at Universiti Kebangsaan Malaysia Medical Centre, Malaysia. PARTICIPANTS: Twelve women with MRKH. INTERVENTIONS: Face-to-face interview and short questionnaire. MAIN OUTCOME MEASURES: Thematic analysis was used to understand participants' experiences. RESULTS: There were 7 themes identified: (1) delayed diagnoses; (2) doctors' roles and attitudes; (3) gender identity; (4) family and society's response; (5) reaction toward infertility; (6) managing sexual intimacy; and (7) coping mechanisms. Several participants consulted their physicians regarding their primary amenorrhea at an opportunistic setting. When they were referred to the gynecologists, they were dismayed at the lack of information given. The term, "MRKH" plays an important role to ease information-seeking. Participants felt that the doctors were insensitive toward them. Mental illness is a significant complication of MRKH. All participants acknowledged that infertility was the hardest part of the condition. The importance of blood lineage affects their outlook on childbearing options. Some were afraid of sexual intimacy and worried that they would not be able to satisfy their partners. Participants gained support and bonded with their counterparts in the MRKH support group. CONCLUSION: A multidisciplinary approach including medical, psychological, and social support is essential for the management of MRKH. Adequate information and sexual education plays the utmost importance in preventing social-related complications of MRKH.

Uterine Transplantation: Evolving Data, Success, and Clinical Importance.

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.

Uterine Transplant: A Risk to Life or a Chance for Life?

Being inherently different from any other lifesaving organ transplant, uterine transplantation does not aim at saving lives but supporting the possibility to generate life. Unlike the kidneys or the liver, the uterus is not specifically a vital organ. Given the non-lifesaving nature of this procedure, questions have been raised about its feasibility. The ethical dilemma revolves around whether it is worth placing two lives at risk related to surgery and immunosuppression, amongst others, to enable a woman with absolute uterine factor infertility to experience the presence of an organ enabling childbirth. In the year 2000, the first uterine transplantation, albeit unsuccessful, was performed in Saudi Arabia from where it has spread to the rest of the world including Sweden, the United States and now recently India. The procedure is, however, still in the preclinical stages and several ethical, legal, social and religious concerns are yet to be addressed before it can be integrated into the clinical setting as standard of care for women with absolute uterine factor infertility.

A Survey of Public Opinion in the United States Regarding Uterine Transplantation.

STUDY OBJECTIVE: To evaluate the opinions and attitudes of the general public regarding uterine transplantation (UTx) in the United States. DESIGN: A cross-sectional study (Canadian Task Force classification II-2). SETTING: A Web-based survey. PATIENTS: A nationally representative sample of adult US residents by age and sex. INTERVENTIONS: A Web-based questionnaire administered in November 2016. MEASUREMENTS AND MAIN RESULTS: Respondents who supported UTx were compared with those who were opposed using log binomial regression to calculate relative risk ratios and 95% confidence intervals. Of the 1444 respondents recruited, 1337 (93%) completed the survey. Ninety respondents (6%) disagreed with the use of in vitro fertilization for any indication and were excluded. Of the remaining 1247 respondents, 977 (78%) supported and 48 (4%) opposed allowing women to undergo UTx. Respondents with higher yearly incomes and education level were more likely to agree that "taking the uterus from one person and putting it into another person is ethical." Respondents who answered that UTx is safe for the donor, recipient, and baby were more likely to believe that UTx is an acceptable, ethical alternative to a gestational carrier. Forty-five percent of respondents believed that UTx should be covered by insurance, whereas 24% did not. CONCLUSION: The majority of respondents in a sample of US residents support UTx, find it ethical, and believe that it is an acceptable alternative to a gestational carrier although support varies. These findings suggest that the US public is in favor of uterine transplantation as a treatment for uterine factor infertility.

Laparoscopic-Assisted Uterus Retrieval From Live Organ Donors for Uterine Transplant: Our Experience of Two Patients.

STUDY OBJECTIVE: To report the first ever laparoscopic-assisted live donor uterus retrieval in 2 patients for uterus transplant. DESIGN: Case study (Canadian Task Force classification III). SETTING: Galaxy CARE Laparoscopy Institute, Pune, India. PATIENTS: Two patients with absolute uterine factor infertility with their mothers as donors. INTERVENTIONS: In vitro fertilization and uterine transplant. MEASUREMENTS AND MAIN RESULTS: A 12-member team was formed, and approval for transplant was obtained from the institutional review board. Pretransplant, in vitro fertilization for both patients was done. Two consecutive uterine transplants were done on 2 successive days. Vessels were harvested laparoscopically in both donors. Uterus and harvested vessels were retrieved by a small abdominal incision to prevent injury and infection. The uterus was transplanted in the recipients by end to side anastomosis of the harvested vessels to external iliac vessels, followed by anchoring of supports of the donor uterus to those of the recipients. Surgical intra- and postoperative parameters, postoperative investigations, and follow-up data of 6 months were measured. Operative time for laparoscopic donor surgery was 4 hours. Bench surgery took 45 minutes. Recipient surgery time was 4 hours. There were no intraoperative or immediate postoperative complications. Both the recipients started menstruating after 34 days and 48 days, respectively, and have had 6 cycles of menses at regular intervals. Uterine artery Doppler showed good flow in both patients. Hysteroscopy-guided cervical biopsies were used as a method of surveillance of graft rejection after uterine transplant. Office hysteroscopy was done after 2 months in both patients, and hysteroscopy-guided endometrial and cervical biopsies were taken. Minimal slough was seen on the endometrium in the patient with Mayer-Rokitansky-Küster-Hauser syndrome, which was removed. Repeat hysteroscopy after 10 days showed a healthy endometrium. CONCLUSIONS: Laparoscopic-assisted uterus donor retrieval is feasible and affords all the advantages of a minimally invasive technique, thereby reducing the morbidity of the procedure. It helps in better dissection of the vessels, shortens the operative time, and helps to minimize tissue handling of the harvested uterus and vessels.

Laparoscopic-Assisted Uterus Retrieval From Live Organ Donors for Uterine Transplant.

STUDY OBJECTIVE: The authors present the first ever laparoscopic-assisted uterus retrieval in a live donor for uterus transplant. DESIGN: A step-by-step surgical demonstration. SETTING: Galaxy CARE Laparoscopy Institute, Pune, India. PATIENTS: Two patients, ages 21 and 26 years, with Mayer-Rokitansky-Küster-Hauser syndrome and Asherman syndrome, respectively, with their mothers as donors. INTERVENTIONS: A 12-member team was formed. After a review of the available literature on uterine transplant, a protocol was formulated and submitted to the Institutional Review Board (IRB). Approval from the Institutional Review Board was obtained. Thorough screening of the candidates was done. Two consecutive uterine transplants were done on 2 successive days. Vessels were harvested laparoscopically in both donors. Uterus was retrieved through a small abdominal incision, to prevent any injury to the uterus and harvested vessels. Uterus was transplanted in the recipients by end-to-side anastomosis of the harvested vessels to the external iliac vessels, followed by anchoring of supports of the donor uterus to those of the recipients. MEASUREMENTS AND MAIN RESULTS: Surgical intra- and postoperative parameters, postoperative investigations, and follow-up data of 4 months. The operative time for laparoscopic donor surgery was 4 hours. Bench surgery took 45 minutes. The recipient surgery was completed in 4 hours. There were no intraoperative or immediate postoperative complications. Both recipients started menstruating after 34 days and 48 days, respectively, and have had 3 cycles of menses at regular intervals to date. After discharge, follow-up cervical biopsies at 3 weekly intervals showed no signs of rejection. Uterine artery Doppler ultrasound showed good flow in both patients. CONCLUSION: Laparoscopic-assisted donor retrieval is feasible and affords all advantages of a minimally invasive technique. It helps in better dissection of vessels, shortens the operative time, and helps minimize tissue handling, thereby reducing the morbidity of the procedure.

Anatomy of the Internal Iliac Vein: Implications for Uterine Transplant.

STUDY OBJECTIVE: Uterine transplantation has proven feasible since the first live birth reported in 2014. To enable attachment of the uterus in the recipient, long vascular pedicles of the uterine and internal iliac vessels were obtained during donor hysterectomy, which required a prolonged laparotomy to the living donors. To assist further attempts at uterine transplantation, our video serves to review literature reports of internal iliac vein anatomy and demonstrate a laparoscopic dissection of cadaver pelvic vascular anatomy. DESIGN: Observational (Canadian Task Force Classification III). SETTING: Academic anatomic laboratory. Institutional Review Board ruled that approval was not required for this study. INTERVENTION: Literature review and laparoscopic dissection of cadaveric pelvic vasculature, focusing on the internal iliac vein. MEASUREMENTS AND MAIN RESULTS: Although the internal iliac artery tends to have minimal anatomic variation, its counterpart, the internal iliac vein, shows much variation in published studies [1,2]. Relative to the internal iliac artery, the vein can lie medially or laterally. Normal anatomy is defined as some by meeting 2 criteria: bilateral common iliac vein formed by ipsilateral external and internal iliac vein at a low position and bilateral common iliac vein joining to form a right-sided inferior vena cava [2]. Reports show 79.1% of people have normal internal iliac vein anatomy by these criteria [2]. The cadaver dissection revealed internal iliac vein anatomy meeting criteria for normal anatomy. CONCLUSION: Understanding the complexity and variations of internal iliac vein anatomy can assist future trials of uterine transplantation.

Uterine viability in the baboon after ligation of uterine vasculature: a pilot study to assess alternative perfusion and venous return for uterine transplantation.

OBJECTIVE: To assess, in two separate groups of baboons, uterine viability after ligation of the uterine veins and uterine viability after ligation of both the uterine arteries and veins, respectively. DESIGN: Prospective, observational study. SETTING: Baboon breeding colony. ANIMAL(S): Six naïve female Papio hamadryas baboons with indicators of normal reproductive function. INTERVENTION(S): Three baboons underwent surgical interruption of the uterine veins bilaterally, and three baboons underwent surgical interruption of the uterine arteries and the uterine veins bilaterally. All baboons also underwent colpotomy, cervico-vaginal reanastomosis, and intraoperative near-infrared fluorescence imaging after vessel ligation. In the postoperative period, transabdominal sonography, vaginoscopy, and endocervical biopsy were performed on all animals. MAIN OUTCOME MEASURE(S): Postoperative uterine and ovarian viability. RESULT(S): Near-infrared imaging confirmed intraoperative perfusion of the uterus and cervico-vaginal anastomosis in all cases. In all subjects, sonography revealed normal uteri, and vaginoscopy revealed well-healed anastomoses. Endocervical biopsies (five of six) demonstrated pathologically normal endocervical tissue without evidence of necrosis. Cyclical sex skin turgescence and menstruation were unanimously observed. CONCLUSION(S): Disruption of bilateral uterine vessels does not affect uterine or ovarian viability in the baboon. Bilateral uterine artery and vein ligation furthers development of a minimally invasive approach to donor hysterectomy.

Deceased donor uterine transplantation.

OBJECTIVE: To share our experience in performing the first-ever deceased-donor uterine transplant in the United States. DESIGN: This video uses an animation and footage from a uterine transplantation procedure to review the steps and techniques involved in performing a uterine transplant. SETTING: Academic, multisite medical center. PATIENT(S): A reproductive-age patient with Mayer-Rokitansky-Kuster-Hauser syndrome. INTERVENTION(S): Transplantation of a viable uterus from a deceased donor. MAIN OUTCOME MEASURE(S): Assessment of posttransplantation uterine graft viability. RESULT(S): This video article describes the essential steps in the uterine transplant process, including selecting an appropriate donor with no history of infertility or uterine malformations. Furthermore, a deceased donor should exhibit brain death but not cardiac death. We also review our inclusion criteria for suitable recipients. In this video we outline the key steps in a uterine transplantation procedure and demonstrate footage from an actual transplant procedure. These steps include establishing bilateral end-to-side vascular anastomoses between the donor uterine artery and vein and the recipient's external iliac vessels. Once this has been completed and reperfusion noted of the donor uterus, connection to the recipient vaginal cuff is then performed. CONCLUSION(S): Uterine transplantation, although currently experimental, has gained the potential to become the first true treatment for uterine factor infertility. This procedure can become a promising option for the approximately 1.5 million women worldwide for whom pregnancy is not possible because of the absence of the uterus or presence of a nonfunctional uterus. Deceased donor uterine transplantation will further serve to broaden accessibility for this procedure.

Uterine Transplants in the Canadian Setting: A Theoretical Framework.

The uterine transplant is an innovative surgical procedure whereby a healthy uterus is transplanted into a woman with uterine factor infertility (UFI) for the purpose of procreation. Twelve uterine transplants have been attempted in the world in the last two decades, and five have led to viable births. While uterine transplantation is still in its experimental stages, it remains unclear whether Canadian centres plan to attempt the procedure in the near future. Herein, I raise several observations that are specific to the Canadian setting and apply the Montreal Criteria for the Ethical Feasibility of Uterine Transplantation to determine whether there is fertile ground for a uterine transplantation program to be adopted in Canada.

Uterine Transplantation: Ethical Considerations within Middle Eastern Perspectives.

The field of reproductive medicine witnessed a breakthrough in September 2014 with the first successful live birth post uterine transplantation. This success represents the culmination of decades' worth of research on infertility and reproductive medicine. This subject of infertility gathers special attention in the Middle East, as childbearing is given paramount importance in the family unit. And as with any new medical advancement, Middle Eastern people look to their religious authorities for guidance. This paper describes the various ethical quandaries related to uterine transplantation, from a perspective of the religious and societal factors that are unique to the Middle East, and embeds them within the conversation of its alternative solutions.