“First Birth from a Deceased Donor Uterus in the United States: From Severe Graft Rejection to Successful Cesarean Delivery” (2020), by Rebecca Flyckt, Tommaso Falcone, and Cristiano Quintini et al.

In 2020, Rebecca Flyckt and colleagues published “First Birth from a Deceased Donor Uterus in the United States: From Severe Graft Rejection to Successful Cesarean Delivery,” hereafter “First Birth from a Deceased Donor,” in the American Journal of Obstetrics and Gynecology. In the article, Flyckt and colleagues explain that they performed one of the first uterus transplantations with a uterus from a deceased donor in the United States and detail how they did so successfully. All deceased donors in the study were considered brain-dead, not cardiac-dead. Uterus transplantation from a deceased donor is a surgical procedure in which a researcher transplants a healthy uterus from a brain-dead, deceased donor into a recipient with a diseased or absent uterus. Prior to 2020, researchers performed several uterus transplantations with live donors that resulted in live births, but there was only one recorded live birth from a deceased uterus donor. Flyckt and colleagues provide summary data about uterus transplantations from deceased donors and compare the efficacy of transplantations from live donors to those from deceased donors. “First Birth from a Deceased Donor” advances the techniques that can make uterus transplants from deceased donors successful, which allows people with uterine disorders the opportunity to become pregnant and have children.

1. Background and Context
2. Article Contents
3. Impacts

Background and Context

Uterus transplantation emerged as a field in the early twenty-first century as a potential treatment for people with uterine infertility disorders. One type is absolute uterine factor infertility, or AUFI, which is a female infertility condition in which the uterus is defective or completely absent. Prior to the publication of “First Birth from a Deceased Donor,” researchers worldwide experimented with live donor and deceased donor uterus transplantations as treatments for AUFI. One of the first recorded attempts at a uterus transplantation from a live donor occurred in 2000 in Jeddah, Saudi Arabia. It resulted in the removal of the uterus after ninety-nine days due to blood clots in the vessels. In 2011, researchers at the Akdeniz University Hospital in Antalya, Turkey, performed one of the first recorded uterus transplantation with a deceased donor uterus. The recipient of the transfer underwent two rounds of in-vitro fertilization, or IVF, in which a physician fertilizes eggs outside the uterus in a petri dish and then transfers them into the uterus to initiate pregnancy. However, there was not a successful birth. In 2012, researchers at the Sahlgrenska University Hospital in Gothenburg, Sweden, performed one of the first recorded uterus transplantation clinical trials with live donor uteruses, which resulted in seven successful surgeries. In 2014, one person from the Swedish clinical trial delivered a healthy infant, which resulted in one of the first recorded live births via uterus transplantation. In 2017, one of the first successful live births from a deceased donor occurred at the Hospital das Clínicas in São Paulo, Brazil. Prior to the publication of “First Birth from a Deceased Donor,” physicians worldwide performed over sixty uterus transplantations that resulted in fifteen live births. Flyckt and colleagues published “First Birth from a Deceased Donor” to develop the study of uterus transplantations and compare the clinical outcomes with live and deceased donors.

After the international success of uterus transplantation and clinical trials, the United States began to participate in the research. In 2015, the Cleveland Clinic in Cleveland, Ohio, started one of the first uterus transplantation clinical trials in the United States, known as The Cleveland Clinic Uterine Transplantation for the Treatment of Uterine Factor Infertility, hereafter The Cleveland Clinic Trial, after it received approval in 2015. The Cleveland Clinic Trial recruited ten people with uterine infertility conditions. In 2016, the researchers from the Cleveland Clinic Trial performed a uterus transplantation from a deceased donor, which resulted in the removal of the organ three weeks later due to bleeding from a damaged artery. In 2017, the researchers performed another uterus transplantation. The recipient went on to deliver one of the first live births from a deceased uterus in the United States. “First Birth from a Deceased Donor” summarizes the clinical case for the recipient and their following pregnancy.

At the time of publication, the authors of the article were all physicians at Cleveland Clinic. Flyckt was an infertility and reproductive surgery physician in the hospital’s Department of Obstetrics and Gynecology and Women’s Health Institute. Six of the co-authors worked alongside her in the same department. Eight of the co-authors worked in the Cleveland Clinic’s Digestive Disease and Surgery Institute. Two co-authors practiced in the Pathology and Laboratory Institute. One co-author researched in the Respiratory Institute, and another co-author specialized in imaging in the Imaging Institute.

Article Contents

The article consists of four sections. In the first section, which functions as an introduction, the authors state that uterus transplantation offers people with uterine infertility disorders an opportunity to become pregnant. They discuss that one of the purposes of the article is to compare the clinical outcomes of live births after uterus transplantations from a uterus from a deceased donor with a uterus from a live donor. In the second section, “Case Presentation,” the researchers discuss that they successfully performed surgical operations for uterus procurement and transplantation. They also explain that the uterus recipient recovered well from one organ rejection episode and a successful pregnancy followed resulting in a cesarean section, or C-section, of a healthy neonate at thirty-four weeks. In the third section, “Comment,” the authors identify the limitations of their study and the implications of their results for future uterus transplantations. They also compare their experimental results to previous literature on uterus transplantations to evaluate the advantages and disadvantages of using deceased and live uterus donors, then discuss issues with the placenta after transplantation and the future applications of uterus transplantations for other fields of biology. In the fourth and last section, “Conclusion,” Flyckt and colleagues predict that deceased donor uterus transplantations will become a common treatment option for people with AUFI.

In the introduction, the Cleveland Clinic team establish that uterus transplantations were previously theoretical, but due to successful experiments, uterus transplantations offer treatment for people with uterine infertility disorders. The authors discuss that earlier researchers performed uterus transplantations from live donors, which resulted in live births in Sweden and Texas. They also explain that one of the first successful live births from a deceased donor uterus occurred in 2018. However, they argue that there is insufficient research to determine the risks and benefits of a deceased donor transplantation versus a live donor transplant because of the small sample size of two. Therefore, the authors argue that there must be additional clinical trials for deceased donor uterus transplantations. Finally, they state that the literature on the placenta, which is an organ that develops in the uterus during pregnancy to provide nutrition to the fetus, during uterus transplantation is limited. The researchers say it is critical to study the development of the placenta during a uterus-transplanted pregnancy.

In the second section, “Case Presentation,” Flyckt and colleagues summarize the clinical procedures for the recipient’s uterus transplantation operation and pregnancy. The authors state that the recipient in “First Birth from a Deceased Uterus” was the second participant in the authors’ Cleveland Clinic Clinical Trial. They explain that the thirty-five-year-old female recipient with AUFI matched with a twenty-four-year-old female brain-dead donor. The authors discuss that the uterus donor was an appropriate donor with no history of infertility or uterine malformations and two previous pregnancies, which resulted in one miscarriage and one live birth. They describe that they procured the uterus by disconnecting its connection to the donor’s pelvic veins and arteries to perform the surgical removal of the donor uterus. The authors report that they published the live video footage of the uterus surgical procurement operation in their article “Deceased Donor Uterine Transplantation.” Following the removal of the donor uterus, the researchers state that they initiated the recipient’s transplantation surgery with an abdominal incision and then performed vascular anastomoses. That surgical procedure connects blood vessels together to facilitate blood flow from the recipient to the donor uterus. The authors conclude that the recipient recovered well with regular menstruation beginning thirty-four days after the transplantation surgery.

Continuing in the second section, the authors discuss that the recipient had one episode of organ rejection, which is when the body’s immune system attacks the transplanted organ, five-months post-operation. Flyckt and colleagues state that the daily oral administration of 6 mg estradiol, a synthetic estrogen the recipient took to bolster hormones that aid pregnancy, induced the episode. The authors identified the episode as a grade three rejection, which is the most severe rejection episode involving significant cell death in the uterine tissue. They administered immunosuppressive therapies, which are intensive drug regiments for organ rejection episodes, to target the body’s antibody and cellular rejection responses. They explain that they monitored the patient via weekly biopsies of the uterine tissue for three months until her body fully recovered from the rejection.

Flyckt and colleagues discuss that pregnancy occurred approximately one year after the initial uterus transplantation surgery due to the prior rejection episodes. The authors state that the patient took 4 mg of estradiol daily to prepare for an embryo transfer. After an unsuccessful first attempt, their second attempt at embryo transfer on November 9, 2018, proved viable. The authors state that they regularly monitored the fetus’s growth and uterus health throughout the pregnancy via ultrasound evaluations and cervical biopsies. They discuss that a grade two, mild-to-moderate, rejection episode of the transplanted uterus occurred at twelve weeks gestation. They successfully resolved the episode within one week via intravenous immunosuppressive therapies. The Cleveland Clinic team states that the recipient received a diagnosis of placenta accreta, which is a serious condition during pregnancy, in which the placenta grows too deeply into the uterine wall, at twenty-one weeks pregnant. The authors state that they scheduled a pre-term C-section for early delivery at thirty-four weeks of pregnancy due to the placenta accrete. The infant received steroid treatments in vitro to accelerate fetal lung growth so it could live outside the uterus. The researchers explain that they performed the elective C-section at thirty-four weeks and two days, which resulted in a healthy neonate. They report that the mother recovered well four days post-operation. They discharged the infant after seven days of monitoring.

In the third section, “Comment,” the Cleveland Clinic team evaluates the results of their experimental study and analyzes the implications of their management of the rejection episodes. The authors state that their demonstration of the live birth from a donation from a deceased donor in the United States reaffirms the scientific belief that the uterus is a resilient organ with the ability to maintain its reproductive capacity during transplantation. The researchers argue that their study demonstrated a unique type of organ rejection with the first rejection episode, known as plasma-cell-rich acute rejection, which is an aggressive form of organ rejection due to the donor’s antibodies. The authors emphasize that the presence of rejection episodes highlights the necessity for regular biopsies of the cervix and uterus post-transplantation. The researchers also explain that their study demonstrates that physicians can treat and manage severe uterus rejection through immunosuppressive therapies to allow for pregnancy. Flyckt and colleagues suggest that the rejection episodes could be due to levels of increased levels of eosinophil, which are white blood cells, which could be early markers for rejection episodes. The authors also discuss that it is essential to monitor cytomegalovirus, or CMV, a type of herpes virus, to prevent rejection episodes.

In the same section, Flyckt and colleagues also compare the effectiveness of live donors with deceased donors for uterus transplantations. The authors explain that the advantages of using a deceased donor include the elimination of risks to the health, well-being, and safety of the donor. They acknowledge that the disadvantages of using a deceased donor uterus include limited organ availability and proximity, a higher chance for an incomplete menstrual and obstetric history, and an inability to plan organ procurements in advance. The researchers compare their results to previous literature reporting on uterus transplantation. They discuss that one of the advantages of uterus transplantations with live uterus donors includes an extensive screening of the donor for a medical reproductive history. However, disadvantages include an increased risk of surgical complications to the donor, including injury to the urinary system and vaginal damage. The authors also emphasize that the long-term risks to the donor are unknown due to the recent development of the uterus transplantation field. They explain that uterus transplantations with deceased donors are at risk of ischemia reperfusion, which is a critical condition, in which blood flow to an organ is suppressed or interrupted during organ transplantation and then restored. That process can cause damage and inflammation to the organ. The authors state that the current study demonstrated no risk of ischemia reperfusion for their recipient, and no evidence of functional impairment of the uterus after the uterus remained under cold temperatures for two hours.

The authors conclude the third section, “Comment,” with a discussion of the potential for complications involving placenta accreta for future uterus transplantation and the applications of the surgeries for additional scientific fields. They state that this study was one of the first reported uterus transplantations with a placenta complication. The authors explain that scientists do not understand the cause of placenta accrete. Possible causes include the severity or number of rejection episodes or the thickness of the recipient’s endometrium, which is the tissue lining the uterus, at the time of embryo transfer. The researchers state that previous research had identified assisted reproductive technology, or ART, and uterine surgery as risk factors for placenta accreta. They conclude that experimental uterus transplantations can treat uterine factor infertility and explain aspects of normal pregnancy, endometrial stem cells and endometrial regeneration, menstruation, early implantation, and placentation.

In the fourth section, “Conclusion,” the researchers state that their demonstration of one of the first live births in the United States from a deceased donor uterus represents a milestone in the field of uterus transplantation. The authors explain that deceased donors may become the preferred donor method for future uterus transplantations, especially for people with AUFI with no suitable living donor or ethical concerns regarding transplantations with a live donor. The Cleveland Clinic team also discusses that the decreased risk to the recipient with a deceased uterus donor offers additional benefits to the approach. The authors explain that they predict deceased donor uterus transplantations will become a common treatment option for people with AUFI.

Impacts

Despite the experimental success the researchers detail in “First Birth from a Deceased Donor,” Flyckt and colleagues received mixed criticism and appreciation from scientists and people with uterine infertility disorders eligible for treatment via uterus transplantation. Following the publication of “First Birth from a Deceased Donor,” The American Journal of Obstetrics and Gynecology published a letter of criticism from researchers at the University of Utah in Salt Lake City, Utah. In the letter, the author advised more bioethical considerations for future uterus transplantation trials, including predetermined and regulatory safety monitoring. Researchers from other institutions shared the same sentiments and argued that there was insufficient data available to determine the efficacy and proper techniques for the procedure.

Despite the criticism, many people with uterine fertility disorders supported the research and argued that uterus transplantation offers them a new treatment for pregnancy. In 2019, Flyckt and colleagues surveyed nineteen people with AUFI interested in uterus transplantation. The survey revealed that the participants perceived the benefits of uterus transplantations, including reproductive autonomy, family health, and societal acceptance, to outweigh the surgical risks. The researchers published their findings in their article “Framing the Diagnosis and Treatment of Absolute Uterine Factor Infertility: Insights from In-Depth Interviews with Uterus Transplant Trial Participants” in AJOB Empirical Bioethics.

“First Birth from a Deceased Donor” established that treatment for people with uterine infertility disorders, specifically AUFI, is possible through uterus transplantation from a deceased donor. Critics argue that researchers must further develop the technique. The article led to further uterus transplantation research within the Cleveland Clinic as well as other medical institutions worldwide. As of 2025, researchers have cited the article over ninety times, and more than 100 uterus transplantations and over forty live births have occurred since researchers began to perform uterus transplantations. The surgical technique for uterus transplantations remains in the early phases of development as of 2025. Researchers worldwide continue to report increased successful transplantation surgeries and live births each year.

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