Despite risks, uterus transplant yields live births

Women with successfully transplanted uterus can conceive and subsequently give birth, although the procedure comes with safety risks for both the recipient and the donor, as shown in a small case study.

A total of 20 women (median age 30 years) with uterine-factor infertility and at least one functioning ovary who underwent uterus transplant were included in the study. All 14 (70 percent) women who had a successful uterus allograft were able to get pregnant and deliver at least one live-born infant. [JAMA 2024;332:817-824]

“Adverse events were common, with medical and surgical risks affecting recipients as well as donors,” the investigators noted.

Six uterus transplants resulted in graft failure, with all occurring within 2 weeks of the transplant. Five of these cases were due to problems with the blood vessel connections/donor selection—either as thrombosis of the arterial inflow or the venous outflow with evidence of parenchymal necrosis, or as existing atherosclerotic changes in the microvasculature of the uterus. In the sixth case, severe bleeding after the transplant led to failure.

Rejection episodes occurred in nine of the 14 successful allografts, with three having multiple occurrences. The first rejection occurred a median of 3.6 months after the transplant. Most episodes were treated with increased immunosuppression or steroids. Mild or borderline cases were monitored without treatment.

Immunosuppression time for the 14 successful uterus recipients was minimized, with a median duration of 21 months. White blood cell counts in all 20 women increased from a median of 6.6 × 109/L at the start of antimetabolite treatment to a median of 10.8 × 109/L at the time of graft hysterectomy, then decreased to a median of 5.8 × 109/L 3 months after the procedure. This decrease never required additional medication.

The highest serum creatinine levels in both nonpregnant and pregnant recipients were within normal limits, with a median of 1.0 mg/dL. Calcineurin inhibitor–induced kidney toxicity occurred in one recipient.

“The long-term impact of immunosuppression in these otherwise healthy women remains unknown. Preliminary data seemed to indicate that kidney function completely or mostly recovered at a follow-up of 12 months from immunotherapy cessation,” the investigators said.

Donor risks

Organs were procured from 18 living donors (median age 37 years, median parity 2) and two deceased donors (30 and 43 years, respectively, parity 2). 

Of the living donors, two had complications after open surgery, including a vaginal tear and faecal impaction. Two others had complications after robot-assisted hysterectomy, including a blocked ureter and thermal damage. Despite these issues, all four donors experienced full recovery, with no long-term consequences over a median follow-up of 5 years and 3 months.

Pregnancy outcomes

Pregnancy occurred after the first embryo transfer in seven recipients, after two embryo transfers in two recipients, and after multiple embryo transfers in five. The first embryo transfer occurred a median of 4.1 months post-transplant.

All 14 women had a childbirth, with two having another. All live births were delivered via caesarean section at a target gestational age of at least 37 weeks. The first babies were born a median of 14.2 months, while the second babies were born a median of 34 months after uterus transplant. Six women had their uterus removed at the time of their first or second childbirth.

“National US data for infertility treatment in women younger than 35 years using their own ova describe a live birth rate of 68.9 percent following any number of cycles. The live birth success rate in this study suggests that a successfully transplanted uterus is capable of functioning at least on par with a native, in situ uterus,” the investigators said. [https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?reportingYear=2020]

The 16 children (nine girls) born after uterus transplant were followed up for a median of 44 months. The median gestational age at live birth was 36 weeks 1 day. None of the children had congenital malformations. One child did not meet developmental milestones at the 12-month examination and subsequently received a diagnosis of autism. At the 18-month examination, two others showed temporary cognitive delays, which later improved.

Defining 'acceptable risk'

In an accompanying editorial, Drs Jessica Walter and Emily Jungheim, both from the Northwestern University in Chicago, Illinois, US, described the findings of the case study as akin to science fiction. [JAMA 2024;332:792-793]

“This seminal study represents a major step forward for patients with uterine-factor infertility. Uterus transplant is the only restorative treatment available to patients with a formerly dysfunctional or absent uterus, who can now, for the first time, carry their own biological child,” Walter and Jungheim wrote.

“Recognition of the profound technical and cross-disciplinary medical achievement is certainly deserved. However, the same complexities of care that make this study so remarkable simultaneously raise questions about how we should define value and acceptable risk in the context of a life-generating rather than life-saving organ transplant,” they added.