Elsevier

The Lancet

Volume 385, Issue 9968, 14–20 February 2015, Pages 607-616
The Lancet

Articles
Livebirth after uterus transplantation

https://doi.org/10.1016/S0140-6736(14)61728-1Get rights and content

Summary

Background

Uterus transplantation is the first available treatment for absolute uterine infertility, which is caused by absence of the uterus or the presence of a non-functional uterus. Eleven human uterus transplantation attempts have been done worldwide but no livebirth has yet been reported.

Methods

In 2013, a 35-year-old woman with congenital absence of the uterus (Rokitansky syndrome) underwent transplantation of the uterus in Sahlgrenska University Hospital, Gothenburg, Sweden. The uterus was donated from a living, 61-year-old, two-parous woman. In-vitro fertilisation treatment of the recipient and her partner had been done before transplantation, from which 11 embryos were cryopreserved.

Findings

The recipient and the donor had essentially uneventful postoperative recoveries. The recipient's first menstruation occurred 43 days after transplantation and she continued to menstruate at regular intervals of between 26 and 36 days (median 32 days). 1 year after transplantation, the recipient underwent her first single embryo transfer, which resulted in pregnancy. She was then given triple immunosuppression (tacrolimus, azathioprine, and corticosteroids), which was continued throughout pregnancy. She had three episodes of mild rejection, one of which occurred during pregnancy. These episodes were all reversed by corticosteroid treatment. Fetal growth parameters and blood flows of the uterine arteries and umbilical cord were normal throughout pregnancy. The patient was admitted with pre-eclampsia at 31 full weeks and 5 days, and 16 h later a caesarean section was done because of abnormal cardiotocography. A male baby with a normal birthweight for gestational age (1775 g) and with APGAR scores 9, 9, 10 was born.

Interpretation

We describe the first livebirth after uterus transplantation. This report is a proof-of-concept for uterus transplantation as a treatment for uterine factor infertility. Furthermore, the results show the feasibility of live uterus donation, even from a postmenopausal donor.

Funding

Jane and Dan Olsson Foundation for Science.

Introduction

Absolute uterine factor infertility is the only major type of female infertility that is still viewed as untreatable. The major causes are congenital absence of the uterus (Rokitansky syndrome, also called Mayer-Rokitansky-Küster-Hauser syndrome), previous hysterectomy, and severe intrauterine adhesions.1, 2, 3, 4 In the UK alone, more than 12 000 women of childbearing age are thought to have absolute uterine factor infertility.5 The available motherhood options for women with this disorder are adoption (to acquire legal motherhood), or pregnancy in a gestational surrogate carrier to acquire genetic motherhood, followed by adoption to also acquire legal motherhood. However, surrogacy is not allowed in many countries because of ethical, legal, or religious reasons.

We have undertaken preclinical research into uterus transplantation for more than a decade, using a step-by-step logical developmental approach, in which we have used several animal species, ranging from rodents to non-human primates.6, 7 Recently, we initiated the first clinical trial of transplantation, involving nine women who received uteri from live donors. Two of the women had to undergo hysterectomy during the initial months, with the causes being uterine artery thrombosis and severe intrauterine infection.8 The other seven women began menstruation during the first 2–3 months and the grafts remained viable, with regular menstruations during the first post-transplantation year. Occasional subclinical episodes of mild rejection were detected on cervical biopsies, which were effectively reversed by short courses of increased immunosuppression.

Except for our clinical trial of nine women, only two other human uterus transplantation efforts have been reported. The first case resulted in progressive uterine necrosis during the initial months, and a fully necrotic uterus was removed 3 months after transplantation.9 The second case involved a uterus from a deceased donor being transplanted into a patient with Rokitansky syndrome.10 The patient underwent embryo transfer 18 months after transplantation and two pregnancies that miscarried before gestational week 6 have been reported.11 No further reports exist about this case.

In this report, we describe the clinical course of the first patient in our cohort who achieved a clinical pregnancy resulting in delivery of a baby.

Section snippets

Patient

In 2013, a 35-year-old patient underwent uterus transplantation at Sahlgrenska University Hospital (Gothenberg, Sweden) as part of our clinical trial of uterus transplantation in nine women with absolute uterine factor infertility (ClinicalTrials.gov number NCT01844362). The study was approved by the regional ethics board of the University of Gothenburg. The donor, recipient, and her male partner had given their written informed consent. The 6-month outcomes of the study have been published.8

Results

The first menstruation in the recipient occurred spontaneously 43 days post-transplantation and continued for 4 days. She then had regular menses with a median interval of 32 days and ranging between 26–36 days. The endometrium showed typical changes in median width (maximum 11·3 mm; range 7·9–15·3 mm). The blood flow velocity waveforms of the uterine arteries were similar on the left and right side and were within the low to normal range throughout the observation period. Median pulsatility

Discussion

Despite remarkable advances in infertility treatment, since the birth of the first in-vitro fertilisation baby in 197816 major forms of uterine factor infertility have remained untreatable. Our demonstration of a livebirth after uterus transplantation in a woman born with no uterus has eradicated the diagnosis of absolute uterine factor infertility.

This livebirth after human uterus transplantation comes after more than a decade of intensive animal research in this specialty by several groups

References (26)

  • K Sieunarine et al.

    Possibilities for fertility restoration: a new surgical technique

    Int Surg

    (2005)
  • M Brannstrom et al.

    Experimental uterus transplantation

    Hum Reprod Update

    (2010)
  • C Diaz-Garcia et al.

    Uterine transplantation research: laboratory protocols for clinical application

    Mol Hum Reprod

    (2012)
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