Niclas Kvarnström

Livebirth after uterus transplantation

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 recipients 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.

Uterus transplantation trial: 1-year outcome.

OBJECTIVE To report the 12-month outcome of seven patients with viable uteri after uterus transplantation (UTx). DESIGN Prospective observational study. SETTING University hospital. PATIENT(S) Seven patients with absolute uterine infertility and viable uteri for 12 months after live-donor UTx. INTERVENTION(S) Predetermined immunosuppression was with tacrolimus and mychophenolate mofetil (MMF) during 6 months, whereupon MMF should be withdrawn. Frequent ultrasound examinations were performed to assess uterine appearance and uterine artery blood flow. Cervical biopsies (for histological detection of rejection) were obtained at preset time points, with temporary adjustments of immunosuppression if there were signs of rejection. Menstruations were systematically recorded. MAIN OUTCOME MEASURE(S) Menstruation, uterine artery blood flow, histology of cervical biopsies, and blood levels of tacrolimus. RESULT(S) All patients showed regular menses after 1-2 months. Uterine artery blood flow was unchanged, with a median pulsatility index of 1.9 (range, 0.5-5.4). Blood levels of tacrolimus were approximately 10, 9, and 8 (μg/L) during months 2, 9, and 12, respectively. Four recipients showed mild inflammation in biopsies after MMF withdrawal and were treated with corticosteroids and azathioprine during the remainder of the 12 months. Subclinical rejection episodes were detected on ectocervical biopsies in five recipients. Histology showed apoptotic bodies and occasional spongiosis in the squamous epithelium. Moderate infiltration of lymphocytes and neutrophils was seen in the epithelial/stromal interface. All rejection episodes were successfully treated for 2 weeks with corticosteroids or dose increments of tacrolimus. CONCLUSION(S) We demonstrate long-term uterine viability after UTx, with continued menstruation and unaltered uterine artery blood flow. Subclinical rejection episodes were effectively reversed by temporary increase of immunosuppression. CLINICAL TRIAL REGISTRATION NUMBER NCT01844362.

Live Donors of the Initial Observational Study of Uterus Transplantation—Psychological and Medical Follow-Up Until 1 Year After Surgery in the 9 Cases

Background The first prospective observational study of uterus transplantation was initiated in 2013 with live donation to 9 women with absolute uterine factor infertility. We explored the medical complications and psychosocial wellbeing of the donors during the first postoperative year. Methods Complications were registered and graded according to the Clavien-Dindo (C-D) classification. Symptoms related to the surgery were registered. Data on length of hospital stay, sick leave, socioeconomic parameters, and life events were obtained. Psychological evaluations (Psychological General Well-Being, Dyadic Adjustment Scale, Hospital Anxiety and Depression Scale [HADS], SF-36) questionnaires focusing on quality of life, mood, and relationship, were conducted at inclusion and at 3, 6, and 12 months after uterus donation. Results One major surgical complication (C-D IIIb) occurred. A ureteric-vaginal fistula developed 2 weeks after uterus procurement. The fistula was surgically repaired. Two self-reported and transient complications (C-D I) were noted (nocturia, meralgia paresthetica). Hospital stays of all donors were 6 days and median sick leave was 56 days (range, 14-132). At inclusion, median scores exceeded the normative values of the Swedish population in Psychological General Well-Being and Dyadic Adjustment Scale. HADS-Anxiety was detected preoperatively in 1 donor. Two donors exceeded 10-point declines in SF-36 summary scores and increased their HADS scores by 6 points during the observation period. All donors returned to their predonation levels of physical health. Conclusions The results support that it is feasible to retrieve a uterus safely from a live donor. Further studies are needed to better evaluate the method.

The history behind successful uterine transplantation in humans

This paper aimed to describe the basic aspects of uterine transplant (UTx) research in humans, including preliminary experiences in rodents and domestic species. Studies in rats, domestic species, and non-human primates validated and optimized the UTx procedure in terms of its surgical aspects, immunosuppression, rejection diagnosis, peculiarities of pregnancy in immunosuppressed patients, and patients with special uterine conditions. In animal species, the first live birth from UTx was achieved in a syngeneic mouse model in 2003. Twenty-five UTx procedures have been performed in humans. The first two cases were unsuccessful, but established the need for rigorous research to improve success rates. As a result of a controlled clinical study under a strictly designed research protocol, nine subsequent UTx procedures have resulted in six healthy live births, the first of them in 2014. Further failed UTx procedures have been performed in China, Czech Republic, Brazil, Germany, and the United States, most of which using living donors. Albeit still an experimental procedure in, UTx is the first potential alternative for the treatment of absolute uterine factor infertility (AUFI).

Live birth after uterus transplantation

ABSTRACTIn the 3 decades since the birth of the first in vitro fertilization baby in 1978, there have been remarkable advances in infertility treatment. Until now, however, absolute uterine factor infertility remained the only major type of female infertility viewed as untreatable. Absolute uterine

Preoperative psychological evaluation of uterus transplant recipients, partners, and living donors: Suggested framework

Uterus transplant has become a real option for women with uterine‐factor infertility to become pregnant and give birth. The screening before uterus transplant consists of a multidisciplinary evaluation and includes the potential recipient, living donor, and, to some extent, the recipients partner and future co‐parent. The psychological evaluation has evolved from broad‐based screening in the first uterus transplant trial, where the aim was to find suitable candidates for a novel experimental procedure with an unknown outcome, to a more directed screening with specific psychological domains for a complex infertility treatment with promising results. This report outlines a consensus by investigators with pioneering experience in the field of the key factors and suggests a framework for psychological evaluation of recipients and their partners as well as for live uterus donors before uterus transplant. We identify the main areas of particular value to the recipient screening (general psychological health, factors associated with infertility, and medication adherence), the partner (general psychological health and factors associated with infertility), and the living donor (psychological health and motivation to donate, especially in the case of the nondirected donor).