Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility.

BACKGROUND: Uterus transplantation from live donors became a reality to treat infertility following a successful Swedish 2014 series, inspiring uterus transplantation centres and programmes worldwide. However, no case of livebirth via deceased donor uterus has, to our knowledge, been successfully achieved, raising doubts about its feasibility and viability, including whether the womb remains viable after prolonged ischaemia. METHODS: In September, 2016, a 32-year-old woman with congenital uterine absence (Mayer-Rokitansky-Küster-Hauser [MRKH] syndrome) underwent uterine transplantation in Hospital das Clínicas, University of São Paulo, Brazil, from a donor who died of subarachnoid haemorrhage. The donor was 45 years old and had three previous vaginal deliveries. The recipient had one in-vitro fertilisation cycle 4 months before transplant, which yielded eight cryopreserved blastocysts. FINDINGS: The recipient showed satisfactory postoperative recovery and was discharged after 8 days' observation in hospital. Immunosuppression was induced with prednisolone and thymoglobulin and continued via tacrolimus and mycophenalate mofetil (MMF), until 5 months post-transplantation, at which time azathioprine replaced MMF. First menstruation occurred 37 days post-transplantation, and regularly (every 26-32 days) thereafter. Pregnancy occurred after the first single embryo transfer 7 months post-transplantation. No blood flow velocity waveform abnormalities were detected by Doppler ultrasound of uterine arteries, fetal umbilical, or middle cerebral arteries, nor any fetal growth impairments during pregnancy. No rejection episodes occurred after transplantation or during gestation. Caesarean delivery occurred on Dec 15, 2017, near gestational week 36. The female baby weighed 2550 g at birth, appropriate for gestational age, with Apgar scores of 9 at 1 min, 10 at 5 min, and 10 at 10 min, and along with the mother remains healthy and developing normally 7 months post partum. The uterus was removed in the same surgical procedure as the livebirth and immunosuppressive therapy was suspended. INTERPRETATION: We describe, to our knowledge, the first case worldwide of livebirth following uterine transplantation from a deceased donor in a patient with MRKH syndrome. The results establish proof-of-concept for treating uterine infertility by transplantation from a deceased donor, opening a path to healthy pregnancy for all women with uterine factor infertility, without need of living donors or live donor surgery. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo and Hospital das Clínicas, University of São Paulo, Brazil.

Markers of malnutrition after intestinal transplantation: the role of IGF-1 and calprotectin.

The objective of this study is to valuate two biomarkers that may guide nutritional assessment during follow up after intestinal transplantation. We performed a retrospective study on prospectively collected data of insulin-like growth factor-1 (IGF-1) and effluent calprotectin in patients undergoing intestinal transplantation. Optimal nutritional status (ONS) was defined by using the Malnutrition Universal Screening Tool (MUST). IGF-1 and calprotectin were correlated with ONS by Pearson correlation. Eighteen cadaveric intestinal transplants were performed over 1,650 days (median follow up 425 days, range 29-1,650 days). Mean IGF-1 and calprotectin were significantly associated with independent nutrition. Seven patients became malnourished on one or more occasions. During malnutrition the mean IGF-1 was 22 ± 14 ng/ml and calprotectin 1,597 ± 1,055 mcg/g. Mean weight during episodes of malnutrition changed from 64.77 ± 8.76 kg to 59.05 ± 8.5 kg (-8.9 ± 1.25%). Both IGF-1 and calprotectin negatively correlated with ONS (Pearson's r, -0.612, p = 0.014). Patients broadly aligned with three groups: nutritionally replete (normal IGF-1 and normal calprotectin), nutritionally equivocal (normal or low normal IGF-1 and high calprotectin), and malnourished (low IGF-1 and high calprotectin). Patients with low IGF-1 and high calprotectin may have a benign clinical presentation. However it is in their interests to have parenteral nutrition restarted pending further investigation.