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

Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility
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DOI:
10.1097/01.ogx.0000557824.84633.0b
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发表时间:
2018-12
期刊:
The Lancet
影响因子:
--
通讯作者:
D. Ejzenberg;W. Andraus;L. Mendes;L. Ducatti;A. Song;R. Tanigawa;V. Rocha-Santos;R. Arantes;J. Soares;P. Serafini;L. Haddad;R. P. Francisco;L. D’Albuquerque;E. Baracat
D. Ejzenberg;W. Andraus;L. Mendes;L. Ducatti;A. Song;R. Tanigawa;V. Rocha-Santos;R. Arantes;J. Soares;P. Serafini;L. Haddad;R. P. Francisco;L. D’Albuquerque;E. Baracat
中科院分区:
其他
文献类型:
--
作者:
D. Ejzenberg;W. Andraus;L. Mendes;L. Ducatti;A. Song;R. Tanigawa;V. Rocha-Santos;R. Arantes;J. Soares;P. Serafini;L. Haddad;R. P. Francisco;L. D’Albuquerque;E. Baracat

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2014年,瑞典成功进行了一系列的子宫移植手术,活体供体子宫移植成为治疗不孕症的现实,鼓舞了全世界的子宫移植中心和项目。然而,据我们所知,没有一例通过已故供体子宫成功分娩的案例,这引起了对其可行性和活力的质疑,包括子宫在长期缺血后是否仍有活力。方法2016年9月,一名32岁先天性子宫缺失(mayer - rokitansky - k<s:1> ster- hauser [MRKH]综合征)的女性在巴西圣保罗大学das医院Clínicas接受了子宫移植手术,供体因蛛网膜下腔出血死亡。捐赠者45岁,有过三次阴道分娩经历。受者在移植前4个月进行一次体外受精,产生8个冷冻囊胚。结果患者术后恢复良好,住院观察8天后出院。用强的松龙和胸腺球蛋白诱导免疫抑制,并继续使用他克莫司和霉酚酸酯(MMF),直到移植后5个月,此时硫唑嘌呤取代MMF。第一次月经发生在移植后37天,此后定期(每26-32天)。妊娠发生在移植后7个月第一次单胚胎移植后。妊娠期子宫动脉、胎儿脐动脉、大脑中动脉血流速度波形未见异常,胎儿生长发育未见异常。移植后或妊娠期未发生排斥反应。她于2017年12月15日剖腹产,接近妊娠第36周。女婴出生时体重2550克,符合胎龄,1分钟时Apgar评分为9,5分钟时为10,10分钟时为10,产后7个月随母亲健康正常发育。子宫在相同的手术过程中切除,同时暂停免疫抑制治疗。我们描述,据我们所知,第一例活产后,子宫移植从一个已故供体患者MRKH综合征。研究结果证实了通过已故供体移植治疗子宫不孕症的概念,为所有子宫因素性不孕症妇女开辟了一条健康怀孕的道路,无需活体供体或活体供体手术。巴西圣保罗<e:1>大学<s:1> <s:1> <s:1>安帕罗基金会<e:1>和巴西圣保罗医院Clínicas。
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.