Prednisolone

New data from the Phase III PEACE III trial showed that XOFIGO ® (radium-223 dichloride) in combination with enzalutamide significantly improved prostate-specific antigen (PSA) response rates (≥90% at 6 and 12 months; 50.5% and 54.9% respectively) compared to enzalutamide alone (34.1% and 37.6% respectively) and the median time to alkaline phosphatase (ALP) normalization was 1.97 months for XOFIGO plus enzalutamide versus 4.47 months for enzalutamide alone (HR 1.42; 95% CI 1.13-1.80) among patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases Results from the Phase II COMRADE clinical trial demonstrated that the combination of olaparib with XOFIGO significantly improved radiographic progression-free survival (rPFS) compared to XOFIGO alone in mCRPC patients with bone metastases, with a median of 8.6 months versus 4.0 months (HR 0.51; 80% CI, 0.37-0.70; 2-sided p=0.005) Results from the two trials will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting WHIPPANY, N.J.--(BUSINESS WIRE)--New data from two clinical trials evaluating XOFIGO® (radium-223 dichloride) in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases will be presented at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting on June 3, 2025. The studies in prostate cancer treatment with XOFIGO, offer potential new insights for patients with mCRPC with bone metastases. XOFIGO is indicated for the treatment of patients with CRPC, symptomatic bone metastases and no known visceral metastatic disease.1 It is the first and only alpha emitting radiopharmaceutical that treats bone metastases in mCRPC approved by the U.S. Food and Drug Administration (FDA). An analysis from the pivotal Phase III PEACE III trial, evaluating XOFIGO in combination with enzalutamide, an androgen receptor pathway inhibitor (ARPI), showed that adding six cycles of XOFIGO to enzalutamide improved prostate-specific antigen (PSA) and alkaline phosphatase (ALP) response rates.2 Notably, PSA response rates ≥90% at 6 and 12 months were 50.5% and 54.9%, respectively, in the combination arm compared to 34.1% and 37.6%, respectively, in the enzalutamide arm alone.2 The analysis also showed that for XOFIGO in combination with enzalutamide the median time to ALP normalization was 1.97 months compared to 4.47 months in the enzalutamide arm (HR 1.42; 95% CI, 1.13-1.80).2 The analysis follows the presentation of the full results from the PEACE III trial, presented as a late-breaking abstract during the Presidential Symposium at ESMO 2024.3 The results demonstrated that the addition of XOFIGO to enzalutamide significantly increased radiological progression-free survival (rPFS) among patients with mCRPC with bone metastases, with a 31% reduction in the risk of progression or death (HR 0.69; 95% CI, 0.54-0.87; p=0.0009) compared to enzalutamide alone.3 At the preplanned interim analysis conducted at 80% of the overall survival (OS) events, the hazard ratio (HR) for OS was 0.69 (95% CI 0.52-0.90; p=0.0031). The safety results were consistent with the established safety profile of XOFIGO, although authors noted the importance of administering bone protective agents (BPAs) to avoid fractures.3 The trial was a collaboration between the European Organization for Research and Treatment of Cancer (EORTC), Clinical Trial Ireland (CTI), the Canadian Urological Oncology Group (CUOG), the Latin American Cooperative Oncology Group (LACOG), and French UNICANCER Urogenital Tumor Study Group (GETUG). The results were consistent with the established safety profile of XOFIGO. Grade 3 or higher treatment emergent adverse events (TEAE) were recorded in 65.6% of patients in the combination arm compared to 55.8% of patients who received enzalutamide alone.2 The most frequent Grade 3 or higher TEAEs in the combination arm were hypertension (34%), fatigue (6%), fracture (5%), anemia (5%) and neutropenia (5%).2 Fractures (either treatment-emergent or post-treatment, symptomatic or pathologic, or with or without BPA use) were reported in 24.3% of patients in the combination arm and in 13.4% of patients in the enzalutamide arm.2 "The PEACE III trial has provided us with valuable insights into the benefits of combining XOFIGO with enzalutamide for patients with metastatic castration-resistant prostate cancer with bone metastases," said Dr. Murilo Luz, Urologic Oncologist, The Mount Sinai Hospital, New York and trial investigator. "This analysis highlights that the combination therapy achieved improvements on PSA and ALP, beyond the known radiographic progression free survival benefit. We are encouraged by these results with this potential compelling therapeutic option, which could provide an additional treatment option for patients." Data from the Phase II COMRADE trial were also presented at the ASCO 2025 Annual Meeting. Results demonstrated that the combination of olaparib with XOFIGO significantly improved radiographic progression-free survival (rPFS) in mCRPC patients compared to XOFIGO alone, with a median of 8.6 months versus 4.0 months (HR 0.51; 80% CI, 0.37-0.70; 2-sided p=0.005).4 56% of patients in the olaparib with XOFIGO and 35% of patients in the XOFIGO arms had grade ≥3 treatment-related adverse events, the most common adverse events on the olaparib with XOFIGO and XOFIGO arms were anemia (22.0%/18.0%), lymphocyte decrease (30.5%/9.1%), platelet decrease (6.8%/3.6%), and neutrophil decrease (5.1%/7.3%), respectively.4 "The results from the PEACE III and COMRADE trials underscore our dedication to exploring combinations, such as XOFIGO with enzalutamide or olaparib. We are hopeful these results will introduce another treatment option for patients with mCRPC and bone metastases who have not progressed viscerally,” said Christine Roth, Executive Vice President, Global Product Strategy and Commercialization and Member of the Pharmaceuticals Leadership Team at Bayer. About PEACE III (EORTC GUCG-1333) The PEACE III trial is an international, randomized, open-label, Phase III trial designed to investigate the efficacy and safety of XOFIGO in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. A total of 446 patients were randomized 1:1 to receive either XOFIGO 55 kBq/kg as an intravenous injection monthly for six cycles in combination with enzalutamide 160mg orally daily or enzalutamide 160mg orally daily. The primary endpoint was radiological progression-free survival (rPFS) by investigator assessment. Key secondary endpoints included overall survival (OS), time to subsequent systemic treatment, pain progression, and symptomatic skeletal event. This trial was a collaboration with several cancer cooperative groups: EORTC, CTI, CUOG, LACOG, and GETUG. About COMRADE II COMRADE is an open-label, randomized Phase II investigator-initiated trial in patients with metastatic castration resistant prostate cancer with bone metastases treated with a combination of olaparib, a PARP inhibitor, and XOFIGO compared to XOFIGO alone, 120 patients were randomized 1:1 to receive either olaparib plus XOFIGO or XOFIGO alone. The primary endpoint was radiographic progression-free survival (rPFS). About XOFIGO® (radium-223 dichloride) Injection1 XOFIGO is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease. Important Safety Information for Xofigo® (radium-223 dichloride) Injection Warnings and Precautions: Bone Marrow Suppression: In the phase 3 ALSYMPCA trial, 2% of patients in the Xofigo arm experienced bone marrow failure or ongoing pancytopenia, compared to no patients treated with placebo. There were two deaths due to bone marrow failure. For 7 of 13 patients treated with Xofigo bone marrow failure was ongoing at the time of death. Among the 13 patients who experienced bone marrow failure, 54% required blood transfusions. Four percent (4%) of patients in the Xofigo arm and 2% in the placebo arm permanently discontinued therapy due to bone marrow suppression. In the randomized trial, deaths related to vascular hemorrhage in association with myelosuppression were observed in 1% of Xofigo-treated patients compared to 0.3% of patients treated with placebo. The incidence of infection-related deaths (2%), serious infections (10%), and febrile neutropenia (<1%) was similar for patients treated with Xofigo and placebo. Myelosuppression–notably thrombocytopenia, neutropenia, pancytopenia, and leukopenia–has been reported in patients treated with Xofigo. Monitor patients with evidence of compromised bone marrow reserve closely and provide supportive care measures when clinically indicated. Discontinue Xofigo in patients who experience life-threatening complications despite supportive care for bone marrow failure Hematological Evaluation: Monitor blood counts at baseline and prior to every dose of Xofigo. Prior to first administering Xofigo, the absolute neutrophil count (ANC) should be ≥1.5 × 109/L, the platelet count ≥100 × 109/L, and hemoglobin ≥10 g/dL. Prior to subsequent administrations, the ANC should be ≥1 × 109/L and the platelet count ≥50 × 109/L. Discontinue Xofigo if hematologic values do not recover within 6 to 8 weeks after the last administration despite receiving supportive care Concomitant Use With Chemotherapy: Safety and efficacy of concomitantchemotherapy with Xofigo have not been established. Outside of a clinical trial, concomitant use of Xofigo in patients on chemotherapy is not recommended due to the potential for additive myelosuppression. If chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy are administered during the treatment period, Xofigo should be discontinued Increased Fractures and Mortality in Combination With Abiraterone Plus Prednisone/Prednisolone: Xofigo is not recommended for use in combination with abiraterone acetate plus prednisone/prednisolone outside of clinical trials. At the primary analysis of the Phase 3 ERA-223 study that evaluated concurrent initiation of Xofigo in combination with abiraterone acetate plus prednisone/prednisolone in 806 asymptomatic or mildly symptomatic mCRPC patients, an increased incidence of fractures (28.6% vs 11.4%) and deaths (38.5% vs 35.5%) have been observed in patients who received Xofigo in combination with abiraterone acetate plus prednisone/prednisolone compared to patients who received placebo in combination with abiraterone acetate plus prednisone/prednisolone. Safety and efficacy with the combination of Xofigo and agents other than gonadotropin-releasing hormone analogues have not been established Embryo-Fetal Toxicity: The safety and efficacy of Xofigo have not been established in females. Xofigo can cause fetal harm when administered to a pregnant female. Advise pregnant females and females of reproductive potential of the potential risk to a fetus. Advise male patients to use condoms and their female partners of reproductive potential to use effective contraception during and for 6 months after completing treatment with Xofigo Administration and Radiation Protection: Xofigo should be received, used, and administered only by authorized persons in designated clinical settings. The administration of Xofigo is associated with potential risks to other persons from radiation or contamination from spills of bodily fluids such as urine, feces, or vomit. Therefore, radiation protection precautions must be taken in accordance with national and local regulations Fluid Status: Dehydration occurred in 3% of patients on Xofigo and 1% of patients on placebo. Xofigo increases adverse reactions such as diarrhea, nausea, and vomiting, which may result in dehydration. Monitor patients’ oral intake and fluid status carefully and promptly treat patients who display signs or symptoms of dehydration or hypovolemia Injection Site Reactions: Erythema, pain, and edema at the injection site were reported in 1% of patients on Xofigo Secondary Malignant Neoplasms: Xofigo contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure may be associated with an increased risk of cancer and hereditary defects. Due to its mechanism of action and neoplastic changes, including osteosarcomas, in rats following administration of radium-223, Xofigo may increase the risk of osteosarcoma or other secondary malignant neoplasms. However, the overall incidence of new malignancies in the randomized trial was lower on the Xofigo arm compared to placebo (<1% vs 2%; respectively), but the expected latency period for the development of secondary malignancies exceeds the duration of follow-up for patients on the trial Subsequent Treatment With Cytotoxic Chemotherapy: In the randomized clinical trial, 16% of patients in the Xofigo group and 18% of patients in the placebo group received cytotoxic chemotherapy after completion of study treatments. Adequate safety monitoring and laboratory testing was not performed to assess how patients treated with Xofigo will tolerate subsequent cytotoxic chemotherapy Adverse Reactions: The most common adverse reactions (≥10%) in the Xofigo arm vs the placebo arm, respectively, were nausea (36% vs 35%), diarrhea (25% vs 15%), vomiting (19% vs 14%), and peripheral edema (13% vs 10%). Grade 3 and 4 adverse events were reported in 57% of Xofigo-treated patients and 63% of placebo-treated patients. The most common hematologic laboratory abnormalities in the Xofigo arm (≥10%) vs the placebo arm, respectively, were anemia (93% vs 88%), lymphocytopenia (72% vs 53%), leukopenia (35% vs 10%), thrombocytopenia (31% vs 22%), and neutropenia (18% vs 5%). Please see the full Prescribing Information for Xofigo (radium 223 dichloride). About Oncology at Bayer Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2024, the Group employed around 93,000 people and had sales of 46.6 billion euros. R&D expenses before special items amounted to 6.2 billion euros. For more information, go to www.bayer.com. © 2025 Bayer BAYER, the Bayer Cross and XOFIGO are registered trademarks of Bayer. Find more information at www.pharma.bayer.com Our online press service is just a click away: www.bayer.us/en/newsroom Follow us on Facebook: http://www.facebook.com/pharma.bayer Follow us on X: https://X.com/BayerUS Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. References XOFIGO ® (radium-223) Injection [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, December 2019. Choudhury A, et al. PSA and alkaline phosphatase changes in the EORTC-1333 PEACE-3 study evaluating the addition of six cycles of radium 223 in metastatic castration-resistant prostate cancer (mCRPC) starting enzalutamide. Abstract 5062. Presented at ASCO 2025. Gillessen S, et al. A randomized multicenter open label phase III trial comparing enzalutamide vs a combination of Radium-223 (Ra223) and enzalutamide in asymptomatic or mildly symptomatic patients with bone metastatic castration-resistant prostate cancer (mCRPC): First results of EORTC-GUCG 1333/PEACE-3. European Society of Medical Oncology 2025 (ESMO) LBA1. September 9, 2024. McKay RR, et al. A multicenter, randomized, phase 2, investigator-initiated ETCTN trial of olaparib + radium-223 vs. radium-223 in men with castration-resistant prostate cancer (CRPC) with bone metastases (BM) (COMRADE): Initial efficacy and biomarker analysis. Abstract 5007. Presented at ASCO 2025.

引言每一个生命的降临，都是一次奇迹，是家庭的喜悦，更是对生命本身的礼赞。然而，对于世界上约五百分之一的育龄女性来说，这份生命的馈赠却被一道隐形的屏障所阻碍——她们渴望孕育，却被诊断为“子宫性不孕症”（Uterine Factor Infertility, UFI）。这片本该承载生命的摇篮，或先天缺失，或因疾病不幸移除，让为人母的梦想变得遥不可及。长久以来，面对这份心碎的诊断，她们的选择仅限于“收养”。然而，无论是血缘的渴望，还是复杂的伦理与法律困境，都让这些选项显得那么不尽完美，甚至充满无奈。想象一下，当生命的本能与现实的残酷正面碰撞，那份无力感该是何等沉重？但对生命与希望的追求，从未停止，一道新的曙光正缓缓升起——那就是革命性的“子宫移植”（Uterus Transplantation, UTx）技术！这项曾经被视为科幻的医学突破，正在一步步变为现实。它不仅让拥有自己亲生骨肉的梦想重燃，更赋予女性亲身经历怀孕、感受生命奇迹的机会。5月23日澳大利亚医学界传来一个振奋全球的重磅消息：澳大利亚皇家妇女医院（Royal Hospital for Women）的医疗团队，成功实现了澳大利亚首例活体子宫移植后的足月活产（live term birth）！这个新生命的诞生，不仅是医学史上的一个里程碑，更意味着对数百万子宫性不孕症患者的无声承诺：你们的梦想，正在被点亮！这不仅是一场精湛的外科手术，更是一次伦理、社会和科技的深度探索。它挑战了我们对生育、血缘和生命意义的传统认知。它带来了无尽的希望，也提出了新的问题。揭秘“子宫性不孕症”：生命的摇篮何以空缺？“子宫性不孕症”（Uterine Factor Infertility, UFI）是一个让许多女性心碎的诊断。它指的是由于子宫的缺失或功能障碍而导致的不孕。据统计，大约每500名育龄女性中就有一人面临UFI的困扰。想象一下，当一个女性渴望成为母亲，却被告知她无法提供一个健康的子宫来孕育生命时，这该是多么沉重的打击。造成UFI的原因多种多样，既有先天性因素，也有后天性因素。先天性子宫缺失，例如“米勒氏管发育不全”（Müllerian duct anomalies），意味着女性天生就没有子宫或子宫发育不完全。而更为常见的情况是，女性可能因为某些疾病或事故，不得不切除子宫。在这项研究的案例中，患者就是因为产后大出血（massive haemorrhage）而不得不进行子宫切除术（hysterectomy），从而失去了生育能力。对于这些女性来说，子宫移植不仅仅是一项手术，更是她们实现为人母梦想的唯一希望。传统上，面对UFI，收养和合法途径的代孕是仅有的选择。然而，这两种方式都各有其局限性。收养固然能带来家庭的完整，但无法满足一些女性对拥有亲生骨肉、体验妊娠过程的渴望。而代孕则牵涉到复杂的法律、伦理和社会问题。例如，在澳大利亚，商业代孕同样是被禁止的，这使得代孕母亲的招募变得非常困难，并且往往只能在“利他”的基础上进行。这种限制导致澳大利亚的“辅助生殖技术治疗周期”（assisted reproductive technology treatment cycles）中，代孕妊娠周期仅占极低的0.3%（2018年数据）。同时，跨国代孕的兴起，也引发了对潜在剥削和医疗风险的担忧。在这样的背景下，子宫移植作为一项创新性的生殖替代方案，正以其独特的优势，为这些女性提供了全新的可能性。澳洲首例，全球瞩目：UTx的里程碑子宫移植的概念自2000年代初期开始研究，但真正取得突破性进展是在2014年。那一年，瑞典团队在全球范围内首次成功实现了子宫移植后的活产，由一位活体捐赠者（living donor）提供的子宫孕育了一个健康的宝宝。自此以后，子宫移植技术在全球范围内得到了飞速发展。截至目前，全球已进行了超过80例子宫移植手术，其中有活体捐赠者提供的子宫，也有已故捐赠者（deceased donor）提供的子宫。这些手术已经成功带来了大约40例活产。澳大利亚在辅助生殖技术领域一直走在世界前沿，拥有坚实的基础和创新传统。早在1980年，世界上第三个通过体外受精（in vitro fertilisation, IVF）技术诞生的婴儿就在澳大利亚降生。1983年，澳大利亚又成功实现了世界上首例捐赠卵子（donor egg）和首例冷冻胚胎妊娠（frozen embryo pregnancy），这些都充分展示了澳大利亚对创新生殖解决方案的承诺。此次在澳大利亚皇家妇女医院、威尔士亲王医院和西米德医院启动的子宫移植研究项目，共招募了六名子宫性不孕症患者，并已成功进行了三例子宫移植手术，所有移植的子宫均来自于活体捐赠者。其中两名受者已经成功分娩了健康的活婴，而第三名受者也正在计划进行胚胎移植（embryo transfer）。该研究重点讨论的，正是这第一例在澳大利亚实现的子宫移植活产案例。这项研究于2023年1月10日在澳大利亚皇家妇女医院启动，并获得了西悉尼地方卫生区人类研究伦理委员会（Western Sydney Local Health District human research ethics committee）的批准，也已在澳大利亚和新西兰临床试验注册中心（Australian and New Zealand Clinical Trials registry）进行了前瞻性注册（注册号ACTRN12622000917730）。患者本人也提供了书面知情同意，允许其病例被公开。这项突破性的研究，不仅是对澳大利亚医学界的巨大肯定，也为全球子宫移植领域贡献了宝贵的经验。移植之路：一位母亲的勇气与坚持这例澳大利亚首例子宫移植活产的成功，凝结了患者、捐赠者、医疗团队的勇气、奉献与智慧。患者与捐赠者：血脉相连的爱这位勇敢的接受者（recipient）是一位31岁的女性，血型为A+，不吸烟，身体质量指数（BMI）为25.7kg/m²。她不孕的原因正是前文所述的产后大出血，导致子宫切除。在接受移植前，她唯一的日常用药是抗抑郁药氟西汀（fluoxetine），每天20毫克。她符合所有预设的移植资格标准。而令人感动的是，子宫的捐赠者（donor）是她的53岁母亲。同样是A+血型，母亲之前曾两次足月经阴道分娩（vaginal delivery），没有吸烟史，身体质量指数（BMI）为26.8kg/m²，且尚未绝经（menopause）。母女之间的“人白细胞抗原”（Human Leukocyte Antigen, HLA）错配程度为3/6，属于可接受范围。移植前，未检测到针对捐赠者的“HLA特异性抗体”（anti-HLA donor-specific antibodies），流式细胞术（flow cytometry）也未发现T细胞或B细胞交叉配型不匹配。此外，母女双方的巨细胞病毒（cytomegalovirus, CMV）检测结果均为阴性（IgG-negative），而EBV检测结果均为阳性（IgG-positive）。这些详细的配型和病毒筛查，是确保移植成功和降低术后风险的关键步骤。母亲的无私奉献，无疑是这场生命接力中最动人的一笔。免疫抑制方案：精密的平衡子宫移植与任何器官移植一样，都面临着“免疫排斥”（organ rejection）的巨大挑战。为了防止受者自身的免疫系统攻击并摧毁移植的子宫，必须实施精密的“免疫抑制方案”（immunosuppression regimen）。这项研究中采用的方案，与用于低免疫学风险肾脏移植（low immunologic risk kidney transplantation）的方案相似，旨在达到最佳的免疫抑制效果，同时最大限度地降低药物副作用。移植手术当天（第0天）和术后第4天，受者接受了两次20毫克的“巴利昔单抗”（basiliximab）静脉注射。同时，在手术当天和术后第1天，还静脉注射了“甲泼尼龙”（methylprednisolone）。这构成了“诱导治疗”（induction therapy）的一部分，旨在迅速降低免疫反应。在诱导治疗之后，受者开始接受“维持治疗”（maintenance therapy），这包括每日口服“他克莫司”（tacrolimus）、“泼尼松龙”（prednisolone）和“吗替麦考酚酯”（mycophenolate mofetil, MMF）。他克莫司的口服剂量为每日两次，其谷浓度（trough target levels）在移植初期（术后9至11毫微克/毫升）和怀孕期间（术后5至8毫微克/毫升）都有严格的监测和调整。泼尼松龙最初每天25毫克，在接下来的12周内逐渐减量，最终调整到每日5毫克的低维持剂量。吗替麦考酚酯（MMF）最初每天两次各1克，在术后第3周减量至每日两次各750毫克。值得注意的是，在术后第9周，MMF被“硫唑嘌呤”（azathioprine）取代（每日2毫克/公斤，或绝对剂量每日150毫克），这一调整是在确认受者“硫嘌呤甲基转移酶”（thiopurine methyltransferase）活性正常后进行的。选择硫唑嘌呤是因为其在孕妇中具有更好的安全性。整个怀孕期间，他克莫司持续使用，并根据胎儿安全性考虑，将目标水平降低至怀孕前剂量的60%（目标水平为5-7毫微克/毫升）。为了确保免疫抑制的有效性并及时发现潜在问题，医疗团队对受者进行了严密的监测。术后第一个月，受者每周三次接受威尔士亲王医院移植团队的审查；第三个月末，审查频率降至每两周一次。每次访视都进行详细的病理学（pathology）检查，包括血液学（haematology）、血清生化（serum biochemistry）（包括肾功能和他克莫司谷浓度）、尿液显微镜检查和培养（urine microscopy and culture），以及蛋白尿（proteinuria）检测。同时，还会评估临床参数，如体重和血压。为了预防感染，受者还接受了抗病毒药（伐昔洛韦, valaciclovir）、抗真菌药（氟康唑, fluconazole，随后是制霉菌素, nystatin drops）和抗肺孢子虫肺炎药（复方新诺明, trimethoprim/sulfamethoxazole）的预防性治疗，这些药物在胚胎移植前停用。最令人鼓舞的是，在整个孕期中，受者没有出现任何器官排斥（rejection）的迹象。这表明医疗团队的免疫抑制方案是成功的，为胎儿的健康发育提供了稳定的内部环境。然而，值得一提的是，免疫抑制的副作用也随之而来，包括病毒性胃肠道感染（viral gastrointestinal infection）和上呼吸道感染（upper respiratory tract infections），这些都是免疫力下降后的常见情况，需要医疗团队的及时处理和干预。孕期之路：期待新生命子宫移植手术后，医疗团队对移植子宫的功能进行了严密监测。在术后，子宫内膜厚度（endometrial thickness）和子宫血供（uterine vascularity）通过超声（ultrasound）和多普勒成像（Doppler imaging）进行监测。在术后第一天以及每次宫颈活检（cervix biopsy）时，都进行了评估。腹部探头放置在腹股沟韧带（inguinal ligament）上方，以评估两侧子宫动脉（uterine arteries）和四个静脉出口的动脉血流速度波形（arterial flow velocity waveforms）。在术后第一个月，每周进行宫颈活检以监测排斥迹象；第二个月，每两周一次；直到怀孕开始，之后在每个孕期进行一次评估。在移植和分娩之间，共采集了九份宫颈活检样本，并根据瑞典团队开发的评分系统进行了组织学评估，以判断是否存在器官排斥。在经历了子宫移植手术的恢复期后，医疗团队选择了最佳时机进行胚胎移植。在子宫移植手术101天（即15周）后，也是吗替麦考酚酯（MMF）治疗停止6周后，一枚“冷冻1级胚胎”（frozen grade 1 blastocyst）在受者的自然排卵周期（natural ovulatory cycle）中被移植入子宫。这一选择背后的考量是为了尽量缩短免疫抑制药物的使用时间，特别是考虑到MMF可能对胎儿的毒性作用。移植后112天，临床妊娠（clinical pregnancy）成功确立，生命之光开始在这片新的土壤中萌芽。怀孕早期，在第7周时，受者出现了早期妊娠出血（early pregnancy bleeding）。尽管超声检查显示胎儿心率（fetal heart rate）良好，且未发现出血原因，这仍让医疗团队和患者保持高度警惕。从孕12周到34周，受者每两周进行一次血压和尿液分析（包括镜检和蛋白尿）检查，34周后改为每周一次，直至分娩。孕期筛查项目也全面展开。在孕11或12周时，进行了“早期妊娠血浆蛋白A”（pregnancy-associated plasma protein A, PAPP-A）、“人绒毛膜促性腺激素”（human chorionic gonadotropin, β-hCG）、“胎盘生长因子”（placental growth factor, PGF）和炎症标志物（inflammatory markers）的筛查。同时，还评估了铁储备（iron store）、肝肾功能（liver and renal function），并进行了“口服葡萄糖耐量试验”（oral glucose tolerance testing, OGTT）。在孕12周或13+6周时，进行了“颈项透明层扫描”（nuchal translucency scanning）以筛查染色体异常（chromosomal abnormalities）和“子痫前期”（pre-eclampsia）风险，并进行了巨细胞病毒（CMV）IgM和IgG检测。从孕16周到34周，定期测量宫颈长度（cervical length）。在孕20周时，通过OGTT检测，受者被诊断出患有“妊娠期糖尿病”（gestational diabetes mellitus）。考虑到她长期使用类固醇（steroid），这被推测为是药物引起的。因此，医疗团队开始对她进行长效胰岛素治疗（long acting insulin treatment），并根据血糖情况调整剂量，最高达到每日26单位。在孕20周时，还进行了详细的胎儿解剖扫描（fetal anatomical scan），以确保胎儿的正常发育。在孕28周和34周时，再次进行了铁、血常规（full blood count）、尿素（urea）、电解质（electrolytes）和肌酐（creatinine）评估，以及肝肾功能检查和抗体筛查。整个孕期中，医疗团队密切结合子宫移植功能评估与胎儿生长发育监测。通过超声评估子宫动脉和脐动脉的“搏动指数”（pulsatility index），并与澳大利亚正常参考值进行比较，确认了胎儿的正常生长和胎盘功能。免疫抑制治疗中的他克莫司、硫唑嘌呤和泼尼松龙持续使用。在孕35周时，受者因头痛和恶心入院，但检查显示血压正常，并在24小时内出院。这个过程中，医疗团队的精细管理和患者的积极配合，是确保胎儿健康成长的关键。爱的降临：分娩与新生经过漫长而充满希望的等待，新生命终于在期待中降临。分娩细节：迎接生命在孕37周时，受者被安排进行了择期剖宫产（elective caesarean delivery）。手术前，她接受了“腰椎-硬膜外联合麻醉”（combined spinal-epidural anaesthesia）以及1克静脉注射“止血环酸”（tranexamic acid）以预防大出血。胎儿呈头位（cephalic position）。手术过程严格按照标准流程进行。医生沿着受者腹部的原有疤痕（从肚脐下方到耻骨联合, below the navel to the pubic bone）进行了正中线开腹切口（midline laparotomy incision）。在切开皮肤后13分钟，又进行了子宫下段切口（lower segment uterine incision），胎儿顺利娩出。脐带正常，有三根血管，无炎症迹象。胎儿娩出后，子宫对10单位肌内注射（intramuscular）催产素（oxytocin）和40单位静脉输注（infused）催产素反应良好，收缩有力。子宫切口采用双层缝合（two layer closure）。手术中，估计的失血量为2.5升，主要来源于左侧子宫静脉复合体（left uterine venous complex），医护人员在此处进行了额外的止血缝合。尽管失血量较大，但受者在术中并未接受输血。分娩前的血红蛋白（haemoglobin）水平为109克/升，分娩后降至77克/升。为了补充铁，受者在产后立即开始接受铁剂输注。在分娩五天后，母婴平安出院。新生儿状况：生命的奇迹这个备受期待的小生命，在出生时各项指标均非常健康。他出生时体重为2990克，身长49厘米，头围34厘米。新生儿的“阿普加评分”（Apgar scores）在出生后1分钟为7分，5分钟时达到9分，这表明他出生时适应良好，生命体征稳定。脐动脉（umbilical artery）的pH值为7.22，脐静脉（umbilical venous）的pH值为7.31，这些数值也都在正常范围内，反映了胎儿在子宫内和分娩过程中的良好氧合状态。尽管出生后婴儿表现出轻微的呼吸窘迫（mildly increased respiratory effort），但通过气道吸引（airway suction）和持续气道正压氧疗（continuous positive airway pressure oxygen therapy）十分钟后，情况迅速好转，他不需要转入重症监护室（intensive care nursery）或接受特殊护理。婴儿出生后顺利开始母乳喂养（breastfed）。在出生后第三天，他出现了轻度黄疸（mild jaundice），并在医院接受了光疗（light therapy）处理。这些都显示了新生儿的健康状况良好，并且在新生儿护理方面得到了及时有效的干预。产后护理与挑战：漫漫康复路母亲在分娩后五天顺利出院。免疫抑制治疗仍在继续，同时为了预防血栓（thrombosis），她还接受了六周的依诺肝素钠（enoxaparin sodium）皮下注射（每日0.4毫升40毫克）。为了支持产后恢复，她还服用了止痛药（analgesics）和泻药（laxatives）。然而，产后并非一帆风顺。出院三天后，她出现了乳腺炎（mastitis），并联系了皇家妇女医院的子宫移植团队。她被转诊到当地医院，接受了口服和静脉注射抗生素治疗。此后，她又经历了两次乳腺炎发作。在产后8周，她开始逐渐断奶（weaning），并在产后12周完全停止母乳喂养。移植子宫的监测也持续进行。产后六周进行的第一次宫颈活检（cervix biopsy）未发现任何器官排斥的迹象。然而，在2024年5月22日和6月3日进行的后续宫颈活检中，检测到了炎症（inflammation）和非特异性排斥（non-specific rejection）的迹象。更进一步的血液检查（2024年5月8日和7月1日）也检测到了“捐赠者特异性抗体”（donor-specific antibodies），这证实了免疫排斥正在发生。为了治疗排斥，受者作为门诊病人接受了连续三天的静脉注射甲泼尼龙（500毫克/天）治疗（2024年7月2日至4日）。尽管接受了治疗，后续的活检仍显示炎症变化与持续性排斥（ongoing rejection）一致。在综合考虑进一步治疗的必要性及其潜在副作用后，受者最终选择在2024年9月12日接受了“子宫摘除术”（explant hysterectomy）。手术通过腹腔镜（laparoscopically）进行，历时2.25小时。手术后，免疫抑制药物（泼尼松龙）的剂量逐渐减少（每月2毫克），并最终于2025年1月10日完全停用。尽管母亲经历了这些挑战，但令人欣慰的是，孩子在出生后一直健康成长。截至目前，婴儿已经15个月大，各项发育指标均达到了预期的里程碑，这无疑是整个医疗团队和家庭最大的慰藉。UTx的深远影响与挑战澳大利亚首例活产的成功，不仅为子宫性不孕症患者带来了福音，也为全球子宫移植领域树立了新的标杆。这项研究的成功，使得从子宫移植到活产的时间，在单一年份内完成，成为迄今为止最短的记录。在瑞典首例UTx成功后，移植子宫在怀孕前通常需要稳定一年；而美国报告的胚胎移植时间最短也达到了移植后183天。此次澳大利亚的经验，将胚胎移植时间缩短至移植后101天（即15周），临床妊娠在移植后112天确立。这种策略不仅缩短了免疫抑制药物的使用时间，降低了潜在的副作用，也大大缩短了患者等待生育的时间，从而减轻了患者的心理和经济负担。然而，子宫移植作为一项复杂且高度专业的医疗程序，其未来发展仍需面对诸多挑战和深思熟虑。伦理与社会考量：生命的重量与责任子宫移植手术不仅仅是外科技术的挑战，更是一系列复杂伦理问题的交织。活体捐赠者的风险与权利： 在该案例中，子宫由患者的母亲捐赠，这属于活体捐赠。活体捐赠者需要经历一次大型手术，伴随着并发症的风险和长期的健康影响。例如，在国际子宫移植协会（International Society of Uterus Transplantation, ISUTx）的登记数据中，35名活体捐赠者中有7名报告了并发症，其中3名被归类为Clavien-Dindo III级或更高，需要手术或介入治疗。因此，确保捐赠者在充分知情、完全自愿且无任何胁迫的情况下作出决定至关重要，尤其是在家庭成员之间进行捐赠时。澳大利亚捐赠者康复良好，表明了安全操作的重要性。长期结果的不确定性： 无论是捐赠者、受者，还是通过移植子宫诞生的孩子，其长期的医疗和心理影响目前仍是未知的。因此，持续的研究和监测对于全面评估UTx的真实效益和风险至关重要。医疗资源的公平分配： 子宫移植是一项耗资巨大且对技术要求极高的医疗程序。将大量的医疗和财政资源投入到UTx，可能会加剧医疗保健领域的不平等，引发关于公平性和可及性的质疑。如何平衡资源分配，确保更多患者能够获得所需的医疗服务，是社会必须面对的挑战。心理影响： 子宫移植对捐赠者和受者的心理影响也不容忽视，包括手术失败可能带来的情感压力。因此，提供全面的心理支持和咨询服务，对于确保患者的身心健康至关重要。子宫的非永久性： 子宫移植并非一劳永逸。大多数移植方案规定，子宫会在完成一到两次成功妊娠后，或在移植后的五年内移除。这意味着受者无法终身保留移植的子宫，这也需要患者有充分的心理准备。成本与效益：一场复杂的算计评估子宫移植的成本效益，是决定其能否在澳大利亚推广的关键。尽管UTx的成本高昂，但与其他不孕不育治疗方案相比，其成本效益并非不可接受。UTx的成本： 根据瑞典首次子宫移植案例的成本分析，包括术前检查、体外受精（IVF）和活体捐赠者子宫移植手术以及术后两个月的费用，总计约12万美元。近年来，由于手术技术的进步、早期胚胎移植以及缩短妊娠等待时间，UTx的成本已有所下降。与其他方案的比较：利他代孕： 在澳大利亚，利他代孕的费用在3.5万至10万美元之间。商业代孕： 在美国，寻求妊娠代孕的费用估计在10万至20万美元之间。值得注意的是，每一次代孕尝试都会产生新的费用。反复IVF： 对于因其他原因导致不孕且预后较差的女性，反复进行卵子刺激（oocyte stimulation）和胚胎移植的费用也可能非常高。例如，一项近期分析显示，对于41-42岁的女性，通过无限制的医疗保险（Medicare）资助实现活产的成本约为76759美元；而对于45岁以上的女性，这一数字飙升至436694美元。综合来看，子宫移植在每例活产的成本上，与代孕等其他方案是相似的。然而，子宫移植的独特优势在于，它将怀孕的风险转移到了意向母亲（intending mother）身上，而非第三方代孕者，这在伦理和法律上具有重要意义。澳洲模式的优势澳大利亚在实体器官移植方面取得了世界领先的临床成果，这得益于其独特的医疗体系和强大的研究协作文化。将这些优势应用于子宫移植领域，有望确保UTx在澳大利亚的成功推广和可持续发展。政府资助的医疗体系： 澳大利亚的医疗体系为公民提供终身政府资助的医疗保健，包括医生费用、检查、药物和住院费用。这种模式确保了患者在治疗过程中能够获得持续的经济支持，减轻了因高昂医疗费用而放弃治疗的风险。全面的数据获取和报告： 澳大利亚拥有完善的成果数据获取和报告机制，数据定期向医疗服务提供者和公众公布。这种透明度有助于持续改进医疗服务质量，发现潜在问题，并促进最佳实践的形成。强大的监管和研究文化： 澳大利亚拥有健全的监管框架、强大的研究-临床协作文化和专业的临床教育体系，这些都为辅助生殖技术的高标准发展提供了保障。澳大利亚UTx研究团队也积极参与了澳大利亚和新西兰移植学会（Transplantation Society of Australia and New Zealand）相关指南的制定，旨在建立活体和已故捐赠者路径的监管框架。参与国际合作： 澳大利亚UTx团队积极向国际子宫移植协会（ISUTx）注册中心贡献数据。由于全球UTx手术数量有限，这种国际合作对于收集和传播信息、确保从研究到临床实践的安全转化至关重要。已故捐赠者的潜力： 尽管目前大多数UTx活产案例都来自活体捐赠者，但考虑到活体捐赠的并发症风险，越来越多地考虑使用已故捐赠者（deceased donor）的子宫将是未来的重要方向。已故捐赠者子宫的器官存活率和活产率虽然略低于活体捐赠者，但随着技术的进步，这一差距正在缩小。澳大利亚的已故器官捐赠者数量在2022年比2021年增加了7.8%，将子宫获取纳入多器官捐赠（multi-organ donation）流程，有望为安全有效的UTx临床服务铺平道路。中心化与公平可及： 像子宫移植这种高成本、低容量、高度专业化的医疗程序，集中化（centralising）管理将有助于优化专业知识、确保最佳实践。将UTx纳入受监管的公共医疗服务体系，能够促进公平可及性，减少患者寻求“医疗旅游”的需要，并与世界卫生大会（World Health Assembly）保护发展中国家人民免受器官和组织剥削的原则相符。澳大利亚子宫移植首例活产的成功，不仅仅是医学技术上的胜利，它更代表着对生命的尊重，对人性的关怀，以及人类对探索未知、突破极限的永恒追求。子宫移植为子宫性不孕症女性带来了新的希望，使她们能够体验怀孕，并与自己的孩子建立生物学上的血缘联系。对患者而言， 这意味着曾经遥不可及的生物学亲子梦想成为现实。她们不仅能拥有与自己血脉相连的骨肉，更能够亲身经历怀孕十月的奇妙旅程，感受胎动，体验分娩的艰辛与喜悦。这对于长期饱受不孕困扰的女性而言，不仅是生理上的修复，更是心理上和情感上的巨大慰藉，极大地提升了她们的生活质量和幸福感。即便最终子宫需要移除，这份亲身孕育的经历，也足以成为她们生命中最珍贵的财富。对医生和医学界而言， 这项成功意味着生殖医学边界的进一步拓展。它验证了复杂移植手术的可行性，深化了对免疫抑制管理、孕期风险评估和产后并发症处理的理解。每一次成功的UTx，都为医疗团队积累了宝贵的经验，有助于他们不断完善手术技术、优化治疗方案、提高患者预后。同时，这项研究也激励着更多医学专业人士投身到前沿医学研究中，培养出更多跨学科的专业人才，推动整个生殖医学和移植医学领域向前发展。同时澳大利亚建立受监管的、高标准的子宫移植中心，将可能吸引来自全球寻求高质量、伦理规范的子宫移植服务的患者。这不仅能促进澳大利亚医疗服务出口，也能带动相关医疗器械、药物研发、专业人才培训等产业的发展，为国家带来可观的经济效益。UTx的成功需要外科手术、免疫学、辅助生殖技术、围产医学（perinatology）等多个学科的紧密协作。这必然会刺激相关领域的科技创新，例如，更精准的成像技术、更安全的免疫抑制药物、更先进的器官保存和移植技术等。这些创新不仅服务于子宫移植，也可能为其他器官移植和生殖健康领域带来溢出效应。子宫移植仍是一项低容量、高度技术化的程序。它的成功和安全性，将继续依赖于持续的研究、国际合作、以及由经验丰富的多学科团队提供的严格审查和支持。参考文献Deans R, Gerstl B, Shand AW, et al. The first live term birth following uterus transplantation in Australia. Med J Aust. Published online May 23, 2025. doi:10.5694/mja2.52682责编|探索君排版|探索君转载请注明来源于【生物探索】声明：本文仅用于分享，不代表平台立场，如涉及版权等问题，请尽快联系我们，我们第一时间更正，谢谢！End往期精选围观Nature | 靶向线粒体VDAC2：破解实体瘤免疫治疗抵抗的"死亡密钥"热文Nature Medicine | 多囊女性子宫内膜藏着什么秘密？——全球首份单细胞图谱揭示治疗新方向热文Nature | 颠覆认知！大脑学习的惊人秘密：你的“潜伏知识”是如何瞬间爆发的？热文Cell | 颠覆认知！染色体形成并非依赖“骨架”，自组织模型重塑教科书热文Science | 为什么我们回想不起三岁前的经历?