一个为期16年的双中心回顾性分析,对儿科单位进行卵巢组织冷冻保存的指征、结果和成果进行了研究。
A 16-year bicentric retrospective analysis of ovarian tissue cryopreservation in pediatric units: indications, results, and outcome.
发表日期:2023
作者:
Marine Grellet-Grün, Béatrice Delepine, Pauline Le Van Quyen, Gerlinde Avérous, Anne Durlach, Cécile Greze, Laetitia Ladureau-Fritsch, Isabelle Lichtblau, Anne-Sophie Canepa, Antoine Liné, Catherine Paillard, Claire Pluchart, Olivier Pirrello, Catherine Rongieres, Ghassan Harika, François Becmeur, Marius Teletin
来源:
Stem Cell Research & Therapy
摘要:
过去几十年来癌症治疗改善了儿童和青少年的生存率。然而,化疗和放疗会导致生殖腺损伤,导致急性卵巢功能衰竭和不育。保存生育力现在已经成为需要生殖毒性治疗的儿童护理的组成部分。卵巢组织冷冻保存(OTC)是一种有效的保留生育力的选择,它允许原始卵泡的长期存储,随后的移植以及内分泌功能和生育能力的恢复。这种技术在成年人中的有效性已经得到充分证明,但对儿科患者的数据很少。目前,OTC代表了保留青春期前女孩潜在生育力的唯一可能性。本研究是对两个法国中心自2004年1月至2020年5月进行的OTC实践的回顾性研究。共有72名小儿科患者在接受恶性或非恶性疾病的生殖毒性治疗之前进行了卵巢组织冷冻保存。卵巢皮质被切割成碎片,组织学评估每平方毫米的卵泡数量。长期随访包括存活率、荷尔蒙和生育状况。OTC时患者的平均年龄为9.3岁[0.2-17],其中29.2%为经过青春期的患者;51名患者患有恶性疾病,21名患者患有非恶性疾病。最常见的诊断包括急性白血病、血红蛋白病和神经母细胞瘤。进行OTC的指征对于81.9%(n = 59)的患者是干细胞移植。对于62.5%(n = 45)的患者,收集了三分之一的卵巢,对于33.3%(n = 24)的患者,收集了整个卵巢,对于4.2%(n = 3)的患者,收集了卵巢的三分之一。每个患者平均冷冻保存17个片段[5-35]。患者的年龄与片段数之间存在相关性(p < 0.001)。局部双侧收获比整个卵巢收获获得更多的片段(p < 0.05)。卵巢组织的组织学分析显示每平方毫米的原始卵泡中位数为6.0个[0.0-106.5],未检测到恶性细胞。年龄和卵泡密度之间存在负相关(p < 0.001)。平均采集后随访时间为92个月[1-188]。共有15名女孩死亡,11名仍在接受其病理治疗,46名完全缓解。所有患者中,29名(40.2%)接受了激素状态评估,其中26名被诊断为早发性卵巢功能不全(POI)(p < 0.001)。其中一名患者进行了解冻卵巢组织移植。对于所有有高风险患上生殖毒性治疗后可能发展POI的女孩,应该提供OTC以给予她们恢复生育力和内分泌功能的可能性的建议。Copyright © 2023 Grellet-Grün, Delepine, Le Van Quyen, Avérous, Durlach, Greze, Ladureau-Fritsch, Lichtblau, Canepa, Liné, Paillard, Pluchart, Pirrello, Rongieres, Harika, Becmeur and Teletin.
Cancer treatments of the last decades improve the survival rate of children and adolescents. However, chemo- and radiotherapy result in gonadal damage, leading to acute ovarian failure and sterility. The preservation of fertility is now an integral part of care of children requiring gonadotoxic treatments. Ovarian tissue cryopreservation (OTC) is an effective fertility preservation option that allows long-term storage of primordial follicles, subsequent transplantation, and restoration of endocrine function and fertility. The efficacy of this technique is well-demonstrated in adults but the data are scarce for pediatric patients. Currently, OTC represents the only possibility of preserving the potential fertility in prepubertal girls.This is a retrospective study of OTC practice of two French centers from January 2004 to May 2020. A total of 72 patients from pediatric units underwent cryopreservation of ovarian tissue before gonadotoxic therapy for malignant or non-malignant diseases. The ovarian cortex was cut into fragments and the number of follicles per square millimeter was evaluated histologically. The long-term follow-up includes survival rate and hormonal and fertility status.The mean age of patients at OTC was 9.3 years [0.2-17] and 29.2% were postpubertal; 51 had malignant diseases and 21 had non-malignant diseases. The most frequent diagnoses included acute leukemia, hemoglobinopathies, and neuroblastoma. Indication for OTC was stem cell transplantation for 81.9% (n = 59) of the patients. A third of each ovary was collected for 62.5% (n = 45) of the patients, a whole ovary for 33.3% (n = 24) of the patients, and a third of one ovary for 4.2% (n = 3) of the patients. An average of 17 fragments [5-35] per patient was cryoconserved. A correlation was found between the age of the patients and the number of fragments (p < 0.001). More fragments were obtained from partial bilateral harvesting than from whole ovary harvesting (p < 0.05). Histological analysis of ovarian tissue showed a median of 6.0 primordial follicles/mm2 [0.0-106.5] and no malignant cells were identified. A negative correlation was found between age and follicular density (p < 0.001). Median post-harvest follow-up was 92 months [1-188]. A total of 15 girls had died, 11 were still under treatment for their pathology, and 46 were in complete remission. Of all patients, 29 (40.2%) were subjected to a hormonal status evaluation and 26 were diagnosed with premature ovarian insufficiency (POI) (p < 0.001). One patient had undergone thawed ovarian tissue transplantation.OTC should be proposed to all girls with high risk of developing POI following gonadotoxic therapies in order to give them the possibility of fertility and endocrine restoration.Copyright © 2023 Grellet-Grün, Delepine, Le Van Quyen, Avérous, Durlach, Greze, Ladureau-Fritsch, Lichtblau, Canepa, Liné, Paillard, Pluchart, Pirrello, Rongieres, Harika, Becmeur and Teletin.