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在控制性卵巢刺激后,卵巢组织冷冻保存可与卵母细胞采集同时进行。

Ovarian tissue cryopreservation can be combined simultaneously with oocyte retrieval after controlled ovarian hyperstimulation.

作者信息

Puy Vincent, Dupeux Margot, Mayeur Anne, Grynberg Michael, Benoit Alexandra, Bendayan Marion, Zhegari Fayçal, Hesters Laetitia, Gallot Vanessa, Prevot Sophie, Frydman Nelly, Sonigo Charlotte

机构信息

Université Paris-Saclay, Assistance Publique Hôpitaux de Paris, Hôpital Béclère, Service de Biologie de la Reproduction CECOS, Clamart, France.

Laboratoire de Développement des Gonades, UMRE008 Stabilité Génétique Cellules Souches et Radiations, Université de Paris, Université Paris-Saclay, CEA, Fontenay-aux-Roses, France.

出版信息

Hum Reprod. 2023 May 2;38(5):860-871. doi: 10.1093/humrep/dead041.

Abstract

STUDY QUESTION

Can ovarian tissue cryopreservation (OTC) be performed after controlled ovarian hyperstimulation (COH)?

SUMMARY ANSWER

Unilateral oophorectomy after transvaginal oocyte retrieval is feasible on stimulated ovaries during one surgical step.

WHAT IS KNOWN ALREADY

In the fertility preservation (FP) field, the timeframe between patient referral and start of curative treatment is limited. Combining oocyte pick-up with ovarian tissue (OT) extraction has been reported to improve FP but COH applied before OT extraction is not currently recommended.

STUDY DESIGN, SIZE, DURATION: This retrospective cohort-controlled study involved 58 patients who underwent oocyte cryopreservation immediately followed by OTC between September 2009 and November 2021. The exclusion criteria were a delay between oocyte retrieval and OTC of >24 h (n = 5) and IVM of oocytes obtained ex vivo in the ovarian cortex (n = 2). This FP strategy was performed either after COH (stimulated group, n = 18) or after IVM (unstimulated group, n = 33).

PARTICIPANTS/MATERIALS, SETTING, METHODS: Oocyte retrieval followed by OT extraction on the same day was performed either without previous stimulation or after COH. Adverse effects of surgery and ovarian stimulation, mature oocyte yield and pathology findings of fresh OT were retrospectively analysed. Thawed OTs were analysed prospectively, for vascularization and apoptosis using immunohistochemistry, when patient consent was obtained.

MAIN RESULTS AND THE ROLE OF CHANCE

No surgical complication occurred after OTC surgery in either group. In particular, no severe bleeding was associated with COH. The number of mature oocytes obtained increased after COH (median = 8.5 (25% = 5.3-75% = 12.0)) compared to the unstimulated group (2.0 (1.0-5.3), P < 0.001). Neither ovarian follicle density nor cell integrity was affected by COH. Fresh OT analysis showed congestion in half of the stimulated OT which was higher than in the unstimulated OT (3.1%, P < 0.001). COH also increased haemorrhagic suffusion (COH + OTC: 66.7%; IVM + OTC: 18.8%, P = 0.002) and oedema (COH + OTC: 55.6%; IVM + OTC: 9.4%, P < 0.001). After thawing, the pathological findings were similar between both groups. No statistical difference in the number of blood vessels was observed between the groups. The oocyte apoptotic rate in thawed OT was not statistically different between the groups (ratio of positive cleaved caspase-3 staining oocytes/total number of oocytes equal to median 0.50 (0.33-0.85) and 0.45 (0.23-0.58) in unstimulated and stimulated groups respectively, P = 0.720).

LIMITATIONS, REASONS FOR CAUTION: The study reports FP from a small number of women following OTC. Follicle density and other pathology findings are an estimate only.

WIDER IMPLICATIONS OF THE FINDINGS

Unilateral oophorectomy can be successfully performed after COH with limited bleeding risk and an absence of impact on thawed OT. This approach could be proposed to post pubertal patients when the number of mature oocytes expected is low or when the risk of residual pathology is high. The reduction of surgical steps for cancer patients also has positive implications for introducing this approach into clinical practice.

STUDY FUNDING/COMPETING INTEREST(S): This work was made possible through the support of the reproductive department of Antoine-Béclère Hospital and of the pathological department of Bicêtre Hospital (Assistance Publique Hôpitaux de Paris, France). The authors have no conflict of interest to disclose in this study.

TRIAL REGISTRATION NUMBER

N/A.

摘要

研究问题

在控制性卵巢刺激(COH)后能否进行卵巢组织冷冻保存(OTC)?

总结答案

在经阴道取卵后进行单侧卵巢切除术,在一个手术步骤中对受刺激的卵巢进行操作是可行的。

已知信息

在生育力保存(FP)领域,从患者转诊到开始根治性治疗的时间有限。据报道,将取卵与卵巢组织(OT)提取相结合可改善生育力保存,但目前不建议在OT提取前应用COH。

研究设计、规模、持续时间:这项回顾性队列对照研究纳入了2009年9月至2021年11月期间58例接受卵母细胞冷冻保存后立即进行OTC的患者。排除标准为取卵与OTC之间延迟>24小时(n = 5)以及在卵巢皮质中体外获得的卵母细胞进行体外成熟培养(IVM)(n = 2)。这种FP策略在COH后(刺激组,n = 18)或IVM后(未刺激组,n = 33)进行。

参与者/材料、设置、方法:在同一天进行取卵后再进行OT提取,要么是在未预先刺激的情况下,要么是在COH后。回顾性分析手术和卵巢刺激的不良反应、成熟卵母细胞产量以及新鲜OT的病理结果。当获得患者同意时,对解冻后的OT进行前瞻性分析,采用免疫组织化学方法分析血管化和细胞凋亡情况。

主要结果及机遇的作用

两组在OTC手术后均未发生手术并发症。特别是,COH未导致严重出血。与未刺激组相比,COH后获得的成熟卵母细胞数量增加(中位数 = 8.5(25% = 5.3 - 75% = 12.0)),未刺激组为2.0(1.0 - 5.3),P < 0.001)。COH对卵巢卵泡密度和细胞完整性均无影响。新鲜OT分析显示,受刺激的OT中有一半出现充血,高于未刺激的OT(3.1%,P < 0.001)。COH还增加了出血性渗出(COH + OTC:66.7%;IVM + OTC:18.8%,P = 0.002)和水肿(COH + OTC:55.6%;IVM + OTC:9.4%,P < 0.001)。解冻后,两组的病理结果相似。两组之间血管数量无统计学差异。解冻后OT中卵母细胞的凋亡率在两组之间无统计学差异(未刺激组和刺激组中裂解的半胱天冬酶 - 3染色阳性卵母细胞/卵母细胞总数的比例分别等于中位数0.50(0.33 - 0.85)和0.45(0.23 - 0.58),P = 0.720)。

局限性、谨慎原因:该研究报告了少量女性在OTC后的生育力保存情况。卵泡密度和其他病理结果仅为估计值。

研究结果的更广泛影响

在COH后可以成功进行单侧卵巢切除术,出血风险有限,且对解冻后的OT无影响。当预期成熟卵母细胞数量较少或残留病理风险较高时,可将这种方法推荐给青春期后患者。减少癌症患者的手术步骤对将这种方法引入临床实践也具有积极意义。

研究资金/利益冲突:这项工作得益于安托万 - 贝克莱尔医院生殖科和比塞特尔医院病理科(法国巴黎公共救助医院)的支持。作者在本研究中没有利益冲突需要披露。

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无。

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