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卵巢组织冷冻保存用于生育力保存的疗效:来自545例病例的经验教训。

Efficacy of ovarian tissue cryopreservation for fertility preservation: lessons learned from 545 cases.

作者信息

Jadoul P, Guilmain A, Squifflet J, Luyckx M, Votino R, Wyns C, Dolmans M M

机构信息

Gynecology Department, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCL) and Cliniques Universitaires Saint-Luc, Avenue Hippocrate, 10, 1200 Brussels, Belgium.

出版信息

Hum Reprod. 2017 May 1;32(5):1046-1054. doi: 10.1093/humrep/dex040.

Abstract

STUDY QUESTION

How effective is ovarian tissue cryopreservation (OTC)?

SUMMARY ANSWER

In our cohort of patients who underwent OTC, premature ovarian failure (POF) rates, return rates and pregnancy rates after autotransplantation were 31.5, 4.4 and 33%, respectively.

WHAT IS KNOWN ALREADY

OTC for fertility purposes has been performed for >20 years now. With over 86 live births reported worldwide and success rates of ~30% after autotransplantation of frozen-thawed ovarian cortex, the procedure should no longer be considered experimental. However, very few publications report the efficacy of this procedure.

STUDY DESIGN, SIZE, DURATION: Cases of ovarian tissue cryobanking for fertility preservation performed between 1997 and 2013 in a single institution were reviewed by analysis of the cryobank database and a prospective questionnaire sent out in March 2015.

PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 545 patients who underwent OTC during this period. The analysis included indications for OTC, survival rates, ovarian function and spontaneous pregnancies after OTC, come-back rates for ovarian tissue transplantation, pregnancy rates after transplantation, and complication and satisfaction rates.

MAIN RESULTS AND THE ROLE OF CHANCE

OTC was performed in this cohort at a mean age of 22.3 ± 8.8 years for oncological indications (79%), benign gynecological pathologies (17.5%) and genetic risks of POF (3.5%). Of the 545 patients, 29% were under 18 years of age at the time of OTC and 15% were prepubertal. While 10% of patients died from their disease, 21 patients (3.9%) underwent autotransplantation, 7 of whom delivered a healthy baby, yielding a post-transplantation live birth rate of 33%. Of 451 patients who were sent the questionnaire, 143 agreed to respond (32%). Nevertheless, ovarian function could not be evaluated in 36% of those who answered. Of 92 evaluable patients, 31.5% were menopausal and 68.5% showed persistent ovarian function. Of 52 women who attempted to conceive naturally, 37 were successful (71%). Among 140 patients who answered the questionnaire, 96% were satisfied with the procedure and only 1 major complication (intra-abdominal hemorrhage) was encountered. Among all the patients, 12% have donated their ovarian cortex for research purposes or have had it destroyed.

LIMITATIONS, REASONS FOR CAUTION: The questionnaire participation rate (32%), limited follow-up (mean 7.6 ± 3.5 years) and use of only clinical criteria for evaluation of ovarian function made it difficult to accurately assess the risk of POF and efficiency of OTC.

WIDER IMPLICATIONS OF THE FINDINGS

Our findings confirm a 30% pregnancy rate after ovarian cortex autotransplantation but also stress the difficulties of evaluating the real efficacy of OTC.

STUDY FUNDING/COMPETING INTEREST(S): No funding was sought for this study and none of the authors have any conflict of interest.

TRIAL REGISTRATION NUMBER

ClinicalTrials.gov Registration ID: CRYOFONOV01.

摘要

研究问题

卵巢组织冷冻保存(OTC)的效果如何?

总结答案

在我们接受OTC的患者队列中,自体移植后的卵巢早衰(POF)发生率、卵巢组织回植率和妊娠率分别为31.5%、4.4%和33%。

已知信息

为保存生育能力而进行的OTC已开展20多年。全球报告了超过86例活产,冻融卵巢皮质自体移植后的成功率约为30%,该手术不应再被视为实验性手术。然而,很少有出版物报道该手术的疗效。

研究设计、规模、持续时间:通过分析冷冻库数据库以及2015年3月发出的一份前瞻性调查问卷,对1997年至2013年在单一机构进行的用于生育力保存的卵巢组织冷冻保存病例进行了回顾。

参与者/材料、环境、方法:在此期间有545例患者接受了OTC。分析内容包括OTC的适应证、生存率、卵巢功能以及OTC后的自然妊娠情况、卵巢组织移植的回植率、移植后的妊娠率、并发症发生率和满意度。

主要结果及机遇的作用

该队列中进行OTC的患者平均年龄为22.3±8.8岁,适应证包括肿瘤性疾病(79%)、良性妇科疾病(17.5%)和POF的遗传风险(3.5%)。545例患者中,29%在进行OTC时年龄小于18岁,15%为青春期前患者。10%的患者死于疾病,21例患者(3.9%)接受了自体移植,其中7例产下健康婴儿,移植后的活产率为33%。在451例收到调查问卷的患者中,143例同意回复(32%)。然而,在回复者中,36%的患者卵巢功能无法评估。在92例可评估的患者中,31.5%处于绝经状态,68.5%显示持续的卵巢功能。在52例尝试自然受孕的女性中,37例成功(71%)。在140例回复调查问卷的患者中,96%对该手术满意,仅出现1例严重并发症(腹腔内出血)。在所有患者中,12%已将其卵巢皮质捐赠用于研究目的或已将其销毁。

局限性、谨慎原因:调查问卷的参与率(32%)、有限的随访时间(平均7.6±3.5年)以及仅使用临床标准评估卵巢功能使得难以准确评估POF的风险和OTC的效果。

研究结果的更广泛影响

我们的研究结果证实卵巢皮质自体移植后的妊娠率为30%,但也强调了评估OTC实际效果的困难。

研究资金/利益冲突:本研究未寻求资金支持,所有作者均无利益冲突。

试验注册号

ClinicalTrials.gov注册号:CRYOFONOV01

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