BACKGROUND Ovarian tissue cryopreservation involves freezing and storing of surgically retrieved ovarian tissue in liquid or vapour nitrogen below –190°C. The tissue can be thawed and transplanted back with the aim of restoring fertility or ovarian endocrine function. The techniques for human ovarian tissue freezing and transplantation have evolved over the last 20 years, particularly in the context of fertility preservation in pre-pubertal cancer patients. Fresh ovarian tissue transplantation, using an autograft or donor tissue, is a more recent development; it has the potential to preserve fertility and hormonal function in women who have their ovaries removed for benign gynaecological conditions. The techniques of ovarian tissue cryopreservation and transplantation have progressed rapidly since inception; however, the evidence on the success of this intervention is largely based on case reports and case series. OBJECTIVE AND RATIONALE The aim of this study was to systematically review the current evidence by incorporating study-level and individual patient-level meta-analyses of women who received ovarian transplants, including frozen–thawed transplant, fresh or donor graft. SEARCH METHODS The review protocol was registered with PROSPERO (CRD42018115233). A comprehensive literature search was performed using MEDLINE, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials from database inception to October 2020. Authors were also contacted for individual patient data if relevant outcomes were not reported in the published manuscripts. Meta-analysis was performed using inverse-variance weighting to calculate summary estimates using a fixed-effects model. OUTCOMES The review included 87 studies (735 women). Twenty studies reported on ≥5 cases of ovarian transplants and were included in the meta-analysis (568 women). Fertility outcomes included pregnancy, live birth and miscarriage rates, and endocrine outcomes included oestrogen, FSH and LH levels. The pooled rates were 37% (95% CI: 32–43%) for pregnancy, 28% (95% CI: 24–34%) for live birth and 37% (95% CI: 30–46%) for miscarriage following frozen ovarian tissue transplantation. Pooled mean for pre-transplant oestrogen was 101.6 pmol/l (95% CI: 47.9–155.3), which increased post-transplant to 522.4 pmol/l (95% CI: 315.4–729; mean difference: 228.24; 95% CI: 180.5–276). Pooled mean of pre-transplant FSH was 66.4 IU/l (95% CI: 52.8–84), which decreased post-transplant to 14.1 IU/l (95% CI: 10.9–17.3; mean difference 61.8; 95% CI: 57–66.6). The median time to return of FSH to a value <25 IU/l was 19 weeks (interquartile range: 15–26 weeks; range: 0.4–208 weeks). The median duration of graft function was 2.5 years (interquartile range: 1.4–3.4 years; range: 0.7–5 years). The analysis demonstrated that ovarian tissue cryopreservation and transplantation could restore reproductive and hormonal functions in women. Further studies with larger samples of well-characterized populations are required to define the optimal retrieval, cryopreservation and transplantation processes. WIDER IMPLICATIONS Ovarian tissue cryopreservation and transplantation may not only be effective in restoring fertility but also the return of reproductive endocrine function. Although this technology was developed as a fertility preservation option, it may have the scope to be considered for endocrine function preservation.

中文翻译：

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用于保留生殖和内分泌功能的新鲜和冷冻卵巢组织移植：系统评价和个体患者数据荟萃分析


背景卵巢组织冷冻保存涉及将手术取出的卵巢组织冷冻并储存在低于 –190°C 的液氮或汽氮中。可以将组织解冻并移植回来，目的是恢复生育能力或卵巢内分泌功能。人类卵巢组织冷冻和移植技术在过去 20 年中不断发展，特别是在青春期前癌症患者的生育力保存方面。使用自体移植物或供体组织进行新鲜卵巢组织移植是最近的发展；它有可能保留因良性妇科疾病而切除卵巢的女性的生育能力和荷尔蒙功能。卵巢组织冷冻保存和移植技术自诞生以来发展迅速；然而，这种干预措施成功的证据主要基于病例报告和病例系列。目的和基本原理本研究的目的是通过对接受卵巢移植（包括冻融移植、新鲜移植或供体移植）的女性进行研究水平和个体患者水平的荟萃分析，系统地回顾当前证据。检索方法 审查方案已在 PROSPERO 注册（CRD42018115233）。使用 MEDLINE、EMBASE、CINAHL 和 Cochrane 对照试验中央注册库进行了从数据库建立到 2020 年 10 月的全面文献检索。如果已发表的手稿中未报告相关结果，我们也会联系作者以获取个体患者数据。使用逆方差加权进行荟萃分析，以使用固定效应模型计算汇总估计值。结果 该评价包括 87 项研究（735 名女性）。 20 项研究报告了≥5 例卵巢移植病例，并被纳入荟萃分析（568 名女性）。生育结果包括妊娠率、活产率和流产率，内分泌结果包括雌激素、FSH 和 LH 水平。妊娠的汇总率为 37% (95% CI: 32–43%)，活产的汇总率为 28% (95% CI: 24–34%)，流产后的汇总率为 37% (95% CI: 30–46%)冷冻卵巢组织移植。移植前雌激素的汇总平均值为 101.6 pmol/l（95% CI：47.9–155.3），移植后增加至 522.4 pmol/l（95% CI：315.4–729；平均差：228.24；95% CI： 180.5–276）。移植前 FSH 的汇总平均值为 66.4 IU/l（95% CI：52.8–84），移植后降至 14.1 IU/l（95% CI：10.9–17.3；平均差 61.8；95% CI：57） –66.6）。 FSH 恢复到 <25 IU/l 值的中位时间为 19 周（四分位数范围：15-26 周；范围：0.4-208 周）。移植物功能的中位持续时间为 2.5 年（四分位数范围：1.4-3.4 年；范围：0.7-5 年）。分析表明，卵巢组织冷冻保存和移植可以恢复女性的生殖和激素功能。需要对特征明确的群体的更大样本进行进一步研究，以确定最佳的检索、冷冻保存和移植过程。更广泛的意义 卵巢组织冷冻保存和移植不仅可以有效恢复生育能力，还可以恢复生殖内分泌功能。尽管该技术是作为生育力保存选项而开发的，但它可能具有保存内分泌功能的考虑范围。