BACKGROUND Freeze-all IVF cycles are becoming increasingly prevalent for a variety of clinical indications. However, the actual treatment objectives and preferred treatment regimens for freeze-all cycles have not been clearly established. OBJECTIVE AND RATIONALE We aimed to conduct a systematic review of all aspects of ovarian stimulation for freeze-all cycles. SEARCH METHODS A comprehensive search in Medline, Embase and The Cochrane Library was performed. The search strategy included keywords related to freeze-all, cycle segmentation, cumulative live birth rate, preimplantation genetic diagnosis, preimplantation genetic testing for aneuploidy, fertility preservation, oocyte donation and frozen-thawed embryo transfer. We included relevant studies published in English from 2000 to 2018. OUTCOMES Our search generated 3292 records. Overall, 69 articles were included in the final review. Good-quality evidence indicates that in freeze-all cycles the cumulative live birth rate increases as the number of oocytes retrieved increases. Although the risk of severe ovarian hyperstimulation syndrome (OHSS) is virtually eliminated in freeze-all cycles, there are certain risks associated with retrieval of large oocyte cohorts. Therefore, ovarian stimulation should be planned to yield between 15 and 20 oocytes. The early follicular phase is currently the preferred starting point for ovarian stimulation, although luteal phase stimulation can be used if necessary. The improved safety associated with the GnRH antagonist regimen makes it the regimen of choice for ovarian stimulation in freeze-all cycles. Ovulation triggering with a GnRH agonist almost completely eliminates the risk of OHSS without affecting oocyte and embryo quality and is therefore the trigger of choice. The addition of low-dose hCG in a dual trigger has been suggested to improve oocyte and embryo quality, but further research in freeze-all cycles is required. Moderate-quality evidence indicates that in freeze-all cycles, a moderate delay of 2-3 days in ovulation triggering may result in the retrieval of an increased number of mature oocytes without impairing the pregnancy rate. There are no high-quality studies evaluating the effects of sustained supraphysiological estradiol (E2) levels on the safety and efficacy of freeze-all cycles. However, no significant adverse effects have been described. There is conflicting evidence regarding the effect of late follicular progesterone elevation in freeze-all cycles. WIDER IMPLICATIONS Ovarian stimulation for freeze-all cycles is different in many aspects from conventional stimulation for fresh IVF cycles. Optimisation of ovarian stimulation for freeze-all cycles should result in enhanced treatment safety along with improved cumulative live birth rates and should become the focus of future studies.

中文翻译：

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卵巢刺激对所有IVF周期的冻结：系统评价。

背景技术对于各种临床适应症而言，所有IVF冷冻周期都变得越来越普遍。但是，尚未明确确定冷冻全周期的实际治疗目标和首选治疗方案。目的和理由我们旨在对冷冻周期所有卵巢刺激的各个方面进行系统的回顾。搜索方法在Medline，Embase和Cochrane库中进行了全面搜索。搜索策略包括与全速冻，周期分割，累计活产率，植入前遗传学诊断，非整倍性，生育力保存，卵母细胞捐赠和冻融胚胎移植相关的植入前遗传学测试的关键词。我们纳入了2000年至2018年间以英文发表的相关研究。结果我们的搜索产生了3292条记录。全面的，69条文章被纳入最终评价。高质量的证据表明，在冷冻的所有周期中，随着取回的卵母细胞数量的增加，累计活产婴儿的出生率也随之增加。尽管在所有冷冻周期中都几乎消除了严重的卵巢过度刺激综合症（OHSS）的风险，但仍存在与回收大量卵母细胞群相关的某些风险。因此，应计划卵巢刺激产生15至20个卵母细胞。卵泡早期是目前卵巢刺激的首选起点，尽管必要时可以使用黄体期刺激。与GnRH拮抗剂治疗方案相关的安全性提高，使其成为冷冻全周期卵巢刺激的首选治疗方案。用GnRH激动剂触发排卵几乎可以完全消除OHSS的风险，而不会影响卵母细胞和胚胎的质量，因此是选择的触发因素。已提出在双重触发中添加低剂量hCG可改善卵母细胞和胚胎质量，但需要对全冷冻周期进行进一步研究。中等质量的证据表明，在整个冷冻周期中，排卵触发中延迟2-3天的中度延迟可能会导致增加数量的成熟卵母细胞而不损害怀孕率。没有高质量的研究评估持续超生理雌二醇（E2）水平对全周期冷冻的安全性和有效性的影响。但是，没有明显的不良反应。关于在所有冷冻周期中晚期卵泡孕酮升高的影响，有相互矛盾的证据。对婴儿的影响在所有方面，全天候周期的卵巢刺激与新鲜IVF周期的常规刺激不同。针对所有冷冻周期优化卵巢刺激应可提高治疗安全性，并提高活产累积率，应成为未来研究的重点。