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体外受精中获取的卵母细胞数量:在疗效和安全性之间取得平衡。

The number of oocytes retrieved during IVF: a balance between efficacy and safety.

机构信息

Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Reproductive Medicine, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.

Department of Reproduction Epidemiology, Tornblad Institute, Department of Clinical Sciences, Lund University, SE-223 62 Lund, Sweden.

出版信息

Hum Reprod. 2018 Jan 1;33(1):58-64. doi: 10.1093/humrep/dex334.

Abstract

STUDY QUESTION

What is the relationship between the number of oocytes collected in fresh IVF treatments and the likelihood of cumulative delivery rate (fresh and frozen) per oocyte aspiration, severe ovarian hyperstimulation syndrome (OHSS) and thromboembolic events?

SUMMARY ANSWER

Cumulative delivery rate per aspiration increases up to 20 oocytes retrieved and then evens out while the incidence of severe OHSS increases more rapidly from around 18 oocytes and thromboembolic events, although rare, occurs in particular if 15 or more oocytes are retrieved.

WHAT IS KNOWN ALREADY?: Previous studies have shown that the number of oocytes retrieved for IVF is a positive predictor of live birth in fresh cycles. Few studies have investigated cumulative live birth rates and OHSS in relation to the number of aspirated oocytes.

STUDY DESIGN, SIZE, DURATION: Retrospective population-based registry study including 39 387 women undergoing 77 956 fresh IVF cycles in the period 2007-2013 and 36 270 consecutive transfers of frozen/thawed embryos in the period 2007-2014.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from The Swedish National Quality Registry of Assisted Reproduction (Q-IVF) including all IVF cycles with oocyte retrieval performed in public or private infertility clinics during the study period, was cross-linked to the National Patient Register regarding diagnostic codes (ICD 10) for severe (OHSS) and thromboembolic events. Oocyte donation cycles were excluded.

MAIN RESULTS AND THE ROLE OF CHANCE

Live birth delivery rate in fresh cycles increased up to 11 oocytes retrieved and then evened out, where the live birth rate was 30.3% for a 34-year-old woman. The cumulative delivery rate per aspiration, including fresh transfer and all subsequent transfers of frozen-thawed embryos (FET cycles) per oocyte retrieval, increased up to approximately 20 oocytes where it reached 45.8%. The adjusted odds ratio (AOR) for live birth by the number of oocytes was 1.064 (95% CI: 1.061; 1.067). The incidence of severe OHSS increased significantly by the number of oocytes, particularly if more than 18 oocytes were retrieved. The AOR for OHSS by the number of oocytes was 1.122 (95% CI: 1.08; 1.137). Thromboembolic events were rare, a total of 16 events in 14 patients were observed, and occurred in particular if 15 or more oocytes were retrieved.

LIMITATIONS, REASONS FOR CAUTION: All FET cycles might not be included. Some embryos cryopreserved between 2010 and 2013 might still result in additional births until 2018. Furthermore the gonadotrophin dose was not included in the Q-IVF Registry in the study period, thus adjustment for dose was not possible.

WIDER IMPLICATIONS OF THE FINDINGS

The results suggest a shift at approximately 18-20 oocytes where the cumulative delivery rate per aspiration levels off and, at the same time, the incidence of severe OHSS increases more rapidly. Thromboembolic events, although rare, should also be taken into consideration at stimulation regimes for IVF. Evaluating data taking both efficacy and the most serious safety aspects into account, is a new approach and of crucial importance both for patients undergoing IVF and their physicians.

STUDY FUNDING/COMPETING INTEREST: Financial support was received through an agreement relating to research and the education of doctors (ALFGBG-70 940) and grant from the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest.

摘要

研究问题

在新鲜的体外受精(IVF)治疗中采集的卵子数量与每个卵子抽吸的累积分娩率(新鲜和冷冻)、严重卵巢过度刺激综合征(OHSS)和血栓栓塞事件之间存在什么关系?

总结答案

每个抽吸的卵子累积分娩率在采集 20 个卵子之前会增加,然后趋于平稳,而严重 OHSS 的发生率从大约 18 个卵子开始迅速增加,血栓栓塞事件虽然罕见,但如果采集了 15 个或更多的卵子,就会特别发生。

已知情况

先前的研究表明,在新鲜周期中,IVF 采集的卵子数量是活产的一个积极预测因素。很少有研究调查与抽吸卵子数量相关的累积活产率和 OHSS。

研究设计、规模、持续时间:回顾性基于人群的注册研究,包括 2007 年至 2013 年期间 39387 名接受 77956 次新鲜 IVF 周期的妇女和 2007 年至 2014 年期间连续 36270 次冷冻/解冻胚胎转移的妇女。

参与者/材料、设置、方法:该研究的数据来自瑞典辅助生殖质量登记处(Q-IVF),包括在研究期间公共或私人不孕诊所进行的所有卵子回收 IVF 周期,并与国家患者登记处关于严重(OHSS)和血栓栓塞事件的诊断代码(ICD 10)进行交叉链接。排除了卵子捐赠周期。

主要结果和机会的作用

新鲜周期的活产分娩率在采集 11 个卵子之前增加,然后趋于平稳,34 岁女性的活产率为 30.3%。每个抽吸的卵子累积分娩率,包括新鲜转移和随后所有冷冻-解冻胚胎(FET 周期)的转移,在采集大约 20 个卵子时达到 45.8%。通过卵子数量调整的活产优势比(AOR)为 1.064(95%CI:1.061;1.067)。严重 OHSS 的发生率随着卵子数量的增加而显著增加,特别是如果采集了 18 个以上的卵子。通过卵子数量调整的 OHSS 的 AOR 为 1.122(95%CI:1.08;1.137)。血栓栓塞事件很少见,总共在 14 名患者中观察到 16 例,特别是如果采集了 15 个或更多的卵子,就会特别发生。

局限性、谨慎的原因:可能没有包括所有的 FET 周期。一些在 2010 年至 2013 年间冷冻的胚胎可能仍会导致额外的生育,直到 2018 年。此外,在研究期间,Q-IVF 登记处没有包括促性腺激素剂量,因此无法进行剂量调整。

研究结果的更广泛意义

研究结果表明,大约在 18-20 个卵子时出现了一个转折点,每个抽吸的卵子累积分娩率趋于平稳,同时严重 OHSS 的发生率迅速增加。尽管血栓栓塞事件很少见,但在进行 IVF 刺激方案时也应考虑到这一点。评估同时考虑疗效和最严重的安全性方面的数据,是一种新的方法,对接受 IVF 的患者及其医生都至关重要。

研究资金/利益冲突:研究得到了一项关于研究和医生教育的协议(ALFGBG-70 940)和 Hjalmar Svensson 研究基金会的资助。作者均无任何利益冲突。

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