STUDY QUESTION Do ongoing pregnancy rates (OPRs) differ in predicted hyperresponders undergoing ART after IVM of oocytes compared with conventional ovarian stimulation (OS) for IVF/ICSI? SUMMARY ANSWER One cycle of IVM is non-inferior to one cycle of OS in women with serum anti-Müllerian hormone (AMH) levels ≥10 ng/ml. WHAT IS KNOWN ALREADY Women with high antral follicle count and elevated serum AMH levels, indicating an increased functional ovarian reserve, are prone to hyperresponse during ART treatment. To avoid iatrogenic complications of OS, IVM has been proposed as a mild-approach alternative treatment in predicted hyperresponders, including women with polycystic ovary syndrome (PCOS) who are eligible for ART. To date, inferior pregnancy rates from IVM compared to OS have hampered the uptake of IVM by ART clinics. However, it is unclear whether the efficiency gap between IVM and OS may differ depending on the extent of AMH elevation. STUDY DESIGN, SIZE, DURATION This study is a retrospective cohort analysis of clinical and laboratory data from the first completed highly purified hMG (HP-hMG) primed, non-hCG-triggered IVM or OS (FSH or HP-hMG stimulation in a GnRH antagonist protocol) cycle with ICSI in predicted hyperresponders ≤36 years of age at a tertiary referral university hospital. A total of 1707 cycles were included between January 2016 and June 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS Predicted hyperresponse was defined as a serum AMH level ≥3.25 ng/ml (Elecsys® AMH, Roche Diagnostics). The primary outcome was cumulative ongoing pregnancy rate assessed 10–11 weeks after embryo transfer (ET). The predefined non-inferiority limit was −10.0%. The analysis was adjusted for AMH strata. Time-to-pregnancy, defined as the number of ET cycles until ongoing pregnancy was achieved, was a secondary outcome. Statistical analysis was performed using a multivariable regression model controlling for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE Data from 463 IVM cycles were compared with those from 1244 OS cycles. Women in the IVM group more often had a diagnosis of Rotterdam PCOS (434/463, 93.7%) compared to those undergoing OS (522/1193, 43.8%), were significantly younger (29.5 years versus 30.5 years, P ≤ 0.001), had a higher BMI (25.7 kg/m2 versus 25.1 kg/m2, P ≤ 0.01) and higher AMH (11.6 ng/ml versus 5.3 ng/ml, P ≤ 0.001). Although IVM cycles yielded more cumulus–oocyte complexes (COCs) (24.5 versus 15.0 COC, P ≤ 0.001), both groups had similar numbers of mature oocytes (metaphase II (MII)) (11.9 MII versus 10.6 MII, P = 0.9). In the entire cohort, non-adjusted cumulative OPR from IVM was significantly lower (198/463, 42.8%) compared to OS (794/1244, 63.8%), P ≤ 0.001. When analysing OPR across different serum AMH strata, cumulative OPR in both groups converged with increasing serum AMH, and OPR from IVM was non-inferior compared to OS from serum AMH levels >10 ng/ml onwards (113/221, 51.1% (IVM); 29/48, 60.4% (OS)). The number of ETs needed to reach an ongoing pregnancy was comparable in both the IVM and the OS group (1.6 versus 1.5 ET’s, P = 0.44). Multivariable regression analysis adjusting for ART type, age, BMI, oocyte number, and PCOS phenotype showed that the number of COCs was the only parameter associated with OPR in predicted hyperresponders with a serum AMH >10 ng/ml. LIMITATIONS, REASONS FOR CAUTION These data should be interpreted with caution as the retrospective nature of the study holds the possibility of unmeasured confounding factors. WIDER IMPLICATIONS OF THE FINDINGS Among subfertile women who are eligible for ART, IVM, and OS resulted in comparable reproductive outcomes in a subset of women with a serum AMH ≥10 ng/ml. These findings should be corroborated by a randomised controlled trial (RCT) comparing both treatments in selected patients with elevated AMH. STUDY FUNDING/COMPETING INTEREST(S) There was no external funding for this study. P.D. has been consultant to Merck Healthcare KGaA (Darmstadt, Germany) from April 2021 till June 2023 and is a Merck employee (Medical Director, Global Medical Affairs Fertility) with Merck Healthcare KGAaA (Darmstadt, Germany) since July 2023. He declares honoraria for lecturing from Merck KGaA, MSD, Organon, and Ferring. The remaining authors declared no conflict of interest pertaining to this study. TRIAL REGISTRATION NUMBER N/A.

中文翻译：

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ART 在预测高反应者中的临床结果：卵母细胞的体外成熟与 IVF/ICSI 的传统卵巢刺激

研究问题 与常规 IVF/ICSI 卵巢刺激 (OS) 相比，卵母细胞 IVM 后接受 ART 的预测高反应者的持续妊娠率 (OPR) 是否存在差异？摘要答案 对于血清抗苗勒氏管激素 (AMH) 水平≥10 ng/ml 的女性，一个周期的 IVM 并不劣于一个周期的 OS。已知的情况 窦卵泡计数高且血清 AMH 水平升高（表明卵巢储备功能增强）的女性在 ART 治疗期间容易出现过度反应。为了避免 OS 的医源性并发症，IVM 已被提议作为预测高反应者的温和方法替代治疗，包括符合 ART 资格的多囊卵巢综合征 (PCOS) 女性。迄今为止，与 OS 相比，IVM 的妊娠率较低，阻碍了 ART 诊所对 IVM 的采用。然而，尚不清楚 IVM 和 OS 之间的效率差距是否会根据 AMH 升高的程度而有所不同。研究设计、规模、持续时间 本研究是对第一个完成的高度纯化 hMG (HP-hMG) 引发、非 hCG 触发的 IVM 或 OS（GnRH 中的 FSH 或 HP-hMG 刺激）的临床和实验室数据的回顾性队列分析。拮抗剂方案）在三级转诊大学医院预测的年龄≤36岁的高反应者中进行ICSI周期。2016 年 1 月至 2022 年 6 月期间总共纳入了 1707 个周期。 参与者/材料、设置、方法 预测的高反应定义为血清 AMH 水平≥3.25 ng/ml（Elecsys® AMH，罗氏诊断）。主要结局是胚胎移植（ET）后10-11周评估的累积持续妊娠率。预定义的非劣效性限度为-10.0%。针对 AMH 层对分析进行了调整。次要结果是妊娠时间，定义为持续妊娠之前的 ET 周期数。使用控制潜在混杂因素的多变量回归模型进行统计分析。主要结果和机会的作用 将 463 个 IVM 周期的数据与 1244 个 OS 周期的数据进行了比较。与接受 OS 治疗的女性 (522/1193, 43.8%) 相比，IVM 组中的女性更常被诊断为鹿特丹 PCOS (434/463, 93.7%)，且年龄明显更年轻（29.5 岁 vs 30.5 岁，P ≤ 0.001）， BMI 较高（25.7 kg/m2 对比 25.1 kg/m2，P ≤ 0.01），AMH 较高（11.6 ng/ml 对比 5.3 ng/ml，P ≤ 0.001）。尽管 IVM 周期产生了更多的卵丘-卵母细胞复合物 (COC)（24.5 与 15.0 COC，P ≤ 0.001），但两组的成熟卵母细胞（中期 II (MII)）数量相似（11.9 MII 与 10.6 MII，P = 0.9）。在整个队列中，IVM 的未调整累积 OPR 显着低于 OS (794/1244, 63.8%) (198/463, 42.8%)，P ≤ 0.001。当分析不同血清 AMH 层的 OPR 时，两组的累积 OPR 随着血清 AMH 的增加而收敛，并且与血清 AMH 水平> 10 ng/ml 以后的 OS 相比，IVM 的 OPR 并不劣于 (113/221, 51.1% (113/221, 51.1%)体外监测）；29/48, 60。4%（操作系统））。IVM 组和 OS 组中达到持续妊娠所需的 ET 数量相当（1.6 与 1.5 ET，P = 0.44）。调整ART类型、年龄、BMI、卵母细胞数量和PCOS表型的多变量回归分析表明，在血清AMH＞10ng/ml的预测高反应者中，COC数量是与OPR相关的唯一参数。局限性、谨慎的原因 这些数据应谨慎解释，因为该研究的回顾性性质可能存在无法测量的混杂因素。研究结果的更广泛意义 在符合 ART、IVM 和 OS 资格的生育力低下的女性中，血清 AMH ≥10 ng/ml 的女性子集的生殖结果相当。这些发现应该得到一项随机对照试验 (RCT) 的证实，该试验比较了选定的 AMH 升高患者的两种治疗方法。研究资助/竞争利益 本研究没有外部资助。PD 于 2021 年 4 月至 2023 年 6 月期间担任 Merck Healthcare KGaA（德国达姆施塔特）的顾问，并自 2023 年 7 月起担任 Merck Healthcare KGAaA（德国达姆施塔特）的默克员工（全球医疗事务生育中心医疗总监）。曾在 Merck KGaA、MSD、Organon 和 Ferring 进行授课。其余作者声明与本研究不存在利益冲突。试用注册号 不适用。